National Toxicology Program

National Toxicology Program
http://ntp.niehs.nih.gov/go/hsdb-121-75-5

CAS Registry Number: 121-75-5 Toxicity Effects

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 1

Names (NTP)

  • Malathion
  • ((DIMETHOXYPHOSPHINOTHIOYL)THIO)-BUTANEDIOIC ACID (9CI)

Human Toxicity Excerpts

  • HUMAN EXPOSURE STUDIES: In experimental study, malathion was found to be a weak contact sensitizer, inducing mild cutaneous reaction in high proportion of subjects.[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-298] **PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: A relatively low acute toxicity of malathion to humans is indicated by the fact that a daily oral dosage of 24 mg given for more than 14 days was necessary to lower blood cholinesterase activities in adult volunteers.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V30 118 (1983)] **PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: In a human experiment in which four men were exposed 1 hr daily for 42 days to 84.8 mg/cu m, there was moderate irritation of the nose and conjunctiva but there were no cholinergic signs or symptoms.[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 2] **PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Alterations of the activities of serum butyrylcholinesterase (BuChE), serum glutamic-oxalacetic transaminase, serum glutamic-pyruvic transaminase and serum aldolase, and the concn of serum albumin in twelve agricultural workers exposed to malathion over a period of six months were examined. Two groups of controls were used, consisting of 30 blood samples each, the first from randomly selected healthy blood donors, and the second from healthy blood donors engaged in manual labor. The mean butyrylcholinesterase activity of the agricultural workers at the end of the exposure period was not significantly different from that of either group of controls. However, ... the enzyme activity of any single subject changed significantly after exposure. A reduction in butyrylcholinesterase activity was noted in 11 of 12 agricultural workers, and six showed a sustained fall until the end of the study. Two showed slight increases over their pre-exposure activities at the end. ... The largest percent changes in the mean values of the agricultural workers during exposure to malathion were decreases in the activities of serum aldolase, serum glutamic-oxalacetic transaminase and serum glutamic-pyruvic transaminase, with that of butyrylcholinesterase changing the least of the four serum enzymes studied. No significant differences were observed in serum albumin concentrations. This study indicates that butyrylcholinesterase depression secondary to malathion exposure under field conditions does occur.[Grech JL; Br J Ind Med 22: 67-71 (1965) as cited in NIOSH; Criteria Document: Malathion p.50 (1976) DHEW Pub. NIOSH 76-205] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Manifestations of acute intoxication may include a mix of muscarinic, nicotinic, and CNS effects. Symptoms of systemic organophosphate toxicity may appear within minutes or hours depending on the route of exposure. Following ingestion of malathion, symptoms may appear rapidly or may be delayed up to 12 hours. Initial signs and symptoms of malathion poisoning may be largely due to excessive muscarinic effects, which may predominate in milder cases; such effects may include nausea, vomiting, abdominal cramps, diarrhea, urinary and/or fecal incontinence, hyperhidrosis, sialorrhea, miosis (pinpoint pupils), bradycardia, lacrimation, and increased nasal, pharyngeal, and bronchial secretions. Anoxia, resulting from retained secretions and pulmonary edema, may result in cyanosis. Nicotinic effects, including muscle fasciculation, muscle weakness, tachycardia, weakness or paralysis of respiratory muscles, and hypotonia, may occur in moderate and severe intoxications. CNS effects may include anxiety, restlessness, and headache. In more severe cases, tremors, confusion, dizziness, drowsiness, a reduction or loss of deep tendon reflexes, seizures, bradycardia, and coma also have been reported; death may occur.[American Society of Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011, p. 3524] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Hyperglycemia and glycosuria ... have been reported following exposure to malathion and other organophosphate insecticides. Severe respiratory distress is the major and most serious symptom of organophosphate toxicity and has been reported frequently following malathion poisoning. Respiratory failure may result from a combination of muscarinic (e.g., increased bronchial secretion, bronchoconstriction, pulmonary edema), nicotinic (e.g., weakness or paralysis of respiratory muscles), and CNS (depression of respiratory centers) effects.[American Society of Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011, p. 3524] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: In children, the signs and symptoms of organophosphate poisoning may be predominantly related to the CNS (e.g., seizures, alterations in mental status including lethargy and coma). Hypotonia, muscle weakness, miosis, and excessive salivation also have occurred in children, while some of the typical cholinergic effects (e.g., bradycardia, muscular fasciculation, excessive lacrimation, sweating, bronchial secretion) may be observed less frequently than in adults. Hyperglycemia, glycosuria, and hyperinsulinemia also have been observed in several children following topical application of malathion in a xylene vehicle formulated for pediculicidal use (not commercially available in the US).[American Society of Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011, p. 3524] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Inadvertent transdermal absorption of malathion has occurred from agricultural formulations, resulting in acute toxicity manifested by excessive cholinergic activity (e.g., increased sweating, salivary and gastric secretion, GI and uterine motility, bradycardia). The potential for transdermal absorption of malathion from the commercially available pediculicidal lotion currently is unknown.[American Society of Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011, p. 3524] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Very large exposures are required to cause symptoms. After inhalation of malathion, breathing and eye effects are the first to appear. These include tightness of the chest, wheezing, a bluish discoloration of the skin, small pupils, aching in and behind the eyes, blurring of the vision, tearing, runny nose, headache, and watering of the mouth. After swallowing malathion, loss of appetite, nausea, vomiting, abdominal cramps and diarrhea may appear within two hr. After skin absorption, sweating and twitching in the area of absorption may occur, usually within 15 minutes to four hr. With severe intoxication by all routes, in addition to the above symptoms, weakness, generalized twitching and paralysis may occur and breathing may stop. In addition, dizziness, confusion, staggering, slurred speech, generalized sweating, irregular or slow heartbeat, convulsions, and coma may occur.[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 1] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: The major signs and symptoms of malathion poisoning are attributable to the potentiation of responses to acetylcholine released from preganglionic, postganglionic cholinergic, and somatic motor nerve endings whenever nerve volleys reach the periphery. In milder cases, the postganglionic stimulation may predominate. ... Signs and symptoms include nausea, vomiting, diarrhea, excessive sweating, salivation, miosis, increased bronchial secretion, bronchial constriction, and the appearance of generalized muscular fasciculations followed by weakness. Central nervous system effects may include anxiety, restlessness, headache, and in more serious cases, tremors, confusion, drowsiness, slurred speech, coma, loss of reflexes, and convulsions.[NIOSH; Criteria Document: Malathion p.35 (1976) DHEW Pub. NIOSH 76-205] **PEER REVIEWED**
  • CASE REPORTS: ... A condition resembling amyoplasia congenita has been reported in an infant following repeated maternal use of 0.5% malathion lotion for treatment of pediculosis capitis during weeks 11-12 of gestation. Little or no fetal activity was noted throughout the second and third trimesters, and the infant died of respiratory insufficiency shortly after birth.[American Society of Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011, p. 3524] **PEER REVIEWED**
  • CASE REPORTS: One adult reportedly survived an estimated ingestion of 60 g (about 1 g/kg) of an agricultural formulation of malathion used as an insecticide. The patient was treated with atropine and pralidoxime iodide and required a tracheostomy and respiratory support.[American Society of Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011, p. 3524] **PEER REVIEWED**
  • CASE REPORTS: Several children developed severe malathion poisoning, including symptoms of hyperglycemia, glycosuria, and hyperinsulinemia, and one died following topical application of malathion 50% in a xylene vehicle formulated for pediculicidal use (not commercially available in the US).[American Society of Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011, p. 3524] **PEER REVIEWED**
  • CASE REPORTS: ... A 42 year old woman ingested a minimum of 120 mL of 50% malathion garden spray. She was admitted to a hospital 30 minutes later, at which time she was comatose, markedly cyanotic, flaccid, devoid of tendon reflexes, and markedly miotic. ... The patient was discharged 5 weeks after admission. Laboratory investigations during the patient's hospital course included determinations of plasma and erythrocyte cholinesterase activities. Serum cholinesterase activity was less than 22% of laboratory normal for the first nine days. Thereafter, the level gradually rose to 100% by the 31st day. The erythrocyte cholinesterase activity was first measured on the 12th day, when it was found to be 10% of normal. It remained between 10 and 25% of normal until the 45th day after hospital admission and then gradually rose to 100% by 130 days after admission. By this time, the patient had been discharged. Hematocrit measurement showed a small drop after admission, from 43 to 37%, and the reticulocyte count never rose above 2%. ... Blood urea levels rose to 77 mg/100 ml of blood during the first 5 days, thereafter returning to normal as the non renal uremia due to diarrhea and hypersecretion was controlled. Electrocardiograms taken immediately after admission and daily thereafter showed a prolongation of the P-R interval that persisted for 5 days, as well as changes in the S-T segment which was reported as consistent with panmyocardial ischemia. These latter changes disappeared gradually as the patient's respiratory function improved.[Goldin AR et al; N Engl J Med 271: 1289-93 (1964) as cited in NIOSH; Criteria Document: Malathion p.23 (1976) DHEW Pub. NIOSH 76-205] **PEER REVIEWED**
