| Chronic maternal methanol inhalation in nonhuman primates (Macaca fascicularis): exposure and toxicokinetics prior to and during pregnancy. | |
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MedLine Citation:
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PMID: 15019954 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Toxicokinetic studies were conducted following daily inhalation exposure to methanol vapor prior to and throughout pregnancy in adult female Macaca fascicularis monkeys. They were part of a larger study to investigate the effects of chronic methanol exposure on maternal reproductive performance and early offspring effects. In a two-cohort study design, 48 females (24/cohort) were assigned to parallel exposure groups at 0 (control), 200, 600, or 1800 ppm methanol vapor for approximately 2.5 h/day, 7 days/week throughout breeding and pregnancy. Blood methanol at 30 min postexposure was monitored biweekly. The time course for the clearance of blood MeOH concentrations following exposure was characterized on four occasions: twice during the prebreeding period and during mid- and late pregnancy. Average blood methanol concentrations at 30 min postexposure were 5, 11, and 35 microg/ml across all four toxicokinetic studies in the 200, 600 and 1800 ppm groups, respectively. Blood concentrations in the 200 ppm group were barely above basal (preexposure) blood methanol concentrations or those observed in the control group (approximately 3 microg/ml). Nonlinear elimination kinetics were observed in most of the 1800 ppm group females. There was a decrease in elimination half-life (7-20%) and an increase in clearance (30%) after 3-months of daily MeOH exposure compared to the initial exposure. There were no statistically significant changes in the first-order blood methanol half-life or clearance during pregnancy, but the mean distribution volume per kilogram body weight decreased by 22% and 17% in the 600 and 1800 ppm groups. Plasma formate levels did not differ between the methanol and control exposure groups. Plasma formate and serum folate concentrations increased slightly over the course of this study in both the exposed and control groups but these increases were not related to methanol exposure. |
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Authors:
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Thomas M Burbacher; Danny D Shen; Bojan Lalovic; Kimberly S Grant; Lianne Sheppard; Doris Damian; Stephen Ellis; Noelle Liberato |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Neurotoxicology and teratology Volume: 26 ISSN: 0892-0362 ISO Abbreviation: Neurotoxicol Teratol Publication Date: 2004 Mar-Apr |
Date Detail:
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Created Date: 2004-03-15 Completed Date: 2004-05-10 Revised Date: 2009-10-26 |
Medline Journal Info:
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Nlm Unique ID: 8709538 Medline TA: Neurotoxicol Teratol Country: United States |
Other Details:
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Languages: eng Pagination: 201-21 Citation Subset: IM |
Affiliation:
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Departments of Pharmacy and Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA 98195, USA. tmb@u.washington.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Inhalation Animals Chromatography, Gas Cohort Studies Female Folic Acid / blood Half-Life Kinetics* Macaca fascicularis / blood Male Methanol / blood, pharmacokinetics, toxicity* Pregnancy Prenatal Exposure Delayed Effects* Solvents / pharmacokinetics, toxicity Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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P30 ES07033/ES/NIEHS NIH HHS; P30 HD02274/HD/NICHD NIH HHS; P51 RR00166/RR/NCRR NIH HHS; R01 ES06673/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Solvents; 59-30-3/Folic Acid; 67-56-1/Methanol |
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