Summary Of Exposure |
A) BACKGROUND: Euphorbiaceae, also known as spurges, are a family of plants found worldwide. They are used as foods, medicines, and industrial uses. As medicinal and toxic agents, they are best known for their purgative, tumor promoting and irritant properties.
B) TOXICOLOGY: The toxicity of Euphorbiaceae depends on the specific plants of the family and the various parts of each plant. For instance, resiniferatoxin, which is an extremely potent capsaicin analog, can be found in Euphorbia resinifera and Euphorbia poissonii. Euphorbia marinata contains a ribosome inactivating protein in its latex. Tumor promotion substances include the ingenane and tigliane diterpene esters, which are also irritants.
C) EPIDEMIOLOGY: Euphorbiaceae plants are found worldwide and thus exposures to people are extremely common. Though most plants in this family are found in tropical areas, there are species found in nontropical areas as well. Prominent plants that people may come in contact with includes cassava, castor oil plants, and poinsettias.
D) WITH POISONING/EXPOSURE
1) MILD TO MODERATE EXPOSURES: Some plants in this family contain irritant diterpene esters that can be irritating. Ingestion may cause oral irritation, gastritis, vomiting and diarrhea. In addition, ingestion may cause a burning sensation of the mouth, throat, lips, and buccal surfaces. Erythema and swelling are also common. After ingesting a soup containing Breynia officinalis, hepatotoxicity was reported. The most commonly reported toxicity is dermal, due to the milky latex excreted by some of these plants that can cause contact erythema, swelling, and the formation of blisters and vesicles.
2) SEVERE EXPOSURES: Systemic symptoms are rare but may include giddiness, electrolyte disturbances (hypokalemia), cardiac toxicity (ECG abnormalities), CNS toxicity (seizures, coma, neuromuscular weakness), renal and respiratory failure and even death. Specifically, cardiac dysrhythmias and hypotension have developed after ingestion of Cleistanthus collinus extract and leaves. In addition, C.collinus can cause respiratory symptoms; the dust of its dried resins is irritating to the nose and lungs and in one case of ingestion, pulmonary edema preceded death. C. collinus toxicity has also caused neurologic symptoms such as giddiness, seizures, coma, progressive neuromuscular weakness and paresis.
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Heent |
3.4.1) SUMMARY
A) WITH POISONING/EXPOSURE 1) Eye irritation may range from simple conjunctivitis to iritis, corneal ulceration, and temporary blindness.
2) Ingestion may cause a burning sensation of the mouth, throat, lips, and buccal surfaces. Erythema and swelling are also common findings.
3.4.2) HEAD
A) Eye irritation and injury are common. Mucous membrane irritation is also common. B) WITH POISONING/EXPOSURE 1) Erythema and swelling may be seen on the faces of children exposed (Spoerke & Temple, 1979).
C) ANIMAL STUDIES 1) Cattle driven through brush containing E. ingens have developed burns of the lips, eyes, and face. Burns have occasionally been so severe as to cause death (Watt & Breyer-Brandwijk, 1962).