  • CASE REPORTS: There is a single report of an association between brief anecdotal exposure to malathion and subsequent fatal aplastic anemia.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V30 118 (1983)] **PEER REVIEWED**
  • CASE REPORTS: To assess effects attributed to malathion which escaped from an overheated tank at a chemical plant in Linden, New Jersey, researchers surveyed seamen subjects (n= 22) on board a nearby tanker and seamen control subjects (n= 22). Self report measurement strategies included a medical review of body systems, the "demoralization" scale reflecting psychological symptoms of distress, demographics, and factors that may buffer stress, specifically, social support and knowledge regarding toxic chemicals. Self reported postincident physical health differences between the two groups of seamen were noted. There were no differences between subjects and control subjects on demoralization levels. Further analysis indicated higher levels of demoralization among less knowledgeable seamen subjects.[Markowitz JS et al; J Occup Med 28 (5): 377-83 (1986)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/3712117?dopt=Abstract" target=new>PubMed Abstract</a>
  • EPIDEMIOLOGY STUDIES: To evaluate the latent neurological effects of organophosphate pesticide poisoning, 100 matched pairs (1 black, 14 Mexican American, and 85 Anglo/Caucasian; 99 pairs were male) of individuals with previous acute organophosphate pesticide poisoning (malathion, 6 cases; results are not given for individual chemicals) and nonpoison controls were examined. No significant difference between the groups was found on audiometric tests, ophthalmic tests, electroencephalograms, or the clinical serum and blood chemistry evaluations. From the neurological examination, abnormalities were demonstrated among the cases only on measures of memory, abstraction, and mood, and on one test of motor reflexes. Differences between the cohorts were more apparent in the neuropsychological tests, and occurred on tests of widely varying abilities, including intellectual functioning, academic skills, abstraction and flexibility of thinking, and simple motor skills. Twice as many cases as controls had Halstead Reitan Battery summary scores in the range characteristic of cerebral damage of dysfunction. Greater distress and complaints of disability for the poisoned subjects were indicated by the Minnesota Multiphasic Personality Inventory and the Patient's and Relative's Assessment of Patient Functioning Inventories.[Savage EP et al; Arch Environ Health 43 (1): 38-45 (1988)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/3355242?dopt=Abstract" target=new>PubMed Abstract</a>
  • SURVEILLANCE: California collects data on most occupational and many non-occupational illnesses and injuries related to pesticide exposure. Most of the occupational incidents are investigated by local agencies. A thorough investigation is conducted on all pesticide-related cases that meet "priority" guidelines: death; hospitalization of 1 or more persons for more than 24 hours with treatment; or 5 or more people with symptoms seeking medical care as a result of the same incident. This report summarizes the priority cases determined to be related to pesticide exposure during 1986. Of the 67 described incidents, involving 583 people ill, 26 (38%) were related to exposure to pesticides applied indoors (residences, offices), either by commercial pest control companies, employees or homeowners. Nearly 200 people (33%) became ill and more than 200 people were evacuated as a result of these types of applications. Most of these incidents were a result of careless application techniques and not following label instructions. Four other incidents, with 33 people ill, were the result of spills in retail stores. In all 4 cases, store employees tried to clean the spill without wearing protective clothing. Two other cases involved exposure via a pesticide being put in a food container. Nineteen of these type of incidents involved a pesticide product containing an organophosphate; most often chlorpyrifos (8 incidents), diazinon (3 incidents), and malathion (5 incidents). There were also 10 cases that resulted from suicide; eight different pesticides were involved. Five incidents involving agricultural workers, as well as 4 incidents involving non-agricultural workers, were primarily the result of allowing pesticides to drift from the target field.[Maddy KT, Edminton S; Vet Hum Toxicol 30 (3); 246-54 (1988)] **PEER REVIEWED**
  • GENOTOXICITY: Concentrations of up to 400 ug/mL of 95% malathion failed to increase chromosomal aberrations in human hematopoietic B411-4, RPMI-1788 & RPMI-7191 cell cultures; however, /others/ ... reported a positive, although not dose related, result in human lymphocytes with 99% pure malathion.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V30 117 (1983)] **PEER REVIEWED**
  • GENOTOXICITY: A significant increase in chromosomal aberrations was found in the lymphocytes of a group of 14 people intoxicated with a commercial formulation of malathion (Fosfotion), as compared with that in healthy controls. Aberrations observed included chromatid breaks, chromatid isobreaks, chromatid exchanges and unstable chromosomal & structural aberrations. No dose effect relationship was evident, since high frequencies of aberrations were also detected in cases of mild intoxication. (The small number of subjects involved & the inappropriateness of the control group used does not permit the association to be established as causal.)[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V30 119 (1983)] **PEER REVIEWED**
  • GENOTOXICITY: Malathion, technical grade, 92%-97% purity, unscheduled DNA synthesis in human diploid fibroblasts WI-38, passage 28, tested with and without activation, cells were exposed for 3 hours in the presence of tritiated thymidine to 0, 10-7, 10-6, 10-5, 10-4, or 10-3 M, 6 flasks without activation and 3 with activation; No cytotoxicity reported except possibly at the highest concentration. No evidence for unscheduled DNA synthesis is reported as increased DPM/ug DNA.[California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summary for Malathion (121-75-5) p.9 (July 30, 1986). Available from, as of February 2, 2012: http://www.cdpr.ca.gov/docs/risk/toxsums/pdfs/367.pdf] **PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • LABORATORY ANIMALS: Acute Exposure: Undiluted technical liquid malathion dropped on rabbit's eye caused slight immediate irritation with conjunctival hyperemia and edema of lids ...[Grant, W. M. Toxicology of the Eye. 2nd ed. Springfield, Illinois: Charles C. Thomas, 1974., p. 640] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Impurities such as O,S,S-trimethyl phosphorodithioate (TMPD) and the S-methyl isomer of malathion (iso-malathion) strongly potentiated the mammalian toxicity of malathion. The potentiation was attributed to inhibition of mammalian liver and serum carboxylesterase. O,O,S-Trimethyl phosphorothioate (TMP), another impurity present in technical grade malathion, proved to be highly toxic. Rats given a single oral dose of O,O,S-trimethyl phosphorothioate at a level as low as 20 mg/kg died over a period of 3 wk, with death occurring with non cholinergic signs of poisoning. O,S,S-Trimethyl phosphorodithioate also caused similar delayed death in rats, O,O,O-trimethyl phosphorothioate, another impurity in technical malathion, was a potent antagonist to the delayed toxicity of O,O,S-trimethyl phosphorothioate. /Impurities of technical grade malathion/[Fukuto TR; J Environ Sci Health 18 (1): 89-117 (1983)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: At 100 ppm /in rats/, no effects were observed, even on red cell cholinesterase activity. In two studies, 500 ppm for 8 weeks also produced no adverse effect on whole blood cholinesterase activity. At 1000 ppm and higher, however, red cell cholinesterase activity was significantly decreased. Ip injection ... for 60 days resulted in a no adverse effect levels of 100 mg/kg without mortality, but dosages of 200 & 300 mg/kg/day resulted in mortality rates of 60 & 100%, respectively.[National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 623] **PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Blood cholinesterase levels in calves given 2 mg/kg of malathion daily for up to 13 days fell to 50%, but promptly returned to normal when admin ceased.[Clarke, M. L., D. G. Harvey and D. J. Humphreys. Veterinary Toxicology. 2nd ed. London: Bailliere Tindall, 1981., p. 151] **PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: A daily dose of 46 mg/kg malathion ip for fifteen days affected the activity of the adrenal gland and liver glycogen in rats. The decrease in the level of adrenaline, noradrenaline, and dopamine indicate that malathion causes increased adrenal medullary function without affecting the cortical activity. The increased glycogen levels in the liver of malathion exposed animals could be attributed to the release of adrenal catecholamines.