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INTERSPECIES COMPARISONS OF A/D RATIOS: A/D RATIOS ARE NOT CONSTANT ACROSS SPECIES
Citation:
Daston, G., J. Rogers, D. Versteeg, T. Sabourin, D. Baines, AND S. Marsh. INTERSPECIES COMPARISONS OF A/D RATIOS: A/D RATIOS ARE NOT CONSTANT ACROSS SPECIES. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-92/024 (NTIS PB92143965), 1991.
Description:
The hypothesis that the ratio of the adult (A) and developmental (D) toxicity of a chemical is constant across animal species has been proposed as the basis for identifying developmental hazards, both from traditional developmental toxicity screens using laboratory mammals and from alternative systems such as the coelenterate attenuata. he purpose of this study was to determine whether A/D ratios are constant across species. he developmental and adult toxicity of fourteen chemicals was assessed in four phylogenetically different species. he chemicals tested were aminopterin, bromodeoxyuridine, cadmium chloride, caffeine, congo red, dinocap, dinoseb, diphenylhydantoin, epinephrine, ethylenethiurea, 2-methoxyethanol, mirex, all-trans retinoic acid and trypan blue. pecies used were to the CD-1 mouse, South African clawed frog, fathead minnow, and fruit fly. regnant mice were exposed to chemicals, either poor by sc injection, on a daily basis from gestation day 6-15, adult toxicity was evaluated during and after treatment, and developmental toxicity was evaluated in fetuses at term. he other species were exposed to test agents for a developmentally comparable period. dults of each species were exposed to test agents for 4, 7 and 6 days, respectively. he route of exposure was via the water column in the two aquatic species and via the diet in Drosophila. tatistical lowest observed effect level (NOEL) and no observed effect level (NOEL) values were generated for adult and developmental toxicity in each species. /D ratios were calculated using both LOEL and NOEL values. he results indicate little concordance of AID among species: ) A/D ratios calculated from LOEL data are within the same order of magnitude for all four species for only four chemicals: dinocap, diphenylhydantoin, epinephrine and mirex; 2) based on NOEL data, again only four have AID ratios for all species in the same order of magnitude, dinocap, diphenylhydantoin, epinephrine and ethylenethiourea. t has been suggested that an AID ratio of 3 or greater is indicative of a developmental hazard. sing this criterion, there was consistent agreement among species only for dinocap (NOEL only), diphenylhydantoin and all-trans retinoic acid. Several statistical analyses for concordance were applied to the data. n no case was A/D found to correlate between species. hese data indicate that A/D ratios are not constant across these representative species, and there is no basis for using A/D for hazard assessment.
