PYRETHROIDS

Classification | Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

Specific Substances

1) C26H21F6NO5
2) 129141 (EPA)
3) GZ2008500 (NIOSH)
4) Cyclopropanecarboxylic acid, 2,2-dimethyl-3-(3-oxo-3-(2,2,2-trifluoro-1-(trifluoromethyl) ethoxy)-1-propenyl)-, cyano(3-phenoxyphenyl)methyl ester, (1R-(1-alpha(S*),3-alpha(Z)))-
5) Ardent
6) RU 38702
7) CAS 101007-06-1

1) C19H26O3
2) 004001 (EPA)
3) GZ1925000 (NIOSH)
4) IMO 3.2, IMO 6.1
5) 4941112 (STCC)
6) (+)-Allelrethonyl (+)-cis,trans-chrysanthemate
7) Type I pyrethroid
8) d-Allethrin
9) d-trans Allethrin
10) Allethrin I
11) Allethrine I
12) Allethrolone ester of chrysanthemummono-carboxylic acid
13) Allyl cinerin
14) Allyl cinerin I
15) Allyl homolog of cinerin I
16) 2-Allyl-4-hydroxy-3-methyl-2-cyclopenten-1-one ester of chrysanthemummonocarboxylic acid
17) d,I-2-Allyl-4-hydroxy-3-methyl-2-cyclopenten-1-one-d,l-chrysanthemum monocarboxylate
18) di-3-Allyl-2-methyl-4-oxocyclopent-2-enyl dl-cis trans chrysanthemate
19) 3-Alyl-4-keto-2-methylcyclopentenyl chrysanthemummonocarboxylate
20) 3-Allyl-2-methyl-4-oxo-2-cyclopenten-1-yl chrysanthemate
21) Allylrethronyl dl-cis-trans-chrysanthemate
22) Bioaltrina (Portuguese)
23) d-trans-chrysanthemate allethrolone
24) D-trans allethrin
25) dl-allethrolone d-trans chrysanthemate
26) Bioallethrin
27) Cinerin I allyl homolog
28) Cyclopropanecarboxylic acid, 2,2-dimethyl-3-(2-methyl-1-propenyl)-, 2-methyl-4-oxo3-(2-propenyl)-2- cyclopenten-1-yl ester
29) Depallethrin
30) 2,2-Dimethyl-3-(2-methyl-1-propenyl) cyclopropanecarboxylic acid 2-methyl-4-oxo-3-(2-propenyl-2-cyclopenten-1-yl) ester
31) Exthrin
32) FDA 1446
33) FMC 249
34) Necarboxylic acid
35) NIA 249
36) OMS 468
37) Pallethrine
38) Pynamin
39) Pynamin-Forte
40) Pyresin
41) CAS 584-79-2

1) C22H19C12NO3
2) GZ1251400 (NIOSH)
3) CAS 67375-30-8

1) C18H21ClO4
2) 218400 (EPA)
3) GZ1452000 (NIOSH)
4) 6-Chloropiperonyl chrysanthemumate
5) Cyclopropanecarboxylic acid, 2,2-dimethyl-3-(2-methylpropenyl)-, 6- chloropiperonyl ester, (+-)-cis, trans-
6) Chrysanthemumic acid 6-chloropiperonyl ester
7) 6-Chloropiperonyl ester of chrysanthemummonocarboxylic acid
8) CAS 70-43-9

1) C23H22ClF3O2
2) 128825 (EPA)
3) GZ1227800 (NIOSH)
4) Cyclopropanecarboxylic acid, 3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethyl-,(2- methyl(1,1'-biphenyl)-3-yl)methyl ester, (Z)- (RTECS)
5) Biphenthrin
6) FMC 54800
7) CAS 82657-04-3

1) C22H26O3
2) 097802 (EPA)
3) GZ1310500 (NIOSH)
4) GZ1227800 (NIOSH)
5) Cyclopropanecarboxylic acid, 2,2-dimethyl-3-(2-methylpropenyl)-, (5-benzyl-3-furyl)methyl ester, d-trans-
6) (+)-trans-Bioresmethrin
7) (+)-trans-Resmethrin
8) 1R-trans-Resemethrin
9) 3-Furanmethanol, 5-benzyl-, 2,2-dimethyl-3-(2-methylpropenyl)cyclopropanecarboxylate, t-(+)-
10) 5-Benzyl-3-furylmethyl(+)-trans-chrysanthemate
11) AI 3-27662
12) Biobenzyfuroline
13) Bioresmethrine
14) Bioresmetrina (Portuguese)
15) d-trans-((5-Benzyl-3-furyl)methyl)chrysanthemumate
16) d-trans-(5-Benzyl-3-furyl)methyl chrysanthemate
17) d-trans-Chrysron
18) d-trans-Resmethrin
19) FMC 18739
20) Isathrine
21) Isatrin
22) NIA-18739
23) NRDC 107
24) Penick 1390
25) Pyrethroid NRDC 107
26) Resbuthrin
27) RU-11484
28) SBP-1390
29) CAS 28434-01-7

1) C22H26O3
2) 097804 (EPA)
3) GZ1430000 (NIOSH)
4) Cyclopropanecarboxylic acid, 2,2-dimethyl-3-(2-methylpropenyl)-, (5-benzyl-3-furyl)methyl ester, (+)-(Z)-
5) Type I pyrethroid
6) (+)-cis-Resmethrin
7) -Benzyl-3-furylmethyl (+)-cis-chrysanthemate
8) 5-Benzyl-3-furylmethyl(1R-cis)-3-(2-methylprop-1-enyl)-2,2-dimethylcyclopropanecarboxylate
9) AI 3-27987
10) FMC 26021
11) NIA 26021
12) NRDC 119
13) RU 12063
14) CAS 35764-59-1

1) C22H18Cl2FNO3
2) 128831 (EPA)
3) GZ1253000 (NIOSH)
4) Cyano(4-fluoro-3-phenoxylphenyl)methyl 3-(2,2-dichloroethenyl)- 2,2-dimethyl-cyclopropanecarboxylate
5) Cyfluthin
6) Cyfluthrine
7) Cyclopropanecarboxylic acid, 2-(2,2-dichlorovinyl)-3,3-dimethyl-, ester with (4-fluoro-3-phenoxphenyl)hydroxyacetonitrile (TSCA)
8) (Rs-alpha-cyano-4-fluoro-3-phenoxybenzyl((Rs,3rs:1rs,3sr)-3-(2,2- dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate
9) Cyfoxylate
10) Responsar
11) Bay FCR 1272
12) Eulan sp
13) Baythroid h
14) Solfac
15) Baythroid
16) FCR 1272
17) CAS 68359-37-5

1) C23H19ClF3NO3
2) 128867 (EPA)
3) Cyclopropanecarboxylic acid, 3-(2-chloro-3,3,3-trifluoro-1-propenyl)- 2,2-dimethyl-, cyano (3-phenoxyphenyl)methyl ester (TSCA)
4) 3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethylcyclopropanecarboxylic acid cyano(3-phenoxyphenyl)methyl ester
5) Type II pyrethroid
6) CAS 68085-85-8

1) C22H19Cl2NO3
2) 109702 (EPA)
3) GZ1250000 (NIOSH)
4) Alpha-cyano-3-phenoxybenzyl 2,2-dimethyl-3-(2,2-dichlorovinyl) cyclopropane carboxylate
5) Cyclopropanecarboxylic acid, 3-(2,2-dichloroethenyl)-2,2-dimethyl-, cyano(3-phenoxyphenyl) methyl ester (TSCA)
6) Type II pyrethroid
7) NRDC 149
8) Wl 43467
9) Supermethrin (veterinary product)Czechoslovak productType II pyrethroidAlpha cyano pyrethroid(Rs)-alpha-cyano-3-phenoxybenzyl-(1rs)-cis-3(2,2-dichlorvinyl)- 2,2-dimethyl cyclopropan carboxylate
10) CAS 52315-07-8

1) C24H25NO3
2) 129013 (EPA)
3) GZ1453500 (NIOSH)
4) Cyclopropanecarboxylic acid, 2,2-dimethyl-3-(2-methyl-1-propenyl)-, cyano(3-phenoxyphenyl) methyl ester (TSCA)
5) CAS 39515-40-7

1) C22H19Br2NO3
2) 097805 (EPA)
3) GZ1233000 (NIOSH)
4) GZ1232000 (NIOSH)
5) Type II pyrethroid
6) Cyclopropanecarboxylic acid, 3-(2,2-dibromoethenyl)-2,2-dimethyl-, cyano(3-phenoxyphenyl) methyl ester, (1R-(1-alpha(S*),3-alpha))- (TSCA)
7) DecamethrinGZ1240000 (NIOSH)GZ1233000 (NIOSH)Cyclopropanecarboxylic acid, 3-(2,2-dibromovinyl)-2,2-dimethyl-, cyano(3-phenoxyphenyl) methyl ester, cis-(+)-Alpha-1-cyano 3-phenoxybenzyl d-cis 2,2-dimethyl-3-(2,2-dibromovinyl) cyclopropane Ru 22974NRDC 161DecamethrineDecisDeltaFMC 45498
8) Decamethrin (cis isomer)NRDC 156GZ1240000 (NIOSH)DecisCyclopropanecarboxylic acid, 3-(2,2-dibromovinyl)-2,2-dimethyl-, cyano(3-phenoxyphenyl) methyl ester, cis-(+)-Alpha-1-cyano 3-phenoxybenzyl d-cis 2,2-dimethyl-3-(2,2-dibromovinyl) cyclopropane carboxylate
9) CAS 52918-63-5

1) C19H26O2
2) 034101 (EPA)
3) GZ1455000 (NIOSH)
4) Dimetrin
5) Cyclopropanecarboxylic acid, 2,2-dimethyl-3-(2-methyl-1-propenyl)-, (2,4-dimethylphenyl) ester
6) 2,4-dimethylbenzyl 2,2-dimethyl-3-(2-methylpropenyl)cyclopropanecarboxylate
7) (2,4-dimethylphenyl)methyl 2,2-dimethyl-3-(2-methyl-1-propenyl) cyclopropanecarboxylate
8) 2,4-dimethylbenzyl ester of cis,trans-chrysanthemumic acid
9) 2,4-dimethylbenzylchrysanthemumate
10) CAS 70-38-2

1) C25H22ClNO3
2) 109303 (EPA)
3) CY1576367, CY1576350 (NIOSH)
4) (s)-cyano(3-phenoxy phenyl)methyl (s)-4-chloro-alpha-(1-methylethyl)benzene acetate
5) CAS 66230-04-4

1) C22H23NO3
2) 127901 (EPA)
3) GZ2090500, GZ2090000 (NIOSH)
4) Cyclopropanecarboxylic acid, 3-(2,2-dichloroethenyl)-2,2-dimethyl-, cyano(3-phenoxyphenyl) methyl ester (TSCA)
5) Type II pyrethroid
6) Fenpropanate
7) CAS 39515-41-8

1) C25H22ClNO3
2) 109301 (EPA)
3) CY1576350 (NIOSH)
4) Benzeneacetic acid, 4-chloro-alpha-(1-methylethyl)-, cyano(3-phenoxyphenyl)methyl ester, (+-)- (TSCA)
5) Alpha-cyano-3-phenoxybenzyl 2-(4-chlorophenyl)isovalerate
6) Alpha-cyano-3-phenoxybenzyl-2-(4-chlorophenyl)-3-methylbutyrate
7) Cyano(3-phenoxyphenyl)methyl 4-chloro-alpha-(1-methylethyl)benzeneacetate
8) Type II pyrethroid
9) Phenvalerate
10) Pydrin
11) Wl 43775
12) S 5602
13) SD 43775
14) CAS 51630-58-1

1) C26H23F2NO4
2) 118301 (EPA)
3) CY1578620 (NIOSH)
4) CAS 70124-77-5

1) C28H22Cl2FNO3
2) CY1578620 (NIOSH)
3) CAS 69770-45-2

1) C26H22ClF3N2O3
2) 109302 (EPA)
3) YV9397100 (NIOSH)
4) DL-Valine, N-(2-chloro-4-(trifluoromethyl)phenyl)-, cyano(3-phenoxyphenyl)methyl ester (TSCA)
5) Alpha-cyano-3-phenoxybenzyl (R)-2-(2-chloro-4-(Trifluoromethyl)anilino -3-methyl-butanoate) [Rs isomer]
6) Cyano(3-phenoxyphenyl)methyl n-(2-chloro-4-(Trifluoromethyl) phenyl) -d-valinate
7) Alpha-cyano-3-phenoxybenzyl n-(2-chloro-alpha, alpha, alpha-trifluoro-p- tolyl)-d-valinate [Rs isomer]
8) Type II pyrethroid
9) Tau-Fluvalinate
10) CAS 69409-94-5

1) C18H22O3
2) GZ2003000 (NIOSH)
3) Cyclopropanecarboxylic acid, 2,2-dimethyl-3-(2-methylpropenyl)-, 5-(2-propynyl)furfuryl ester
4) 5-(2-Propynyl)-2-furfuryl chrysanthemumcarboxylate
5) 5-Propargyl-2-furylmethyl dl-cis,trans-chrysanthemate
6) 5-Propargylfurfuryl chrysanthemate
7) Prothrin
8) Pynamin D
9) CAS 23031-38-1

1) C21H26O4
2) 466300 (EPA)
3) GZ1640000 (NIOSH)
4) (+-)-furethionyl (+-)-cis, trans-chrysanthemate
5) Cyclopropanecarboxylic acid, 2,2-dimethyl-3-(2-methylpropenyl-, ester with (+-)-2-furfuryl- 4-hydroxy-3-methyl-2-cyclopenten-1-one, (+-)-cis, trans-
6) CAS 17080-02-3

1) C17H22N2O4
2) 004006 (EPA)
3) CAS 72963-72-5

1) C23H24O4S
2) GZ1266550 (NIOSH)
3) Beilstein Reference Number: BRN 1605066
4) Cyclopropanecarboxylic acid, 3-((dihydro-2-oxo-3(2H)-thienylidene)methyl)-2,2-dimethyl-,(5- (phenylmethyl)-3-furanyl)methyl ester, (1R-(1-alpha,3-alpha(E)))-
5) cis-Kadethrin
6) 1R,cis-RU 15525
7) ENT 29117
8) RU 15525
9) CAS 58769-20-3