[Gowda H et al; Indian J Med Res 77 (Dec): 847-51 (1983)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: In a 21-day dermal toxicity study in rabbits groups of 6 male and 6 female New Zealand rabbits were treated dermally with undiluted technical malathion (94% a.i.) at dose levels of 0, 50, 300 or 1000 mg/kg/day for 6 hours/day, 5 days/week for 3 weeks. Assessments included clinical signs and mortality, dermal effects, food consumption, body weight, hematology and clinical chemistry (including ChE activity of plasma, erythrocytes and brain). Gross necropsy was performed on all animals. The weight of the liver, kidneys, gonads and adrenals were recorded. Histopathology was performed on the following tissues for the high dose and control groups: adrenals, kidneys, liver, ovaries, skin (treated area), skin (mammary area), testes/epididymis and gross lesions. With the exception of a dose-related decreased ChE activity in both males and females at 1000 and 300 mg/kg/day, no treatment-related toxic effects (other than one possible mortality in the 1000 mg/kg/day group attributable to acute mucoid gastroenteritis) were observed in the study. No clinical signs were noted and there were no treatment-related changes in body weights, food consumption, hematology, clinical chemistries, gross necropsies, organ weights or histopathology. Dermal reactions at the application site were not observed. For males, the NOAEL and LOAEL, respectively, for ChEI /cholinesterase inhibition/ were considered to be the following: for plasma inhibition, 50 and 300 mg/kg/day (-13%); for RBC inhibition, 50 and 300 mg/kg/day (-18%); for brain (cerebrum) inhibition, 300 and 1000 mg/kg/day (-65%); and for brain (cerebellum) inhibition, 300 and 1000 mg/kg/day (-41%). For females, the comparable NOAELs and LOAELs were the following: for plasma inhibition, 50 and 300 mg/kg/day (- 17%); for RBC inhibition, 50 and 300 mg/kg/day (-26%); for brain (cerebrum) inhibition, 50 and 300 mg/kg/day (-19%); and for brain (cerebellum) inhibition, 300 and 1000 mg/kg/day (-49%). The NOAEL was 50 mg/kg/day and the LOAEL was 300 mg/kg/day based on inhibition of plasma and RBC ChE activity in males and females and on inhibition of brain (cerebrum) ChE activity in females. The overall systemic NOAEL was 300 mg/kg/day and the overall systemic LOAEL was 1000 mg/kg/day based on possible mortality (1 male).[EPA/Office of Pollution Prevention and Toxic Substances; Malathion: Updated Revised Human Health Risk Assessment for the Reregistration Eligibility Decision Document (RED) EPA-HQ-OPP-2004-0348-0004. Available from, as of February 2, 2012: http://www.regulations.gov/#!home] **PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: In a subchronic (13-week) inhalation study, groups of Sprague-Dawley rats (15/sex/concentration) were exposed in whole body inhalation chambers to malathion (96.4%) at aerosol concentrations of 0, 0.1, 0.45, or 2.01 mg/L for 6 hours/day, 5 days/week for 13 weeks. Assessments included those of clinical signs, body weight, food consumption, ophthalmoscopic examinations, hematology, clinical chemistry (including ChE activity of plasma, erythrocytes and brain), urinalysis and gross and histopathology of Guideline required tissues. Treatment had no effects on survival, body weights or food consumption. Cholinergic signs observed at 2.01 mg/L and sporadically in a few animals at the lower doses included red staining of the urogenital areas, excess salivation and ungroomed oily fur. Treatment-related histopathological lesions were seen in the nasal cavity and the larynx of both sexes of rats at all concentrations tested. The lesions in the nasal cavity were characterized as slight to moderate degeneration and/or hyperplasia of the olfactory epithelium which was locally extensive. The lesions of the larynx were characterized as epithelial hyperplasia, with squamous keratinization occurring in some rats. In addition, the olfactory/respiratory epithelial junction was severely affected in most animals. For systemic toxicity, a NOAEL was not established and the LOAEL was 0.1 mg/kg/day based on histopathologic lesions of the nasal cavity and larynx. Inhibition of plasma and red blood cell ChE activity was observed in female rats at 0.45 mg/L and above. In male rats, inhibition of ChE activity was observed in plasma at 2.01 mg/L and in red blood cells at > 0.45 mg/L. Inhibition of brain ChE activity was seen only at the highest concentration. For ChEI /cholinesterase inhibition/, a NOAEL was established for plasma and red blood cells at 0.1 mg/L with a LOAEL of 0.45 mg/L.[EPA/Office of Pollution Prevention and Toxic Substances; Malathion: Updated Revised Human Health Risk Assessment for the Reregistration Eligibility Decision Document (RED) EPA-HQ-OPP-2004-0348-0004. Available from, as of February 2, 2012: http://www.regulations.gov/#!home] **PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Female Sprague Dawley rats were placed on a drinking solution of 1 ppm malathion dissolved in water for 6 months. Hepatic morphology, basically hepatocyte degeneration, was altered. Prolonged prothrombin time and partial thromboplastin time were the only changes in clotting activity.[Lox CD, Davis JR; Ecotoxicol Environ Safety 7 (6): 546-51 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6662056?dopt=Abstract" target=new>PubMed Abstract</a>
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: IgE antibody mediated and cell mediated hypersensitivity to malathion was evaluated in BALB/c mice. To elicit malathion specific antibodies of the IgE class, a conjugate of the anhydride of the diacid metabolite of malathion with keyhole limpet hemocyanin was administered ip with aluminum hydroxide as adjuvant. Serums collected following 3 sequential sensitizations were tested for specific IgE with the passive cutaneous anaphylaxis (PCA) test in rats. Anhydride coupled to bovine serum albumin was used as the challenge antigen. Specific IgE was produced following the second and third sensitization in the mice receiving 1 ug of conjugate. Malathion applied epicutaneously for 2 days or over 4 wk failed to elicit delayed type hypersensitivity. Anhydride specific IgE antibodies were not detected by the passive cutaneous anaphylaxis test in the serum of mice treated epicutaneously for 4 wk.[Cushman JR, Street JC; Toxicol Appl Pharmacol 70 (1): 29-42 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6612736?dopt=Abstract" target=new>PubMed Abstract</a>
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: beta-Glucuronidase activity increased in the liver of adult male rats in a dose dependent manner with malathion treatment (orally, for 3 wk). Low protein diets, however, appeared to reduce the enzyme activity. In protein deprived rats, there was initially a decrease in the activity of the enzyme which was greater after pesticide treatment.[Bulusu S, Chakravarty I; Bull Environ Contam Toxicol 36 (1): 73-80 (1986)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/3940570?dopt=Abstract" target=new>PubMed Abstract</a>
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Groups of 50 male and 50 female weanling Charles River B6C3F1 mice were fed diets containing 8000 or 16000 mg/kg malathion (purity 95%, impurities unspecified) for 80 weeks and observed for 14-15 weeks. A matched control group comprising 10 animals of each sex was observed for 95 weeks ... an additional pooled control group of 50 animals of each sex was used ... In high dose group, which received a max tolerated dose, 94% of the males & 88% of the females were still alive at end of the experiment; survival was ... lower in low dose and control /animals/ ... In female mice, no statistically significant increase in tumor incidence was found. In male mice the incidences of hepatocellular carcinomas plus neoplastic nodules were: 2/10 in matched controls, 8/49 in pooled controls, 7/48 in the low dose group and 17/49 in the high dose group (Cochran-Armitage test for positive trend, p= 0.041 (using matched controls) or p= 0.019 (using pooled controls); fisher exact test, high-dose versus pooled controls, p= 0.031). When a time adjusted analysis was performed, eliminating ... male mice that died before week 52 of study, the following incidences resulted: matched controls, 2/9; pooled controls, 8/48; low-dose, 7/47; & high-dose 17/49. ... /tests did not show/ these incidences to be significant when the matched controls were used ... .[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V30 113 (1983)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Three groups of 50 male and 50 female fischer 344 rats, six wk old, were fed diets containing malathion (purity, 95%; impurities unspecified) at concentrations of 0, 2000, or 4000 mg/kg for 103 weeks. They were observed for a further 2 to 3 weeks & then killed; surviving rats in the matched control group were killed after 105-106 weeks of study. Of the male rats, 88% of the control group, 86% of the low dose group & 80% of the high dose group survived the experimental period; while of the females, 94% of the control group, 98% of the low dose group & 90% of the high dose group were still alive at termination of the expreiment. Females may not have received a max tolerated dose, as indicated by gain in body wt. No statistically significant increase in tumor incidence was found in female rats. In male rats, the incidence of adrenal pheochromocytomas appeared to increase in the low dose group (11/48) compared with the control group (2/49, p= 0.006), whereas in the high dose group only 6/49 pheochromocytomas were seen.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V30 114 (1983)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Following long-term oral administration of technical grade malathion to rodents via dietary supplementation, increased incidences of hepatocellular neoplastic lesions were observed in B6C3F1 mice dosed for 18 months at malathion doses greater than 1500 mg/kg/day, and in female F344 rats dosed for 2 years at malathion doses greater than 400 mg/kg/day. These tumors occurred only in association with severe hepatic toxicity and chronic suppression of acetylcholinesterase activity, or at doses causing excessive mortality. Based on body surface area, doses at which carcinogenic effects were observed in rodents following life-time exposures to malathion were approximately 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. Actual systemic exposures are expected to be less than 10% of the administered dose.