An attempt to explain interindividual variability in 24-h urinary excretion of inorganic arsenic metabolites by C57 BL/6J mice.
Forty C57 BL/6J mice, injected subcutaneously with 0.5 mg/kg arsenic as sodium arsenite, were examined for 24-h urinary excretion of total arsenic metabolites, creatinine and S-adenosylmethionine (SAM) and for 24-h faecal excretion of arsenic and levels of arsenic in the blood, liver, kidneys, lung, skin, spleen and bone at 24-h post-dose. Total urinary arsenic metabolites were calculated by summing up the inorganic (Asi), monomethylated (MMA) and dimethylated (DMA) derivatives directly measured by selective arsine generation-atomic absorption spectrometry (AG-AAS) or were measured by AG-AAS following complete mineralization. Both sets of results showed interindividual differences varying by as much as 7-fold and correlated with the 24-h urinary excretion of both SAM (r = 0.84 and r = 0.86, respectively) and creatinine (r = 0.82 and r = 0.87, respectively). There was interindividual variability of about a 30-fold range in 24-h faecal excretion of arsenic which correlated inversely with 24-h urinary excretion of arsenic metabolites (r = -0.69) and 24-h urinary excretion of both creatinine (r = -0.70) and SAM (r = -0.67). Body tissue levels of arsenic were low and not related to 24-h urinary excretion of arsenic metabolites, SAM and creatinine. Taken together, the results indicate that differences in the profile of urinary arsenic excretion and in the retention of arsenic in a particular organ do not contribute to interindividual variability in 24-h urinary excretion of arsenic metabolites by C57 BL/6J mice, but that variability in faecal excretion does, at least in part. It is speculated that there is most likely a predominant contribution from a diffuse tissue retention of arsenic or from a third route of arsenic elimination, i.e. respiratory, to this phenomenon in view of the small faecal contribution.
Laboratory of Chemical Toxicology of the Environment, Faculty of Pharmacy, Chatenay-Malabry, France.
P
P
Telolahy
G
G
Morel
J L
JL
Cluet
H M
HM
Yang
N
N
Thieffry
J
J
de Ceaurriz
D000818:Animals; D001151:Arsenic / Q000097:blood / Q000378:metabolism / Q000652:urine*; D018053:Arsenites / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D003404:Creatinine / Q000652:urine; D005243:Feces / Q000737:chemistry; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D012015:Reference Standards; D015203:Reproducibility of Results; D012436:S-Adenosylmethionine / Q000652:urine; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D017670:Sodium Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D013054:Spectrophotometry, Atomic; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013439:Sulfhydryl Reagents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity
D018053:Arsenites; D017670:Sodium Compounds; D013439:Sulfhydryl Reagents; C017947:sodium arsenite; D012436:S-Adenosylmethionine; D003404:Creatinine; D001151:Arsenic