1) C21H20Cl2O3
2) 109701 (EPA)
3) GZ1255000 (NIOSH)
4) 3-phenoxybenzyl (+-)-3-(2,2-dichlorovinyl)-2,2- dimethylcyclopropanecarboxylate
5) Cyclopropanecarboxylic acid, 3-(2,2-dichlorovinyl)-2,2-dimethyl-, 3-phenoxybenzyl ester, (+-)-, (cis,trans)- (TSCA)
6) Type I pyrethroid
7) Permetrina (Portuguese)
8) (3-Phenoxyphenyl)methyl 3-(2,2-dichlorethenyl)-2,2- dimethylcyclopropanecarboxylate
9) Ndrc-143
10) Ectiban
11) A13-29158
12) S-3151
13) Pounce
14) BW-21-z
15) Ambush
16) SBP-1513
17) FMC 33297
18) PP 557
19) CAS 52645-53-1

1) C23H26O3
2) 069005 (EPA)
3) GZ1255000 (NIOSH)
4) Type I pyrethroid
5) Fenothrin
6) Phenoxythrin
7) D-phenothrin
8) CAS 26002-80-2
9) 3-phenoxybenzyl-(1RS, 3RS: 1RS, 3SR)-2,2-dimthyl-3-(2-methylprop-1-enyl) Cyclopropanecarboxylate

1) C19H24O3
2) 128722 (EPA)
3) CAS 23031-36-9

1) C22H26O3
2) 097801 (EPA)
3) GZ1310000 (NIOSH)
4) 195022 (NSC)
5) Type I pyrethroid
6) ARI-B
7) Benzofuroline
8) Benzyfuroline
9) (5-Benzyl-3-furyl)methyl 2,2-dimethyl-3-(2-methylpropenyl)cyclopropanecarboxylate
10) (5-Benzyl-3-furyl) methyl-2,2-dimethyl-3-(2-methylpropenyl)-cyclopropane-carboxylate
11) 5-Benzyl-3-furylmethyl(+-)-cis,trans-chrysanthemate
12) Chryson
13) Crossfire
14) Cyclopropanecarboxylic acid, 2,2-dimethyl-3-(2-methylpropenyl)-,(4(2- benzyl)furyl)methyl ester
15) Cyclopropanecarboxylic acid, 2,2-dimethyl-3-(2-methylpropenyl)-,(5-benzyl-3-furyl)methyl ester (TSCA))
16) Dimethyl 3-(2-methyl-1-propenyl)cyclopropanecarboxylate
17) Enforcer
18) FMC 17370
19) FOR-SYN
20) NIA 17370
21) NRDC 104
22) OMS-1206
23) Penick 138L
24) Penncapthrin
25) Pyresthrin
26) Premgard
27) Pynosect
28) Resmetrina (Portuguese)
29) SBP-1382
30) SB Penick 1382
31) Synthrin
32) CAS 10453-86-8

1) C17H14ClF7O2
2) 128912 (EPA)
3) GZ1227850 (NIOSH)
4) CAS 79538-32-2

1) C19H25NO4
2) 069003 (EPA)
3) GZ1710000 (NIOSH)
4) GZ1730000 (NIOSH)
5) 2,3,4,5-Tetrahydrophthalimidomethylchrysanthemate
6) 3,4,5,6-Tetrahydrophthalimidomethyl cis and trans dl chrysanthemummono- carboxylic acid
7) 3,4,5,6-Tetrahydro-phthalimidomethylester der dl-cis-trans-chrysanthemum- saeure (German)
8) (1-Cyclohexane-1,2-dicarboxyimido)methyl chrysanthemumate
9) Cyclopropanecarboxylic acid, 2,2-dimethyl-3-(2-methyl-1-propenyl)-, (1,3,4,5,6,7-hexahydro-, 1,3-dioxo-2h-isoindol-2-yl)methyl ester
10) Type II pyrethroid
11) Phthalthrin
12) SP-1103
13) Tetramethrine (French)
14) Tetramethrin racemic 1:4 mixtureC19H25NO4.4C19H25NO4GZ1720000 (NIOSH)Phthalthrin racemic mixture
15) CAS 7696-12-0

1) C22H19Br4NO3
2) 121501 (EPA)
3) GZ2009500 (NIOSH)
4) Cyclopropanecarboxylic acid, 2,2-dimethyl-3-(1,1,2,2,- tetrabromoethyl)-, cyano-(3-phenoxy phenyl)methyl ester (TSCA)
5) Type II pyrethroid
6) CAS 66841-25-6

1.2.1) MOLECULAR FORMULA
1) Molecular formulae for some common pyrethroids are as follows: (HSDB, 2006; Agency for Toxic Substances and Disease Registry (ATSDR), 2003)Acrinathrin: C26H21F6NO5Allethrin: C19H26O3Alphacypermethrin: C22H19C12NO3Barthrin: C18H21ClO4Bifenthrin: C23H22ClF3O2Bioresmethrin: C22H26O3Cismethrin: C22H26O3Cyfluthrin: C22H18Cl2FNO3Cyhalothrin: C23H19ClF3NO3Cypermethrin: C22H19Cl2NO3Cyphenothrin: C24H25NO3Decamethrin: C22H19Br2NO3Deltamethrin: C22H19Br2NO3Dimethrin: C19H26O2Esfenvalerate: C25H22ClNO3Fenpropathrin: C22H23NO3Fenvalerate: C25H22ClNO3Flucythrinate: C26H23F2NO4Flumethrin: C28H22Cl2FNO3Fluvalinate: C26H22ClF3N2O3Furamethrin: C18H22O3Furethrin: C21H26O4Imiprothrin: C17H22N2O4Kadethrin: C23H24O4SPermethrin: C21H20Cl2O3Phenothrin: C23H26O3Prallethrin: C19H24O3Resmethrin: C22H26O3Teflurin: C17H14ClF7O2Tetramethrin: C19H25NO4Tralomethrin: C22H19Br4NO3

Available Forms Sources

1) Pyrethroids are synthetic esters similar to the pyrethrins. Except for deltamethrin, pyrethroids consist of a complex isomer mix with differing isomeric ratios, which may account for their wide range in toxicity (HSDB, 2006; Agency for Toxic Substances and Disease Registry (ATSDR), 2003).

a) Resmethrin, for example, is a mixture of two isomers. Commercial formulations contain approximately 70% trans-isomer (bioresmethrin) and approximately 30% cis-isomer (cismethrin) (HSDB, 2006; ILO, 1998).

2) Pyrethroids are classified into first generation (Type I) and second generation (Type II) groups based on their structure and clinical characteristics. As some pyrethroids (fenpropathrin, cyphenothrin) exhibit intermediate properties, these classes are not absolute. Common characteristics of these two types are (Agency for Toxic Substances and Disease Registry (ATSDR), 2003; Krieger, 2001):

a) Type I: esters of chrysanthemic acid and alcohols; furan ring and terminal side chain moieties; unstable outdoors (sensitive to light, air, and temperature). Some Type I pyrethroids are allethrin, cismethrin, permethrin, phenothrin, resmethrin, and tetramethrin.
b) Type II: photolabile moieties replaced by dichlorovinyl, dibromovinyl substituents and aromatic rings; 3-phenoxybenzyl alcohol derivatives in the alcohol moiety; stable outdoors. Some Type II pyrethroids are cyhalothrin, cypermethrin, deltamethrin, fenpropathrin, fenvalerate, fluvalinate, and tralomethrin.

3) Pyrethroids are specially modified to resist photolysis and to improve their stability in the natural environment. Some, like allethrin, are combined with piperonyl butoxide or other synergists, to enhance pest control effectiveness. Many more congeners like permethrin, which have the more stable halovinyl derivatives, are under development (HSDB, 2006; Agency for Toxic Substances and Disease Registry (ATSDR), 2003).
4) Many pyrethroids are formulated in petroleum distillates for spray applications. Some are sold in cans pressurized by propellants. Examples of pyrethroid formulations include (HSDB, 2006; Meister, 2003; Budavari, 2001; Tomlin, 2000; Hartley & Kidd, 1990):

1) aerosols: allethrin, cyfluthrin, fenpropathrin, resmethrin, tetramethrin
2) aqueous pressurized spray: fenpropathrin
3) coil: allethrin
4) dusts: cyphenothrin, permethrin
5) emulsifiable liquid concentrate: allethrin, cyfluthrin, cypermethrin, cyphenothrin, deltamethrin, esfenvalerate, fenpropathrin, permethrin, resmethrin, tetramethrin, tralomethrin
6) flowable (suspended powder in liquid): deltamethrin, esfenvalerate
7) fumigant.: cyphenothrin
8) gel: tralomethrin
9) granules: cyfluthrin
10) mat (for electric vaporizer): allethrin
11) micro capsule: cyphenothrin
12) oil liquid or spray: allethrin, cyfluthrin, cyphenothrin, fenpropathrin, resmethrin, tetramethrin
13) smokes: permethrin
14) spray (aerial) - applied in combination with other insecticides (tetramethrin, malathion): resmethrin
15) thermal fogging (smoke) concentrate: deltamethrin
16) transparent emulsion: fenpropathrin
17) ultra-low volume (ULV) concentrate: cypermethrin, deltamethrin, esfenvalerate, permethrin
18) wettable powder: cyfluthrin, cypermethrin, cyphenothrin, deltamethrin, permethrin

1) Pyrethroids are modern synthetic insecticides similar chemically to natural pyrethrins, but modified to increase their stability and effectiveness in indoor and outdoor environments (HSDB, 2006).

1) Pyrethroids are used to control a wide variety of insects and pests in both commercial and household settings (HSDB, 2006; Taplin & Meinking, 1996). Common pyrethroids include permethrin, which is available as a 1% creme rinse for treating head lice (Prod Info Nix(R) Creme Rinse, permethrin 1%, 2001) and as a 5% topical cream for treating body lice (Prod Info Elimite(R) Cream, permethrin 5%, 2000).
2) Examples of common protective uses include (HSDB, 2006; Meister, 2003; Budavari, 2001; Tomlin, 2000; Hartley & Kidd, 1990):

1) animal ectoparasites: allethrin, cyhalothrin (Boophilus microplus, Haematobia irritans - cattle); Bovicola ovis, Linognathus spp., Melophagus ovinus - sheep), deltamethrin; esfenvalerate; permethrin
2) animal facilities (horse stables): cyhalothrin, resmethrin
3) crops (cereals, corn, cotton, coffee, potatoes, tobacco, tea, rice, vines, fruit, vegetables, ornamentals): esfenvalerate (especially for pests resistant to organochlorine, organophosphorus, and carbamate insecticides); fenpropathrin (especially mites); fenvalerate; tralomethrin
4) fabric protection: fenpropathrin
5) forests: esfenvalerate, permethrin
6) greenhouses (white flies): fenpropathrin, resmethrin
7) households (flies, mosquitoes, cockroaches, bedbugs): deltamethrin, esfenvalerate, permethrin
8) mosquito nets: permethrin
9) non-cropland: esfenvalerate, fenvalerate
10) pet sprays and shampoo: resmethrin
11) public health: deltamethrin (Chagas disease in South America; malaria control in Central America and Africa); permethrin (body lice); resmethrin [combined with other insecticides (tetramethrin, malathion) to control mosquitoes]
12) soil insects (crops): teflurin
13) stored commodities (cereals, grains, coffee beans, dry beans): deltamethrin
14) wood preservative: deltamethrin, permethrin

3) Approved uses of specific pyrethroids periodically change, hence applicators should routinely consult with federal, state, and local authorities (HSDB, 2006).

Overview

Life Support

Clinical Effects

0.2.1)

A) USES: Pyrethroids are highly active insecticides, synthetic forms of chemically-similar natural pyrethrins derived from Chrysanthemum cinerariaefolium. Common pyrethroids include permethrin which is available to treat head and body lice.
B) PHARMACOLOGY: Pyrethroids act directly on insect nerve axons, they bind to open sodium channels and markedly prolong axonal sodium channel depolarization, causing a prolonged sodium current to flow which leads to hyperexcitation of the nervous system. Delayed repolarization and paralysis of the pests consequentially occurs. Pyrethroids have a much lower toxic effect in mammals than in insects. They are powerful paralytic poisons in insects, causing "quick knockdown" and in sufficient dosage, death. These agents are active against a broad range of pests, including lice, ticks, fleas, mites, and other arthropods.
C) TOXICOLOGY: Paresthesia caused by pyrethroids is a result of a direct dermal effect on intracutaneous nerve endings at very low doses. It is thought to be secondary to repetitive firing in peripheral skin nerves. Pyrethroids are divided into two types based on their structures and clinical manifestation in overdose. Most type I pyrethroids (eg, permethrin, allethrin, biuallethine, cismethrin, permethrin, phenothrin, resmethrin, tetramethrin) do not contain a cyano group while type II pyrethroids (eg, cyhalothrin, cypermethrin, deltamethrin, fenpropathrin, fenvalerate, esfenvalerate) do. These classes are not absolute as some pyrethroids exhibit intermediate properties.
D) EPIDEMIOLOGY: Exposures to pyrethroids are common but significant toxicity is rare and usually due to allergic reactions.
E) WITH THERAPEUTIC USE

1) The most common adverse effects are mucous membrane, dermal or ocular irritation. Exposure may trigger bronchospasm in asthmatics.

F) WITH POISONING/EXPOSURE

1) Type II pyrethroids are generally more toxic than type I pyrethroids. Type I pyrethroid poisoning include severe fine tremor, marked reflex hyperexcitability, sympathetic activation, paresthesia (dermal exposure), and hyperthermia. Some authors describe Type I pyrethroid poisoning as a "T-syndrome" (coarse tremors). Systemic effects of Type II poisoning include profuse watery salivation, coarse tremor, sympathetic activation, increased extensor tone, moderate reflex hyperexcitability, seizures, choreoathetosis, paresthesia (dermal exposure), pulmonary edema, hyperglycemia, and coma. Type II pyrethroid poisoning is sometimes referred to as a "CS-syndrome" (choreoathetosis or clonic seizures and salivation). Intermediate pyrethroids (fenpropathrin, cyphenothrin) which possess properties of both type I and type II pyrethroids may cause tremors with profuse salivation, a combination of T and CS syndromes.
2) INHALATION EXPOSURE: Headache, dizziness, burning or itching of the face, airway irritation, rhinitis, sneezing, pulmonary edema, and hypersensitivity reactions characterized by pneumonitis, cough, dyspnea, wheezing, chest pain, and bronchospasm. Rare cases of respiratory paralysis and cardiopulmonary arrest have been reported.
3) OCULAR EXPOSURE: Eye irritation, burning, itching, corneal damage, periorbital edema.
4) INGESTION EXPOSURE: Burning sensation in the mouth, laryngitis, pharyngitis, nausea, vomiting, diarrhea, abdominal cramps, gastritis, paresthesias, headache, dizziness, hyperexcitability, seizures, and coma. Large ingestions can cause abdominal pain and vomiting followed by coma and seizures within 20 to 60 minutes.
5) CHRONIC EXPOSURE: Allergic dermatitis, alopecia, facial dysesthesias, personality changes, sensomotor polyneuropathy, memory and concentration deficits.
6) In cases of ingestion or inhalation of pyrethroid emulsions, it should be noted that excipients such as xylene and surfactants may contribute to toxicity, particularly dysesthesias. Xylene is also a CNS depressant, which may contribute to impaired consciousness with ingestion.