3.4.3) EYES
A) WITH POISONING/EXPOSURE 1) KERATOPATHY/KERATOCONJUNCTIVITIS as well as temporary blindness has been reported in various references after direct contact between the irritant latex and the eye (Shlamovitz et al, 2009; Markby et al, 1989; Kingsbury, 1964; Crowder & Sexton, 1964). a) Hartmann (1940) reported a case where a patient developed corneal edema, conjunctival hemorrhage, serofibrinous exudate into the anterior chamber, and a vitreous haze after instillation of the latex of Euphorbia peplus. The eye healed without sequelae within 14 days. b) Initial contact with Euphorbia sap produced epitheliopathy with immediate burning and photophobia without visual loss. Epithelial slough delayed healing. The epithelial defect required almost 9 days for recovery. After healing there were no visual defects or loss of vision (Scott & Karp, 1996). c) KERACONJUNCTIVITIS: A 40-year-old man developed severe pain and rapid changes in visual acuity (right eye: 20/200; left eye 20/40 {normal vision: 20/20 bilaterally}) after contact with the sap of a pencil cactus (Euphorbia tirucalli). An ocular exam showed hyperemic conjunctivae with bilaterally diffuse punctuate opacification of the corneal epithelium. The patient was treated with repeated doses of proparacaine with only temporary pain relief. Pain was eventually managed with copious eye irrigation, topical anesthetics, steroids and antibiotic ointment. Approximately 16 hours after exposure, an ophthalmology exam showed no new symptoms and the patient was discharged to home. Long term outcome was unknown, because the patient was lost to follow-up (Shlamovitz et al, 2009). d) UVEITIS: A group of 7 patients with ocular exposure to various Euphorbia species (identified via a specimen of the plant) were studied for ocular effects. Initial symptoms were stinging or a burning pain in the eyes, lacrimation, photophobia, and often blurred vision. Various degrees of decreased visual acuity were noted in all patients. 1) Ocular damage ranged from mild epithelial keratoconjunctivitis to severe keratitis with stromal edema, corneal epithelial sloughing and anterior uveitis. One to two weeks was required for resolution of the symptoms. The species involved were E. milli, E. characias, E. characias subsp. wulfenii, E. palustris, E. platyphyllos, and E. robbiae (Eke et al, 2000).
2) IRITIS as well as lid swelling, keratitis and severe conjunctivitis has been reported when the latex of Euphorbiaceae has been placed in the eye (Lisch, 1980). 3) BLINDNESS: Temporary blindness and intense pain has been caused by E. ingens, E. lactea, E. tirucalli, and others (Watt & Breyer-Branwijk, 1962). 4) CORNEAL SCARRING as well as ulceration, iridocyclitis and total anterior staphyloma was seen in four cases of ocular exposure to the latex of E. royleana (Sofat et al, 1972; Sood et al, 1971). 5) MIOSIS: Pupillary constriction was seen in a fatal case of ingestion of E. helioscopia (Vlachos et al, 1978). 6) CONJUNCTIVITIS: A child with ocular exposure to Euphorbia myrsinites developed conjunctivitis of the right eye (Eberle et al, 1999). 7) DIPLOPIA followed by significant PTOSIS and OCULOMOTOR PALSY was reported in a woman following ingestion of Cleistanthus collinus extract (Eswarappa et al, 2003). 8) CASE SERIES: After a group of villagers (n=19) ingested a soup containing Breynia officinalis stems, 2 patients experienced blurred vision (Lin et al, 2003). B) ANIMAL STUDIES 1) DOGS: The latex of E. lactea was tested on anesthetized dogs. Three drops of undiluted latex were placed in the eyes of the dogs and allowed to spread over the cornea and onto the conjunctiva. The eyes were not rinsed or treated in any other way. a) There did not appear to be any immediate reaction, but within 3 hours the eyes were red and had slight swelling of the conjunctiva. The cornea was clear. Hemorrhage and swelling of the conjunctiva, as well as a mucous discharge was seen in 7 to 12 hours.
b) The cornea was now cloudy. For the next 18 to 24 hours the cases worsened with the peak corneal hazing appearing at 24 to 36 hours. By 48 to 72 hours there was considerable improvement.
2) A concentration of 0.35% of the latex from Euphorbia splendens was irritating to the eyes of tested rabbits (Freitas et al, 1991). 3.4.5) NOSE
A) WITH POISONING/EXPOSURE 1) SNEEZING: The dried latex of E. resinifera is very irritating and may cause violent sneezing if the dust is inhaled (Mitchell & Rook, 1979).
3.4.6) THROAT
A) WITH POISONING/EXPOSURE 1) IRRITATION: Ingestion of the latex may produce a severe burning sensation of the throat (Frohne & Pfander, 1983).
2) INCIDENCE: According to the AAPCC Toxic Exposure Surveillance System (TESS) for 1992 through 1999, 28.5% and 15% of patients experienced oral irritation and throat irritation, respectively, following Euphorbia spp. plant ingestions (Mrvos et al, 2001).
