Malathion

CAS RN: 121-75-5

Health Effects

0.2.1 SUMMARY OF EXPOSURE
  • 0.2.1.1 ACUTE EXPOSURE
    • A) WITH THERAPEUTIC USE
      • 1) The following are signs and symptoms from organophosphates in general, which are due to the anticholinesterase activity of this class of compounds. All of these effects may not be documented for malathion, but could potentially occur in individual cases.
      • 2) USES: Malathion is a nonsystemic acaracide and insecticide and is considered the least toxic of the organophosphates. Malathion is also used in the treatment of pediculus humanus capitis (head lice and their ova) infections of the scalp hair.
      • 3) TOXICOLOGY: Organophosphates competitively inhibit pseudocholinesterase and acetylcholinesterase, preventing hydrolysis and inactivation of acetylcholine. Acetylcholine accumulates at nerve junctions, causing malfunction of the sympathetic, parasympathetic, and peripheral nervous systems and some of the CNS. Clinical signs of cholinergic excess can develop.
      • 4) EPIDEMIOLOGY: Exposure to organophosphates is common, but serious toxicity is unusual in the US.
    • B) WITH POISONING/EXPOSURE
      • 1) EFFECTS FOLLOWING THERAPEUTIC USE
        • a) Systemic effects have not been reported with topical use of malathion 0.5% solution used in the treatment of pediculus humanus capitis (head lice). The solution is manufactured in an isopropyl alcohol (78%) vehicle which can produce local irritation to the skin. If inadvertent ingestion of malathion solution occurs, the effects of isopropyl alcohol toxicity should be considered. Refer to ISOPROPYL ALCOHOL document for more information.
      • 2) ORGANOPHOSPHATE POISONING EFFECTS
        • a) MILD TO MODERATE POISONING: MUSCARINIC EFFECTS: Can include bradycardia, salivation, lacrimation, diaphoresis, vomiting, diarrhea, urination, and miosis. NICOTINIC EFFECTS: Tachycardia, hypertension, mydriasis, and muscle cramps.
        • b) SEVERE POISONING: MUSCARINIC EFFECTS: Bronchorrhea, bronchospasm, and acute lung injury. NICOTINIC EFFECTS: Muscle fasciculations, weakness, and respiratory failure. CENTRAL EFFECTS: CNS depression, agitation, confusion, delirium, coma, and seizures. Hypotension, ventricular dysrhythmias, metabolic acidosis, pancreatitis, and hyperglycemia can also develop.
        • c) DELAYED EFFECTS: Intermediate syndrome is characterized by paralysis of respiratory, cranial motor, neck flexor, and proximal limb muscles 1 to 4 days after apparent recovery from cholinergic toxicity, and prior to the development of delayed peripheral neuropathy. Manifestations can include the inability to lift the neck or sit up, ophthalmoparesis, slow eye movements, facial weakness, difficulty swallowing, limb weakness (primarily proximal), areflexia, and respiratory paralysis. Recovery begins 5 to 15 days after onset. Distal sensory-motor polyneuropathy may rarely develop 6 to 21 days following exposure to some organophosphate compounds, however, it has not yet been reported in humans after exposure to malathion. Characterized by burning or tingling followed by weakness beginning in the legs which then spreads proximally. In severe cases, it may result in spasticity or flaccidity. Recovery requires months and may not be complete.
        • d) CHILDREN: May have different predominant signs and symptoms than adults (more likely CNS depression, stupor, coma, flaccidity, dyspnea, and seizures). Children may also have fewer muscarinic and nicotinic signs of intoxication (i.e., secretions, bradycardia, fasciculations and miosis) as compared to adults.
        • e) INHALATION EXPOSURE: Organophosphate vapors rapidly produce mucous membrane and upper airway irritation and bronchospasm, followed by systemic muscarinic, nicotinic and central effects if exposed to significant concentrations.
0.2.3 VITAL SIGNS
  • 0.2.3.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Fever has been reported following ingestion of malathion. Hypothermia has been reported in one adult following a mixed ingestion with organophosphates.
0.2.4 HEENT
  • 0.2.4.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Miosis, lacrimation and blurred vision are common findings in organophosphate poisoning. Mydriasis may be seen in severe poisonings. Excessive salivation may occur after malathion poisoning.
0.2.5 CARDIOVASCULAR
  • 0.2.5.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Bradycardia and tachycardia can occur following ingestion. Hypotension or hypertension may develop with severe toxicity. Conduction disturbances have been reported with malathion exposure.
0.2.6 RESPIRATORY
  • 0.2.6.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) MUSCARINIC EFFECTS may produce bronchorrhea or bronchospasm, and an increase in bronchial secretions following malathion exposure.
0.2.7 NEUROLOGIC
  • 0.2.7.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) EARLY EFFECTS - Malathion poisoning has produced typical neurologic effects of organophosphate poisoning. Giddiness, anxiety, headache, and restlessness followed by ataxia, drowsiness, and confusion are common with moderate to severe exposures. Fasciculations, profound weakness, coma and seizures may develop in severe cases. CNS depression and seizures may be more common in children than adults.