0.2.20)

A) Permethrin is classified as US FDA pregnancy category B. No teratogenic potential to acrinathrin was shown in rat and rabbit studies. There are no adequate and well-controlled studies in pregnant women to determine the teratogenicity of permethrin. It is not known if permethrin affects the quantity or composition of breast milk. Maternal use of topical preparations generally carries less risk than systemically administered drug; risk to the infant should be considered relative to the inherent toxicity of the drug. The Centers for Disease Control and prevention recommends the use of permethrin for the treatment of lice infestations during lactation.

0.2.21)

A) Congenital leukemia has been reported in an infant whose mother abused permethrin during pregnancy. A case-control study showed increased metabolite levels of pyrethroid pesticides in urine to be associated with an approximate 2-fold increased risk of childhood acute lymphocytic leukemia (ALL).

Laboratory Monitoring

Treatment Overview

0.4.2)

A) TREATMENT OF MILD TO MODERATE TOXICITY

1) Treatment is symptomatic and supportive. Manage mild hypotension with IV fluids.

B) TREATMENT OF SEVERE TOXICITY

1) Treatment is symptomatic and supportive. Treat severe hypotension IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine if unresponsive to fluids. Treat seizures with IV benzodiazepines; barbiturates or propofol may be needed if seizures persist or recur. Administer neuromuscular blocking agents with continuous EEG monitoring in refractory patients to avoid hyperthermia and muscle destruction. In patients with acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required.

C) DECONTAMINATION

1) PREHOSPITAL: Prehospital gastrointestinal decontamination is generally not recommended due to the potential for rapid onset of seizures and CNS depression after substantial ingestion. Spontaneous vomiting is common after ingestion of type II pyrethroids.
2) HOSPITAL: Activated charcoal is not routinely recommended as most exposures are trivial. With large ingestions patients are at risk for abrupt onset of seizures or mental status depression. Charcoal administration should be limited to patients with a severely toxic ingestion who are awake and able to protect their airway or who have been intubated. Consider aspiration of gastric contents with a small nasogastric tube if it can be performed soon after a large ingestion of a concentrated insecticide solution.
3) INHALATION EXPOSURE: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta-2 agonist and corticosteroids.
4) OCULAR EXPOSURE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persists, patient should be seen in a healthcare facility.
5) DERMAL EXPOSURE: Remove contaminated clothing and wash exposed area thoroughly with soap and water. A physician may need to examine the area if irritation or pain persists.

D) AIRWAY MANAGEMENTS

1) Endotracheal intubation should be performed in patients with excessive drowsiness and the inability to protect their own airway.

E) ANTIDOTE

1) None.

F) HYPERSENSITIVITY REACTION

1) MILD/MODERATE: Antihistamines with or without inhaled beta agonists, corticosteroids or epinephrine. SEVERE: Oxygen, aggressive airway management, antihistamines, epinephrine, corticosteroids, ECG monitoring, and IV fluids.

G) ACUTE LUNG INJURY

1) Lung injury may be more likely to occur due to the excipients (eg, piperonyl butoxide). Supplemental oxygen; PEEP and mechanical ventilation may be needed. Consider surfactant in severe cases of acute lung injury.

H) PARESTHESIAS

1) Topical vitamin E application may be effective in treating paresthesias.

I) EXCESSIVE SALIVATION

1) Severe salivation may be treated with intravenous atropine. Drying of excessive secretion is a preferable indicator of adequate atropinization rather than heart rate or pupil size.

J) ENHANCED ELIMINATION PROCEDURE

1) Pyrethroid compounds are rapidly metabolized by the body; extracorporeal methods of elimination would not be expected to enhance their elimination.

K) PATIENT DISPOSITION

1) HOME CRITERIA: Asymptomatic patients with inadvertent ingestions of small amounts, and dermal or inhalation exposures can be managed at home.
2) OBSERVATION CRITERIA: A patient with symptoms or a history of large or deliberate ingestion should be observed in an emergency department for at least 4 to 6 hours for any signs of CNS depression or seizures or the development of delayed pulmonary symptoms. The possibility of coingestants, such as hydrocarbons and organophosphate or carbamate insecticides, should be considered.
3) ADMISSION CRITERIA: All patients who develop severe symptoms or have moderate symptoms that do not resolve over 6 to 12 hours of observation, should be admitted.
4) CONSULT CRITERIA: Consult a medical toxicologist or poison center for patients with severe toxicity or in whom the diagnosis is uncertain.

L) PHARMACOKINETICS

1) Absorption: Oral: pyrethroids are rapidly absorbed. Peak serum concentrations have been reported at 4 hours. Widely distributed, sequestered in lipids. Rapidly metabolized by ester hydrolysis, with metabolites subsequently eliminated in the urine. Dermal: Pyrethroids are highly lipophilic, passing through cell membranes and are absorbed slowly through the skin, which usually prevents systemic toxicity. However, a significant reservoir of pyrethroid may remain bound to the epidermis.

M) DIFFERENTIAL DIAGNOSIS

1) Irritating gas exposures such as chlorine and chloramine. Also can mimic substances that can trigger bronchospasm especially in asthmatic patients.

0.4.3)

A) Inhaled pyrethroids evoke stimulation of peripheral sense organs which makes it relatively easy to sense high level exposures. Generally, victims leave the area of high level pyrethroid exposure prior to attaining significant acute toxicity.
B) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.

0.4.4)

A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.

0.4.5)

A) OVERVIEW

1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
2) Vitamin E topical application is highly effective in relieving paresthesias.

Range Of Toxicity

Clinical Effects

Summary Of Exposure

1) The most common adverse effects are mucous membrane, dermal or ocular irritation. Exposure may trigger bronchospasm in asthmatics.

Vital Signs

3.3.3)

A) WITH POISONING/EXPOSURE

1) HYPERTHERMIA may occur following type I pyrethroid poisoning (Ray, 1991).

3.3.5)

A) WITH POISONING/EXPOSURE

1) Decreased pulse rate may occur following severe exposures to type I or type II pyrethroids (Gotoh et al, 1998).

Heent

3.4.3)

A) WITH POISONING/EXPOSURE

1) PERIORBITAL EDEMA has been described during hypersensitivity reactions (Culver et al, 1988) and in homeowners after their houses were sprayed (Moretto, 1991).
2) IRRITATION: Eye burning, itching and irritation may result from exposure to fumes or spray or direct ocular contamination (Fuortes, 1999; Lessenger, 1992).
3) CORNEAL DAMAGE: May result from ocular exposures, probably due to organic-solvent carrier (Ray, 1991).

3.4.5)

A) WITH POISONING/EXPOSURE

1) RHINITIS and sneezing have been reported (Newton & Breslin, 1983; Moretto, 1991) and nasal irritation was reported following inhalation (Fuortes, 1999).

a) INCIDENCE: Sneezing and rhinorrhea occurred in 32% of workers exposed to the pyrethroids deltamethrin or fenvalerate (He et al, 1988).

3.4.6)

A) WITH POISONING/EXPOSURE

1) PHARYNGITIS: A sore, scratchy throat has been reported (Paton & Walker, 1988; (Gotoh et al, 1998; Anon, 2000). Oral burning sensation and laryngitis have been reported following ingestion (Gotoh et al, 1998). Throat irritation has been reported following inhalational exposure (Fuortes, 1999).

a) In an observational and retrospective study, sore throat was reported in 9 (16.1%) of 56 cases of pyrethroid poisoning (amount ingested: 50 to 300 mL) (Cha et al, 2014).

2) TASTE PERVERSION: An oily taste and burning sensation of the mouth developed in a 74-year-old woman who inadvertently sprayed an insecticide containing pyrethrins, pyrethroids, kerosene and a chlorofluorocarbon propellant into her mouth (Grant & Schuman, 1993). The burning sensation resolved over 5 months but the taste disorder persisted.

Cardiovascular

3.5.2)

A) TACHYARRHYTHMIA

1) CASE SERIES: Sinus tachycardia was reported in 10 cases of pyrethroid exposure (He et al, 1989).
2) Type II pyrethroids may increase cardiac contractility both directly by action on cardiac muscle and by circulating and locally released catecholamines (Ray, 1991).
3) In an observational and retrospective study, sinus tachycardia was reported in 11 (21.2%) of 56 cases of pyrethroid poisoning (amount ingested: 50 to 300 mL) (Cha et al, 2014).

B) PROLONGED QT INTERVAL

1) WITH POISONING/EXPOSURE

a) In an observational and retrospective study, prolonged QT interval was reported in 40 (76.9%) of 56 cases of pyrethroid poisoning (amount ingested: 50 to 300 mL) (Cha et al, 2014).

C) ATRIAL FIBRILLATION

1) WITH POISONING/EXPOSURE

a) In an observational and retrospective study, atrial fibrillation was reported in 1 (1.9%) of 56 cases of pyrethroid poisoning (amount ingested: 50 to 300 mL) (Cha et al, 2014).

D) HYPOTENSIVE EPISODE

1) Sequelae of hypoxia and hypotension may occur in rare, life-threatening cases (Ray, 1991; He et al, 1989).
2) In an observational and retrospective study, hypotension (systolic blood pressure of less than 90 mmHg), an atypical presentation, was reported in 6 (10.7%) of 56 cases of pyrethroid poisoning (amount ingested: 50 to 300 mL). Atypical presentations (ie, respiratory failure, hypotension, pneumonia, acute kidney injury, seizure, and Glasgow Coma Scale of less than 15) developed in 39.3% of patients and predictors of these conditions included a pyrethroid ingestion of greater than 250 mL and serum lactate of greater than 3.5 mmol/L (Cha et al, 2014).

Respiratory

3.6.2)

A) ACUTE ALLERGIC REACTION

1) Hypersensitivity reactions and asthma-like symptoms characterized by pneumonitis, cough, dyspnea, wheezing, chest pain, and bronchospasm may occur, depending on the compound. Persistent respiratory tract irritation, coughing and systemic hypersensitivity symptoms were reported in a family following inhalational exposure to permethrin crop spray (Fuortes, 1999).

a) Sneezing and rhinorrhea were noted in 32% of workers exposed to deltamethrin or fenvalerate (He et al, 1988).

2) CASE SERIES: Shortness of breath, chest tightening and wheezing developed in several workers exposed to a pyrethroid pesticide inadvertently introduced into air conditioning ducts (Lessenger, 1992). Three of these patients (2 of whom smoked) had persistent wheezing 7 months after exposure.
3) CASE SERIES: Shortness of breath developed in 2 of 18950 (0.0106%) patients exposed to a pyrethroid pediculicide (Andrews et al, 1992).

B) DYSPNEA

1) WITH POISONING/EXPOSURE

a) In an observational and retrospective study, dyspnea was reported in 5 (8.9%) of 56 cases of pyrethroid poisoning (amount ingested: 50 to 300 mL) (Cha et al, 2014).

C) ACUTE LUNG INJURY

1) Acute, severe poisoning following exposure to a type II pyrethroid may result in non-cardiogenic pulmonary edema (He et al, 1989).
2) CASE SERIES (INCIDENCE): Pulmonary edema was noted in 16 of 344 (4.6%) pyrethroid ingestions, but no mention was made of the solvent's effects (He et al, 1989).

D) RESPIRATORY FAILURE

1) Death due to respiratory depression may occur following severe poisoning (Ray, 1991; Poulos et al, 1982).
2) CASE REPORT (ADULT): A 45-year-old developed respiratory paralysis and died following ingestion of beans cooked in a small amount of cypermethrin 10% (Poulos et al, 1982).
3) In an observational and retrospective study, respiratory failure requiring ventilator support, an atypical presentation, was reported in 10 (17.9%) of 56 cases of pyrethroid poisoning (amount ingested: 50 to 300 mL). Atypical presentations (ie, respiratory failure, hypotension, pneumonia, acute kidney injury, seizure, and Glasgow Coma Scale of less than 15) developed in 39.3% of patients and predictors of these conditions included a pyrethroid ingestion of greater than 250 mL and serum lactate of greater than 3.5 mmol/L (Cha et al, 2014).

E) PNEUMONIA

1) WITH POISONING/EXPOSURE

a) In an observational and retrospective study, pneumonia, an atypical presentation, was reported in 4 (7.1%) of 56 cases of pyrethroid poisoning (amount ingested: 50 to 300 mL). Atypical presentations (ie, respiratory failure, hypotension, pneumonia, acute kidney injury, seizure, and Glasgow Coma Scale of less than 15) developed in 39.3% of patients and predictors of these conditions included a pyrethroid ingestion of greater than 250 mL and serum lactate of greater than 3.5 mmol/L (Cha et al, 2014).

Neurologic

3.7.2)

A) CENTRAL NERVOUS SYSTEM FINDING

1) CASE SERIES (OCCUPATIONAL): A survey of cotton farmers (3113 pyrethroid spraymen), conducted in 1987 and 1988, found 26% developed symptoms which included abnormal facial sensations, dizziness, headache, fatigue, nausea, or loss of appetite. Only 10 subjects with significant systemic symptoms, including listlessness or muscular fasciculations, were diagnosed as having mild occupational acute pyrethroid toxicity. The incidence was noted to be 0.31% in subjects exposed to pure pyrethroids and 0.38% in pyrethroid organophosphate mixtures (Chen et al, 1991).

B) PARESTHESIA

1) Skin contamination with high doses of type II pyrethroids may commonly cause severe, transient skin paresthesia (Ray & Forshaw, 2000; Wilks, 2000; Soderlund et al, 2000; Pauluhn, 1996; Miyamoto et al, 1995). Type I pyrethroids and natural pyrethrins also possess this activity, but it is much weaker, and not usually recognized (Miyamoto et al, 1995). Stinging or burning of the extremities, frequently in a stocking-and-glove distribution, may be followed by numbness (Ray & Forshaw, 2000; Budavari, 1996). Burning, tingling, itching, or numbness most often occurs in the facial area. Doses causing paresthesia are generally far lower than those causing central or systemic toxicity; thus, paresthesia is considered a localized irritant effect which generally disappears within 24 hours (Wilks, 2000; He et al, 1989; Le Quesne et al, 1980).

a) A characteristic syndrome of paresthesias consisting of stinging, burning, and numbness has been described in one-third of persons occupationally exposed to the synthetic pyrethroid fenvalerate (Tucker & Flannigan, 1983).
b) In a health survey of 199 workers who divided and packaged pyrethroids and were exposed via inhalation and dermal exposures, 2 out of 3 had symptoms of burning sensations and tightness or numbness. One third had abnormal facial sensations, dizziness, fatigue, sniffs and sneezes. No other clinical symptoms were noted (He et al, 1988).

