Age-dependent differences in the susceptibility of rats to deltamethrin.
Separate groups of weanling and adult rats were exposed to both behaviorally active and lethal doses of deltamethrin to examine age-dependent toxicity of a pyrethroid over a wide dose range. The acoustic startle response (ASR) was selected for comparison at low doses since it is a sensitive, quantifiable biological indicator of pyrethroid effects in rats. Acute mortality was included for comparison at the upper limit of the dose-response. Deltamethrin was administered by gavage as a single dose in corn oil for all tests. Effects on the ASR were comparable in 21- and 72-day-old rats, with a 4-mg/kg dose decreasing ASR amplitude by approximately 50% (ED50) at both ages. By comparison LD50 values in 11-, 21- and 72-day old male rats were 5.1, 11, and 81 mg/kg, respectively. Thus, 11- and 21-day-old male rats were 16 and 7 times, respectively, more sensitive than adults to acute lethality. The concentration of deltamethrin was measured in whole-brain tissue from weanling and adult males treated with ED50 and LD50 doses. The brain concentration of deltamethrin at the ED50 dose of 4 mg/kg was higher in weanling rats than adults. This suggests a possible functional difference, with weanling rats being less susceptible than adults to a low dose. By comparison, there was an equivalent concentration of deltamethrin in brain tissue following an LD50 dose of 12 mg/kg in weanling rats and 80 mg/kg in adults. These results support age-related differences in pharmacokinetics as the basis for the markedly greater sensitivity of young rats to a lethal dose of deltamethrin.
Sheets
L P
LP
Miles Inc., Agriculture Division, Toxicology, Stilwell, Kansas 66085.
Doherty
J D
JD
Law
M W
MW
Reiter
L W
LW
Crofton
K M
KM
D000161:Acoustic Stimulation; D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D005260:Female; D007928:Lethal Dose 50; D008297:Male; D009570:Nitriles; D011722:Pyrethrins / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D013216:Reflex, Startle / Q000187:drug effects
D009570:Nitriles; D011722:Pyrethrins; C017180:decamethrin