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Cardiovascular |
3.5.2) CLINICAL EFFECTS
A) LOW BLOOD PRESSURE 1) WITH POISONING/EXPOSURE a) CASE REPORT: A 24-year-old man ingested 40 to 50 Cleistanthus collinus leaves and approximately 48 hours after admission showed evidence of toxin-induced vasodilatation (ie, hypotension, tachycardia, low CVP, oliguria and increased urinary osmolality). The patient recovered following supportive efforts including fluid and electrolyte replacement and N-acetylcysteine therapy (Benjamin et al, 2006).
b) CASE REPORTS: Two women intentionally ingested Cleistanthus collinus extract (the liquid was extracted from crushed boiled leaves which were identified by forensic medical and toxicology experts) and developed persistent hypotension that was unresponsive to therapy (i.e., crystalloids, dopamine, norepinephrine and dobutamine). Both died following the development of pulseless electrical activity that did not respond to resuscitation efforts (Eswarappa et al, 2003).
B) ELECTROCARDIOGRAM ABNORMAL 1) WITH POISONING/EXPOSURE a) CASE REPORTS 1) Following intentional ingestion of Cleistanthus collinus extract (the liquid was extracted from crushed boiled leaves; leaves were identified by forensic medical and toxicology experts), two women developed several electrocardiographic abnormalities, which included ST segment depression (0.5 mm in lateral chest leads - V5, V6), asystolic cardiac arrest, and finally pulseless electrical activity in both patients. Neither patient responded to aggressive resuscitation measures, and died within 52 hours and 6 days of exposure, respectively (Eswarappa et al, 2003).
C) TIGHT CHEST 1) WITH POISONING/EXPOSURE a) CASE SERIES: After a group of villagers (n=19) ingested a soup containing Breynia officinalis stems, 4 and 7 patients experienced chest tightness and palpitation, respectively (Lin et al, 2003).
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Respiratory |
3.6.2) CLINICAL EFFECTS
A) IRRITATION SYMPTOM 1) WITH POISONING/EXPOSURE a) Synadendium cupulare is a known irritant and vesicant. The vapors given off by the plant are said to be irritant and may produce effects even when held at arm's length (Mitchell & Rook, 1979).
B) ACUTE LUNG INJURY 1) WITH POISONING/EXPOSURE a) CASE REPORT: Increasing hypoxia, dyspnea, tachypnea, and bilateral peripheral alveolar infiltrates on chest x-ray were observed in a 24-year-old man after ingesting 40 to 50 Cleistanthus collinus leaves. Mechanical ventilation with PEEP were used to manage his ARDS. The patient was extubated on hospital day 10 and lung shadows disappeared within 3 weeks (Benjamin et al, 2006).
b) CASE REPORT: Pulmonary edema was reported in one fatal case where a child sucked on the latex of E. helioscopia (Vlachos et al, 1978). Most exposures do not result in serious pulmonary symptoms.
C) RESPIRATORY FAILURE 1) WITH POISONING/EXPOSURE a) Respiratory failure requiring mechanical ventilation was reported secondary to progressive neuromuscular weakness following an ingestion of Cleistanthus collinus extract (the liquid was extracted from crushed boiled leaves; leaves were identified by forensic medical and toxicology experts). The patient died from cardiac toxicity 6 days after exposure (Eswarappa et al, 2003).
D) RESPIRATORY FINDING 1) WITH POISONING/EXPOSURE a) CASE SERIES: After a group of villagers (n=19) ingested a soup containing Breynia officinalis stems, dyspnea (n=1) and tachypnea (n=1) were reported (Lin et al, 2003).
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Neurologic |
3.7.2) CLINICAL EFFECTS
A) CENTRAL NERVOUS SYSTEM FINDING 1) WITH POISONING/EXPOSURE a) CASE SERIES: After a group of villagers (n=19) ingested a soup containing Breynia officinalis stems, vertigo (n=3), malaise (n=2), tremor (n=2), headache (n=2), drowsiness (n=1) were reported (Lin et al, 2003).
