A multidisciplinary approach to toxicological screening: III. Neurobehavioral toxicity.
The neurobehavioral effects of 10 known toxicants were examined as part of a multidisciplinary screening battery. The toxicants included carbaryl (CAR), triadimefon (TDM), heptachlor (HEP), chlordane (CDN), diethylhexyl phthalate (DEHP), carbon tetrachloride (CCl4), phenol, trichloroethylene (TCE), tetrachloroethylene (PER or perchlorethylene), and dichloromethane (DCM or methylene chloride). A functional observational battery and motor activity measurements were conducted before exposure, at specified times after an acute exposure, and during and after 14-d exposure. Severity scoring analysis was used to generate profiles of effect. The pesticides, CAR, TDM, HEP, and CDN, displayed the most acute neurotoxicity and were active at lower proportions of their respective acute LD50 values than were the solvents or the industrial chemicals. Although CAR and TDM showed little or no neurobehavioral effects with repeated dosing, cumulative neurotoxicity and lethality were evident with HEP and CDN. Phenol produced acute convulsive effects, and the most prominent finding with repeated exposure was lethality. DEHP displayed no neurobehavioral toxicity. The organic solvents, TCE, PER, CCl4, and DCM, produced various degrees of general nervous system depression following acute administration of high dose levels. Repeated dosing produced little or no effect with TCE or PER, marked physiological changes with CCl4, and cumulative toxicity and lethality with DCM. Some results of these studies were unexpected and should provide impetus for further research. Overall, these findings illustrate the utility of these screening methods.
Moser
V C
VC
Neurotoxicology Division (MD-74B), Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Cheek
B M
BM
MacPhail
R C
RC
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004051:Diethylhexyl Phthalate / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007928:Lethal Dose 50; D009043:Motor Activity / Q000187:drug effects*; D009498:Neurotoxins / Q000008:administration & dosage / Q000633:toxicity; D010575:Pesticides / Q000633:toxicity*; D019800:Phenol; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012997:Solvents / Q000008:administration & dosage / Q000633:toxicity*
D009498:Neurotoxins; D010575:Pesticides; D010636:Phenols; D012997:Solvents; D019800:Phenol; D004051:Diethylhexyl Phthalate