Comparative toxicology

Barbara Moimho, PhD, DABT, Principal Scientist, Toxicology, Comparative Biology and Safety Sciences, Amgen, Inc., One Amgen Center Drive, Mail Stop MS-29-2-A, Thousand Oaks, CA 91320, E-mail bmounho amgen. 

The Enzymic-Immunologic Method in Clinical and Forensic Toxicology. Comparative Analysis in Diphenyl-hydantoin Assays Carried Out with EMIT [Enzyme-Multiplied Immunoassay Technique] and Gas Chromatography... 

Table 16. Toxicological Properties of Cyclic Ketones Compared with Aliphatic Ketones ...

Compare the strengths and weaknesses of health effects information obtained from epidemiological, clinical, and toxicological studies. 

If tlie pollutant causes iui acute non carcinogenic risk, tlie inaximuin one hour concentration is used for C, and tlie acute reference exposure limit is used for tlie REL. Likewise, if tlie pollutant causes a clironic non carcinogenic risk, tlie one year average concentration is used, as is tlie clironic reference exposure limit. In tliis procedure, a Iiazard index is calculated for each pollutant separately, and tlien tlie indices are summed for each toxicological endpoint (i.e., tlie respiratory system, tlie central nervous system, etc.). Finally, tlie total hazard index is tlien compared to a value wliich is considered significant. 

The pharmacological activities of the isomers should be compared in vitro and in vivo in both animals and humans. Separate toxicological evaluation of the enantiomers would not usually be required when the profile of the racemate was relatively benign but unexpected effects - especially if unusual or near-effective doses in animals or near planned human exposure - would warrant further studies with the individual isomers. 

Toxicology Many companies are known to use gene expression profiling to assess the potential toxicity of lead compounds. This approach may require a database of reference compounds with known pharmacological and toxicological properties. Lead compounds can be compared to the database to predict compound-related or mechanism-related toxicity [5]. 

Ema M, Kurosaka R, Amano H, Ogawa Y (1995) Comparative developmental toxicity of butyltin trichloride, dibutyitin dichloride and tributyitin chloride in rats. Journal of Applied Toxicology, 15(4) 297-302. 

Penninks AH, Seinen W (1982) Comparative toxicity of alkyltin and estertin stabilizers. Food and Chemical Toxicology, 20 909-916. 

Seinen W, Vos JG, van Spanje I, Snoek M, Brands R, Hooykaas H (1977a) Toxicity of organotin compounds. II. Comparative in vivo and in vitro studies with various organotin and organolead compounds in different animal species with special emphasis on lymphocyte cytotoxicity. Toxicology and Applied Pharmacology, 42(1) 197-212. 

Jobling, S., Casey, D., and Rodgers-Gray, T. et al. (2003). Comparative responses of molluscs and fish to environmental estrogens and an estrogenic effluent. Aquatic Toxicology. 65, 205-220. 

Mizutani, T., Hidaka, K., Ohe, T., and Matsumoto, M. (1977). A comparative study on accumulation and elimination of tetrachlorobiphenyl isomers in mice. Bulletin of Environmental Contamination and Toxicology 18, 452-461. 

Sandahl, J.F, Baldwin, D.H., and Jenkins, J.J. et al. (2005). Comparative thresholds for acetylcholinesterase inhibition and behavioural impairment in Coho Salmon exposed to chlorpyriphos. Environmental Toxicology and Chemistry 24, 136-145. 

Walker, C.H. (1994a). Comparative toxicology. In E. Hodgson and P. Levi (Eds.) Introduction to Biochemical Toxicology, Norwalk, CT Appleton and Lange, 193-218. 

Watanuki, H., Yamaguchi, T., and Sakai, M. (2002). Suppression in function of phagocytic cells in common carp Cyprinus carpio L. injected with estradiol, progesterone or 11-ketotestosterone. Comparative Biochemistry and Physiology C—Toxicology and Pharmacology 132, 407 13. 

A 52-week study in monkeys was designed to evaluate ocular effects. Despite the absence of adverse toxicological effects at the highest dose tested (20 mg/kg body weight per day), the study was considered inappropriate for the establishment of an ADI in view of the much higher doses used in several other studies and found to be without effects. The available comparative toxicokinetic data for humans and rats indicated that studies of toxicity in rats could be used to derive an ADI. 

Mogilnicka, E.M. and Webb, M. (1981) Comparative studies on the distribution of gold, copper and zinc in the livers and kidneys of rats and hamsters after treatment with sodium gold-195-labeled-aurofhiomalate. Journal of Applied Toxicology, 1, 287—291. 

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