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MALATHION 129 3. HEALTH EFFECTS inhibited as early as 1 hour after being gavaged with 126 mg/kg of malathion, but showed a considerable recovery by the next day. Repeated dosings, however, caused a higher degree of inhibition with increased signs of poisoning (Machin and McBride1989). This indicates that there was a parallel effect on the neural acetylcholinesterase of the rabbits, and that there can be cumulative inhibition. In organophosphorus insecticides with slower dephosphorylation, the use of nucleophiles such as pyridine aldoxime methiodide is a useful treatment of poisoning. In the case of dimethylphosphorus esters like malathion, the benefit seems unpredictable. In the fatal case of a 45-year-old man who ingested 50–90 mL of 50% malathion, for example, 3 grams of 2-pyridine aldoxime methochloride given within 3 hours when erythrocyte cholinesterase activity was
MALATHION 130 3. HEALTH EFFECTS plasma or RBC cholinesterase activity. However, administration of 0.34 mg malathion/kg/day for 56 days caused a maximum depression of 25% in plasma cholinesterase approximately 3 weeks after cessation of treatment. A similar depression in RBC cholinesterase was observed, but occurred later. No clinical manifestations of toxicity were noted throughout the study. The high selective toxicity of malathion is due to its rapid hydrolysis by carboxylesterase in mammals and the general lack of this enzyme in most insect pests. This enzyme is inhibited by several of the impurities that accompany technical malathion as well as other organophosphorus esters including ethylp-nitrophenyl thionobenzenephosphonate (EPN) and triorthotolyl phosphate (TOTP). The effective dose of malathion preparations depends greatly on the carboxylesterase inhibition, which in turn is determined by the level of impurities. Experimental inhibition of most carboxylesterase by TOTP dramatically lowered acute LD50 of malathion preparations, from 1,600 to 20 mg/kg in one case and from 415 to 7.5 mg/kg in another (Main and Braid 1962) in male Sprague-Dawley rats. 3.5.3 Animal-to-Human Extrapolations Malathion exerts most of its toxic effects through cholinergic disruption both in humans and in other mammalian species. Data obtained with rodent models are clearly relevant to humans as they share basic physiology both in the function of the nervous system and in the metabolic pathways. Because of these similarities, basic clinical signs of poisoning are similar in humans and in rodents when they are exposed to sufficient doses of malathion. In details, however, extrapolation of animal data to humans becomes difficult due mainly to differences in pharmakokinetics. The situation is exacerbated by the unique dependence of malathion toxicity on the degree of hydrolysis by carboxylesterases. In humans, hepatic carboxylesterase activities appear similar to those in rat liver. Unlike rats, however, humans lack detectable levels of malathion carboxylesterase in the serum; the enzyme is also absent in human erythrocytes (Main and Braid 1962). Further confirmation of the general absence of malathion carboxylesterase in the serum of healthy humans was provided by Talcott et al. (1982). About 30% of blood donors had detectable levels of malathion carboxylesterase activity in serum, activity ranging from 0.1 to 7.2 units/mL; no relation to age, sex, or race was noted. Positive correlations between serum ALT and malathion carboxylesterase were noted among 46 hospital patients. In addition, the two enzymes in the serum of a patient hospitalized for acetaminophen poisoning were observed to rise and decline in parallel, with the peak being reached on day 4. These data suggest that the low level of malathion carboxylesterase found in some human serum is a reflection of liver damage. The lack of malathion
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TOXICOLOGICAL PROFILE FOR MALATHION
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MALATHION iii UPDATE STATEMENT A To
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MALATHION viii Managing Hazardous M
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MALATHION xi PEER REVIEW A peer rev
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MALATHION xiv 3.2.3.2 Systemic Effe
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MALATHION xvii LIST OF FIGURES 3-1.
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MALATHION 1 1. PUBLIC HEALTH STATEM
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MALATHION 11 1. PUBLIC HEALTH STATE
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MALATHION 14 2. RELEVANCE TO PUBLIC
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MALATHION 24 3. HEALTH EFFECTS oral
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MALATHION 26 3. HEALTH EFFECTS sing
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≤
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MALATHION 30 3. HEALTH EFFECTS Resp
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MALATHION 32 3. HEALTH EFFECTS Rena
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MALATHION 34 3. HEALTH EFFECTS Stud
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MALATHION 36 3. HEALTH EFFECTS Fran
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MALATHION 38 3. HEALTH EFFECTS more
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MALATHION 40 3. HEALTH EFFECTS the
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a Key to figure 1 2 3 4 5 6 Species
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a Key to figure 15 16 17 18 Species
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a Key to figure 24 25 26 27 28 29 S
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a Key to figure 40 41 42 43 44 45 S
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a Key to figure 55 56 57 58 59 60 S
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a Key to figure 67 68 69 70 Species
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a Key to figure 83 84 85 86 87 88 8
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a Key to figure 91 Species (Strain)
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a Key to figure 93 94 Species (Stra
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≤
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≤
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MALATHION 64 3.2.2.2 Systemic Effec
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MALATHION 66 3. HEALTH EFFECTS 1965
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MALATHION 68 3. HEALTH EFFECTS Hepa
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MALATHION 70 3. HEALTH EFFECTS appr
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MALATHION 72 3. HEALTH EFFECTS an u
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MALATHION 74 3. HEALTH EFFECTS Meta
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MALATHION 76 3. HEALTH EFFECTS clas
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MALATHION 179 6. POTENTIAL FOR HUMA
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MALATHION 187 6.3.2.1 Air 6. POTENT
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MALATHION 216 7. ANALYTICAL METHODS
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MALATHION 224 7.3.1 Identification
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MALATHION 226 8. REGULATIONS AND AD
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MALATHION 238 9. REFERENCES *Agency
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MALATHION 240 9. REFERENCES *Barnes
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MALATHION 242 9. REFERENCES *Brown
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MALATHION 244 9. REFERENCES *Choi P
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MALATHION 248 9. REFERENCES Ehrich
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MALATHION 250 9. REFERENCES EPA. 20
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MALATHION 252 9. REFERENCES *Gaines
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MALATHION 264 9. REFERENCES Mohn G.
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MALATHION 266 9. REFERENCES NIOSH.
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MALATHION 268 9. REFERENCES *Prabha
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MALATHION 276 9. REFERENCES Viccell
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MALATHION 278 9. REFERENCES Yess NJ
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MALATHION 280 10. GLOSSARY Ceiling
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MALATHION 282 10. GLOSSARY Mutagen
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MALATHION 284 10. GLOSSARY Risk—T
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MALATHION A-2 APPENDIX A are not ex
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MALATHION A-4 APPENDIX A Was a conv
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MALATHION A-6 APPENDIX A Was a conv
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MALATHION A-8 APPENDIX A If an inha
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MALATHION A-10 Uncertainty Factors
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MALATHION B-2 Interpretation of Min
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MALATHION B-4 APPENDIX B (8) NOAEL
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1 2 3 4 12 → → → → → Key
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MALATHION C-1 APPENDIX C. ACRONYMS,
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MALATHION C-3 APPENDIX C MFO mixed
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MALATHION C-5 > greater than $ grea
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