[US Natl Inst Health; DailyMed. Current Medication Information for OVIDE (malathion) lotion (December 2011). Available from, as of January 30, 2012: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=2024030e-b00d-4fcc-b51d-45dc86933749] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Malathion (99.4% pure) was fed in diet to Fischer 344, CDF (F-344) CrlBR (90/sex/dose) at 0, 100/50 (reduced day 113), 500, 6000 and 12000 ppm for 24 months. Thirty-five/sex/dose (satellite) were sacrificed at 12 months. Systemic NOEL = 500 ppm (Mortality sharply increased in males at > 6000 ppm and in females at 12000 ppm. Body weight was significantly decreased in males at > 6000 ppm and in females at 12000 ppm. Effects were observed in hematology and clinical chemistry were observed in both sexes at > 6000 ppm. Absolute and relative kidney and liver weights were significantly increased in both sexes at 12 and 24 months. Absolute and relative spleen (12 months) and thyroid/parathyroid (12 and 24 months) weights were increased in males at > 6000 ppm. Histopathology showed an increase in nasal mucosal pathology in both sexes at > 6000 ppm. Subacute-chronic inflammation/chronic nephropathy was increased in incidence and severity at 12 months in both sexes, primarily at 12000 ppm.) No evidence of ocular toxicity from ophthalmoscopic or electroretinographic examinations was observed. Absolute and relative kidney and liver weights were significantly increased in both sexes at 12 and 24 months. Absolute and relative spleen (12 months) and thyroid/parathyroid (12 and 24 months) weights were increased in males at > 6000 ppm. Histopathology showed an increase in nasal mucosal pathology in both sexes at > 6000 ppm. Subacute-chronic inflammation/chronic nephropathy was increased in incidence and severity at 12 months in both sexes, primarily at 12000 ppm.) ChE NOEL = 500 ppm (Plasma, erythrocyte and brain cholinesterase activity was significantly decreased, primarily at > 6000 ppm.) Oncogenicity NOEL = 500 ppm (There was an increased incidence in hepatocellular adenomas and carcinomas in females at > 6000 ppm. An increase in nasoturbinal adenoma was observed in males at > 6000 ppm.)[California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summary for Malathion (121-75-5) p.2 (July 30, 1986). Available from, as of February 2, 2012: http://www.cdpr.ca.gov/docs/risk/toxsums/pdfs/367.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Malathion (AC 6,601) 95.0%, was given to beagle dogs at 0, 62.5, 125 and 250 mg/kg/day by gelatin capsule, 7 days a week for 1 year, 6/sex/dose. No mortalities, no interim sacrifices. Systemic NOEL = 125 mg/kg/day, body weight depression, changes in hematological parameters and serum enzymes. ChE NOEL < 62.5 mg/kg/day. No adverse effect.[California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summary for Malathion (121-75-5) p.3 (July 30, 1986). Available from, as of February 2, 2012: http://www.cdpr.ca.gov/docs/risk/toxsums/pdfs/367.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Malaoxon (92.5% pure), was fed in diet to Fischer 344 rats (85/sex/dose) at 0, 20, 1000, or 2000 ppm for at least 24 months. Ten rats/sex/group (satellite) were sacrificed at 3, 6 and 12 months. Systemic NOEL = 20 ppm/day (There were increased deaths in both sexes at > 1000 ppm. Emaciation at > 1000 ppm (females) and at 2000 ppm (males) was observed. Decreased body weight and food utilization efficiency were observed in both sexes at 2000 ppm. Increased absolute and relative liver, kidney and adrenal weights occurred in males at 2000 ppm. Females showed decreased absolute and relative spleen weights at 2000 ppm. Histopathology showed increased chronic inflammation, epithelial hyperplasia and squamoid metaplasia in both respiratory and olfactory nasal mucosa in males at 2000 ppm and in females at > 1000 ppm. In lung increased edema, interstitial inflammation, purulent and granulomatous inflammation were observed at > 1000 ppm (males) and at 2000 ppm (females). Increased chronic inflammation in tympanic spaces occurred at > 1000 ppm (males) and at 2000 ppm (females). Stomach muscularis mineral deposits were observed at > 1000 ppm in both sexes.) No treatment-related effects on ophthalmology were reported. ChE NOEL = 20 ppm (Plasma, RBC and brain ChE were significantly decreased in both sexes at > 1000 ppm.) Oncogenicity NOEL > 2000 ppm (There was no oncogenic effect due to malaoxon.) Possible adverse effect (Increased nasal, tympanic and lung pathology and decreased plasma, RBC and brain ChE were observed in both sexes.) /Malaoxon/[California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summary for Malathion (121-75-5) p.2 (July 30, 1986). Available from, as of February 2, 2012: http://www.cdpr.ca.gov/docs/risk/toxsums/pdfs/367.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Malathion was injected at concentration of 3.99 or 6.42 mg/egg into the yolk sacs of 50 hen eggs incubated for 5 days. Twenty five control eggs were used. The eggs injected with malathion produced chicks exhibiting sparse plumage, micromelia, overall growth retardation, and beak defects.[Greenberg J, Laham QN; Can J Zool 47: 539-42 (1969) as cited in NIOSH; Criteria Document: Malathion p.74 (1976) DHEW Pub. NIOSH 76-205] **PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Daily administration of malathion (46 mg/kg, ip) to female rats for 15 days prior to mating caused a significant reduction in the litter size and survival of pups. Though different traits of reproduction were not affected significantly, a slight effect was observed in viability index and lactation index in malathion treated animals.[Kumar R, Uppal RP; J Environ Biol 7 (1): 35-9 (1986)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Malathion (technical grade, 95% pure) was fed to rats at a dietary concentration of 4000 mg/kg (approximate daily intake, 240 mg/kg bw) for two generations. Males and females 70-100 days of age were bred after 10 weeks on test; survival of the progeny of days 7 and 21 after birth was found to be reduced, and the surviving offspring showed growth retardation and an increased incidence of ring-tail disease.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V30 115 (1983)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Reproduction studies performed with malathion in rats at doses over 180 fold greater than those anticipated in a 60 kg adult (based on body surface area and assuming 100% bioavailability) revealed no evidence of impaired fertility.[US Natl Inst Health; DailyMed. Current Medication Information for OVIDE (malathion) lotion (December 2011). Available from, as of January 30, 2012: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=2024030e-b00d-4fcc-b51d-45dc86933749] **PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: There was no evidence of teratogenicity in studies in rats and rabbits at doses up to 900 mg/kg/day and 100 mg/kg/day malathion, respectively. A study in rats failed to show any gross fetal abnormalities attributable to feeding malathion up to 2,500 ppm (about 200 mg/kg/day) in the diet during a three - generation evaluation period. These doses were approximately 40 to 180 times higher than the dose anticipated in a 60 kg adult (based on body surface area and assuming 100% bioavailability).[US Natl Inst Health; DailyMed. Current Medication Information for OVIDE (malathion) lotion (December 2011). Available from, as of January 30, 2012: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=2024030e-b00d-4fcc-b51d-45dc86933749] **PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Malathion, 94% purity, was administered in the diet to groups of 25 male and 25 female rats at dose levels of 0 (vehicle control), 550, 1700, 5000, or 7500 ppm for two generations, two litters per generation. At 7500 ppm, maternal gestational and lactation weights were consistently reduced in both litters of both generations, with statistical significance being obtained in the first pregnancy and both lactation periods of the P-1 generation. Pup weaning weights on day 21 post partum were consistently reduced at both 5000 and 7500 ppm, reaching statistical significance for all litters at 7500 ppm, and the first P-1 and second F-1 litters at 5000 ppm. At 7500 ppm, the postnatal growth retardation persisted through adulthood, with no indication of catch-up growth. Reproductive parameters were not adversely affected. Developmental NOEL = 1700 ppm; > 200 mg/kg/day (postnatal growth retardation); Parental NOEL = 5000 ppm; > 400 mg/kg/day (reduced body weight); Reproductive NOAEL = 7500 ppm (HDT); > 600 mg/kg/day. ... No adverse reproductive health effect is noted.[California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summary for Malathion (121-75-5) p.7 (July 30, 1986). Available from, as of February 2, 2012: http://www.cdpr.ca.gov/docs/risk/toxsums/pdfs/367.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Malathion (AC 6,601), technical grade, purity 94.0%, was administered to groups of 25 Crl:CD (SD) BR female rats by gavage on days 6 through 15 of gestation at doses of 0 (corn oil vehicle control), 200, 400 or 800 mg/kg/day. The only significant finding in the dams was an increased incidence of urine stained abdominal fur at 800 mg/kg/day. Fetal parameters were unaffected by treatment and no adverse effect was noted. Maternal and Developmental NOEL = >800 mg/kg/day (the high dose tested).[California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summary for Malathion (121-75-5) p.7 (July 30, 1986). Available from, as of February 2, 2012: http://www.cdpr.ca.gov/docs/risk/toxsums/pdfs/367.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Malathion, 92.4%, was administered by gavage to groups of 20 inseminated New Zealand rabbits at doses of 0, 25, 50 or 100 mg/kg/day on day 6-18 of gestation. Maternal weight gain during dosing was statistically reduced at 50 and 100 mg/kg/day. Mean numbers and percent fetal resorptions were also elevated at these two doses. The number of unexplained unscheduled deaths were elevated above historical control values in the low dose group, but did not achieve statistical significance. In addition, there was no evidence for a dose response effect. Maternal NOEL = 25 mg/kg/day (reduced weight gain during dosing); Developmental NOEL = 25 mg/kg/day (increase in resorptions). ... No adverse developmental health effects are noted.[California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summary for Malathion (121-75-5) p.8 (July 30, 1986). Available from, as of February 2, 2012: http://www.cdpr.ca.gov/docs/risk/toxsums/pdfs/367.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Malathion admin orally at 20-40 mg/kg for 2-19 days to juvenile rats caused a reduction of spermatogenic cells and Leydig cells. /From table; purity not given/[National Research Council. Drinking Water and Health, Volume 6. Washington, D.C.: National Academy Press, 1986., p. 75] **PEER REVIEWED**
