CARBACHOL CHLORIDE

Carbachol chloride is a direct-acting cholinergic compound (Budavari, 1989; Reynolds, 1993). As such, it is used as a miotic agent in human medicine and as a parasympathomimetic agent in large animal veterinary medicine (ie, for colic in horses) (Budavari, 1989; EPA, 1985).

FORMS

Carbachol chloride occurs as hygroscopic, hard, white or faintly yellow prismatic crystals or as a crystalline powder. It is odorless or has a slight amine-like odor. It is very soluble in water, is slightly soluble in methanol or ethanol, and is practically insoluble in acetone, chloroform, and ether (HSDB, 1993).

-CLINICAL EFFECTS

GENERAL CLINICAL EFFECTS

CHOLINERGIC SYNDROME -

Carbachol chloride is a direct-acting cholinergic compound.
Carbachol chloride is used as a miotic in human medicine and a parasympathomimetic in large animal veterinary medicine (ie, for colic in horses). It is used as a miotic agent in intraocular surgery, where it has been shown to be less toxic to the endothelium than acetylcholine. It had no substantial toxic effects on the corneal endothelium when injected intracamerally in cats.
Carbachol chloride is used as eye drops to lower intraocular pressure in glaucoma, by instillation into the anterior chamber of the eye to produce miosis in cataract surgery, in the treatment of intestinal atony and urinary retention, and to halt paroxysmal supraventricular tachycardia.

Carbachol chloride can be used to lower intraocular pressure in glaucomatous dogs. It has been used experimentally to increase blood pressure and produce cardiovascular stimulant effects in experimental animals when infused directly into the cerebral ventricles. It causes seizures and brain damage when injected directly into the amygdala or hippocampus of rats.
Carbachol chloride can be absorbed following ingestion or dermal contact. At the time of this review, no data were found on whether or not it can be systemically absorbed by inhalation, although it did increase airway resistance in sheep and human volunteers following inhalation exposure by direct stimulation of airway smooth muscle. In normal and asthmatic human subjects, bronchoconstriction induced by inhaled carbachol chloride could be prevented by prior inhalation of cromolyn sodium.
Carbachol directly stimulates muscarinic sites, but also stimulates acetylcholine release and has pronounced nicotinic effects on the neuromuscular skeletal muscle junction, postganglionic autonomic nervous system, and adrenal medulla.

Typical CHOLINERGIC symptoms include MUSCARINIC EFFECTS (miosis, flushing, bradycardia, bronchospasm, increased bronchial secretions, involuntary urination and/or defecation, nausea, vomiting, sweating, lacrimation, salivation, hypotension, hypothermia, and seizures). CARBACHOL also produces NICOTINIC EFFECTS (muscle cramps, fasciculations, weakness, paralysis, tachycardia, and hypertension).

Carbachol chloride releases toxic and irritating fumes of chloride, ammonia, and oxides of nitrogen when heated to decomposition. Inhalation exposure to such fumes would be predicted to result in respiratory tract irritation with bronchospasm, chemical pneumonitis, or noncardiogenic pulmonary edema.

Editor's Note: An ERG guide with information appropriate to this material does not exist.

ACUTE CLINICAL EFFECTS

Carbachol chloride can be absorbed following ingestion or dermal contact (EPA, 1985). No data were found on whether or not it can be systemically absorbed by inhalation, although it did increase airway resistance in human volunteers and sheep following inhalation by direct stimulation of airway smooth muscle (Abraham et al, 1984; (Dubois & Dautrebande, 1958; Fabbri et al, 1983).

Typical cholinergic symptoms include MUSCARINIC EFFECTS of miosis, flushing, bradycardia, bronchospasm, increased bronchial secretions, involuntary urination and/or defecation, nausea, vomiting, sweating, lacrimation, salivation, hypotension, hypothermia, and seizures (Sax & Lewis, 1989; JEF Reynolds , 1991; C Gelman , 1993; Sangster et al, 1979).

With CARBACHOL, NICOTINIC EFFECTS include muscle cramps, fasciculations, weakness, paralysis, tachycardia, and hypertension (Sax & Lewis, 1989; JEF Reynolds , 1991; C Gelman , 1993).

Direct contact with the eye can produce miosis, myopia, difficulty in visual accommodation, ciliary spasm, ocular pain, and eyelid twitching (C Gelman , 1993). Effects on the heart can include arrhythmias and heart block (Sax & Lewis, 1989). Effects on the lung can include bronchospasm and pulmonary edema, either of which may be life-threatening (Dubois & Dautrebande, 1958; Fabbri et al, 1983). Effects on the muscles can include cramps, weakness, fasciculations and paralysis (Reynolds, 1993; (C Gelman , 1993). CNS effects can include headache, vertigo, dizziness, tremors, seizures, and coma (Sax & Lewis, 1989; C Gelman , 1993). Gastrointestinal effects can include incontinence and nausea (Reynolds, 1993; (C Gelman , 1993; Sax & Lewis, 1989).

