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MALATHION 41 3. HEALTH EFFECTS 124.1 mg/kg, whereas in preweaning (14–16 days old) and adult (3–4 months) rats, oral LD50 values were 386.8 and 925.4 mg/kg, respectively (Lu et al. 1965). This difference was also observed for 4-day cumulative LD50s (Lu et al. 1965). Similar findings were reported by Mendoza (1976) and Mendoza and Shields (1976) who also observed that the decrease in susceptibility more or less paralleled increases in the activities of esterases in various tissues. For example, using acetylthiocholine as substrate, a single dose of 8,000 mg/kg of malathion inhibited brain esterase by 85% in 18-day-old pups, while in 1-day-old pups, the same degree of inhibition was achieved with a dose of only 500 mg/kg. In dogs, single doses of up to 4,000 mg/kg of 98% pure malathion in a gelatin capsule were not lethal, although the observation period was not indicated (Frawley et al. 1957). In rabbits, a single dose of 1,200 mg/kg of 95% pure malathion killed five out of six animals 6 hours after dosing; there were no deaths with 600 mg/kg (Weeks et al. 1977). In all of the species examined, death was preceded by signs of cholinergic stimulation such as salivation, respiratory distress, tremors, and convulsions. Deaths in animals also have been reported in intermediate-duration studies. In a 6-week dietary study, five out of five male and female Osborne-Mendel rats administered approximately 2,816 mg/kg/day technical malathion (95% pure) died by week 3 (NCI 1978); no deaths were reported at 1,408 mg/kg/day. Deaths were also observed among male and female Fischer-344 rats administered approximately 1,399 mg/kg/day technical malathion, but not at #700 mg/kg/day in a 13-week feed study (NCI 1979a). Also, 4 out of 10 male, but no female B6C3F1 mice died following dietary administration of approximately 6,432 mg/kg/day of technical malathion for 3 weeks (NCI 1978); no deaths occurred with approximately 3,216 mg/kg/day malathion or less. Significant increased mortality was observed among male Fischer-344 rats administered approximately 166 mg/kg/day of technical malathion (95% pure) in the diet for 2 years (NCI 1979a). A more recent bioassay reported a significant increase in deaths not attributed to cancer among male Fischer-344 rats given approximately 359 mg/kg/day technical malathion (97.1% pure) or higher doses (Daly 1996a). No significant increase in mortality was seen in the females that received up to 868 mg malathion/kg/day (Daly 1996a). The LOAEL values for death in each species and duration category are recorded in Table 3-2 and plotted in Figure 3-2.
a Key to figure 1 2 3 4 5 6 Species (Strain) Exposure/ Duration/ Frequency (Specific Route) ACUTE EXPOSURE System Table 3-2 Levels of Significant Exposure to Malathion - Oral NOAEL (mg/kg/day) Less Serious LOAEL Serious (mg/kg/day) (mg/kg/day) Reference Chemical Form Death Rat (Wistar) once (GO) 1500 (LD50 96.8% pure) Lu et al. 1965 3697 (LD50 99.6% pure) 925 b (LD50 95% pure) Rat (Wistar) once (GO) 386.8 (LD50 in preweaning) Lu et al. 1965 925.4 (LD50 in adult) Rat (Wistar) 4 d 1 x/d (GO) 124.1 b (LD50 in newborn) Lu et al. 1965 1599 (4-day cumulative LD50 in adult rats) 331.2 b (4-day cumulative LD50 in preweaning rats) Rat (Wistar) once (GO) 707 (LD50 in 6-day old) Mendoza 1976 1085 (LD50 in 12-day old) Rat (Sprague- Dawley) Mouse (ICR) 1806 (LD50 in 17-day old) 209 b (LD50 in 1-day old) once Umetsu et al. 1977 12500 (LD50 of recrystallized) (G) 9500 b (LD50 of 99.3% pure) 2 d 1 x/d (GO) 2357 (LD50 for l-malathion) 1014 b F (LD50 for d-malathion) Hassan and Dauterman 1968
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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 122 V E N O U S BLOOD 3.
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MALATHION 175 6.1 OVERVIEW 6. POTEN
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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 280 10. GLOSSARY Ceiling
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MALATHION 282 10. GLOSSARY Mutagen
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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-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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