  • LABORATORY ANIMALS: Neurotoxicity: Malathion (technical, batch AC 6,601, 93.6% purity), administered by gavage with protection (intramuscular injection of atropine sulfate at 10.0 mg/kg) at 1007.5 mg/kg to 60 hens. Survivors (21 hens) were re-dosed with protection at 852.5 mg/kg on day 21. Negative control (1.87 mL and 1.15 mL of tap water on day 1 and day 21 respectively) and positive control (TOTP at 500 mg/kg) groups of 15 hens. 39 of the 60 hens dosed on day 1 at 1007.5 mg/kg died by day 15, the remaining 21 birds survived through day 21. 7 of the 21 birds re-dosed at 852.5 mg/kg on day 21 died by day 28. 14 survived through day 42. Reversible moderate/severe ataxia to paralysis of legs and wings and inability to stand reported in all malathion treated hens through day 4 and again, after redosing on day 21, through day 25. 10 hens/group for histopathology unremarkable for malathion treated group.[California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summary for Malathion (121-75-5) p.10 (July 30, 1986). Available from, as of February 2, 2012: http://www.cdpr.ca.gov/docs/risk/toxsums/pdfs/367.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Neurotoxicity: Malathion technical (96.4% pure) was administered by gavage in a single dose (volume = 5 mL) to Sprague-Dawley Crl:CD BR rats (27/sex/dose) at 0 (vehicle = corn oil), 500, 1000 or 2000 mg/kg. Dosing was followed by a 15 day observation period. Systemic NOEL = 500 mg/kg (The FOB showed an increase in salivation on day 0 at > 1000 mg/kg in both sexes and in females on day 7 at 2000 mg/kg. Males showed red deposits on nose & eyes at 2000 mg/kg and on mouth at > 1000 mg/kg on day 0. Females had red deposits on eyes day 14 at 2000 mg/kg. Males showed very soiled/crusty fur and pale mucous membranes day 0 and females had crusty deposits on mouth day 14. There was a significant decrease in rotarod performance for males on day 14 at 2000 mg/kg. Males had decreased ambulatory and total motor activity at 2000 mg/kg. Females had decreased absolute & relative midbrain values and increased relative whole brain, brain stem & cerebral cortex weight values on day 15 at 2000 mg/kg. Males at 2000 mg/kg (day 7) showed relative olfactory region weight increases. At 2000 mg/kg males had lumbar root axonal degeneration, lumbar dorsal fiber digestion chambers, tibial nerve digestion chambers & retinal rosette formation.) ChE NOEL = 500 mg/kg (Both sexes at 2000 mg/kg showed decreased RBC & plasma ChE. Males showed some decrease in brain ChE at > 1000 mg/kg.) Possible adverse effect: Both sexes showed neurotoxicity at 2000 mg/kg.[California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summary for Malathion (121-75-5) p.10 (July 30, 1986). Available from, as of February 2, 2012: http://www.cdpr.ca.gov/docs/risk/toxsums/pdfs/367.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Neurotoxicity: Malathion technical (96.4% pure) was fed in diet to Sprague-Dawley Crl:CDBR rats (25/sex/dose) at 0 (diet), 50, 5000 and 20000 ppm for 91 consecutive days. Systemic NOEL = 5000 ppm (Clinical effects were observed in both sexes at 20000 ppm. Body weights and food consumption were significantly decreased at 20000 ppm. Males (1/5) had digestion chambers in the lumbar dorsal root fibers and the peroneal nerve at 20000 ppm. Another 1/5 males had swollen axons and demyelination in the sciatic nerve at 20000 ppm. These were the only findings. Relative brain & brain region weights were increased (relative to body weights) in both sexes and cerebellum weights were decreased in females (relative to brain weights) at 20000 ppm.) Neurological NOEL = 5000 ppm (Both sexes showed an increase in soiled fur and females showed red deposits on the nose at 20000 ppm. Forelimb grip strength was decreased at 20000 ppm in both sexes.) ChE NOEL = 50 ppm (Plasma and RBC ChE was significantly decreased in both sexes at > at 5000 ppm. Brain ChE was significantly decreased in both sexes at 20000 ppm.) ... Possible adverse effect for neurotoxicity.[California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summary for Malathion (121-75-5) p.11 (July 30, 1986). Available from, as of February 2, 2012: http://www.cdpr.ca.gov/docs/risk/toxsums/pdfs/367.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Neurotoxicity: Malathion technical (96.4% pure) was administered /by inhalation/ ... to Sprague-Dawley CD (Crl:CD(SD)BR) rats (15/sex/dose) at 0 (room air), 0.10, 0.45 and 2.0 mg/L (whole body exposure, 6 hours/day, 5 days/week) for 13 weeks. A systemic NOEL was not achieved (Clinical signs were increased in both sexes at all doses. Males had significant increases in organ/BW% in liver, lungs/trachea & kidney at 2.0 mg/L and in organ/brain wt% in liver and kidneys at 2.0 mg/L. Males also had a significant increase in lungs/trachea & kidney weights at 2.0 mg/L. Females showed a significant increase in organ/BW% in liver at > 0.45 mg/L and a significant increase in relative (to brain weight) weight at 2.0 mg/L. Possible adverse effect: The nasal cavity showed an increase in degeneration and/or hyperplasia of the olfactory epithelium at all treatment levels in both sexes.) ChE NOEL = 0.1 mg/L (Males showed a significantly decreased brain ChE at 2.0 mg/L. RBC ChE was reduced significantly in males at > 0.45 mg/L. Females showed a significantly decreased brain ChE at 2.0 mg/L. RBC ChE was significantly decreased at 0.45 mg/L and 2.0 mg/L. Plasma ChE was significantly decreased at 2.0 mg/L.)[California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summary for Malathion (121-75-5) p.11 (July 30, 1986). Available from, as of February 2, 2012: http://www.cdpr.ca.gov/docs/risk/toxsums/pdfs/367.pdf] **PEER REVIEWED**
  • GENOTOXICITY: Six pesticides, one of which was malathion, induced a significant increase of sister chromatid exchange frequencies in a dose dependent fashion in cultured Chinese hamster cell line V79. The six in decreasing order of sister chromatid exchanges induction are methyl parathion, demeton, trichlorfon, dimethoate, malathion, & methidathion. Cells were exposed to malathion for 28 hr at concentration of 10, 20, 40, ug/mL, respectively. All test compounds caused a delay in cell cycle.[Chen HH et al; Mutat Res 88 (3): 307-16 (1981)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/7254224?dopt=Abstract" target=new>PubMed Abstract</a>
  • GENOTOXICITY: Pure malathion was tested for DNA damaging and mutagenic activity in Bacillus subtilis and Salmonella typhimurium tester strains and was found to be moderately mutagenic without metabolic activation.[SHIAU SY ET AL; MUTAT RES 71 (2): 169-79 (1980)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6771645?dopt=Abstract" target=new>PubMed Abstract</a>
  • GENOTOXICITY: Malathion was ineffective in inducing sex linked recessive lethal mutations in Drosophila melanogaster fed solutions containing 0.25 or 0.5 mg/L of the compound.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V30 117 (1983)] **PEER REVIEWED**
  • GENOTOXICITY: The clastogenic effect of malathion was studied in mice given ip injections of 115, 230, or 460 mg/kg. Results in mice injected with 115 mg/kg of malathion were not different from controls. At 230 mg/kg, increasing the frequencies of abnormal metaphases and chromosomal aberrations were noted in animals killed 6 or 24 hr after injection. Mice injected with 460 mg/kg, exhibited significant increments of abnormal metaphases, gaps, breaks, and chromatid exchanges in relation to controls.[Dulout FN et al; Mutat Res 122 (2): 163-7 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6656807?dopt=Abstract" target=new>PubMed Abstract</a>
  • GENOTOXICITY: The Tradescantia micronucleus (Trad-MCN) bioassay was utilized to determine the genotoxicity of malathion. Results of sixteen experiments indicated that malathion vapors at 0.15-0.25% induced significantly higher (0.05) micronucleus frequencies above the controls and altered the nuclear structure to form unequal sized nuclei and multiple breaks in each of the 4 cells of a tetrad. It also caused degeneration of nuclei, protrusions on nuclei, and inhibition of cell growth. Higher doses (greater than 0.25%) were toxic.[Ma TH et al; Environ Mutagen 5 (2): 127-37 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6861722?dopt=Abstract" target=new>PubMed Abstract</a>
  • GENOTOXICITY: Both technical grade (94-96.5%) and purified (98-99%) malathion have been reported to cause 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 reported to be positive, whereas an in vivo chromosomal aberration study of >99% pure malathion was reported to be negative. Furthermore, mice exposed to malathion in their drinking water for 7 weeks demonstrated no evidence of chromosome damage in bone marrow cells, spermatogonia, or primary spermatocytes.[US Natl Inst Health; DailyMed. Current Medication Information for OVIDE (malathion) lotion (December 2011). Available from, as of January 30, 2012: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=2024030e-b00d-4fcc-b51d-45dc86933749] **PEER REVIEWED**
  • GENOTOXICITY: Malathion ( 95.2% purity) was tested by the plate incorporation assay with Salmonella typhimurium strains TA1535, TA1537, TA1538, TA98 and TA100 as well as with Escherichia coli strain WP2 uvrA-. Concentrations tested were 0 (DMSO), 100, 500, 1000, 2500 or 5000 ug/plate with triplicate plates per concentration and two trials. Bacteria were plated with and without activation with S-9 prepared from livers of male Sprague-Dawley rats ... . Positive controls with and without activation for each strain were effective. No increases in revertants with any strain were reported. No adverse effect.[California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summary for Malathion (121-75-5) p.8 (July 30, 1986). Available from, as of February 2, 2012: http://www.cdpr.ca.gov/docs/risk/toxsums/pdfs/367.pdf] **PEER REVIEWED**
  • GENOTOXICITY: Malathion, technical grade, 92-97% pure was fed in the diet for 7 weeks to 20 ICR/SIM male mice/group at 0, 1250, 2500 or 5000 mg/kg, before the animals were mated 1:2 for one week over 8 intervals. No evidence of a dominant lethal effect reported.[California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summary for Malathion (121-75-5) p.9 (July 30, 1986). Available from, as of February 2, 2012: http://www.cdpr.ca.gov/docs/risk/toxsums/pdfs/367.pdf] **PEER REVIEWED**
  • GENOTOXICITY: Malathion (94%) was given by oral gavage to Sprague-Dawley rats as a single dose. Based on a preliminary trial, doses selected were 0 (corn oil), 0.4, 0.8 and 1.6 mL/kg, equivalent to 0.5, 1.0 and 2.0 g/kg based on density of 1.25. There were 5/sex/group for the definitive assay with sacrifices at 12, 24 and 48 hours post-treatment. Mitotic indices as well as aberrations were scored. Fifty cells per animal per sex per group were evaluated for aberrations excluding gaps. There was no effect on the incidence of aberrations and only a possible slight decrease in the MI at 24 and 48 hours in the high dose groups. No adverse effect.[California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summary for Malathion (121-75-5) p.9 (July 30, 1986). Available from, as of February 2, 2012: http://www.cdpr.ca.gov/docs/risk/toxsums/pdfs/367.pdf] **PEER REVIEWED**