B) SEIZURE 1) WITH POISONING/EXPOSURE a) CASE REPORT: Seizures were seen in a child who ingested the latex of E. helioscopia (Vlachos et al, 1978). Most cases do not result in serious neurologic symptoms.
C) COMA 1) WITH POISONING/EXPOSURE a) CASE REPORT: Coma preceded death in a fatal case of ingestion of E. helioscopia (Vlachos et al, 1978).
D) DIZZINESS 1) WITH POISONING/EXPOSURE a) GIDDINESS: May be seen in cases of ingestion (Frohne & Pfander, 1983).
E) FLACCID PARALYSIS 1) WITH POISONING/EXPOSURE a) Progressive neuromuscular weakness and hyporeflexic flaccid quadriparesis was reported in a woman following intentional ingestion of Cleistanthus collinus extract (the liquid was extracted from crushed boiled leaves; leaves were identified by forensic medical and toxicology experts). The patient died from cardiac toxicity 6 days after exposure (Eswarappa et al, 2003).
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Gastrointestinal |
3.8.2) CLINICAL EFFECTS
A) EDEMA 1) WITH POISONING/EXPOSURE a) Oral exposure to Syndendium grantii has caused swelling of the lips, erythema, of the mouth, and increased drooling (Spoerke et al, 1985; Vlachos et al, 1978).
B) GASTROINTESTINAL IRRITATION 1) WITH POISONING/EXPOSURE a) Individuals who ingested the caper spurge (E. lathyris) have developed a severe burning sensation of the mouth and throat (Mitchell & Rook, 1979).
C) NAUSEA AND VOMITING 1) WITH POISONING/EXPOSURE a) Vomiting has been reported when the resin from E. resinifera and Hippomane mancinella has been ingested (Mitchell & Rook, 1979; Caddy, 1894). It has also been reported following ingestion of Cleistanthus collinus extract (from the leaf of the plant) (Eswarappa et al, 2003).
b) CASE SERIES: After a group of villagers (n=19) ingested a soup containing Breynia officinalis stems, 10 and 7 patients experienced nausea and vomiting, respectively (Lin et al, 2003).
c) INCIDENCE: Nausea and vomiting have been reported in 4.4% and 24% of patients following Euphorbia spp. plant ingestions, according to the AAPCC TESS for 1992 through 1999 (Mrvos et al, 2001).
D) DIARRHEA 1) Diarrhea has been reported when the resin from E. resinifera and Hippomane mancinella has been ingested (Mitchell & Rook, 1979; Caddy, 1894). It has also been reported following the ingestion of Cleistanthus collinus extract (from the leaf of the plant) (Eswarappa et al, 2003).
2) CASE SERIES: After a group of villagers (n=19) ingested a soup containing Breynia officinalis stems, 14 patients experienced diarrhea (Lin et al, 2003).
3) Diarrhea, which may be bloody, followed by severe gastritis, may be seen after ingestion of plants containing the diterpene esters such as Hippomane manacinella (Lampe & McCann, 1985).
E) ABDOMINAL PAIN 1) WITH POISONING/EXPOSURE a) CASE SERIES: After a group of villagers (n=19) ingested a soup containing Breynia officinalis stems, 3 and 9 patients experienced abdominal pain and fullness, respectively (Lin et al, 2003).
F) APTYALISM 1) WITH POISONING/EXPOSURE a) CASE SERIES: After a group of villagers (n=19) ingested a soup containing Breynia officinalis stems, 6 patients experienced dry mouth (Lin et al, 2003).
G) DECREASE IN APPETITE 1) WITH POISONING/EXPOSURE a) CASE SERIES: After a group of villagers (n=19) ingested a soup containing Breynia officinalis stems, 5 patients experienced poor appetite (Lin et al, 2003).
H) HEARTBURN 1) WITH POISONING/EXPOSURE a) CASE SERIES: After a group of villagers (n=19) ingested a soup containing Breynia officinalis stems, 4 and 1 patients experienced heartburn and belching, respectively (Lin et al, 2003).