2) ONSET and DURATION: Typically, dysesthesias begin from 0.5 to 1 hour to several hours after dermal exposure and often resolve within 24 hours (Tucker & Flanigan, 1983) Paton & Walker, 1988). Aggravating factors include: light, wind, or heating. There is usually no inflammatory reaction (no erythema, no edema), no functional or histopathological changes (Miyamoto et al, 1995).
3) PYRETHROIDS vs PYRETHRINS: Paresthesias from natural pyrethrins are less intense than those from synthetic agents (pyrethroids) (Ray, 1991) (Martin & Hester, 1941).

a) Differences are also noted between synthetic pyrethroids. The degree of paresthesia was 4-times greater for fenvalerate, a 5-cyano derivative, than for permethrin, a non-cyano type 1 pyrethroid (Flannigan et al, 1985a). Type II pyrethroids (cyano derivatives) evoke more intense paresthesias than do type I pyrethroids (noncyano derivatives) (Pauluhn, 1996).

4) FACIAL DYSESTHESIAS: Exposure to synthetic pyrethroids may result in abnormal facial sensations. Cheeks and periorbital areas are most frequently affected (LeQuesne et al, 1980; (He et al, 1988).

a) INCIDENCE: Effects occurred in 70% to 83% of exposed workers.
b) ONSET: Dysesthesias developed within 30 minutes to 3 hours of exposure.
c) DURATION: Effects dissipated within 24 hours.

5) OCCUPATIONAL EXPOSURES are noted to be associated with paresthesias without clinical symptoms, usually associated as erythema, edema or vesiculation (Tucker et al, 1984).
6) ELECTROMYOGRAPHY, ELECTROENCEPHALOGRAPHY and neurologic examination showed slowing of neuronal conduction and diffuse right lower extremity neuropathy in a woman who applied a pyrethroid insecticide over her entire body several times daily for 3 months. She applied an overlay of mineral oil after spraying the insecticide, followed by a repeat spraying of the insecticide (Robertson & Mueller, 1997).

C) SEIZURE

1) CASE REPORT (CHILDREN): Two brothers (4-year-old and 3-year-old) developed generalized tonic-clonic seizures followed by unconsciousness and thrashing behavior after each ingested a mosquito coil (allethrin). Both patients regained consciousness after 36 hours of supportive therapy (Garg & Garg, 2004).
2) Massive ingestion (e.g., inadvertent preparation of food in pyrethroid product) may cause headaches, fasciculation, and seizures (Ray, 1991). Fasciculation and seizures are seen following type II pyrethroid poisoning, while fine tremors may occur after type I pyrethroid poisoning. Seizures may rarely be followed by paralysis in humans (Narahashi et al, 1992).
3) CASE SERIES: Seizures were reported in 34 cases of PYRETHROID exposure, 5 were occupational and the remainder accidental (He et al, 1989).
4) CASE REPORT (ADULT): A 45-year-old developed seizures after ingesting beans cooked in a small amount of cypermethrin 10% instead of oil (Poulos et al, 1982).
5) In an observational and retrospective study, seizure, an atypical presentation, was reported in 2 (3.6%) of 56 cases of pyrethroid poisoning (amount ingested: 50 to 300 mL). Atypical presentations (ie, respiratory failure, hypotension, pneumonia, acute kidney injury, seizure, and Glasgow Coma Scale of less than 15) developed in 39.3% of patients and predictors of these conditions included a pyrethroid ingestion of greater than 250 mL and serum lactate of greater than 3.5 mmol/L (Cha et al, 2014).
6) PRALLETHRIN (CASE REPORT): A 20-year-old woman developed generalized tonic clonic seizures after ingesting 2 bottles of mosquito repellent All-Out (prallethrin 1.6% w/w liquid, 35 mL in each bottle, total dose of 1120 mg). Despite supportive therapy, including diazepam and phenytoin, her seizures persisted. Her seizures eventually resolved after receiving propofol. She was discharged 7 days after presentation (Chandra et al, 2013).

D) CENTRAL NERVOUS SYSTEM DEFICIT

1) CASE SERIES: Disturbances in consciousness (drowsiness, coma) were reported in 51 of 344 cases (15%) of pyrethroid ingestion (He et al, 1989). CNS depression with coma may occur following type II pyrethroid poisoning.

a) ONSET: Large doses of pyrethroid concentrates caused coma within 20 minutes.

2) CASE REPORT (CHILDREN): Two brothers (4-year-old and 3-year-old) developed generalized tonic-clonic seizures followed by unconsciousness and thrashing behavior after each ingested a mosquito coil (allethrin). Both patients regained consciousness after 36 hours of supportive therapy (Garg & Garg, 2004).
3) CASE REPORT (ADULT): A 45-year-old became unconscious after ingesting beans cooked in a small amount of cypermethrin 10% (Poulos et al, 1982).
4) CASE REPORT (ADULT): A 59-year-old male was found unconscious after ingesting about 600 mL of a 20% permethrin emulsion. Initial Glasgow Coma Scale score was 11/15 with incomprehensible speech the most notable deficit. A component of the emulsion, xylene, most likely contributed to the impaired consciousness. The patient recovered following symptomatic therapy (Gotoh et al, 1998).
5) In an observational and retrospective study, a Glasgow Coma Scale score of less than 15, an atypical presentation, was reported in 19 (33.9%) of 56 cases of pyrethroid poisoning (amount ingested: 50 to 300 mL). Atypical presentations (ie, respiratory failure, hypotension, pneumonia, acute kidney injury, seizure, and Glasgow Coma Scale of less than 15) developed in 39.3% of patients and predictors of these conditions included a pyrethroid ingestion of greater than 250 mL and serum lactate of greater than 3.5 mmol/L (Cha et al, 2014).

E) DIZZINESS

1) INCIDENCE: Dizziness occurred in 60.6% of pyrethroid exposures in one series (He et al, 1989).
2) In an observational and retrospective study, dizziness was reported in 2 (3.6%) of 56 cases of pyrethroid poisoning (amount ingested: 50 to 300 mL) (Cha et al, 2014).

F) CENTRAL STIMULANT ADVERSE REACTION

1) Absorption of very large quantities (200 to 500 mL of concentrate) of pyrethroids has resulted in muscular fasciculations, drowsiness, coma, and seizures (He et al, 1989). Ray & Forshaw (2000) described two pyrethroid poisoning syndromes: type I produces reflex hyperexcitability and fine tremor; type II produces salivation, hyperexcitability, choreoathetosis, and seizures. Sympathetic activation is produced by both types of pyrethroids.

a) Symptoms are dependent on nervous system pyrethroid concentration (Dorman & Beasley, 1991).

G) CHOREOATHETOSIS

1) Choreoathetosis may be seen following type II pyrethroid poisoning (Ray & Forshaw, 2000; Miyamoto et al, 1995). These pyrethroids typically produce a choreoathetosis/salivation syndrome (CT-syndrome) in humans, characterized by sinuous writhing seizures accompanied by profuse salivation (Miyamoto et al, 1995; Soderlund & Bloomquist, 1989).

H) TREMOR

1) Type I pyrethroids (noncyano compounds) typically produce a tremor syndrome (T-syndrome) in animal poisonings characterized by coarse tremor, prostration, and increased sensitivity to external stimuli (Miyamoto et al, 1995; Soderlund & Bloomquist, 1989). Intermediate pyrethroids (fenpropathrin and cyphenothrin), which possess properties of both type I and type II pyrethroids, may cause tremors with profuse salivation, a combination of T and CS syndromes (Soderlund et al, 2000).
2) In an observational and retrospective study, tremor was reported in 1 (1.8%) of 56 cases of pyrethroid poisoning (amount ingested: 50 to 300 mL) (Cha et al, 2014).

I) HEADACHE

1) CASE SERIES: Headache occurred in 44.5% of pyrethroid exposures in one series (He et al, 1989).

J) ALTERED MENTAL STATUS

1) Chronic sequelae following acute topical pyrethroid poisonings have included reduced intellectual performance (20% to 30% reduction of mental endurance), personality changes, dysacousia, tinnitus, sensomotor-polyneuropathy (mostly in the lower legs) and orthostatic hypotonia. These findings came from a series of 4 adult cases which were analyzed over 2 years or more following toxic exposures (Muller-Mohnssen, 1999).
2) CASE SERIES: Six cases of chronic pyrethroid intoxication in living quarters, where a causal link between acute complaints and exposure could be established or not ruled out, were reported. In all of the six cases NO irreversible peripheral or central nervous system lesions could be found (Altenkirch et al, 1996).
3) CASE REPORT: Following 13 years of occupational exposure to pyrethroid insecticides, a 45-year-old woman was reported to have developed neurologic symptoms, which developed in a progressive manner. Clinical manifestations included loss of strength and performance, tiredness, apathy, a sensation of coldness, dysphoria, memory and concentration deficits, headache, decreased olfactory sensitivity, cardiac dysrhythmia and hypotension (Mitsche et al, 2000).

3.7.3)

A) ANIMAL STUDIES

1) CENTRAL NERVOUS SYSTEM ABNORMALITIES

a) PYRETHROID-BASED MOSQUITO REPELLENT: One animal study evaluated the effect of exposure of rat pups during early developmental stages to a pyrethroid-based mosquito repellent (allethrin, 3.6% w/v, 8 hours per day) inhalation on blood-brain barrier permeability. It was found that this exposure during early prenatal/postnatal/perinatal life may cause central nervous system abnormalities(Sinha et al, 2004).

Gastrointestinal

3.8.2)

A) TENESMUS

1) CASE REPORT (ADULT): A 45-year-old man developed nausea, prolonged vomiting with colicky pain, tenesmus, and diarrhea within a few minutes of eating lunch consisting of beans cooked with a small amount of cypermethrin 10% (Poulos et al, 1982).

B) VOMITING

1) INCIDENCE: Vomiting was reported in 56.8% of pyrethroid ingestions in one series and developed within 10 to 60 minutes (He et al, 1989; Shi et al, 1985). Among 3 persons exposed to resmethrin insecticide, symptoms of nausea, vomiting and diarrhea were reported (Anon, 2000). Nausea and vomiting, sometimes prolonged, are common after type II pyrethroid poisoning.
2) In an observational and retrospective study, nausea and vomiting were reported in 29 (51.8%) of 56 cases of pyrethroid poisoning (amount ingested: 50 to 300 mL) (Cha et al, 2014).

C) GASTRITIS

1) CASE REPORT: Hematemesis due to erosive gastritis was described after ingestion of 900 mL of water contaminated by deltamethrin (Hou, 1986).
2) CASE REPORT: Fiberscopic examination revealed mild erosive gastritis after the ingestion of about 600 mL of a 20% permethrin emulsion in an adult. Vomiting and diarrhea were extensive (Gotoh et al, 1998).

D) ABDOMINAL PAIN

1) WITH POISONING/EXPOSURE

a) In an observational and retrospective study, abdominal pain was reported in 19 (33.9%) of 56 cases of pyrethroid poisoning (amount ingested: 50 to 300 mL) (Cha et al, 2014).

E) EXCESSIVE SALIVATION

1) Poisoning with a type II pyrethroid commonly results in excessive salivation (Ray & Forshaw, 2000; Miyamoto et al, 1995). These pyrethroids typically produce a choreoathetosis/salivation syndrome (CT-syndrome) in humans, characterized by sinuous writhing seizures accompanied by profuse salivation (Miyamoto et al, 1995; Soderlund & Bloomquist, 1989). Intermediate pyrethroids (fenpropathrin and cyphenothrin), which possess properties of both type I and type II pyrethroids, may cause tremors with profuse salivation, a combination of T and CS syndromes (Soderlund et al, 2000).
2) Seizures and excessive salivation developed in a 20-year-old woman after ingesting 2 bottles of mosquito repellent, All-Out (prallethrin 1.6% w/w liquid, 35 mL in each bottle, total dose of 1120 mg) (Chandra et al, 2013).

Hepatic

3.9.3)

A) ANIMAL STUDIES

1) HEPATOCELLULAR DAMAGE

a) Chronic exposure has been reported to cause liver damage in animals (Lewis, 1996).

Genitourinary

3.10.2)

A) RENAL IMPAIRMENT

1) WITH POISONING/EXPOSURE

a) In an observational and retrospective study, acute kidney injury, an atypical presentation, was reported in 6 (10.7%) of 56 cases of pyrethroid poisoning (amount ingested: 50 to 300 mL). Atypical presentations (ie, respiratory failure, hypotension, pneumonia, acute kidney injury, seizure, and Glasgow Coma Scale of less than 15) developed in 39.3% of patients and predictors of these conditions included a pyrethroid ingestion of greater than 250 mL and serum lactate of greater than 3.5 mmol/L (Cha et al, 2014).

Acid-Base

3.11.2)

A) ACIDOSIS

1) Metabolic acidosis may be seen on arterial blood gas analysis following severe exposures (Gotoh et al, 1998). Acid metabolites from pyrethroids may contribute to the acidosis.
2) In an observational and retrospective study, metabolic acidosis was reported in 14 (25%) of 56 cases of pyrethroid poisoning (amount ingested: 50 to 300 mL) (Cha et al, 2014).

Hematologic

3.13.2)

A) LYMPHOCYTOPENIA

1) CASE REPORT: A 45-year-old woman, exposed occupationally to pyrethroid insecticides over a 13 year period, was noted to have an abnormally low lymphocyte count (<20%), with the lymphocyte-stimulating test (MTT) showing an irregular 3-day time course. Pyrethroids caused a significant decrease in cell proliferation (p<0.001 ranked pair test, Wilcoxon matched-pairs signed-ranks test) (Mitsche et al, 2000).

Dermatologic

3.14.2)

A) HYPERSENSITIVITY REACTION

1) Pyrethroids can cause allergic dermatitis, but not as severe or as frequently as pyrethrins (Fuortes, 1999; Budavari, 1996; Lisi, 1992). The usual lesion is a mild erythematous dermatitis with vesicles, papules in moist areas, and intense pruritus; a bulbous dermatitis may also develop (Ray, 1991; He et al, 1989; Hathaway et al, 1996).
2) CASE REPORTS: Three patients of a household developed urticaria, characterized by pruritic, raised erythematous lesions of the face and trunk following unintentional exposure to a permethrin crop spray (Fuortes, 1999).

