Strain-dependent disposition of inorganic arsenic in the mouse.
Recent studies have suggested that polymorphisms in the methylation of inorganic arsenic (iAs) exist in animals and humans. Methylation of iAs is an important step in the elimination of arsenic. The objective of this study was to examine whether there are differences in iAs disposition, and hence methylation, between three strains of mice. Ninety-day-old female mice (strains: C3H/HeNCrlBR, C57BL/6NCrlBR, and B6C3F1/CrlBR) were administered [73As]arsenate or [73As]arsenite orally at dose levels of 0.5 or 5.0 mg As/kg. Another group of mice were administered [73As]arsenate (5.0 mg As/kg) intraperitoneally (i.p.). Disposition of [73As] was assessed by whole-body counting, and analysis of urine, feces and tissues for radioactivity. Urine was analyzed by chromatography for arsenic metabolites. Several strain- and dose-related effects in the disposition of [73As] were observed with both arsenicals. After oral administration, the clearance of [73As]arsenate, measured by whole-body counting, was dependent on the strain. However, because there was no strain dependence on clearance of [73As]arsenate administered i.p., the effect after oral administration may be due to a difference in absorption of arsenate between the strains. With increased oral dose of arsenate and arsenite, the clearance of [73As] was slower and there was higher tissue retention of [73As]. The percentage of metabolites excreted in urine also was affected by the administered dose. With increased dose, the percentage of arsenite and monomethylarsonic acid were significantly increased, and dimethylarsinic acid decreased. However, our results suggest there is no overall difference between these strains of mice with respect to disposition of iAs. A better understanding of the role of phenotype in the disposition and toxicity of iAs would reduce the uncertainty in arsenic risk assessment.
Hughes
M F
MF
Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA. hughes.michaelf@epamail.epa.gov
Kenyon
E M
EM
Edwards
B C
BC
Mitchell
C T
CT
Thomas
D J
DJ
D000818:Animals; D001149:Arsenates / Q000493:pharmacokinetics; D001151:Arsenic / Q000493:pharmacokinetics* / Q000652:urine; D018053:Arsenites / Q000493:pharmacokinetics; D001711:Biotransformation; D005260:Female; D007274:Injections, Intraperitoneal; D008745:Methylation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011042:Poisons / Q000493:pharmacokinetics* / Q000652:urine; D013045:Species Specificity; D014018:Tissue Distribution
D001149:Arsenates; D018053:Arsenites; D011042:Poisons; C015001:arsenite; D001151:Arsenic; C025657:arsenic acid