In normal and asthmatic human subjects, the bronchoconstriction induced by inhaled carbachol chloride could be prevented by prior inhalation of cromolyn sodium (Fabbri et al, 1983). It is possible, though not proven, that cromolyn sodium may have some prophylactic value in preventing symptoms from occupational inhalation exposures.

CHRONIC CLINICAL EFFECTS

Blurred vision, hyperemia of the conjunctiva, accommodation spasm, a burning sensation, and difficulty with night vision and reading have been seen with chronic topical therapeutic use in the eyes (C Gelman , 1993). Lowered intraocular pressure is one of the therapeutic effects of carbachol (Reynolds, 1993; (C Gelman , 1993).

-RANGE OF TOXICITY

MINIMUM LETHAL EXPOSURE

GENERAL/SUMMARY

The minimum lethal human dose to this agent has not been delineated.

MAXIMUM TOLERATED EXPOSURE

CASE REPORTS

ADULT

An 84-year-old man developed bradycardia, hypotension, AV dissociation, miosis, bronchorrhea, and diaphoresis after ingesting 400 to 500 mg carbachol. He then developed asystole, from which he was resuscitated and recovered, but died two weeks after exposure for unknown reason (Schulz et al, 2006).

PEDIATRIC

A dose of 0.5 milligram/kilogram orally produced cholinergic attacks, but was not fatal to a 10-year-old child (Sangster et al, 1979).

Carcinogenicity Ratings for CAS51-83-2 :

ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
EPA (U.S. Environmental Protection Agency, 2011): Not Listed
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
NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
MAK (DFG, 2002): Not Listed
NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

TOXICITY AND RISK ASSESSMENT VALUES

EPA IRIS

EPA Risk Assessment Values for CAS51-83-2 (U.S. Environmental Protection Agency, 2011):

Not Listed

TOXICITY VALUES

References: (RTECS, 1996)
- LD50- (INTRAPERITONEAL)MOUSE:
- LD50- (INTRAVENOUS)MOUSE:
- LD50- (ORAL)MOUSE:
- LD50- (SUBCUTANEOUS)MOUSE:
- LD50- (INTRAPERITONEAL)RAT:
- LD50- (INTRAVENOUS)RAT:
- LD50- (ORAL)RAT:
- LD50- (SUBCUTANEOUS)RAT:
- LDLo- (ORAL)DOG:
- LDLo- (SUBCUTANEOUS)DOG:
- LDLo- (SUBCUTANEOUS)GUINEA_PIG:
- TDLo- (INTRAMUSCULAR)HUMAN:
- TDLo- (INTRAVENOUS)HUMAN:

-STANDARDS AND LABELS

WORKPLACE STANDARDS

ACGIH TLV Values for CAS51-83-2 (American Conference of Governmental Industrial Hygienists, 2010):

Not Listed

AIHA WEEL Values for CAS51-83-2 (AIHA, 2006):

Not Listed

NIOSH REL and IDLH Values for CAS51-83-2 (National Institute for Occupational Safety and Health, 2007):

Not Listed

OSHA PEL Values for CAS51-83-2 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

Not Listed

OSHA List of Highly Hazardous Chemicals, Toxics, and Reactives for CAS51-83-2 (U.S. Occupational Safety and Health Administration, 2010):

Not Listed

ENVIRONMENTAL STANDARDS

EPA CERCLA, Hazardous Substances and Reportable Quantities for CAS51-83-2 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA CERCLA, Hazardous Substances and Reportable Quantities, Radionuclides for CAS51-83-2 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA RCRA Hazardous Waste Number for CAS51-83-2 (U.S. Environmental Protection Agency, 2010b):

Not Listed
Editor's Note: The D, F, and K series waste numbers and Appendix VIII to Part 261 -- Hazardous Constituents were not included. Please refer to 40 CFR Part 261.

EPA SARA Title III, Extremely Hazardous Substance List for CAS51-83-2 (U.S. Environmental Protection Agency, 2010):

Listed as: Carbachol Chloride
Reportable Quantity, in pounds: 500

Only the statutory or final RQ is shown. For more information, see 40 CFR table 302.4.