  • GENOTOXICITY: Malathion (technical, batch AC 6,601, 94%) was tested with primary hepatocytes from male Sprague-Dawley rats. After a preliminary range-finding assay, the concentrations used in the UDS assay were 0 (DMSO, untreated or ethanol), 0.02, 0.04, 0.08, 0.12 or 0.16 uL/mL with an 18 hour incubation in the presence of 10 mCi/mL (3)H-thymidine. Incorporation of thymidine into nuclei was quantitated by autoradiography with 150 nuclei per concentration scored in morphologically normal cells in the 0.02 through 0.12 uL/mL groups. The positive control was 2-AAF and that treatment gave the anticipated results with 100% of nuclei having > 5 net grains. Treatment with malathion did not induce an increase in unscheduled DNA synthesis. No adverse effect with hepatocytes.[California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summary for Malathion (121-75-5) p.10 (July 30, 1986). Available from, as of February 2, 2012: http://www.cdpr.ca.gov/docs/risk/toxsums/pdfs/367.pdf] **PEER REVIEWED**
  • ALTERNATIVE and IN VITRO TESTS: Malathion in concn greater than 1 ug/ml was toxic to primary cultures of chick embryo fibroblasts.[Wilson BW, Walker NE; Proc Soc Exp Biol Med 121: 1260-4 (1966) as cited in NIOSH; Criteria Document: Malathion p.76 (1976) DHEW Pub. NIOSH 76-205] **PEER REVIEWED**
  • ALTERNATIVE and IN VITRO TESTS: The effect of O,O,S-trimethyl phosphorothioate (OOS-TMP), an impurity in malathion, on immune responses such as antigen presentation, antibody production, and cytotoxic T-lymphocyte (CTL) function was examined in vitro. The roles of non enzymatic and enzymatic glutathione (GSH) conjugation of O,O,S-trimethyl phosphorothioate in these responses were studied. Antibody responses to T-dependent and T-independent antigens were evaluated after (i) direct culture with spleen or B cells; (ii) cocultivation of B cells with T cells with and without preincubation of O,O,S-trimethyl phosphorothioate with glutathione fortified cytosol. Antigen presentation by macrophages was also assessed after such treatment as compared to untreated controls. O,O,S-trimethyl phosphorothioate preincubated with glutathione had an inhibitory effect on the cytotoxic T lymphocyte and the direct hemolytic plaque forming cell responses. This was found to be mediated by a direct inhibitory effect on macrophages, T and B cells of the immune system and not through the generation of regulatory suppressor T cells. Thus, the mode of suppressive action of O,O,S-trimethyl phosphorothioate in vitro is due to inhibition of lymphocytic proliferation. This is only possible in the presence of glutathione which was determined to be a prerequisite for the induction of O,O,S-trimethyl phosphorothioate suppressive effect. /O,O,S-trimethyl phosphorothioate/[Thomas IK, Imamura T; Toxicol Appl Pharmacol 83 (3): 456-64 (1986)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/2939594?dopt=Abstract" target=new>PubMed Abstract</a>
  • IMMUNOTOXICITY: The effect of in vivo administration of malathion on cellular, humoral, and mitogenic responses was examined. Acute (50% LD50) or subacute (10% LD50/day for 14 days) treatment with malathion in vivo did not affect the in vivo generation of specific antibody secreting cells to sheep red blood cells or cytotoxic T-lymphocytes to allogeneic tumor. Acute treatment with 50% LD50 purified malathion did not affect body weight, splenic cell number, or thymus size. However, mitogenic responses to concanavalin A and lipopolysaccharide was significantly enhanced on all days tested following acute administration of malathion. In contrast, subacute treatment with malathion did not affect mitogenic response to concanvalin A or lipopolysaccharide, but led to a significant decrease in thymic cell number.[Rodgers KE et al; Pest Biochem Physiol 25 (3): 358-65 (1986)] **PEER REVIEWED**
  • IMMUNOTOXICITY: In a subchronic study, mice, rats and rabbits were exposed to malathion at a dose levels of 20, 50, or 100 ppm (approximately 1-30 mg/kg/d depending on species) in the diet for 12, 22 or 13 weeks respectively. Significant suppression of humoral response (PFC and antibody titers) in a dose-time dependent relationship after both primary and secondary immunization was observed in the mice and rats from six to eight weeks after exposure began until study termination. The study authors stated that the effects of malathion on immune responses are more dependent on time than on dose, suggesting a threshold susceptibility to exposure.[EPA/Office of Pollution Prevention and Toxic Substances; Malathion: Updated Revised Human Health Risk Assessment for the Reregistration Eligibility Decision Document (RED) EPA-HQ-OPP-2004-0348-0004. Available from, as of February 2, 2012: http://www.regulations.gov/#!home] **PEER REVIEWED**
  • IMMUNOTOXICITY: The time course of immune modulation induced by acute treatment with O,S,S-trimethyl phosphorodithioate, an impurity in techincal formulations of malathion, was examined in female C57BL/6 mice. The immune parameters studied included the generation of cytotoxic T lymphocytes to alloantigen (H-2 incompatible) and antibody secreting cells to sheep red blood cells, proliferative response to the mitogens, and interleukin-2 production. Acute administration of the non-toxic doses of O,S,S-trimethyl phosphorodithioate, ie 20 or 40 mg/kg, led to an elevation in the generation of a cytotoxic T lymphocyte response on day 1 or 7, respectively. At 20 mg/kg O,S,S-trimethyl phosphorodithioate, the antibody response was elevated at day 3. However, at a dose of 40 mg/kg O,S,S-trimethyl phosphorodithioate, the antibody response was suppressed at day 1 following treatment. Following acute administration of 60 or 80 mg/kg O,S,S-trimethyl phosphorodithioate, the generation of an antibody and cytotoxic T lymphocytes responses was suppressed at all time points tested with 1 exception. One day following treatment at a dose of 60 mg/kg O,S,S-trimethyl phosphorodithioate, there was no change in the cytotoxic T lymphocytes response. At day 7 following treatment, the mitogenic responses to lipopolysacharide and phytochemagglutinin were elevated at administered. ... The proliferative response to concanavalin A was elevated in a dose dependent manner. Interleukin-2 production was suppressed following acute administration of 60 or 80 mg/kg O,S,S-trimethyl phosphorodithioate all doses of O,S,S-trimethyl phosphorodithioate at all time points tested and at all doses tested on day 5 following treatment.[Rogers KE, et al; Toxicology 51 (2-3): 241-54 (1988)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/3051516?dopt=Abstract" target=new>PubMed Abstract</a>
  • OTHER TOXICITY INFORMATION: Impurities can be produced through improper storage of malathion as evidenced by a 35% increase in the acute toxicity of technical malathion stored at 40 deg C for 6 months.[USEPA/Office of Pesticide Programs; Malathion RED-Ecological Effects Hazard Assessment (part 2). p.53 Identification Number: EPA-HQ-OPP-2004-0348-0024 (August 2005). Available from, as of March 27, 2012: http://www.regulations.gov/#!home] **PEER REVIEWED**
  • OTHER TOXICITY INFORMATION: Two organophosphorus impurities of technical malathion (insecticide), isomalathion and O,S,S-trimethyl phosphorodithioate, were examined for their effects on the in vivo metabolism of malathion in rats. Both impurities were confirmed to be potent in vivo inhibitors of plasma, liver, and kidney malathion carboxylesterases at relatively low doses.[Ryan DL, Fukuto TR; Pest Biochem Physiol 21 (3): 349-57 (1984)] **PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LD50 Rat male oral 1375 mg/kg[Farm Chemicals Handbook 1989. Willoughby, OH: Meister Publishing Co., 1989., p. C-180] **PEER REVIEWED**
  • LD50 Rat (female) oral 1000 mg/kg[Farm Chemicals Handbook 1989. Willoughby, OH: Meister Publishing Co., 1989., p. C-180] **PEER REVIEWED**
  • LD50 Dog intraperitoneal 1.51 ml/kg (19% soln)[National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 623] **PEER REVIEWED**
  • LD50 Rabbit percutaneous 4100 mg/kg[Farm Chemicals Handbook 1989. Willoughby, OH: Meister Publishing Co., 1989., p. C-180] **PEER REVIEWED**
  • LD50 Rat intraperitoneal 750 mg/kg[National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 623] **PEER REVIEWED**
  • LD50 Mouse intraperitoneal 420-474 mg/kg[National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 623] **PEER REVIEWED**
  • LD50 Chicken subcutaneous 1400 mg/kg[ITII. Toxic and Hazarous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1982., p. 308] **PEER REVIEWED**
  • LD50 Guinea pig oral 570 mg/kg[National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 623] **PEER REVIEWED**
  • LD50 Rat subcutaneous 1000 mg/kg[National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 623] **PEER REVIEWED**
  • LD50 Rat percutaneous > 4444 mg/kg[National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 623] **PEER REVIEWED**
  • LD50 Rat oral 290 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2271] **PEER REVIEWED**
  • LC50 Rat inhalation 43,790 ug/cu m/4 hr[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2271] **PEER REVIEWED**
  • LD50 Rat ip 250 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2271] **PEER REVIEWED**
  • LD50 Rat iv 50 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2271] **PEER REVIEWED**
  • LD50 Mouse oral 190 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2271] **PEER REVIEWED**
  • LD50 Mouse skin 2330 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2271] **PEER REVIEWED**
  • LD50 Mouse ip 193 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2271] **PEER REVIEWED**
  • LD50 Mouse sc 221 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2271] **PEER REVIEWED**
  • LD50 Mouse iv 184 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2271] **PEER REVIEWED**
  • LD50 Dog ip 1857 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2271] **PEER REVIEWED**
  • LD50 Rabbit oral 250 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2271] **PEER REVIEWED**
  • LD50 Rabbit skin 4100 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2271] **PEER REVIEWED**
  • LD50 Rat (female) oral 1400 mg/kg[Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 736] **PEER REVIEWED**
  • LD50 Rabbit dermal 2460 to 6150 mg/kg[Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 736] **PEER REVIEWED**