      • 2) INTERMEDIATE SYNDROME - Characterized by the development of proximal weakness and paralysis 12 hours to 7 days after exposure and following resolution of cholinergic symptoms. It is unresponsive to pralidoxime or atropine; treatment is supportive.
      • 3) DELAYED POLYNEUROPATHY - Distal sensory-motor polyneuropathy may develop 6 to 21 days following exposure; recovery may be slow or incomplete.
0.2.8 GASTROINTESTINAL
  • 0.2.8.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Nausea, vomiting, abdominal cramps, and diarrhea are common muscarinic effects. Fecal and urinary incontinence have been reported with malathion poisoning. Several cases of acute pancreatitis have also been associated with ingestion.
0.2.14 DERMATOLOGIC
  • 0.2.14.1 ACUTE EXPOSURE
    • A) WITH THERAPEUTIC USE
      • 1) Skin irritation may occur with therapeutic malathion lotion.
    • B) WITH POISONING/EXPOSURE
      • 1) Organophosphates including malathion can be absorbed transdermally. Diaphoresis is common with acute exposure.
0.2.15 MUSCULOSKELETAL
  • 0.2.15.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) NICOTINIC EFFECTS may produce generalized muscle fasciculations, muscle cramps, and eventually weakness following malathion exposure.
0.2.19 IMMUNOLOGIC
  • 0.2.19.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Dermal sensitization to malathion has been reported following skin exposure. It has not been reported with therapeutic use of malathion lotion.
0.2.20 REPRODUCTIVE HAZARDS
  • A) Malathion 0.5% topical lotion has a Pregnancy Category B rating.
  • B) Malathion 0.5% topical lotion for head lice therapy is Pregnancy Category B.
  • C) ANIMAL STUDIES - There was no evidence of teratogenicity in studies in rats and rabbits given malathion. Malathion can inhibit microsomal enzyme systems; it has been suggested that it should be investigated for possible effects on pregnancy.
  • D) HUMAN STUDIES - Detectable malathion metabolites in maternal urine have been linked to abnormal neonatal reflexes.
0.2.21 CARCINOGENICITY
  • 0.2.21.1 IARC CATEGORY
    • A) IARC Carcinogenicity Ratings for CAS121-75-5 (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: Malathion
        • b) Carcinogen Rating: 2A
      • 1) The agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans. This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals. In some cases, an agent (mixture) may be classified in this category when there is inadequate evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals and strong evidence that the carcinogenesis is mediated by a mechanism that also operates in humans. Exceptionally, an agent, mixture or exposure circumstance may be classified in this category solely on the basis of limited evidence of carcinogenicity in humans.
  • 0.2.21.2 HUMAN OVERVIEW
    • A) Malathion has been classified as probably carcinogenic to humans (Group
    • 2A) by IARC following a systematic review and evaluation. However, a long term study of pesticide applicators found no overall increased risk of cancer related to malathion exposure.
    • B) Long term oral administration of technical grade malathion to rodents produced an increase in hepatocellular neoplastic lesions.
  • 0.2.21.3 ANIMAL OVERVIEW
    • A) In animal studies, increased hepatocellular adenoma or carcinoma in mice, increased thyroid carcinoma, hepatocellular adenoma, and mammary gland adenocarcinoma in rats were observed (Guyton et al, 2015).
    • B) Long term oral administration of technical grade malathion to rodents produced an increased incidence of hepatocellular neoplastic lesions in mice dosed for 18 months at malathion doses of 1500 mg/kg/day, and in female F344 rats dosed for 2 years at malathion doses greater than 400 mg/kg/day. Severe hepatic toxicity and chronic suppression of acetylcholinesterase activity was associated with these tumors. On a body surface area adjusted basis, this dose was estimated to be 14- to 26-fold greater than the maximum dose anticipated in a 10 kg child following a single use of malathion lotion (assuming 100% bioavailability; the actual expected absorption is less than 10% of the administered dose) (Prod Info OVIDE
    • (R) topical lotion, 2005).
    • C) Both malathion and malaoxon were carcinogenic in rats exposed by ingestion, and malathion also caused liver tumors in mice (Reuber, 1985). Malathion may increase the carcinogenic effect of other chemicals by inhibiting the enzymes required for their metabolism (Silinskas & Okey, 1975).
0.2.22 GENOTOXICITY
  • A) Carcinogenesis, mutagenesis and impairment of fertility have not been studied in pharmaceutical grade malathion lotion (Prod Info OVIDE
  • (R) topical lotion, 2005).
  • B) Technical grade (94% to 96.5%) and purified (98% to 99%) malathion have produced chromosomal aberrations and sister chromatid exchanges in vitro in human and hamster cell lines. In vivo chromosomal aberration and micronucleus studies of technical-grade malathion are considered positive, while an in vivo chromosomal aberration study of greater than 99% pure malathion was negative. It has been suggested that the observed genetic activity may be due to impurities found in malathion (Prod Info OVIDE
  • (R) topical lotion, 2005).
  • C) In animal, human, and in vitro studies, malathion induced DNA and chromosomal damage. malathion was not mutagenic in bacteria mutagenesis tests (Guyton et al, 2015).
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