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Carbofuran disposition in the rat after aerosol inhalation
Author(s) -
Ferguson Paul W.,
Jewell Sarah A.,
Krieger Robert I.,
Raabe Otto G.
Publication year - 1982
Publication title -
environmental toxicology and chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.1
H-Index - 171
eISSN - 1552-8618
pISSN - 0730-7268
DOI - 10.1002/etc.5620010307
Subject(s) - carbofuran , pharmacokinetics , carbamate , inhalation , chemistry , ingestion , inhalation exposure , zoology , toxicity , particle size , environmental chemistry , chromatography , pharmacology , biochemistry , pesticide , biology , organic chemistry , anatomy , ecology
[ 14 C‐]Carbonyl carbofuran toxicity, metabolism and pharmacokinetics in male Sprague‐Dawley rats were studied after 4.1 μm (50 min, 0.2 and 1.2 μg/L) and 1.5 μm (70 min, 0.2 μg/L) aerodynamic diameter monodisperse aerosol exposures. Regional carbofuran deposition for each particle size was similar to human and rodent models for insoluble aerosols. Total carbofuran deposition was greater than expected in the rodent model but similar to that in human models. 3‐Hydroxycarbofuran/carbofuran ratios in gastrointestinal tract and liver (1.3, 3 × greater after 4.1 μm) provided additional deposition indices. Rapid in vitro solubility t 1/2 (17 min) for 4.1 μm particles and minimal differences in plasma carbamate (% total 14 C/animal) after varied particle size exposure indicated primary clearance by dissolution, irrespective of deposition site. Carbofuran (1.2 μg/L, 4.1μm) inhibited red blood cell acetylcholinesterase (55% at 10 min postexposure with recovery by 2 h). Eight‐hour 14 C metabolic fate in 14 CO 2 (31–38%), urine (9–12%), feces (2–5.5%) and carcass (44–58%) were similar for each particle size. Carbamate pharmacokinetics measured for 2 h postexposure to 4.1 μm particles described monoexponential elimination. Plasma half‐lives for carbofuran (36 min) and 3‐hydroxycarbofuran (62 min) were similar to those previously determined after oral and i.v. exposures.