Sensitivity of species to chemicals: dose-response characteristics for various test types (LC(50), LR(50) and LD(50)) and modes of action.
While variable sensitivity of model species to common toxicants has been addressed in previous studies, a systematic analysis of inter-species variability for different test types, modes of action and species is as of yet lacking. Hence, the aim of the present study was to identify similarities and differences in contaminant levels affecting cold-blooded and warm-blooded species administered via different routes. To that end, data on lethal water concentrations LC50, tissue residues LR50 and oral doses LD50 were collected from databases, each representing the largest of its kind. LC50 data were multiplied by a bioconcentration factor (BCF) to convert them to internal concentrations that allow for comparison among species. For each endpoint data set, we calculated the mean and standard deviation of species' lethal level per compound. Next, the means and standard deviations were averaged by mode of action. Both the means and standard deviations calculated depended on the number of species tested, which is at odds with quality standard setting procedures. Means calculated from (BCF) LC50, LR50 and LD50 were largely similar, suggesting that different administration routes roughly yield similar internal levels. Levels for compounds interfering biochemically with elementary life processes were about one order of magnitude below that of narcotics disturbing membranes, and neurotoxic pesticides and dioxins induced death in even lower amounts. Standard deviations for LD50 data were similar across modes of action, while variability of LC50 values was lower for narcotics than for substances with a specific mode of action. The study indicates several directions to go for efficient use of available data in risk assessment and reduction of species testing.
Radboud University Nijmegen, Institute for Water and Wetland Research, Department of Environmental Science, 6500 GL Nijmegen, The Netherlands. Electronic address: A.J.Hendriks@science.ru.nl.
A Jan
AJ
Hendriks
Jill A
JA
Awkerman
Dick
D
de Zwart
Mark A J
MA
Huijbregts
D004305:Dose-Response Relationship, Drug; D015386:Hazardous Substances / Q000633:toxicity*; D007928:Lethal Dose 50; D008962:Models, Theoretical; D018570:Risk Assessment; D013045:Species Specificity; D018675:Toxicity Tests
D015386:Hazardous Substances
LC(50); LD(50); Narcosis; Species sensitivity distribution