The conduct of a two-generation reproductive toxicity study via dermal exposure in the Sprague-Dawley rat--a case study with KBR 3023 (a prospective insect repellent).
KBR 3023, 1-(1-methyl-propoxycarbonyl)-2-(2-hydroxyethyl)-piperidine, a prospective insect repellent being developed by the Bayer Corporation, was evaluated for reproductive toxicity in the Sprague-Dawley rat. As the intended human use of the test compound is topical, the test system was also exposed to the compound via the dermal route. Specifically, the adult rats (P generation) were fitted with Elizabethan collars, to reduce the likelihood of oral ingestion, and dermally administered either 0, 50, 100, or 200 mg KBR 3023/kg body weight throughout the study (5 d/week) beginning at the onset of the 10-week premating period and continuing through the mating, gestation, and lactation phases. Clinical signs and changes in body weight and food consumption were assessed throughout the study. All adults and neonates underwent a gross necropsy examination. Tissues retained for microscopic examination from all adult animals included the kidney, liver, pituitary, reproductive organs, and samples of skin from the shaved dose site. In addition to the parameters noted above, the animals were evaluated for the effect of the test compound on estrous cycling, mating, fertility, gestation length, litter size, pup sex ratio, and pup viability. There were no test compound-related clinical signs or effects on body weight or food consumption observed in either the adults or the pups during any phase of the study. There were no compound-related effects on any reproductive or litter parameters. Dermal findings at the dose site (acanthosis and hyperkeratosis) were noted in both generations. Other than the dermal findings, no compound-related necropsy findings were seen in either the adults or the pups. No compound-related histopathologic findings were noted in the reproductive tissues of either the males or females. Based on these results, KBR 3023, administered as described in this study at dose levels as high as 200 mg/kg body weight (the physical limit of dermal application for this compound), did not demonstrate any reproductive toxicity.
Astroff
A B
AB
Bayer Corporation, Toxicology Department, Stilwell, Kansas 66085, USA.
Freshwater
K J
KJ
Young
A D
AD
Stuart
B P
BP
Sangha
G K
GK
Thyssen
J H
JH
D000287:Administration, Topical; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004971:Estrus / Q000187:drug effects; D005260:Female; D007302:Insect Repellents / Q000008:administration & dosage / Q000633:toxicity*; D008098:Litter Size / Q000187:drug effects; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*
D007302:Insect Repellents; D010880:Piperidines; C483506:picaridin