Threshold Planning Quantity, in pounds:

500/10,000
Amount necessary to be covered by this standard. See 40 CFR 355.30.

Note(s): Not Listed

EPA SARA Title III, Community Right-to-Know for CAS51-83-2 (40 CFR 372.65, 2006; 40 CFR 372.28, 2006):

Not Listed

DOT List of Marine Pollutants for CAS51-83-2 (49 CFR 172.101 - App. B, 2005):

Not Listed

EPA TSCA Inventory for CAS51-83-2 (EPA, 2005):

Listed as: Ethanaminium, 2-[(aminocarbonyl)oxy]-N,N,N-trimethyl-, chloride

LABELS

NFPA

NFPA Hazard Ratings for CAS51-83-2 (NFPA, 2002):

Not Listed

-PERSONAL PROTECTION

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

PROTECTIVE CLOTHING

CHEMICAL PROTECTIVE CLOTHING. Search results for CAS 51-83-2.

Specific recommendations and test data for this chemical were not found in the available manufacturers' product literature. A complete list of consulted manufacturers and references is presented below.

-PHYSICAL HAZARDS

FIRE HAZARD

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

FLAMMABILITY CLASSIFICATION

NFPA Flammability Rating for CAS51-83-2 (NFPA, 2002):

Not Listed

FIRE CONTROL/EXTINGUISHING AGENTS

Editor's Note: An ERG guide with information appropriate to this material does not exist.

NFPA Extinguishing Methods for CAS51-83-2 (NFPA, 2002):

Not Listed

EVACUATION PROCEDURES

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

AIHA ERPG Values for CAS51-83-2 (AIHA, 2006):

Not Listed

DOE TEEL Values for CAS51-83-2 (U.S. Department of Energy, Office of Emergency Management, 2010):

Listed as Carbachol Chloride
TEEL-0 (units = mg/m3): 3
TEEL-1 (units = mg/m3): 7.5
TEEL-2 (units = mg/m3): 15
TEEL-3 (units = mg/m3): 15
Definitions:

TEEL-0: The threshold concentration below which most people will experience no adverse health effects.
TEEL-1: The airborne concentration (expressed as ppm [parts per million] or mg/m(3) [milligrams per cubic meter]) of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic, nonsensory effects. However, these effects are not disabling and are transient and reversible upon cessation of exposure.
TEEL-2: The airborne concentration (expressed as ppm or mg/m(3)) of a substance above which it is predicted that the general population, including susceptible individuals, could experience irreversible or other serious, long-lasting, adverse health effects or an impaired ability to escape.
TEEL-3: The airborne concentration (expressed as ppm or mg/m(3)) of a substance above which it is predicted that the general population, including susceptible individuals, could experience life-threatening adverse health effects or death.

AEGL Values for CAS51-83-2 (National Research Council, 2010; National Research Council, 2009; National Research Council, 2008; National Research Council, 2007; NRC, 2001; NRC, 2002; NRC, 2003; NRC, 2004; NRC, 2004; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; United States Environmental Protection Agency Office of Pollution Prevention and Toxics, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; 62 FR 58840, 1997; 65 FR 14186, 2000; 65 FR 39264, 2000; 65 FR 77866, 2000; 66 FR 21940, 2001; 67 FR 7164, 2002; 68 FR 42710, 2003; 69 FR 54144, 2004):

Not Listed

NIOSH IDLH Values for CAS51-83-2 (National Institute for Occupational Safety and Health, 2007):

Not Listed

CONTAINMENT/WASTE TREATMENT OPTIONS

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

SMALL LEAK/SPILL

Editor's Note: An ERG guide with information appropriate to this material does not exist.

LARGE LEAK/SPILL

Editor's Note: An ERG guide with information appropriate to this material does not exist.

-PHYSICAL/CHEMICAL PROPERTIES

MOLECULAR WEIGHT

182.65 (Budavari, 1996)

DESCRIPTION/PHYSICAL STATE

Carbachol chloride is a hard prismatic crystalline solid. It is hygroscopic and odorless. On standing in an open container, it develops a faint odor resembling an aliphatic amine (Budavari, 1996).

SOLUBILITY

IN WATER

1g/1 mL (Budavari, 1989)

IN ORGANIC SOLVENTS

1g/50 mL of alcohol (Budavari, 1989)
1g/10 mL of methanol (Budavari, 1989)
Insoluble in chloroform and ether (Budavari, 1996).

-REFERENCES

GENERAL BIBLIOGRAPHY

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62 FR 58840: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 1997.

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66 FR 21940: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2001.

67 FR 7164: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2002.

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CARBACHOL CHLORIDE

Classification | Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents