Pharmacokinetics of inhaled [14C]methanol and methanol-derived [14C]formate in normal and folate-deficient cynomolgus monkeys

Toxicology and Applied Pharmacology
D C DormanM A Medinsky

Abstract

Large-scale use of methanol (MeOH) as an automotive fuel may increase exposure of the public to MeOH vapor, necessitating the need for additional data for an adequate human health risk assessment. Formate is accepted as the toxic metabolite of MeOH, its metabolism is folate-dependent, and potentially sensitive folate-deficient subpopulations (e.g., pregnant women) exist that may be at higher risk to low-level methanol exposure. This study determined the pharmacokinetics of [14C]MeOH and [14C]formate in normal and folate-deficient (FD) monkeys following inhalation of environmentally relevant concentrations of [14C]MeOH. Four normal adult female cynomolgus monkeys were anesthetized (isoflurane) and exposed by lung-only inhalation to 10, 45, 200, and 900 ppm [14C]MeOH for 2 hr. Monkeys were then placed on a FD diet until folate concentrations consistent with moderate deficiency (29-107 ng/ml) developed in red blood cells and then reexposed to 900 ppm (900-FD) for 2 hr. Average (+/- SD) end-of-exposure blood [14C]MeOH concentrations were 0.65 +/- 0.3, 3.0 +/- 0.8, 21 +/- 16, 106 +/- 84, and 211 +/- 71 microM, while average (+/- SD) peak blood [14C]formate concentrations were 0.07 +/- 0.02, 0.25 +/- 0.09, 2.3 +/- 2.9, 2.8 +/- 1.7, a...Continue Reading

Citations

Jun 17, 2008·Metabolism: Clinical and Experimental·Abdulrazaq A H SokoroDenis C Lehotay
Jul 17, 1998·Toxicology and Industrial Health·R PoonV Valli
Aug 10, 2017·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Bhushan M Kapur, Marta Baber
Jul 1, 1995·Teratology·D C DormanF Welsch
Apr 3, 2015·Physiological Reviews·Yuri L DorokhovTatiana V Komarova
Aug 28, 2012·Journal of Biosciences·Ashok Iyyaswamy, Sheeladevi Rathinasamy
Sep 10, 2002·Journal of Toxicology. Clinical Toxicology·Donald G BarcelouxAmerican Academy of Clinical Toxicology Ad Hoc Committee on the Treatment Guidelines for Methanol Poisoning
Apr 15, 2004·Reproductive Toxicology·Michael ShelbyNTP-CERHR Expert Panel

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