Toxicity Screening of Single Dose of Inorganic and Organic Arsenics on Hematological and Serum Biochemical Parameters in Male Cynomolgus Monkeys.

Kyung-Su Park,Eui-Sik Han,Jung-Duck Park,Young-Na Yum,Choong-Yong Kim,Jin-Young Lee,Kang-Hyun Han,Seong-Jin Choi,Ruth Im,Jeong-Doo Heo

doi:10.5487/tr.2008.24.3.219

Abstract

A screening study of the acute toxicity of organic arsenics such as arsenobetaine and arsenocholine, a product of arsenic methylation metabolite, and inorganic arsenic was carried out to examine hematological and serum biochemical parameters in cynomolgus monkeys (Macaca fascicularis). We found soft and liquid feces, and vomiting in all treated groups with inorganic and organic arsenics. The monkeys in inorganic arsenic-treated group showed a significant increase in vomiting frequency compared with those in three organic arsenics-treated groups. These results suggest that inorganic arsenic might be more toxic than three other organic arsenics tested. The monkeys in inorganic arsenic-treated group showed a decrease in platelet and an increase in monocyte on day 4 and the monkeys in arsenocholine-treated group showed an increase in reticulocyte percentage on day 8. The monkeys in inorganic-treated group also showed decreases in AST and ALT values and the monkeys in arsenobetaine-treated group showed a decrease in AST value and an increase in T-CHO value. However, these hematological and biochemical changes were within the physiological ranges, showing that the single dose of inorganic and organic arsenics did not affect at least hematological and serum biochemical parameters. The present study of toxicity with single dose of arsenics provides valuable indicators for longer term study of toxicity of repeated doses of arsenics in primates.

Highlights

Arsenic (As) is an ubiqitous element found in food and water, and is a potent toxicant that may exist in several oxidation states
We investigated the toxicity of organic arsenics, and one of the final products of arsenic methylation (DMA), and inorganic arsenic using hematological and serum biochemical parameters and these parameters will be indicator for the study of toxicity of the repeated dose of arsenicals in cynomolgus monkeys
On day 4, the monkeys in inorganic arsenictreated group showed a decrease in platelet in high dose group, and an increase in monocyte percentage compared with those of control group

Summary

Introduction

Arsenic (As) is an ubiqitous element found in food and water, and is a potent toxicant that may exist in several oxidation states. A certain food, such as marine fish, contains substantial levels of arsenic forms (e.g., arsenobetaine and arsenocholine), the toxicity is relatively low compared to the toxicity in inorganic aresenics (Mandai and Suzuki, 2002; Vahter, 2000). Arsenocholine is detected at low levels, about 0.3% total arsenics, from shrimp and conch, and it is thought to be a candidate of arsenobetaine precursor in Trivalent arsenic, an arsenite form, has a high affinity for protein sulfhydryl groups, but it seems to be selective in reacting with closely spaced dithiols which are common in DNA-binding proteins, transcription factors, and DNA-repair enzymes.

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