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Absorption, Distribution and Excretion

  • Following the administration of (3)H-O,O,S-trimethyl phosphorothioate (OOS-tmp), an impurity of malathion, to rats, substantial amount of radiolabeled material were covalently bound to lung with a concomitant depletion of glutathione (GSH). Other organs showing significant radioactivity were liver, kidneys, and ileum. The max accummulation occurred in the tissues within 6 hr, and reached a plateau between 6-12 hr. The covalent binding was possibly due to a metabolite(s) of (3)H-O,O,S-trimethyl phosphorothioate and the metabolite(s) was involved in the mechanism of toxicity of (3)H-O,O,S-trimethyl phosphorothioate. Pulmonary glutathione may have played a protective role against (3)H-O,O,S-trimethyl phosphorothioate induced lung toxicity. /(3)H-O,O,S-trimethyl phosphorothioate/[IMAMURA T, HASEGAWA L; TOXICOL APPL PHARMACOL 72 (3): 476-83 (1984)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6710498?dopt=Abstract" target=new>PubMed Abstract</a>
  • ... When (14)C-malathion ... was applied /to human skin/ 7, 9, and 23% were absorbed through forearm, abdomen, and forehead, respectively.[The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 2: A Review of the Literature Published Between 1970 and 1971. London: The Chemical Society, 1972., p. 144] **PEER REVIEWED**
  • ... (14)C-Malathion was absorbed and rapidly excreted in rats. Eight hr after oral dose, 44% of (14)C had been excreted in urine and 47% still remained in GI tract, whereas after 24 hr, 83% had been excreted in urine, 6% in feces, 3% in expired air, and 8% remained in GI tract.[The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 1: A Review of the Literature Published Between 1960 and 1969. London: The Chemical Society, 1970., p. 78] **PEER REVIEWED**
  • Excretion of (32)P after an oral dose of (32)P-malathion to lactating cow was less rapid. 69% was excreted in 4 day urine, 8% in feces, & 0.2% in milk. Since excretion of (32)p was very slow after that time, its incorporation into body tissues had probably occurred, & its release was dependent on turnover rates of those tissues.[The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 1: A Review of the Literature Published Between 1960 and 1969. London: The Chemical Society, 1970., p. 78] **PEER REVIEWED**
  • Percutaneous absorption of chronically applied malathion was determined in man and chronic absorption was compared to single dose absorption. (14)C-Malathion was applied topically to the ventral forearm of human male volunteers. This procedure was followed by repeated administration of non radioactive malathion to the same site. (14)C-Malathion was reapplied on day 8 when urinary excretion of radioactivity from the first application reached minimum detectable levels. Percutaneous absorption from the first administration was 4.48% of the applied dose. Absorption from the second administration was 3.53%. Therefore, the single dose application data are relevant for predicting toxic potential for long term exposure.[Wester RC et al; Toxicol Appl Pharmacol 68 (1): 116-9 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6845371?dopt=Abstract" target=new>PubMed Abstract</a>
  • Eight autopsy samples from an individual who had ingested a large amount of malathion were analyzed. Malathion was present in all samples except liver. The highest concentrations were found in gastric contents (8621 ppm) and adipose tissue (76.4 ppm). Malaoxon was identified in some tissues at very low levels; a significant amount was found only in fat (8.2 ppm). Malathion monocarboxylic acid & malathion dicarboxylic acid were found in greater abundance: 221 ppm in bile, 106 ppm in kidney, and 103 ppm in the gastric contents.[MORGADE C, BARQUET A; J TOXICOL ENVIRON HEALTH 10 (2): 321-5 (1982)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/7143485?dopt=Abstract" target=new>PubMed Abstract</a>
  • Measurement was made of: the ether extractable phosphates in the urine of an adult man who had been administered malathion in a single oral dose of 58 mg (0.84 mg/kg). A total of 23% of the ingested dose was recovered in the ether extractable, urinary phosphate fraction of the urine during the first 16.3 hours. 97% of this recovered dose was excreted in the first 7.5 hours. ... Based on experiments in rats injected ip or fed (32)P-labeled malathion, /it was/ found that an average of 69 and 36%, respectively, of the malathion excreted in the urine to be recoverable in the ether extractable fraction.[Mattson AM, Sedlak VA; J Agric Food Chem 8: 107-10 (1960) as cited in NIOSH; Criteria Document: Malathion p.40 (1976) DHEW Pub. NIOSH 76-205] **PEER REVIEWED**
  • ... Seven percent of total metabolites in feces /from cows given malathion orally/ was chloroform soluble, of which 85% was malathion and 12% malaoxon. The milk contained a small amount of malathion metabolites (9.2% of total dose after 7 days); of this, only 29% was extractable out of milk and partitioned in favor of water over benzene, indicating the absence of either malathion or malaoxon.[White-Stevens, R. (ed.). Pesticides in the Environment: Volume 1, Part 1, Part 2. New York: Marcel Dekker, Inc., 1971., p. 166] **PEER REVIEWED**
  • No malathion residues were found 24 hr after the exposure of pinfish to 75 ug/L; only malathion monoacid was detected in the gut.[Murty, A.S. Toxicity of Pesticides to Fish. Volumes I, II. Boca Raton, FL: CRC Press Inc., 1986., p. V1 91] **PEER REVIEWED**
  • Malathion is absorbed systemically following ingestion, topical application to skin and mucous membranes, or inhalation of dusts or aerosols.[American Society of Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011, p. 3525] **PEER REVIEWED**
  • The potential for transdermal absorption of malathion from the 0.5% pediculicidal lotion commercially available in the US has not been specifically studied to date. Results of a study in healthy adults using several different aqueous- and alcohol-based formulations of topical malathion 0.5% (not the preparation commercially available in the US) indicate that small amounts of the drug are absorbed following application to the scalp; the extent of absorption was similar between the aqueous and alcoholic formulations.[American Society of Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011, p. 3525] **PEER REVIEWED**
  • Following topical application to the skin of malathion in an acetone vehicle (not commercially available in the US), approximately 8% of the dose was absorbed. In another study, approximately 4.5% of a single dose of malathion was absorbed following topical application to forearm skin (5 mg/sq cm); there was no increase in transdermal absorption when the topical dose was repeated once daily for 8 days. Inadvertent transdermal absorption of malathion has occurred from agricultural formulations, resulting in acute toxicity.[American Society of Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011, p. 3525] **PEER REVIEWED**
  • Information on distribution of malathion into human body tissues and fluids following topical application is not available. Following ingestion of agricultural insecticidal formulations, malathion is widely distributed into body tissues and fluids including kidneys, blood, liver, bile, spleen, heart, adipose tissue, brain, lungs, and muscles.[American Society of Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011, p. 3525] **PEER REVIEWED**
  • It is not known if malathion crosses the placenta or is distributed into milk following topical application to the skin. Malathion was not detected in milk samples from nursing women who resided in geographic areas that received extensive aerial spraying with an agricultural formulation of malathion for insect control.[American Society of Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011, p. 3525] **PEER REVIEWED**
  • Malathion and its metabolites are excreted in urine; the monocarboxylic and dicarboxylic acid metabolites of malathion also are excreted in bile. In one study following topical application to the scalp of aqueous- or alcohol-based preparations of malathion (not the preparation commercially available in the US), approximately 0.2-3.2% of the applied malathion dose was eliminated in the urine as metabolites within 96 hours.[American Society of Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011, p. 3525] **PEER REVIEWED**
  • A rat metabolism study showed that orally administered malathion is excreted primarily in the urine (80-90%) in the first 24 hours following exposure, with lesser amounts excreted in the feces. Radioactivity did not bioaccumulate in any of the organ/tissues analyzed.[EPA/Office of Pollution Prevention and Toxic Substances; Malathion: Updated Revised Human Health Risk Assessment for the Reregistration Eligibility Decision Document (RED) EPA-HQ-OPP-2004-0348-0004. Available from, as of February 2, 2012: http://www.regulations.gov/#!home] **PEER REVIEWED**
  • Malathion (unlabeled at 94.6% and (14)C-labeled at 98%) was given by oral gavage to 5/sex/group of Sprague-Dawley (Crl:CD BR) rats at single doses of 40 or 800 mg/kg or 15 doses of unlabeled malathion at 40 mg/kg followed by a 16th dose of radioactive malathion. Excretion was followed for 72 hours before sacrifice of the animals and measurement of tissue content. Most of the malathion was excreted in the first 12 hours predominantly in the urine of both males and females. Less than 1% was retained in the tissues with the level in the liver being the highest.[California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summary for Malathion (121-75-5) p.11 (July 30, 1986). Available from, as of February 2, 2012: http://www.cdpr.ca.gov/docs/risk/toxsums/pdfs/367.pdf] **PEER REVIEWED**
  • The American cockroach was treated by topical application of (14)C-malathion. The distribution of the label within the body tissues was found to be both rapid and extensive. As much as 40% of the applied label was still present superficially in the cuticle even 24 hr post-application. The overall tissue ranking order for (14)C label was found to be: foregut > digestive tract contents > skeletal muscle > fat body > hindgut > midgut > nerve cord > brain > malpighian tubules. Malathion, malaoxon and malathion monoacids were detected in the nerve cord plus brain, the digestive tract, skeletal muscle and fat body at 1, 2 and 24 hr after topical application of the insecticide. At 24 hr post-application a significant proportion of malathion remained unmetabolized in all tissues examined. The highest levels of metabolic transformation were found in the digestive tract and fat body. Insects were prostrate 24 hr after topical application of (14)C-malathion. In these insects the greatest concentration of malathion and monoacids (expressed in relation to unit tissue wt) was found in the digestive tract. On the other hand, the nerve cord and brain contained the greatest concentration of malaoxon. About 18% of applied (14)C-malathion label partitioned into the tissue aqueous phase up to 24 hr after topical application but very little applied label was expired as (14)CO2 or excreted. Although a neurotoxic action may be the cause of prostration and death, the extensive dissemination of malathion and its products belies the concept of any tissue specificity. The hemolymph, after an initial sharp rise in malathion content, maintained a steady malathion level over the 24 hr experimental periods suggesting that the hemolymph is the main distributor of the insecticide to the various body tissues.[Dales MJ et al; Comp Biochem Physiol C Comp Pharmacol Toxicol 92 (1): 155-62 (1989)] **PEER REVIEWED**

