Arsenic acid

Endpoint summary

Additional information

Tam (1979) found that 58% of the ⁷⁴As (as arsenic acid) dose was excreted in the urine in the first 5 days after dosing. As a part of the absorbed dose is excreted, in most species, in the bile, it can be considered that, at the dose considered, the majority of the arsenic acid ingested orally will be absorbed. Pulmonary absorption of deposited arsenic in the lungs is also considered as almost complete (ATSDR, 2007). Dermal absorption was important in vitro on mice skin with liquid sodium arsenate (62%) with the major part remaining into the skin. In vitro percutaneous absorption of the low dose from water with human skin resulted in 24 hours receptor fluid accumulation of 0.93 ± 1.1% dose and skin concentration (after washing) of 0.98 ± 0.96%. Receptor fluid accumulation plus skin concentration gave an absorption value of 1.9%.

A comparative toxicokinetic study (Csanaky, 2002) in five animal species (Wistar rats, CFLP mice, English Shorthair guinea pigs, golden Syrian hamsters and New Zealand White rabbits) was performed to determine the excretion of sodium arsenate (AsV) and its metabolites. Anaesthetised bile duct-cannulated were injected with AsV at 50 µmol/kg bw intravenously. All species injected with AsV excreted arsenic mainly into urine. Bile contained almost exclusively trivalent arsenic (AsIII and/or MMAsIII), whereas AsV, AsIII and DMAsV appeared in urine. Except for guinea pigs, which do not methylate arsenic, the other species formed MMAsIII and excreted it into bile. Due to greater amount of hepatic AsIII methyltransferase, rats were efficient producers of MMAsIII, excreting more than 8% of the dose of AsIII or AsV in 2 hours as MMAsIII. Similar type of metabolites have been identified in human (Tam, 1979) in a study in which a group of six adult male humans were given a single oral dose of gelatin capsules containing radioactive arsenic. 58% of the ⁷⁴As dose was excreted in the urine in the first 5 days after dosing. Proportion of chemical species of arsenic in the urine was as follows: 51% dimethylarsinic acid, 21% monomethylarsenic compound and 27% inorganic arsenic. Under the test conditions, 51% dimethylarsinic acid and 21% monomethylarsenic compound (probably methylarsonic acid) were found to be the major metabolites of inorganic arsenic excreted in urine within 5 days of dosing. In fact in human proportion of the different methylated metabolites may depend upon the methylation pattern of each individual (quoted in Concha 2002); on the other hand the same author found out that arsenic methylation efficiency of an individual was remarkably stable over time. Several PBPK models have been set up (Gentry, 2004; Yu, 1999) in part in order to explain interspecies differences, especially for carcinogenic potential. Sodium arsenic has also been administered to pregnant CD-1 mice at 20 (i.p.) or 40 (p.o.) mg/kg bw on gestation Day 18. Fetal arsenic uptake and loss were more rapid following i.p. than p.o. and peak fetal As⁺⁵ was almost five fold higher following i.p. treatment. Arsenic metabolites (MMA and DMA) were found in the fetuses up to 83% of total fetal arsenicals by 24 hours.