A multidisciplinary approach to toxicological screening: IV. Comparison of results.
Toxicity data collected under standardized test conditions may be of the utmost importance in health risk assessment, in which human exposure limits are often derived from laboratory experiments. A standardized approach to data collection is also important for evaluating the sensitivity and specificity of test methods used to determine toxic potential. Several experiments were undertaken to determine the effects of chemical exposures using a multidisciplinary screening battery, which included tests for systemic, neurological and developmental toxicity. The effects of 1- and 14-d exposures to 10 chemicals on systemic and neurological indices of toxicity were determined in female F344 rats using standardized test batteries. Parallel experiments determined chemical effects on prenatal and postnatal development following exposure of the dams for 14 d. The chemicals included four pesticides (carbaryl, triadimefon, chlordane, and heptachlor), four solvents (trichloroethylene, tetrachloroethylene, carbon tetrachloride, and dichloromethane), and two industrial compounds (phenol and diethylhexyl phthalate). The results showed that the chemicals produced markedly different qualitative patterns of effect on systemic, neurological, and developmental indices of toxicity. Differences in the pattern of systemic and neurological effects were also obtained that depended on dosing duration. Quantitative analyses indicated that the highest ineffective dose as well as the lowest effective dose could vary by as much as two orders of magnitude across the different indices of toxicity. These results clearly show that a test battery focused on a single endpoint of toxicity cannot be used to accurately predict either qualitatively or quantitatively a chemical's systemic, neurological, and developmental toxicity profile.
MacPhail
R C
RC
Neurotoxicology Division (MD-74B), Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Berman
E
E
Elder
J A
JA
Kavlock
R J
RJ
Moser
V C
VC
Narotsky
M G
MG
Schlicht
M
M
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D007928:Lethal Dose 50; D009498:Neurotoxins / Q000633:toxicity; D010575:Pesticides / Q000633:toxicity*; D019800:Phenol; D010636:Phenols / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012997:Solvents / Q000633:toxicity*
D009498:Neurotoxins; D010575:Pesticides; D010636:Phenols; D012997:Solvents; D019800:Phenol; D004051:Diethylhexyl Phthalate