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Metabolism/Metabolites

  • Malathion is rapidly metabolized in vivo principally by hydrolysis of the carboxyl ester linkage to inactive metabolites by carboxylesterases. Because this detoxification reaction occurs much more rapidly in mammals than in susceptible insects, malathion exhibits a relative degree of selective toxicity in insects.[American Society of Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011, p. 3525] **PEER REVIEWED**
  • Malathion also is oxidized by the hepatic microsomal monooxygenase system to malaoxon, an active, toxic metabolite. Metabolism of malaoxon typically occurs at a faster rate than its formation from malathion, and little accumulation of this highly toxic metabolite occurs in mammals.[American Society of Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011, p. 3525] **PEER REVIEWED**
  • Malathion is metabolically converted to its structurally similar metabolite, malaoxon (oxidation of the P=S moiety to P=O), in insects and mammals. Both malathion and malaoxon are detoxified by carboxyesterases leading to polar, water-soluble, compounds that are excreted. Mammalian systems show greater carboxyesterase activity, as compared with insects, so that the toxic agent malaoxon builds up more in insects than in mammals. This accounts for the increased toxicity of malathion in insects.[EPA/Office of Pollution Prevention and Toxic Substances; Malathion: Updated Revised Human Health Risk Assessment for the Reregistration Eligibility Decision Document (RED) EPA-HQ-OPP-2004-0348-0004. Available from, as of February 2, 2012: http://www.regulations.gov/#!home] **PEER REVIEWED**
  • Unchanged malathion was typically found to be the major residue in rats. Dicarboxilic acid and monocarboxilic acid metabolites account for the majority of the radioactivity. In the rat study, radioactivity did not bioaccumulate in any of the organ/tissues analyzed.[EPA/Office of Pollution Prevention and Toxic Substances; Malathion: Updated Revised Human Health Risk Assessment for the Reregistration Eligibility Decision Document (RED) EPA-HQ-OPP-2004-0348-0004. Available from, as of February 2, 2012: http://www.regulations.gov/#!home] **PEER REVIEWED**
  • Although eight radiolabeled metabolites were observed in urine /following a dose of labeled-malathion/, greater than 80% of the radioactivity in urine was represented by the diacid (DCA) and monoacid (MCA) metabolites. The remaining radiolabeled metabolites were identified as components of "peak A" and "peak B". It was determined that between 4 and 6% of the administered dose was converted to malaoxon, the more active ChE inhibiting metabolite of malathion.[EPA/Office of Pollution Prevention and Toxic Substances; Malathion: Updated Revised Human Health Risk Assessment for the Reregistration Eligibility Decision Document (RED) EPA-HQ-OPP-2004-0348-0004. Available from, as of February 2, 2012: http://www.regulations.gov/#!home] **PEER REVIEWED**
  • In vivo, malaoxon is the active ChE-inhibiting, oxon metabolite of malathion. Under some conditions, malaoxon can be formed as an environmental breakdown product of malathion.[EPA/Office of Pollution Prevention and Toxic Substances; Malathion: Updated Revised Human Health Risk Assessment for the Reregistration Eligibility Decision Document (RED) EPA-HQ-OPP-2004-0348-0004. Available from, as of February 2, 2012: http://www.regulations.gov/#!home] **PEER REVIEWED**
  • Malathion (unlabeled at 94.6% and (14)C-labeled at 98%) was given by oral gavage to 5/sex/group of Sprague-Dawley (Crl:CD BR) rats at single doses of 40 or 800 mg/kg or 15 doses of unlabeled malathion at 40 mg/kg followed by a 16th dose of radioactive malathion. ...Ten metabolites were identified by GC/MS of material eluted from HPLC. The major metabolites were the a and b isomers of the monocarboxylic acid derivative and the dicarboxylic acid derivative of malathion.[California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summary for Malathion (121-75-5) p.11 (July 30, 1986). Available from, as of February 2, 2012: http://www.cdpr.ca.gov/docs/risk/toxsums/pdfs/367.pdf] **PEER REVIEWED**
  • Selective toxicity to insects has been accounted for by differences in metabolism. (32)P-malathion is rapidly metabolized in mice, rats, and dogs, principally by hydrolysis of the ethyl ester bonds to give malathion monoester and malathion diacid, whereas in insects oxidn to malaoxon and cleavage of the phosphate thioester bond to give O,O-dimethyl-phosphorodithionate and -phosphorothionate are the principal routes of metabolism.[Parke, D. V. The Biochemistry of Foreign Compounds. Oxford: Pergamon Press, 1968., p. 204] **PEER REVIEWED**
  • Malathion ... requires activation to /malaoxon/ ... to become an active anticholinesterase agent. ... The conversion of malathion to malaoxon is a reaction carried out by the liver microsomal monooxygenase system. Competing with the activation of malathion are enzymes responsible for its degradation to non-toxic metabolites. These are ... characterized as phosphatases and carboxylesterases or aliesterases. Products of reactions catalyzed by these enzymes are malathion monoester, various phosphoric acids & demethylated product. ... The degradation rate of malaoxon exceeds the activation rate of malathion, so there is ... little accumulation of the toxic activation product in mammalian systems.[National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 622] **PEER REVIEWED**
  • Metabolite of malathion found in cow feces: dimethyl phosphate. /From table/[DeRoetth A Jr, Am J Ophthalmol 59: 586-92 (1965) as cited in NIOSH; Criteria Document: Malathion p.168 (1976) DHEW Pub. NIOSH 76-205] **PEER REVIEWED**
  • Metabolites of malathion in cow, rat, and dog urine and serum are desmethyl malathion and malathion diacid. /From table/[O'Brien RD; Insecticides - Action and Metabolism p.32-107 (1967) as cited in NIOSH; Criteria Document: Malathion p.168 (1976) DHEW Pub. NIOSH 76-205] **PEER REVIEWED**
  • A metabolite of malathion in mouse urine and serum is desmethyl malathion. /From table/[NIOSH; Criteria Document: Malathion p.168 (1976) DHEW Pub. NIOSH 76-205] **PEER REVIEWED**
  • Two organophosphorus impurities of technical malathion (insecticide), isomalathion and O,S,S-trimethyl phosphorodithioate, were examined for their effects on the in vivo metabolism of malathion in rats. Both impurities were confirmed to be potent in vivo inhibitors of plasma, liver, and kidney malathion carboxylesterases at relatively low doses. Pretreatment of rats with these impurities followed by administration of (14)C malathion resulted in changes in the quantities of certain malathion metabolites excreted in the urine. Compared to the corn oil pretreated controls, the most notable change in the impurity pretreated animals was in the decrease in the amount of malathion diacid excreted along with a commensurate increase in the amount of excreted malathion alpha monoacid. An increase in malaoxon metabolites in the urine of impurity pretreated rats was indicated, suggesting that more malaoxon was originally produced in these animals.[Ryan DL, Fukuto TR; Pest Biochem Physiol 21 (3): 349-57 (1984)] **PEER REVIEWED**
  • By using high specific activity malathion and ion exchange chromatography, a total of 11 metabolites were isolated from the German cockroach, American cockroach, ... common Housefly, and seven metabolites from the white mouse. The principal metabolites isolated from the mouse were monoethyl ester of malathion (86%), dimethyl phosphorothioic acid (13%), dimethyl phosphorodithioic acid (5%), 10% of an unknown metabolite. Relative amount of various metabolites obtained were similar between roaches, which in turn were slightly different from flies. ... Level of malaoxon was ... greater in cockroach than in mouse at any time after injection, eg, at 1 hr after injection /of malathion/ there was 10 times more malaoxon per g of animal. Relative proportions of metabolites indicates greater P=S to P=O activation in insects compared to mammals ...[White-Stevens, R. (ed.). Pesticides in the Environment: Volume 1, Part 1, Part 2. New York: Marcel Dekker, Inc., 1971., p. 165] **PEER REVIEWED**
  • The hydrolysis of malathion by rabbit liver oligomeric and monomeric carboxylesterase results in the formation of a mixture of an alpha and beta monoacid. The oligomeric carboxylesterase produced an alpha/beta ratio of monoacids of 4.55, and the monomeric carboxylesterase produced an alpha/beta ratio of monoacids of 2.33. Kinetic studies demonstrated that the Km values were the same for the corresponding reactions which produced alpha monoacid, or beta monoacid with the same enzyme. Since both carboxylesterases are electrophoretically pure, the kinetic data strongly supports the theory that the reactions which produced alpha and beta monoacids are catalyzed by the same active site.[Lin PT et al; Pest Biochem Physiol 20 (2): 232-7 (1983)] **PEER REVIEWED**
  • In man, malathion is metabolized by (1) hydrolytic cleavage of ethyl groups from the succinic acid moiety of the molecule by carboxylesterase enzymes; and (2) hydrolysis of the succinate moiety from the dialkyl thiophosphate.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V30 119 (1983)] **PEER REVIEWED**
  • In susceptible insects, malathion is metabolized principally to malaoxon (a more potent anticholinesterase agent), which contributes to the insecticidal effects of the drug.[American Society of Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011, p. 3524] **PEER REVIEWED**
  • Malaoxon, active anticholinesterase metabolite of malathion ... has aliesterases inhibiting activity.[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-298] **PEER REVIEWED**
  • TOXICITY OF MALATHION IS POTENTIATED BY O-ETHYL O-PARA-NITROPHENYL PHOSPHOROTHIOATE, TRI-O-TOLYLPHOSPHATE, & SOME OTHER ORGANOPHOSPHORUS CMPD. IT IS POSTULATED THAT THIS POTENTIATION RESULTS FROM THE INHIBITION OF CARBOXYLESTERASE OR ALIESTERASE ENZYMES RESPONSIBLE FOR DEGRADATION OF MALATHION IN MAMMALS. PRESUMABLY, THIS MECHANISM WOULD LEAD TO INCR FORMATION OF MALAOXON, THE ACTIVATION PRODUCT, BECAUSE THE ENZYMES RESPONSIBLE FOR DEGRADATION OF MALAOXON WOULD BE INHIBITED.[National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 622] **PEER REVIEWED**

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TSCA Test Submissions

  • Malathion (CAS # 121-75-5) was evaluated for cytotoxicity in study to evaluate the validity of in vitro testing for direct reuse water toxicity in mammalian systems. As a quick, inexpensive, reproducible, and sensitive means of detection, if this test is also a valid reflection of toxicity in mammals, it would be highly beneficial in assessing the potability of direct reuse water and in prescribing mode of water treatment. Continuous L-cell cultures (mouse or rat, 26 cultures/assay, >200,000 cells/culture) in minimal medium with 1% fetal bovine serum were exposed to 12 graded doses (unspecified) in ethanol solution for 72 to 96 hours. A reflection of effects on growth and reproduction of the indicator cells, the change in protein synthesis as determined by calorimetric Lowry method was chosen to quantify the cytotoxicity in 6 cultures/assay at 24, 48, 72 and 96 hours after initiation of study. A concentration of 32 mg/L was toxic to L-cells. Levels greater than 1 mg/L inhibited protein production in a time-dependent manner; cells exposed in vitro to 18 mg/L demonstrated static protein synthesis by the third day, with protein loss evident at Day 4. The effect was less pronounced in response to a 10 mg/L malathion exposure, although this level halved protein synthesis (LC50). An LC10 was 2.0 mg/L. The authors suggested that the timed response might be due to altered cellular metabolism or intracellular accumulation of malathion. The LC50 (10 mg/L) was both significantly lower than the NOEL in chronic animal studies (100-1000 and 100 ppm in rats and dogs, respectively) and higher than WHO/FAO's maximum daily intake standard (0.02 mg/kg/day). However, a positive relationship was established in both instances by a two-way ANOVA statistical method, indicating a relevant toxicological result with the cell culture bioassay. Malathion, a non-persistent (biodegradable) and poorly soluble insecticide of low relative mammalian toxicity that is rarely found in drinking water, bears no EPA-derived drinking water standard limit. Using an EPA convention for calculation of drinking water maximum limits and either the same historical minimal effect level or WHO/FAO data, the resultant standard (0.03 or 0.15 mg/L respectively) would be undetectable with the tissue culture bioassay.[U S Dept of the Army; The Development of a Test for the Potability of Water Treated by Direct Reuse System (Contract No. DADA-17-73-C-3013) (Final Report); 04/21/80; EPA Document No. 40-8069226; Fiche No. OTS0517889] **UNREVIEWED**
  • Malathion (CAS # 121-75-5) was evaluated for acute oral toxicity in study of strain-specific differences in Fischer 344-derived (CDF) and Sprague-Dawley (SPB) rats (5/sex/strain/group) administered single oral doses of 252 to 3980 mg/kg by oral gavage. Groups of female rats of both strains received doses of 252, 500, 1000, 2000, and 3980 mg/kg, while groups of male rats also received doses of 2520 mg/kg. Additional groups of Sprague-Dawley males only received doses of 2100 and 2250 mg/kg. Single-dose oral LD50's, based on a moving average method, were 2101 and 2102 mg/kg for SPB males and females and 1875 and 1898 mg/kg for CDF male and female rats, respectively. Clinical signs of toxicity, associated with doses of 500 and above throughout 14-day post-gavage observation, included lethargy, total body tremors, bluish face (1000-3980 mg/kg, SPB females only), piloerection, heightened tail color (2000 mg/kg, 5/5 SPB males only), gasping, and convulsions. No significant treatment-related changes in bodyweight were noted in either strain. Upon necropsy of both surviving and decedent rats, gross lesions were limited to focal corneal cloudiness, which was more prevalent in the CDF males. The authors concluded, however, that the overall response between these strains of rat were comparable.[Dow Chem Co; A Comparison of Single-Dose Oral LD50's for SPB; 05/01/92; EPA Document No. 88-920002473; Fiche No. OTS0537283] **UNREVIEWED**

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Footnotes

1 Source: the National Library of Medicine's Hazardous Substance Database, 12/12/2012.

The NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.