I) TASTE SENSE ALTERED 1) WITH POISONING/EXPOSURE a) CASE SERIES: After a group of villagers (n=19) ingested a soup containing Breynia officinalis stems, one patient experienced bitter taste in the mouth (Lin et al, 2003).
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Hepatic |
3.9.2) CLINICAL EFFECTS
A) INJURY OF LIVER 1) WITH POISONING/EXPOSURE a) CASE SERIES: In one case series, 18 of 19 patients (11 men and 8 women) developed abnormal liver function tests (LFT) after ingesting an average of 130 mL (30 to 900 mL) of soup containing Breynia officinalis stems. Diarrhea, nausea and chilly sensations, abdominal fullness, and vomiting were reported by 14, 10, 9, and 7 patients, respectively. The observed maximum median level of ALT was 647 Units/L (range 89-9440 Units/L), AST 314 Units/L (range: 47 to 7756 Units/L), alkaline phosphatase 251 Units/L (range: 224 to 278 Units/L), gamma glutamyl transpeptidase 106 Units/L (range: 84 to 313 Units/L), total bilirubin 2.2 (1.6 to 2.8), and direct bilirubin 0.5 (0.5 to 0.8). One patient who ingested 60 mL of the soup (the smallest amount) did not develop abnormal LFTs. When hepatitis markers were measured, 5 of the 18 patients who developed abnormal LFTs were positive for HBsAg and 2 were positive for anti-HCVAb. Three of the 5 patients with abnormal total and direct bilirubin were also positive for HBsAG and one was positive for anti-HCVAb. Following supportive therapy, all liver function abnormalities resolved within 6 months of exposure (Lin et al, 2003).
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Genitourinary |
3.10.2) CLINICAL EFFECTS
A) ACUTE RENAL FAILURE SYNDROME 1) WITH POISONING/EXPOSURE a) CASE REPORT: A 29-year-old man with a history of stable nephrotic syndrome developed acute renal failure after the ingestion of Euphorbia paralias (ie, boiled the plant) as a herbal treatment for edema approximately 10 days prior to admission. Initial laboratory studies included a serum creatinine of 1835 micromol/L and urea of 44.6 mmol/L and severe hypoproteinemia. An ultrasound showed enlarged kidneys and a renal biopsy was positive for glomerulosclerosis and associated with acute tubular injury. Treatment included intermittent hemodialysis and corticosteroid therapy; urinary volume and creatinine normalized over 48 days. Six months later the patient still had an elevated serum creatinine (240 micromol/L) (Boubaker et al, 2013).
b) CASE REPORT: Acute renal failure developed in a fatal exposure to an ingestion of Cleistanthus collinus extract (the liquid was extracted from crushed boiled leaves which were identified by forensic medical and toxicology experts) in a woman (Eswarappa et al, 2003). Along with elevations in BUN and serum creatinine, the patient developed polyuria (3450 mL of urine over 22 hours) approximately 5 days after exposure. This was followed by progressive oliguria (250 mL over 14 hours) until her death from cardiac toxicity.
B) RENAL TUBULAR ACIDOSIS 1) WITH POISONING/EXPOSURE a) Renal tubular acidosis (ie, increased potassium loss, hyperchloremic metabolic acidosis, and normal serum anion gap) occurred in a 24-year-old man after ingesting 40 to 50 Cleistanthus collinus leaves. The diagnosis was confirmed by a positive urinary anion gap despite low serum bicarbonate. Treatment included IV sodium bicarbonate to correct acidosis, followed by Shohl's solution and potassium citrate by Ryle's tube. The patient was also treated with N-acteylcysteine and distal RTA improved over a 2 week period. The patient made a complete recovery (Benjamin et al, 2006). Distal renal tubular acidosis was also suspected in another patient with Cleistanthus collinus toxicity (Eswarappa, 2007).
C) OLIGURIA 1) WITH POISONING/EXPOSURE a) CASE SERIES: After a group of villagers (n=19) ingested a soup containing Breynia officinalis stems, one patient experienced oliguria (Lin et al, 2003). In another case, an adult ingested 40 to 50 Cleistanthus collinus leaves and developed oliguria (Benjamin et al, 2006).