B) ALOPECIA

1) Chronic sequelae to pyrethroid insecticide exposure has included alopecia (Mitsche et al, 2000; Muller-Mohnssen, 1999).

C) INJECTION SITE REACTION

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 36-year-old man developed only pain and a dime-sized area of erythema at the injection site after injecting 6 mL of a pyrethroid-containing product (Real Kill Ant and Roach killer 2; containing tralomethrin 0.01% and D-trans-allethrin 0.05%) into his antecubital fossa and 2 mL subcutaneously into his abdomen in a suicide attempt. His vital signs and all laboratory test results were normal. Following 4 hours of observation, his symptoms resolved completely (LoVecchio & Knight, 2005).

3.14.3)

A) ANIMAL STUDIES

1) RASH

a) Extensive animal studies with various synthetic pyrethroids have failed to show primary irritant effects or sensitizing properties (Miyamoto, 1976a; Knox & Tucker, 1982) Knox et al, 1983). Prolonged repeated daily exposure in rabbits resulted in mild erythema (Flannigan et al, 1985).

Musculoskeletal

3.15.2)

A) COMPARTMENT SYNDROME

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Following the subcutaneous injection of pyrethroid insecticide in her right arm, a 30-year-old woman developed severe swelling of the affected limb, edema, pain, tension, and compartment syndrome. A fasciotomy and superficial muscle debridement, with split-thickness skin grafting for coverage of the open wound were performed and she recovered without further sequelae (Aydin et al, 2004).

Endocrine

3.16.2)

A) HYPERGLYCEMIA

1) A large increase in serum glucose concentration may be seen following severe poisoning with a type II pyrethroid insecticide (Ray, 1991).
2) PREDICTOR OF OUTCOME: In a single institutional, retrospective cohort study, the clinical and laboratory features of 104 patients with type II pyrethroid poisoning were reviewed to determine whether hyperglycemia at presentation can predict the outcome in these patients. Overall, a complication rate of 26.9% and a mortality rate of 2.9% were observed. Respiratory failure, acidosis, and hypotension were the most common complications. A significantly higher incidence of complications was observed in diabetic patients as compared with non-diabetic patients (63.6% vs 22.6%; P = 0.004); however, mortality rate did not differ significantly (9.1% in diabetics vs 2.2% in non-diabetics; P = 0.193). In non-diabetic patients (n=93), patients with complications had a higher frequency of hyperglycemia, abnormalities in radiograph, depressed mentality (GCS 13 or lower), lower PaCO2 and HCO3 levels, and higher WBC and AST levels at the time of admission than non-complicated group. In these non-diabetic patients, hyperglycemia was a useful factor to predict the critical complications; however, because of the small number of patients with diabetes mellitus (n=11), no significant predictor factor for complications was observed (Kim et al, 2015).

B) HYPERCORTISOLISM

1) Serious poisoning with either type I or type II pyrethroids causes marked adrenal activation with increases in adrenaline and noradrenaline accompanying motor signs. Deltamethrin (type II pyrethroid) causes increased corticosteroid secretion at even lower doses (Ray & Forshaw, 2000).

Immunologic

3.19.2)

A) SEQUELA

1) Muller-Mohnssen (1999) reported pathological autoimmune disorders in some patients after more than 2 years following acute dermal exposures to pyrethroids. The following autoimmune diseases included: scleroderma-like syndrome, myasthenia-like syndrome with progressive muscle atrophy, autoimmune-hemolysis and autoimmune-thrombocytopenic purpura. Immune disorders resulting in opportunistic infections, particularly Candida infections of the gastrointestinal tract, were also reported. A causal relationship to exposure could not be established.
2) CASE REPORT: A 45-year-old woman, exposed occupationally to pyrethroids over a 13-year period, was found to have a change in factors regulating her immune system, which paralleled the pyrethroid intoxication. An increased allergy response was significant, which developed in a progressive manner (Mitsche et al, 2000). A causal relationship to exposure could not be established.

Reproductive

3.20.1)

3.20.2)

A) LACK OF EFFECT

1) ACRINATHRIN: No teratogenic potential to acrinathrin was shown in rat and rabbit studies (Anon, 1998).
2) PERMETHRIN: There are no adequate and well-controlled studies in pregnant women to determine the teratogenicity of permethrin. No adverse effect on reproductive function was seen at an oral dose of 180 mg/kg/day in a 3-generation rat study (Prod Info Elimite(R) Cream, permethrin 5%, 2000).

B) ANIMAL STUDIES

1) CENTRAL NERVOUS SYSTEM ABNORMALITIES

a) PYRETHROID-BASED MOSQUITO REPELLENT: In a study in rat pups, prenatal (gestational days 1 to 20), postnatal (days 1 to 30) and perinatal (gestation days 1 to 20 and postnatal days 1 to 30) exposure to a pyrethroid-based mosquito repellent (allethrin, 3.6% w/v, 8 hours per day) was associated with increased permeability of the blood brain barrier to sodium fluorescein but not Evans blue. This effect persisted 1 week after the exposure ceased (Sinha et al, 2004).

3.20.3)

A) PREGNANCY CATEGORY

1) Permethrin is classified as US FDA pregnancy category B (Prod Info Elimite(R) Cream, permethrin 5%, 2000).
2) The Centers for Disease Control and prevention recommends the use of permethrin for the treatment of lice infestations during pregnancy (Centers for Disease Control and Prevention, 2010).

B) AUTISM SPECTRUM DISORDER

1) In a study (the Childhood Autism Risks from Genetics and Environment [CHARGE] study) that tracked the risk of autism spectrum disorder (ASD) or developmental delay with gestational exposure to agricultural pesticides (n=970), residential proximity of mothers to organophosphate, chlorpyrifos, or pyrethroid pesticides during pregnancy was associated with an increased risk of ASD in children. Application of organophosphates within 1.25 km of a pregnant woman's home during gestation was associated with a significant 60% increased risk for ASD in her offspring, with a higher risk with third-trimester exposure (adjusted odds ratio [OR] 2). Second-trimester chlorpyrifos application within 1.5 km of the mother's home more than doubled the ASD risk of her offspring (adjusted OR, 3.3). Children of mothers residing near pyrethroid insecticide applications preconception (adjusted OR, 1.82) or during the third trimester (adjusted OR, 1.87) were at significantly greater risk for ASD. Overall exposure to pesticides during gestation was more significantly common in males (31%) than females (26%). Of the children diagnosed with ASD (n=486), approximately two-thirds had full-syndrome autism or autistic disorder (68%) and one-third had autism spectrum disorder (32%) (Shelton et al, 2014). Further research on this topic may provide more information.

C) DECREASED BIRTH WEIGHT

1) A cohort of 454 mother-infant pairs was examined to determine the presence of a correlation between pyrethroid insecticides exposure and maternal and infant health. The study revealed an association between increased maternal total urinary levels of five pyrethroid metabolites and decreased birth weights but not with birth length, gestational duration, or head circumference (Ding et al, 2015).

3.20.4)

A) BREAST MILK

1) Pyrethroids were detected in human milk samples obtained from lactating mothers from Spain (n=6), Colombia (n=27), or Brazil (n=20) at concentration levels ranging from 1.45 to 24.2 ng/g lipid weight (lw). Cypermethrin was detected in all of the human milk samples while permethrin, lambda-cyhalothrin, and fenvalerate/esfenvalerate were detected in most samples. There were no traces of resmethrin, fluvalinate, cifluthrin, or phenotrin in any of the milk samples. Cypermethrin was detected at concentration values of up to 16.4 ng/g lw while tetramethrin, lamba-cyhalothrin, bifenthrin, permethrin, fenvalerate/esfenvalerate, and deltamethrin/tralomethrin were detected at concentrations up to 14.8, 8.77, 7.48, 5.19, 3.11, and 1.86 ng/g lw, respectively. There were no statistically significant differences in the results obtained from rural areas compared with urban areas and there was no relationship detected between pyrethroid concentration levels and maternal age. Domestic insecticide use did not appear to affect pyrethroid levels in the breast milk samples (Corcellas et al, 2012).
2) PERMETHRIN: In lactating South African women who lived in areas where permethrin was commonly used in dusting powder and for gardening, pyrethroid concentrations in breast milk were below the accepted limits (range, 7.3 to 48.4 mcg/L) (Sereda et al, 2009; Bouwman et al, 2006).
3) PERMETHRIN: It is not known if permethrin affects the quantity or composition of breast milk. Maternal use of topical preparations generally carries less risk than systemically administered drug; risk to the infant should be considered relative to the inherent toxicity of the drug. The Centers for Disease Control and prevention recommends the use of permethrin for the treatment of lice infestations during lactation (Centers for Disease Control and Prevention, 2010), and the World Health Organization considers permethrin to be compatible with breastfeeding (Anon, 2002). Short-term treatment with permethrin in breastfeeding women poses minimal risk to the infant.
4) PERMETHRIN: In five infants whose mothers used permethrin during the breastfeeding period, no adverse reactions were reported (Ito et al, 1993).

3.20.5)

A) INFERTILITY

1) FENVALERATE: One study found that occupational fenvalerate exposure may induce a significant increase in sperm DNA damage (DNA strand breaks). This DNA damage may carry mutations into the next generation or result in male infertility (Bian et al, 2004).

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS82657-04-3 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

B) IARC Carcinogenicity Ratings for CAS97-11-0 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

C) IARC Carcinogenicity Ratings for CAS68359-37-5 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

D) IARC Carcinogenicity Ratings for CAS68085-85-8 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

E) IARC Carcinogenicity Ratings for CAS52315-07-8 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

F) IARC Carcinogenicity Ratings for CAS52918-63-5 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) IARC Classification

a) Listed as: Deltamethrin
b) Carcinogen Rating: 3

1) The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.

G) IARC Carcinogenicity Ratings for CAS66230-04-4 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

H) IARC Carcinogenicity Ratings for CAS39515-41-8 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

I) IARC Carcinogenicity Ratings for CAS51630-58-1 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) IARC Classification

a) Listed as: Fenvalerate
b) Carcinogen Rating: 3

J) IARC Carcinogenicity Ratings for CAS69409-94-5 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

K) IARC Carcinogenicity Ratings for CAS52645-53-1 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) IARC Classification

a) Listed as: Permethrin
b) Carcinogen Rating: 3

L) IARC Carcinogenicity Ratings for CAS26002-80-2 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

M) IARC Carcinogenicity Ratings for CAS10453-86-8 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

N) IARC Carcinogenicity Ratings for CAS7696-12-0 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

O) IARC Carcinogenicity Ratings for CAS66841-25-6 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

3.21.2)

3.21.3)

A) CONGENITAL LEUKEMIA

1) PERMETHRIN: For 2 years before becoming pregnant, a 27-year-old woman began to overuse aerosolized permethrin for her arachnophobia. At 35 weeks gestation, she presented to the hospital in premature labor. She spontaneously delivered an infant weighing 2300 g showing no vital signs. The infant was successfully resuscitated with a stable heart rate of 140 beats/minute. The infant's initial WBC count was 400,000 mcg/L with an excess of myeloid blast cells. Bone marrow examination confirmed a diagnosis of congenital acute myeloid leukemia. The infant died from multiorgan failure 48 hours after birth. The authors hypothesized that permethrin crossing the placenta caused the leukemia(Borkhardt et al, 2003).

B) ACUTE LYMPHOCYTIC LEUKEMIA

1) A case-control study showed increased metabolite levels of pyrethroid pesticides in urine to be associated with an approximate 2-fold increased risk of childhood acute lymphocytic leukemia (ALL) (total metabolites odds ratio, 2.75, 95% CI, 1.43 to 5.29). From 2010 to 2011, 176 children aged 0 to 14 years and diagnosed with ALL were observed along with a control group of 180 children without ALL and matched for age, sex, birth weight, ethnicity, parent age at child’s birth, and breastfeeding status (Ding et al, 2012).

3.21.4)

A) PULMONARY CARCINOMA

1) PERMETHRIN: No tumorigenicity was reported in three carcinogenicity bioassays in rats. Increases in pulmonary adenomas were seen in 3 mouse carcinogenicity bioassays. When permethrin was given in food at a concentration of 5000 ppm, female mice showed an increased incidence of pulmonary alveolar-cell carcinomas and benign liver adenomas (Prod Info Elimite(R) Cream, permethrin 5%, 2000).

Genotoxicity

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Monitor vital signs and mental status.
B) Monitor serum electrolytes, glucose and renal function in symptomatic patients, those with severe vomiting, and those with large ingestions.
C) Monitor pulse oximetry, chest radiograph and pulmonary function in patients with respiratory symptoms.
D) Institute continuous cardiac monitoring and obtain an ECG in patients with significant symptoms.
E) Pyrethroid plasma concentrations are not readily available or useful in guiding treatment.

4.1.2)

A) BLOOD/SERUM CHEMISTRY

1) Plasma noradrenaline (in type I and II pyrethroid poisoning) and adrenaline (more so in type II pyrethroid poisoning) concentrations may be elevated following significant poisoning. Serum glucose concentrations may be increased following type II pyrethroid poisoning. Results of other routine laboratory tests are often normal (Ray, 1991; He et al, 1989).
2) Monitor arterial blood gases in patients with metabolic acidosis.

4.1.3)

A) URINARY LEVELS

1) FENVALERATE: Workers exposed to air concentrations of fenvalerate of 0.0555 +/- 0.134 mg/m(3), as well as skin contact, had urinary levels of 1.02 to 18.6 mcg/L. Five days after discontinuation of exposure, the levels were 0.2 to 0.7 mcg/L (He et al, 1988).

Radiographic Studies

1) Obtain a chest x-ray to evaluate for pulmonary edema in patients with respiratory signs and symptoms.

Methods

1) PYRETHROIDS: A color test with 2-2 (2-aminoethylamine) ethanol produces red to violet color in the presence of pyrethroidal substances. It is not suitable for analysis of pyrethroids in body fluids, except, possibly at extraordinary concentrations.

1) DELTAMETHRIN and FENVALERATE have been analyzed by gas chromatography with electron capture detector at levels of 0.2 g/L. The method has been used to determine pyrethroids in packers, spraymen and acute pyrethroid poisoning (Wu et al, 1994).
2) PERMETHRIN: Gotoh et al (1998) described a high-performance liquid chromatography method for the determination of permethrin isomers in human serum following a suicidal ingestion. Only parent compounds were measured; standards for metabolites were not available. A peak serum concentration of 868 nanograms/milliliter was reported at 4 hours post-ingestion.
3) PYRETHROIDS: A capillary gas chromatography method in combination with mass selective detection (MSD) for the determination of pyrethroids in plasma and metabolites in urine was developed. The method was developed for biological monitoring following indoor use of pyrethroid insecticides. For cypermethrin metabolites, the limits of determination ranged between 0.5 and 1 microgram/liter of urine. Concentrations of pyrethroids (cyfluthrin, cypermethrin and permethrin) in plasma were below the limits of detection (< 5 mcg/L) (Leng et al, 1997; Leng et al, 1996; Leng et al, 1996a).

Treatment

Life Support

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) All patients who develop severe symptoms or have moderate symptoms that do not resolve over 6 to 12 hours of observation, should be admitted.

6.3.1.2) HOME CRITERIA/ORAL

A) Asymptomatic patients with inadvertent ingestions of small amounts, and dermal or inhalation exposures can be managed at home.

6.3.1.3) CONSULT CRITERIA/ORAL

A) Consult a medical toxicologist or poison center for patients with severe toxicity or in whom the diagnosis is uncertain.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) A patient with symptoms or a history of large or deliberate ingestion should be observed in an emergency department for at least 4 to 6 hours for any signs of CNS depression or seizures or the development of delayed pulmonary symptoms. The possibility of coingestants, such as hydrocarbons and organophosphate or carbamate insecticides, should be considered.

Monitoring

Oral Exposure

6.5.1)

A) ORAL EXPOSURE

1) Prehospital gastrointestinal decontamination is generally not recommended due to the potential for rapid onset of seizures and CNS depression after substantial ingestion. Spontaneous vomiting is common after ingestion of type II pyrethroids.

B) INHALATION EXPOSURE

1) Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta-2 agonist and corticosteroids.

C) OCULAR EXPOSURE

1) Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persists, patient should be seen in a healthcare facility.

D) DERMAL EXPOSURE

1) Remove contaminated clothing and wash exposed area thoroughly with soap and water. A physician may need to examine the area if irritation or pain persists.

6.5.2)

A) SUMMARY

1) Activated charcoal is not routinely recommended as most exposures are trivial. With large ingestions patients are at risk for abrupt onset of seizures or mental status depression. Charcoal administration should be limited to patients with a severely toxic ingestion who are awake and able to protect their airway or who have been intubated. Consider aspiration of gastric contents with a small nasogastric tube if it can be performed soon after a large ingestion of a concentrated insecticide solution.
2) If a pyrethroid has been ingested in a dosage less than 5 mg/kg, then the risk of hydrocarbon pneumonitis may well exceed the toxic hazard of the insecticide, and the need for any gastrointestinal decontamination should be reconsidered.

B) ACTIVATED CHARCOAL

1) CHARCOAL ADMINISTRATION

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

2) CHARCOAL DOSE

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

b) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

C) GASTRIC LAVAGE

1) Consider aspiration of gastric contents with a small nasogastric tube if it can be performed soon after a large ingestion of a concentrated insecticide solution. Control agitation and manage airway if necessary first.

6.5.3)

A) MONITORING OF PATIENT

1) Monitor vital signs and mental status.
2) Monitor serum electrolytes, glucose and renal function in symptomatic patients, those with severe vomiting, and those with large ingestions.
3) Monitor pulse oximetry, chest radiograph and pulmonary function in patients with respiratory symptoms.
4) Institute continuous cardiac monitoring and obtain an ECG in patients with significant symptoms.
5) Pyrethroid plasma concentrations are not readily available or useful in guiding treatment.

B) SEIZURE

1) Seizures following type II pyrethroid ingestions may be severe and prolonged, up to 40 seizures/day lasting for several days (He et al, 1989).
2) SUMMARY

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

3) DIAZEPAM

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

4) NO INTRAVENOUS ACCESS

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

5) LORAZEPAM

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2010; Chin et al, 2008).

6) PHENOBARBITAL

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

7) OTHER AGENTS

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

8) RECURRING SEIZURES

a) If seizures are not controlled by the above measures, patients will require endotracheal intubation, mechanical ventilation, continuous EEG monitoring, a continuous infusion of an anticonvulsant, and may require neuromuscular paralysis and vasopressor support. Consider continuous infusions of the following agents:

1) MIDAZOLAM: ADULT DOSE: An initial dose of 0.2 mg/kg slow bolus, at an infusion rate of 2 mg/minute; maintenance doses of 0.05 to 2 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: 0.1 to 0.3 mg/kg followed by a continuous infusion starting at 1 mcg/kg/minute, titrated upwards every 5 minutes as needed (Loddenkemper & Goodkin, 2011).
2) PROPOFOL: ADULT DOSE: Start at 20 mcg/kg/min with 1 to 2 mg/kg loading dose; maintenance doses of 30 to 200 mcg/kg/minute continuous infusion dosing, titrated to EEG; caution with high doses greater than 80 mcg/kg/minute in adults for extended periods of time (ie, longer than 48 hours) (Brophy et al, 2012); PEDIATRIC DOSE: IV loading dose of up to 2 mg/kg; maintenance doses of 2 to 5 mg/kg/hour may be used in older adolescents; avoid doses of 5 mg/kg/hour over prolonged periods because of propofol infusion syndrome (Loddenkemper & Goodkin, 2011); caution with high doses greater than 65 mcg/kg/min in children for extended periods of time; contraindicated in small children (Brophy et al, 2012).
3) PENTOBARBITAL: ADULT DOSE: A loading dose of 5 to 15 mg/kg at an infusion rate of 50 mg/minute or lower; may administer additional 5 to 10 mg/kg. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: A loading dose of 3 to 15 mg/kg followed by a maintenance dose of 1 to 5 mg/kg/hour (Loddenkemper & Goodkin, 2011).
4) THIOPENTAL: ADULT DOSE: 2 to 7 mg/kg, at an infusion rate of 50 mg/minute or lower. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusing dosing, titrated to EEG (Brophy et al, 2012)

b) Endotracheal intubation, mechanical ventilation, and vasopressors will be required (Brophy et al, 2012) and consultation with a neurologist is strongly advised.
c) Neuromuscular paralysis (eg, rocuronium bromide, a short-acting nondepolarizing agent) may be required to avoid hyperthermia, severe acidosis, and rhabdomyolysis. If rhabdomyolysis is possible, avoid succinylcholine chloride, because of the risk of hyperkalemic-induced cardiac dysrhythmias. Continuous EEG monitoring is mandatory if neuromuscular paralysis is used (Manno, 2003).

9) ANIMAL STUDIES: Following type II pyrethroid poisoning in rats, pentobarbital was reported to be effective therapy, probably due to its dual action as a chloride channel agonist and a membrane stabilizer (Ray & Forshaw, 2000).

C) ANAPHYLAXIS

1) SUMMARY

a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.

2) BRONCHOSPASM

a) ALBUTEROL

1) ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007). CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 mg/kg (up to 10 mg) every 1 to 4 hours as needed, or 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).

3) CORTICOSTEROIDS

a) Consider systemic corticosteroids in patients with significant bronchospasm.
b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).

4) MILD CASES

a) DIPHENHYDRAMINE

1) SUMMARY: Oral diphenhydramine, as well as other H1 antihistamines can be used as indicated (Lieberman et al, 2010).
2) ADULT: 50 milligrams orally, or 10 to 50 mg intravenously at a rate not to exceed 25 mg/min or may be given by deep intramuscular injection. A total of 100 mg may be administered if needed. Maximum daily dosage is 400 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
3) CHILD: 5 mg/kg/24 hours or 150 mg/m(2)/24 hours. Divided into 4 doses, administered intravenously at a rate not exceeding 25 mg/min or by deep intramuscular injection. Maximum daily dosage is 300 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).

5) MODERATE CASES

a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).

6) SEVERE CASES

a) EPINEPHRINE

1) INTRAVENOUS BOLUS: ADULT: 1 mg intravenously as a 1:10,000 (0.1 mg/mL) solution; CHILD: 0.01 mL/kg intravenously to a maximum single dose of 1 mg given as a 1:10,000 (0.1 mg/mL) solution. It can be repeated every 3 to 5 minutes as needed. The dose can also be given by the intraosseous route if IV access cannot be established (Lieberman et al, 2015). ALTERNATIVE ROUTE: ENDOTRACHEAL ADMINISTRATION: If IV/IO access is unavailable. DOSE: ADULT: Administer 2 to 2.5 mg of 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube. CHILD: DOSE: 0.1 mg/kg to a maximum of 2.5 mg administered as a 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube (Lieberman et al, 2015).
2) INTRAVENOUS INFUSION: Intravenous administration may be considered in patients poorly responsive to IM or SubQ epinephrine. An epinephrine infusion may be prepared by adding 1 mg (1 mL of 1:1000 (1 mg/mL) solution) to 250 mL D5W, yielding a concentration of 4 mcg/mL, and infuse this solution IV at a rate of 1 mcg/min to 10 mcg/min (maximum rate). CHILD: A dosage of 0.01 mg/kg (0.1 mL/kg of a 1:10,000 (0.1 mg/mL) solution up to 10 mcg/min (maximum dose 0.3 mg) is recommended for children (Lieberman et al, 2010). Careful titration of a continuous infusion of IV epinephrine, based on the severity of the reaction, along with a crystalloid infusion can be considered in the treatment of anaphylactic shock. It appears to be a reasonable alternative to IV boluses, if the patient is not in cardiac arrest (Vanden Hoek,TLet al,null).

7) AIRWAY MANAGEMENT

a) OXYGEN: 5 to 10 liters/minute via high flow mask.
b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TLet al,null).
d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).

8) MONITORING

a) CARDIAC MONITOR: All complicated cases.
b) IV ACCESS: Routine in all complicated cases.

9) HYPOTENSION

a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.

1) VASOPRESSORS: Should be used in refractory cases unresponsive to repeated doses of epinephrine and after vigorous intravenous crystalloid rehydration (Lieberman et al, 2010).
2) DOPAMINE: Initial Dose: 2 to 20 micrograms/kilogram/minute intravenously; titrate to maintain systolic blood pressure greater than 90 mm Hg (Lieberman et al, 2010).

10) H1 and H2 ANTIHISTAMINES

a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).

1) DIPHENHYDRAMINE: ADULT: 25 to 50 milligrams via a slow intravenous infusion or IM. PEDIATRIC: 1 milligram/kilogram via slow intravenous infusion or IM up to 50 mg in children (Lieberman et al, 2010).

b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).

11) DYSRHYTHMIAS

a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TLet al,null). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.

12) OTHER THERAPIES

a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TLet al,null).

D) ACUTE LUNG INJURY

1) In animal studies, pulmonary edema is not reported in animals given pyrethroids without surfactants. Thus, it is likely that pulmonary edema is due to the excipients, such as piperonyl butoxide. Positive pressure ventilation would be a logical choice for therapy in these cases (Bateman, 2000).
2) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
3) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).

a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)

4) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
5) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
6) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
7) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
8) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).

E) BRONCHOSPASM

1) BRONCHOSPASM SUMMARY

a) Administer beta2 adrenergic agonists. Consider use of inhaled ipratropium and systemic corticosteroids. Monitor peak expiratory flow rate, monitor for hypoxia and respiratory failure, and administer oxygen as necessary.

2) ALBUTEROL/ADULT DOSE

a) 2.5 to 5 milligrams diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three doses. If incomplete response, administer 2.5 to 10 milligrams every 1 to 4 hours as needed OR administer 10 to 15 milligrams every hour by continuous nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.5 milligram by nebulizer every 30 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).

3) ALBUTEROL/PEDIATRIC DOSE

a) 0.15 milligram/kilogram (minimum 2.5 milligrams) diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.25 to 0.5 milligram by nebulizer every 20 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).

4) ALBUTEROL/CAUTIONS

a) The incidence of adverse effects of beta2-agonists may be increased in older patients, particularly those with pre-existing ischemic heart disease (National Asthma Education and Prevention Program, 2007). Monitor for tachycardia, tremors.

5) CORTICOSTEROIDS

a) Consider systemic corticosteroids in patients with significant bronchospasm. PREDNISONE: ADULT: 40 to 80 milligrams/day in 1 or 2 divided doses. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 or 2 divided doses (National Heart,Lung,and Blood Institute, 2007).

F) ATROPINE

1) Cases of severe salivation due to type II pyrethroid poisoning have been treated with intravenous atropine. Doses of 0.5 to 10 mg were used, which led to improvement in salivation and pulmonary signs in a few severe cases (He et al, 1989).
2) Drying of excessive secretions is a preferable indicator of adequate atropinization rather than heart rate or pupil size.

G) HYPOTENSIVE EPISODE

1) Sequelae of hypoxia and hypotension may occur in rare, life-threatening cases.
2) SUMMARY

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

3) DOPAMINE

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

4) NOREPINEPHRINE

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

Inhalation Exposure

6.7.1)

A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

6.7.2)

A) PULMONARY EDEMA

1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).

3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).

B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

6.8.1)

A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

6.9.1)

A) DERMAL DECONTAMINATION

1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
2) Following dermal exposures, symptoms persisted for several hours, even following dermal decontamination, due to pyrethroid penetration into the skin (Bateman, 2000).

6.9.2)

A) VITAMIN E

1) SUMMARY

a) Oil of vitamin E preparations appear effective as long as they contain vegetable oils such as corn oil, sesame oil, safflower oil or wheat germ oil (i.e. Roche Chemical and Nature's Bounty formulations).
b) It appears that the use of oil of vitamin E is effective in preventing and treating the dermal effects caused by any of the synthetic pyrethroids now on the market (Prod Info Elimite(R) Cream, permethrin 5%, 2000; Ray & Forshaw, 2000; Tucker et al, 1984).

2) PREVENTION OF DERMAL EFFECTS CAUSED BY FENVALERATE

a) PYDRIN(R) INSECTICIDE
b) Oil of vitamin E used prior to exposure keeps the tingling or sunburn feeling from developing.
c) Apply oil of vitamin E at the start of the day and every 4 hours throughout the working day or after washing. Apply a light coating to exposed skin.
d) A heavy coating or more frequent applications are unnecessary (Tucker et al, 1984).
e) Since this therapy seems only effective prior to exposure to the pyrethroid, the role of vitamin E in patients having symptoms from excess dermal exposure is debatable (Bateman, 2000).

3) TREATMENT OF BURNING AND STINGING CAUSED BY PYDRIN(R) EXPOSURE

a) Apply oil of vitamin E as soon as possible after start of symptoms and after washing. Apply a light coating to the affected areas. A heavy coating or more frequent applications are unnecessary (Tucker et al, 1984).

4) CASE SERIES - Application of vitamin E following topical permethrin or fenvalerate prevented the development of paresthesias in 6 human volunteers (Flannigan et al, 1985a).

B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

1) Pyrethroid compounds are rapidly metabolized by the body; extracorporeal methods of elimination would NOT be expected to enhance their elimination.

Abstracts

Case Reports

1) DELTAMETHRIN: A 21-year-old woman ingested 30 mL of 2.5% (750 mg) deltamethrin. Headache and muscle fasciculations developed 5.5 hours postingestion. Muscle fasciculations spread to all extremities, which was followed by seizures 8 hours later.

a) Seizures consisted of upper limb flexion, opisthotonus, cyanosis, and loss of consciousness. They were very frequent (up to 40 times/day) in the first 5 days postingestion and continued for two weeks.
b) Laboratory tests revealed normal CSF except for the Pandy test (+) and increased GABA and glycine contents. Plasma noradrenaline was 0.636 mcg/mL (normal, 0.292 mcg/mL) and plasma adrenaline levels were 0.256 mcg/mL (normal, 0.008 mcg/mL). Results of other routine laboratory tests were normal.
c) Treatment was symptomatic and supportive; seizures were treated with diazepam and were not well controlled until the second week after onset. Recovery was gradual, with hospital discharge 3 weeks after initial admission (He et al, 1989).

Range Of Toxicity

Summary

Therapeutic Dose

7.2.1)

A) SPECIFIC SUBSTANCE

1) PERMETHRIN 1% CREME RINSE - The recommended dose of permethrin 1 percent creme rinse (NIX(R)) is enough to saturate hair and scalp (especially behind the ears and on the nape of the neck). Individual bottles contain 59 mL or it is also available in a 2-bottle (59 mL each) family pack. Rinse after 10 minutes. A single application is usually sufficient. If live lice are observed 7 days or more after the first application, a second treatment should be given (Prod Info Nix Creme Rinse, 2004).
2) PERMETHRIN 5% TOPICAL CREAM - Thoroughly massage into skin from the head to the soles of the feet. Usually 30 grams is sufficient for an average adult. Remove the cream after 8 to 14 hours by washing. One application is usually curative (Prod Info Elimite Cream, 2003).

7.2.2)

A) SPECIFIC SUBSTANCE

a) The manufacturer recommends that this product should NOT be used on children less than 2 months of age (Prod Info Nix Creme Rinse, 2004).

2) PERMETHRIN 5% TOPICAL CREAM - Thoroughly massage into skin from the head to the soles of the feet. Remove cream by washing (shower or bath) after 8 to 14 hours. Infants should be treated on the scalp, temple and forehead. This product is safe for pediatric patients 2 months of age and older. Safety and effectiveness in infants less than 2 months old have not been established. One application is usually curative (Prod Info Elimite Cream, 2003).

Minimum Lethal Exposure

1) SPECIFIC SUBSTANCE

a) CYPERMETHRIN: A 45-year-old man died following ingestion of beans cooked in a small amount of cypermethrin 10% instead of oil. Analysis of the stomach revealed 0.7 gram cypermethrin (Poulos et al, 1982).
b) FENVALERATE: Two patients died following ingestion of an unknown quantity of fenvalerate; one patient died due to seizures, and the other died because of pulmonary edema (He et al, 1989).

Maximum Tolerated Exposure

1) A 36-year-old man developed only pain and a dime-sized area of erythema at the injection site after injecting 6 mL of a pyrethroid-containing product (Real Kill Ant and Roach killer 2; containing tralomethrin 0.01% and D-trans-allethrin 0.05%) intravenously into his antecubital fossa and 2 mL subcutaneously into his abdomen in a suicide attempt. Vital signs and laboratory studies were normal. Following 4 hours of observation, his symptoms resolved completely (LoVecchio & Knight, 2005).
2) Ingestion of very large quantities (200 to 500 mL of concentrate) of pyrethroids has resulted in muscular fasciculations, drowsiness, coma, and seizures, often within 20 minutes of ingestion (He et al, 1989). Frequency of seizures may be 10 to 30 times a day in the first week, then gradually decrease with recovery in 2 to 3 weeks.
3) Following ingestions, initial gastrointestinal symptoms (nausea, vomiting, and abdominal pain) may develop within 10 minutes to 1 hour after exposure (He et al, 1989).
4) In an observational and retrospective study of 56 cases of pyrethroid poisoning, typical adverse effects (eg, nausea, vomiting, abdominal pain, sore throat, dyspnea, dizziness, and tremor) were reported after ingestion of 50 to 300 mL of pyrethroids. Atypical presentations (ie, respiratory failure, hypotension, pneumonia, acute kidney injury, seizure, and Glasgow Coma Scale of less than 15) developed in 39.3% of patients and predictors of these conditions included a pyrethroid ingestion of greater than 250 mL and serum lactate of greater than 3.5 mmol/L (Cha et al, 2014).
5) Following occupational exposure to insecticide mist, initial symptoms of burning or facial itching or dizziness may develop 4 to 6 hours later. This may be followed by systemic symptoms which can develop as late as 48 hours following exposure (He et al, 1989).
6) CYPERMETHRIN: Family members who ate beans cooked in a small amount of cypermethrin 10% developed less severe symptoms than the 45-year-old man who died (Poulos et al, 1982).
7) DELTAMETHRIN: Seizures were reported in an adult who ingested 30 mL of a 2.5% formulation (750 mg) (He et al, 1989).
8) PERMETHRIN: Following the ingestion of 600 mL of 20% permethrin emulsion a 59-year-old man was found unconscious with vomitus and diarrhea. He arrived at the ED one hour after the ingestion. Metabolic acidosis was reported. No clinical neurotoxicity other than impaired consciousness occurred. The patient recovered following symptomatic therapy. The quantities of ingredients in the ingested emulsion were calculated as: permethrin 143 grams, xylene 361 grams, and surfactant 64 grams (Gotoh et al, 1998).
9) PRALLETHRIN (CASE REPORT): A 20-year-old woman developed generalized tonic clonic seizures after ingesting 2 bottles of mosquito repellent All-Out (prallethrin 1.6% w/w liquid, 35 mL in each bottle, total dose of 1120 mg). Despite supportive therapy, including diazepam and phenytoin, her seizures persisted. Her seizures eventually resolved after receiving propofol. She was discharged 7 days after presentation (Chandra et al, 2013).
10) CHRONIC FEEDING STUDIES in animals indicate that the toxicities of pyrethroids are of a low order in mammals (Ray, 1991).
11) CHRONIC or frequent exposure to low concentrations of pyrethroids in humans (e.g., treatment of mosquito nets) poses only a remote risk of systemic toxicity (Zaim et al, 2000).

1) Rat pups given various acute toxic doses of pyrethroids via gavage showed that for type I pyrethroids, there was no evidence that the animals are more sensitive than adults at any dose level. With type II pyrethroids, young pups (neonates) were markedly more sensitive than adults to a lethal dose, but not to lower doses that are relevant for dietary risk assessment. The increased susceptibility of the neonate to high doses of type II pyrethroids is associated with the neonate's relatively limited metabolic capacity for detoxification. There were no sex-related differences (Sheets, 2000).

Serum Plasma Blood Concentrations

7.5.2)

A) TOXIC CONCENTRATION LEVELS

1) SPECIFIC SUBSTANCES

a) PERMETHRIN - One hour after a 59-year-old male ingested an estimated 143 grams of permethrin, serum permethrin concentration was reported to be 214 nanograms/milliliter. Peak concentration was reported as 868 nanograms/milliliter at 4 hours after ingestion (Gotoh et al, 1998).

Workplace Standards

1) Not Listed

AA)

1) Not Listed

AB)

1) Not Listed

AC)

1) Not Listed

AD)

1) Not Listed

AE)

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Biphenthrin
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

AF)

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

AG)

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Baythroid
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

AH)

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Cyhalothrin/Karate
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

AI)

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Cypermethrin
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

AJ)

a) 3 : The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.

4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

AK)

AL)

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Danitol
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

AM)

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Pydrin
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 3 ; Listed as: Fenvalerate

AN)

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Fluvalinate
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

AO)

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Permethrin
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 3 ; Listed as: Permethrin

AP)

AQ)

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Resmethrin
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

AR)

AS)

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Tralomethrin
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

AT)

1) Not Listed

AU)

1) Not Listed

AV)

1) Not Listed

AW)

1) Not Listed

AX)

1) Not Listed

AY)

1) Not Listed

AZ)

1) Not Listed

BA)

1) Not Listed

BB)

1) Not Listed

BC)

1) Not Listed

BD)

1) Not Listed

BE)

1) Not Listed

BF)

1) Not Listed

BG)

1) Not Listed

BH)

1) Not Listed

Toxicity Information

7.7.1)

A) Acrinathrin

1) LD50- (ORAL)MOUSE:

a) >5000 mg/kg (RTECS, 2006)

2) LD50- (ORAL)RAT:

a) >5000 mg/kg (RTECS, 2006)

3) LD50- (SKIN)RAT:

a) >2 g/kg (RTECS, 2006)

B) Allethrin

1) LD50- (ORAL)MOUSE:

a) 370 mg/kg (RTECS, 2006)

2) LD50- (SKIN)MOUSE:

a) 1200 mg/kg (RTECS, 2006)

3) LD50- (ORAL)RAT:

a) 685 mg/kg (RTECS, 2006)

4) LD50- (SKIN)RAT:

a) 2500 mg/kg (RTECS, 2006)

C) Bioallethrin

1) LD50- (INHALATION)MOUSE:

a) >2 g/m(3) (RTECS, 2006)

2) LD50- (ORAL)RAT:

a) 685 mg/kg (RTECS, 2006)

3) LD50- (SKIN)RAT:

a) 2500 mg/kg (RTECS, 2006)

D) Cypermethrin

1) LD50- (ORAL)MOUSE:

a) 24570 mcg/kg (RTECS, 2006)

2) LD50- (ORAL)RAT:

a) 57,500 mcg/kg -- somnolence, convulsions or effect on seizure threshold (RTECS, 2006)

3) LD50- (SKIN)RAT:

a) >1600 mg/kg (RTECS, 2006)

E) Deltamethrin

1) LD50- (ORAL)MOUSE:

a) 20 mg/kg -- somnolence, convulsions or effect on seizure threshold, increased urine volume (RTECS, 2006)

2) LD50- (ORAL)RAT:

a) 9360 mcg/kg -- somnolence, convulsions or effect on seizure threshold, increased urine volume (RTECS, 2006)

3) LD50- (SKIN)RAT:

a) >800 mg/kg (RTECS, 2006)

F) Fenothrin, Racemic mixture

1) LD50- (ORAL)RAT:

a) >10,000 mg/kg (RTECS, 2006)

G) Fenvalerate

1) LD50- (ORAL)MOUSE:

a) 185 mg/kg -- tremor, convulsions or effect on seizure threshold, ataxia (RTECS, 2006)

2) LD50- (ORAL)RAT:

a) 70,200 mcg/kg -- lacrimation, excitement, ataxia (RTECS, 2006)

3) LD50- (SKIN)RAT:

a) >5 g/kg (RTECS, 2006)

H) Furamethrin, Racemic mixture

1) LD50- (ORAL)MOUSE:

a) 1950 mg/kg (RTECS, 2006)

I) Permethrin

1) LD50- (ORAL)MOUSE:

a) 424 mg/kg (RTECS, 2006)

2) LD50- (SKIN)MOUSE:

a) >10 g/kg (RTECS, 2006)

3) LD50- (ORAL)RAT:

a) 383 mg/kg (RTECS, 2006)

4) LD50- (SKIN)RAT:

a) 1750 mg/kg (RTECS, 2006)

J) Piperonyl butoxide

1) LD50- (ORAL)RAT:

a) 6150 mg/kg (RTECS, 2006)

K) Resmethrin

1) LD50- (ORAL)MOUSE:

a) 300 mg/kg (RTECS, 2006)

2) LD50- (SKIN)MOUSE:

a) >5 g/kg (RTECS, 2006)

3) LD50- (SKIN)RAT:

a) 3 g/kg (RTECS, 2006)

L) Tetramethrin

1) LD50- (ORAL)MOUSE:

a) 1 g/kg (RTECS, 2006)

2) LD50- (SKIN)MOUSE:

a) >15 g/kg (RTECS, 2006)

3) LD50- (ORAL)RAT:

a) 4640 mg/kg (RTECS, 2006)

4) LD50- (SKIN)RAT:

a) >2500 mg/kg -- tremor, excitement, increased urine volume (RTECS, 2006)

Pharmacology Toxicology

Pharmacologic Mechanism

Toxicologic Mechanism

1) TYPE I - Type I pyrethroids, including permethrin, allethrin, tetramethrin and d-phenothrin, do not contain an alpha-cyano group (He, 1994; Narahashi et al, 1992). Poisoning in animals is characterized by tremors, hyperexcitation, seizures, ataxia and paralysis (Ray & Forshaw, 2000; He, 1994; Narahashi et al, 1992; Soderlund & Bloomquist, 1989).

a) Permethrin is a photostable synthetic pyrethroid which is a mixture of cis and trans isomers. The cis isomer exhibits higher mammalian toxicity than the trans isomer, which is more rapidly metabolized to inactive metabolites and excreted (Taplin & Meinking, 1996).

2) TYPE II - Type II pyrethroids (cypermethrin, fenvalerate, deltamethrin, cyhalothrin) contain an alpha-cyano group (He, 1994; Ray & Forshaw, 2000). The intensity of repetitive discharge due to depolarizing after potential varies greatly with pyrethroid structure; generally, the type II pyrethroids develop continued depolarization of resting membrane, which leads to conduction block (Miyamoto et al, 1995). Poisoning in animals is characterized by salivation, chewing, burrowing, choreoathetosis, and hypersensitivity to external stimuli. They cause a lower action potential amplitude, marked membrane depolarization, and eventual total neural activity blockade. The mechanism involves the GABA receptor (Miyamoto et al, 1995). Diazepam, following high, repeated doses, reverses the effects of Type II, but not of Type I pyrethroids (Coats, 1990).

a) Free cyanide does NOT appear to participate in the toxicity manifestation (Miyamoto et al, 1995).

1) In animal studies, Pauluhn (1996) confirmed that type II pyrethroids (containing a cyano group) acted as pure sensory irritants, with effects observed being non-cumulative and transient in nature. Concomitant respiratory tract inflammation did not occur.

Physicochemical

Physical Characteristics

Ph

Molecular Weight

1) Allethrin: 302.45
2) Bifenthrin: 422.9
3) Bioresmethrin: 338.4
4) Dimethrin: 286.39
5) Cyfluthrin: 434.29
6) Cyhalothrin: 449.86
7) Cypermethrin: 416.30
8) Deltamethrin: 505.2
9) Esfenvalerate: 419.9
10) Fenpropathrin: 349.43
11) Flucythrinate: 451.48
12) Flumethrin: 510.4
13) Fluvalinate: 502.93
14) Permethrin: 391.29
15) Phenothrin: 350.46
16) Resmethrin: 338.4
17) Tefluthrin: 418.7
18) Tetramethrin: 331.41
19) Tralomethrin: 665.0

Other

1) Pyrethroid odors range from odorless (cypermethrin, deltamethrin), to mild (cyhalothrin), to aromatic (cyfluthrin), to chrysanthemate (resmethrin) (Agency for Toxic Substances and Disease Registry (ATSDR), 2003).

