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首页> 美国政府科技报告 >Pharmacokinetics of Methanol and Formate in Female Cynomolgus Monkeys Exposed toMethanol Vapors
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Pharmacokinetics of Methanol and Formate in Female Cynomolgus Monkeys Exposed toMethanol Vapors

机译：雌性食蟹猴甲醇和甲酸盐暴露于乙醇蒸气中的药代动力学

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The authors' objective was to determine the pharmacokinetics of (sup 14)C-methanol and (sup 14)C-formate in normal and folate-deficient monkeys after exposure to (sup 14)C-methanol vapors at environmentally relevant concentrations: below the threshold limit value (TLV), at the TLV of 200 parts per million (ppm), and above the TLV. Four normal adult female cynomolgus monkeys were individually anesthetized with isoflurane, and each was exposed by endotracheal intubation to 10, 45, 200, or 900 ppm (sup 14)C-methanol for 2 hours. The amounts of exhaled (sup 14)C-methanol and (sup 14)CO(sub 2), blood concentrations of (sup 14)C-methanol and (sup 14)C-formate, and (sup 14)C-methanol and (sup 14)C-formate excreted in urine were linearly related to methanol exposure concentration. For all exposures, blood concentrations of (sup 14)C-methanol-derived formate were 10 to 1000 times lower than endogenous blood formate concentrations (100 to 200 mM) reported for monkeys and were several orders of magnitude lower than levels of formate known to be toxic. Since the metabolism of formate in primates depends on the availability of tetrahydrofolate, the same four monkeys were next placed on a folate-deficient diet until folate concentrations in red blood cells consistent with moderate folate deficiency (29 to 107 ng/mL) were achieved. Monkeys were then reexposed to 900 ppm (sup 14)C-methanol for a similar 2-hour period. Even with a reduced folate status, monkeys exposed to 900 ppm methanol for 2 hours had a peak concentrations of methanol-derived formate that were well below the endogenous levels of formate. Although these results represent only a single exposure and therefore preclude broad generalizations, they do suggest the body contains sufficient folate stores to effectively detoxify small doses of methanol-derived formate from exogenous sources.

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