D) COLOR OF URINE 1) WITH POISONING/EXPOSURE a) CASE SERIES: After a group of villagers (n=19) ingested a soup containing Breynia officinalis stems, one patient experienced tea-colored urine (Lin et al, 2003).
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Acid-Base |
3.11.2) CLINICAL EFFECTS
A) METABOLIC ACIDOSIS 1) WITH POISONING/EXPOSURE a) CASE REPORT: Metabolic acidosis was observed in a 24-year-old man after ingesting 40 to 50 Cleistanthus collinus leaves. Cardiac toxicity, distal renal tubular acidosis and ARDS were also present. The patient recovered following supportive care which included mechanical ventilation and N-acteylcysteine therapy (Benjamin et al, 2006).
b) CASE REPORTS: Metabolic acidosis was reported in two fatal cases of intentional Cleistanthus collinus extract ingestion (patients drank liquid extracted from crushed boiled leaves). In one patient, life-threatening metabolic acidosis, along with cardiac and neuromuscular toxicity did not occur until approximately 4 days after exposure. The other patient died within 52 hours of exposure (Eswarappa et al, 2003).
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Hematologic |
3.13.2) CLINICAL EFFECTS
A) PLATELET AGGREGATION 1) WITH POISONING/EXPOSURE a) PLATELET AGGREGATION: The toxin of Mabea excelsea (esters of 5-deoxy-13-hydroxy-ingenol) have the ability to induce human platelet aggregation at a median dose of 2.4 mcg/mL (Markby et al, 1989).
B) LEUKOCYTOSIS 1) WITH POISONING/EXPOSURE a) CASE SERIES: After a group of villagers (n=19) ingested a soup containing Breynia officinalis stems, 2 patients developed a transient leukocytosis [WBC 25,200/mm(3) and 16,600/mm(3)] with neutrophil counts as high as 87.6% and 88.9% the first day after exposure, returning to normal 4 days after the ingestions (Lin et al, 2003).
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Dermatologic |
3.14.2) CLINICAL EFFECTS
A) FLUSHING 1) WITH POISONING/EXPOSURE a) CASE SERIES: After a group of villagers (n=19) ingested a soup containing Breynia officinalis stems, one patient experienced flushing (Lin et al, 2003).
B) BULLOUS ERUPTION 1) WITH POISONING/EXPOSURE a) SKIN LESIONS: Contact with the irritant latex may produce blisters and lesions that are then open to secondary infection (Markby et al, 1989; Kinghorn, 1980; Kinghorn & Evans, 1975). b) TYPICAL PRESENTATION 1) In most cases there is no immediate discomfort, but in about 4 hours there may be a burning sensation of the affected area. Within 8 hours this sensation may be severe and red streaking and blistering may appear. A fine papular rash, vesicles, or large bullae may be seen (Calnan, 1975).
2) The erythema usually subsides within the first 48 hours, but the blisters may not be healed for 4 to 7 days (Spoerke et al, 1985; Spoerke & Temple, 1979; Rook, 1965).
3) CASE SERIES: The undiluted latex of the ornamental succulent plant Euphorbia hermentiana was tested on 5 Caucasian subjects. Follicular dermatitis was noted when the latex was used in an open test on the flexor forearm. Bullae, vesiculation (with desquamation and hyperpigmentation) was observed in closed testing on the flexor surfaces of the upper arms. Signs of irritation remained for over a week (Worobec et al, 1981).
3.14.3) ANIMAL EFFECTS
A) ANIMAL STUDIES 1) SKIN NECROSIS a) INJECTION of the latex from Synadenium into the skin of guinea pigs produced necrosis and sloughing (Thorold, 1953).
2) IRRITATION a) Dermal exposure to the latex of Euphorbia splendens was irritating to the skin of rabbits in concentrations greater than 0.5% (Freitas et al, 1991).
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Musculoskeletal |
3.15.2) CLINICAL EFFECTS
A) PAIN 1) WITH POISONING/EXPOSURE a) CASE SERIES: After a group of villagers (n=19) ingested a soup containing Breynia officinalis stems, muscle pain (n=1), bone pain (n=1) and lumbar soreness (n=1) were reported (Lin et al, 2003).