Animal Toxicology

Clinical Effects

11.1.1)

A) Environmental exposure (fumigation of housing) has resulted in restlessness, hyperactivity, and decreased food intake within minutes following return to a previously treated area (Zwart, 1988).

11.1.3)

A) As with cats, the most consistent sign is body tremors. Additional signs, especially with the more toxic alpha-cyano PYRETHROIDS include vomiting, diarrhea, dyspnea, disorientation, and seizures. The signs usually occur within a few hours of exposure (Dorman, 1987).
B) Following exposure to a veterinary product containing both DEET and fenvalerate, dogs exhibited hypersalivation, abnormal chewing motions, vomiting, ataxia, and depression. After showing these signs, clinical improvement occurred within 4 to 24 hours (Mount et al, 1991).

11.1.6)

A) Typically tremors will become apparent several hours following exposure. The tremors (mainly a peripheral effect) begin on the face and progress elsewhere, lasting up to 24 to 48 hours (Dorman, 1987). Usual effects of toxicosis in cats include primarily neurologic abnormalities of muscle tremors, agitation, ataxia, and seizures (Meyer, 1999). Seizures have developed within 24 hours, and in some cases by 2 hours, following a toxic dermal application.

1) PYRETHROIDS with an alpha cyano group may produce more central nervous system effects including writhing seizures, severe tremors, profuse salivation, vomiting, and diarrhea. Irritation of the skin or eyes may occasionally occur (Dorman, 1987).

B) Following exposure to a veterinary product containing both DEET and fenvalerate,cats exhibited restlessness, tremors, hypersalivation, seizures, vomiting, ataxia,respiratory distress, and death (Mount et al, 1991).
C) PERMETRHIN toxicity was reported in 27 cats. Clinical signs of permethrin toxicity in these cats are as follows (Gray, 2000):

SIGNS	NUMBER OF CASES
Seizures	16
Tremor/Fasciculation	10
Ataxia	4
Collapse	4
Hypersalivation	7
Hyperesthesia	3
Coma	1
Mydriasis	5
Blindness	2
Dyspnea	2
Loss of smell	1
Loss of taste	1
Emesis	3
Fixed pupils	1

11.1.7)

A) All of these compounds are very toxic for fish. The clinical signs for rainbow trout first include increased cough rate and later include tremors, violent head shaking, and twisting or writhing seizures. The fish died approximately 11 hours after exposure (Bradbury, 1987).

11.1.9)

A) Supermethrin is an alpha-cyano pyrethroid, similar in structure to cypermethrin, with clinical signs of toxicity resembling those seen with cyanide intoxication. In sheep, doses above 1500 mg/kg cause nervous irritability, head and neck tremors, lacrimation, diarrhea with foul-smelling feces, and increased micturition. Doses above 2700 mg/kg produces ataxia, tonic-clonic seizures, and death within 24 to 48 hours. High levels of free cyanide were detected in the rumen and liver of sheep receiving doses above 2700 mg/kg (Legath et al, 1992).

11.1.12)

A) Rats exhibit typical whole body tremors. Profuse salivation and writhing seizures (choreoathetosis) accompany toxicosis due to alpha-cyanopyrethroids.

Treatment

11.2.1)

A) GENERAL TREATMENT

1) Because the mechanism of action of pyrethroids is slow in closing of the sodium channel activation gate, there is a wide disparity in dosages between those producing minor adverse signs and serious intoxication.

a) Thus minor side effects may be noted on close examination, but with little necessity for treatment in most cases.
b) Salivation may be increased enough to be annoying, but other than controlling tremor activity, treatment is seldom necessary.

11.2.2)

A) GENERAL

1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.

11.2.4)

A) GASTRIC DECONTAMINATION

1) GENERAL TREATMENT

a) SUMMARY -

1) Exposure is usually related to topical application and secondary oral ingestion from grooming. Bathing may be helpful in limiting progression and/or duration of signs.
2) Pyrethrins and pyrethroids are highly lipid soluble and of negligible water solubility; therefore, for bathing or washing to be most effective it should be carried out using a mild detergent.

a) The ASPCA NAPCC recommends dermal decontamination using a mild hand dish detergent and water (Meyer, 1999).

3) Emetics must be used with caution because of the prevalent signs and the presence of petroleum distillate solvents.
4) DOGS AND CATS - If oral exposure is suspected, gastric lavage and/or administration of activated charcoal with an osmotic cathartic (magnesium or sodium sulfate) may be used.

b) EMESIS -

1) Emetics must be used with caution because of the prevalent signs and the presence of petroleum distillate solvents.
2) If within 2 hours of exposure, emesis may be induced with 1 to 2 milliliters/kilogram syrup of ipecac per os.
3) Do not use an emetic if the animal is hypoxic. In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage.
4) Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times (Kirk, 1986).

c) ACTIVATED CHARCOAL -

1) Dose: 2 grams/kilogram per os or via stomach tube.

11.2.5)

A) GENERAL TREATMENT

1) The signs due to effects on sodium channels are peripheral in nature and typically will not require therapy.
2) Those due to central actions are more severe and may necessitate the use of sedatives. At least some of the more severe central effects appear to result from binding of the alpha-cyanopyrethroids at GABA receptors interfering with inhibitory control of neural impulses.

a) Diazepam (1 mg/kg, IV) may be the most specific agent for use in control of these effects (Valentine, 1990).
b) Alternatively methocarbamol (50 to 150 mg/kg IV) or barbiturates may be used (Valentine, 1990).
c) Phenothiazine tranquilizers should NOT be used (Valentine, 1990).

3) DOGS AND CATS - Maintain vital functions: insure a patent airway, correct electrolyte/fluid imbalances and keep the animal warm and quiet.
4) CATS - Tremors should be controlled with intravenous methocarbamol 55 to 220 mg/kg of body weight, administered rapidly at a rate not to exceed 2 mL/min. Discontinue briefly as cat relaxes, then resume until desired effect is achieved. Maximum dose is 330 mg/kg. If seizures are present, administer diazepam or pentobarbital, or mask induction with isoflurane prior to tremor control with methocarbamol (Meyer, 1999).

Range Of Toxicity

11.3.1)

A) GENERAL

1) TOPICAL - The pyrethrins and pyrethroids are generally available for topical application in various concentrations ranging from 0.01% to 10% depending on the use and animal species involved.
2) ORAL - At present, there are no preparations intended for internal use.

11.3.2)

A) GENERAL COMMENTS -

1) The pyrethrins and pyrethroids (synthetic pyrethrins) are generally considered to be among the most potent insecticides. Mammalian toxicity is relatively low compared to insects. They are, however, quite toxic to fish.
2) Of great importance in determining toxicity is formulation of the product. The compounds have high lipid and low aqueous solubility and are 5 to 10 times more toxic in an organic solvent.
3) In addition, toxicity potential may differ considerably between cis and trans isomers of the synthetic pyrethroids.
4) Depending on the specific compound, dermal toxicity is somewhat less than oral.
5) LD50 (Valentine, 1990)

COMPOUND	ORAL RAT LD50, mg/kg
Allethrin	680-860
Cypermethrin	500 corn oil/4,100 aqueous
Deltamethrin	100 corn oil/5,000 aqueous
Fenvalerate	450 DMSO/>3,200 aqueous
Flumethrin	>10,000 aqueous
Permethrin	2,000 to 4,000 aqueous
Pyrethrin	900 to 1,200

B) CAT

1) Cats appear to be among the most sensitive species and laboratory rodents and rabbits the least.
2) A study of one veterinary product containing both DEET (9%) and fenvalerate (0.09%) found that 10% or more of a 7 ounce can/kilogram body weight sprayed oncats caused fatalities (Mount et al, 1991).
3) The toxicity range for oral permethrin, one of the safer pyrethroids, is 200 mg/kg in cats.

C) DOG

1) A study of a product with 9% DEET and 0.9% fenvalerate, showed that dogs tolerated being sprayed with 40% of a can/kilogram body weight and developed only mild clinical signs. Spraying into the subject's mouth or self-grooming after dermal exposure was 50 to 150 times more likely to cause toxic effects. The study was not able to prove whether DEET or fenvalerate causedthese effects (Mount et al, 1991).

D) FISH -

1) The 96 hour LC50 for most of the pyrethroids is less than 10 mcg/L for most fish.
2) Fish are very sensitive to pyrethroids; the 48 hour LC50 for technical grade fenvalerate is 1.13 mcg/L for fathead minnows and 0.67 mcg/L for bluegill. In rainbow trout exposure to 412 +/- 50 mcg/L resulted in death in 10.9 +/- 1.5 hours (Bradbury, 1987).

E) POULTRY

1) The toxicity range for oral permethrin, one of the safer pyrethroids, is from greater than 2,000 mg/kg in chickens to greater than 4,000 mg/kg in rabbits.

F) RABBIT

1) The toxicity range for oral permethrin, one of the safer pyrethroids, is from greater than 2,000 mg/kg in chickens to greater than 4,000 mg/kg in rabbits.

Continuing Care

11.4.1)

11.4.1.2) DECONTAMINATION/TREATMENT

A) GENERAL TREATMENT

11.4.2)

11.4.2.2) GASTRIC DECONTAMINATION

A) GASTRIC DECONTAMINATION

1) GENERAL TREATMENT

a) SUMMARY -

a) The ASPCA NAPCC recommends dermal decontamination using a mild hand dish detergent and water (Meyer, 1999).

b) EMESIS -

c) ACTIVATED CHARCOAL -

1) Dose: 2 grams/kilogram per os or via stomach tube.

11.4.3)

11.4.3.5) SUPPORTIVE CARE

A) CAT

1) Maintain fluid and nutritional support. Normal body temperature should be maintained, as hypothermia may aggravate clinical signs of permethrin toxicosis (Meyer, 1999).

Kinetics

11.5.1)

A) GENERAL

1) All pyrethroids are absorbed from the gastrointestinal tract, especially whenformulated in an organic solvent vehicle. Dermal absorption is usually somewhat lower than oral absorption.

11.5.2)

A) GENERAL

1) These compounds are highly lipid soluble and are well distributed throughout the body except brain (Marei et al, 1982).

11.5.3)

A) GENERAL

1) All pyrethroids are subject to oxidative processes via mixed function oxidases mainly in the liver.

a) The pyrethroids undergo ester cleavage, hydroxylation and conjugation with glucuronide, glycine, and sulfate.
b) The cyanogroup, if present, is biotransformed to thiocyanate and eliminated more slowly than the remainder of the compound (Ruzo, 1978).

2) COWS - Approximately 25% of fenvalerate is excreted in feces, present for up to 1 week after the last feeding (of 15 ppm). Less than 1% is excreted in milk as the parent compound.
3) SHEEP - Fed to lambs, fenvalerate may persist for several weeks in liver, kidney, and muscle and longer in fat.

11.5.4)

A) GENERAL

1) There is limited information available on the specific kinetic parameters for the various pyrethroids. Based on persistent effects, the elimination half-lives appear to be in the range of several hours (shortest for pyrethrin and longest for the alpha-cyanopyrethroids).

Pharmacology Toxicology

1) The predominant action of pyrethroids is on voltage dependent sodium channels (Dorman & Beasley, 1991). The pyrethroids bind to open sodium channels markedly prolonging sodium influx; the prolongation is exaggerated with alpha-cyanopyrethroids.

a) These effects appear to be closely tied to the occurrence of repetitive discharges and the development of tremors in the animal (Clark & Brooks, 1989).

2) An additional action primarily by alpha-cyanopyrethroids is thought to occurby inhibition of GABA binding in inhibitory pathways in the brain, possiblyaccounting for the additional symptomatology with these compounds (Valentine, 1990).

Sources

1) There are a variety of preparations available primarily for control of fleas, mites, and ticks. These preparations include dips, dusts, sprays, shampoos, lotions (ears), and foggers for use with dogs, cats, birds, and horses. Treated ear tags are available for cattle.

a) The preparations may contain pyrethrins and/or synthetic pyrethroids; allethrin, permethrin, fenvalerate, and resmethrin (the latter two being alpha-cyanoderivatives).

2) The pyrethrins and pyrethroids are very commonly formulated in combination with piperonyl butoxide, which is intended to inhibit pyrethrin metabolism by the insect, increasing insecticide potency. Organophosphates and/or carbamates may also be included.

a) The clinical signs for the latter compounds are similar to those for pyrethroids. In cases of intoxication with the combination products, atropinemay be useful in distinguishing the origin of the signs.

Other

1) SPECIFIC TOXIN

a) Fenvalerate is formulated as a combination product with N, N-diethyl-m-toluamide (DEET) to improve efficacy.

1) Both compounds produce similar signs and although DEET (LD50 of 2 g/kg orally in rats) is of similar toxicity as the pyrethroids, there may be greater likelihood of intoxication for the combination than when either compound is used alone.
2) The propensity for penetration of DEET across intact skin may enhance absorption of the pyrethroids.
3) The clinical signs for the combination product in cats include hypersalivation, tremors, ataxia, vomiting, anorexia, depression, dyspnea, periodic hyperactivity, and paddling seizures. Toxicoses appear to be more prevalent in females (Dorman, 1990).
4) Supplemental product labeling for dogs and cats indicates that this product should not be used on pregnant cats, or cats less than 1 year old; dogs less than 3 months old; and sick, elderly, or debilitated pets.

References

General Bibliography

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FeedBack

PYRETHROIDS

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Vital Signs

Heent

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Respiratory

Neurologic

Gastrointestinal

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Acid-Base

Hematologic

Dermatologic

Musculoskeletal

Endocrine

Immunologic

Reproductive

Carcinogenicity

Genotoxicity

Monitoring Parameters Levels

Radiographic Studies

Methods

Life Support

Patient Disposition

Monitoring

Oral Exposure

Inhalation Exposure

Eye Exposure

Dermal Exposure

Enhanced Elimination

Case Reports

Summary

Therapeutic Dose

Minimum Lethal Exposure

Maximum Tolerated Exposure

Serum Plasma Blood Concentrations

Workplace Standards

Toxicity Information

Pharmacologic Mechanism

Toxicologic Mechanism

Physical Characteristics

Ph

Molecular Weight

Other

Clinical Effects

Treatment

Range Of Toxicity

Continuing Care

Kinetics

Pharmacology Toxicology

Sources

Other

General Bibliography