B) SERUM CREATININE RAISED 1) WITH POISONING/EXPOSURE a) CASE REPORT: An elevated serum creatinine kinase (total 883 Units/L and CK-MB 123 U/L) concentration was reported in a 24-year-old man after ingesting 40 to 50 Cliestanthus collinus leaves (Benjamin et al, 2006).
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Endocrine |
3.16.3) ANIMAL EFFECTS
A) ANIMAL STUDIES 1) ENDOCRINE DISORDER a) PROGESTIN: In vitro studies of the phorbol ester TPA on gonadotropin stimulated steroidogenesis in primary cultures of rat ovarian granulosa and testicular Leydig cells showed inhibition of progestin biosynthesis and decreases in FSH-stimulated pregnenolone biosynthesis (Welsh et al, 1984).
b) PROLACTIN: In vitro treatment of pituitary tumor cells with the phorbol ester TPA increases prolactin and decreases growth hormone secretion by these cells (Osborne & Tashijan, 1981; Jaken et al, 1981; Blumberg, 1980).
c) INSULIN: The secretion of insulin was stimulated by the phorbol ester TPA (Malaisse et al, 1980; Blumberg, 1980) (Virgi et al, 1978).
d) LH LEVELS: In cultured rat pituitary cells were increased by treatment with TPA, as was adrenocorticotropic hormone secretion (Naor & Catt, 1981; Smith & Vale, 1980).
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Immunologic |
3.19.2) CLINICAL EFFECTS
A) ACUTE ALLERGIC REACTION 1) WITH POISONING/EXPOSURE a) Specific IgE was found in the serum of subjects who developed severe urticaria- type, pruritic, allergic reactions at the site of contact with Euphorbias characias latex. In three of seven subjects, the pruritus was generalized. Examination of the latex did not find phorbol or ingenol derivatives. Prick tests with the latex were positive (Ballero et al, 1999).
b) Occupational allergy due to exposure to the pollen of Euphorbia fulgens has been reported in growers. Symptoms included tracheobronchitis or bronchial asthma. Intracutaneous tests for allergy were done using pollen extracts. The subjects were positive even in high dilution. The allergen was found only in the pollen, not in the latex or other parts of the plant (Hausen et al, 1976).
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Carcinogenicity |
3.21.2) SUMMARY/HUMAN
A) The diterpene esters found in these plants are co-carcinogenic, meaning that they promote the growth of cancers when cancer inducing agents are present. We were not able to find actual human cases where these agents were held responsible for inducing cancer.
3.21.3) HUMAN STUDIES
A) CARCINOMA 1) COCARCINOGENIC ACTIVITY - Has been seen with many of the diterpene esters found in the Euphorbiaceae (Zayed et al, 2001; (Hecker, 1976; Berenblum, 1975). These chemicals promote the growth of tumors induced by a carcinogen.
2) Most of the experiments involving the carcinogenic effects have been done in animals, and experiments proving these effects in humans are lacking (Kinghorn, 1979).
B) NEOPLASM 1) Repeated applications of a tumor-promoting chemical to the skin may lead to hyperplasia but not necessarily to cancer (Boutwell, 1974).
3.21.4) ANIMAL STUDIES
A) CARCINOMA 1) COCARCINOGENIC ACTIVITY - Has been seen with many of the diterpene esters found in the Euphorbiaceae (Zayed et al, 2001; (Hecker, 1976; Berenblum, 1975). These chemicals promote the growth of tumors induced by a carcinogen.
2) Most of the experiments involving the carcinogenic effects have been done in animals, and experiments proving these effects in humans are lacking (Kinghorn, 1979).
B) NEOPLASM 1) ANTITUMOR PRINCIPLES - Have also been isolated. An extract from Euphorbia lathyris (L.) showed antineoplastic activity against sarcoma 180 ascites in mice. It appears the active agent was ingenol-3-hexadecanoate (Itokawa et al, 1989).
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