Hydronephrosis in rats associated with postnatal exposure to a fatty acid oxidation inhibitor.
Methyl palmoxirate, an inhibitor of long-chain fatty acid oxidation, was administered by gavage (0, 1, 5, or 20 mg/kg/day) to female rats over the last third of gestation and throughout lactation. Weight gain (mid- and high-dosage group) and survivability (high-dosage group) were significantly (p less than or equal to 0.05) reduced in offspring of methyl palmoxirate-treated dams as compared to control offspring. Mid- and high-dosage male offspring found dead after Day 4 of lactation exhibited grossly distended bladders and renal pelves. A dosage-related increased incidence of dilated renal pelves was observed in both sexes at necropsy of 21-day-old mid- and high-dosage group pups. Microscopic examination of the urinary tracts of a number of affected pups revealed renal parenchymal atrophy and urethral obstruction. Drug disposition studies indicated lactating pups were exposed to significant amounts of methyl palmoxirate via mammary secretions. Cross-fostering experimentation suggested that some of the adverse effects observed in offspring were due to lactational, rather than in utero, exposure.
Kenel
M F
MF
Department of Toxicology, McNeil Pharmaceutical, Spring House, Pennsylvania 19477.
Krayer
J H
JH
Ng
K T
KT
Kircher
C H
CH
D000818:Animals; D001806:Blood Urea Nitrogen; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000633:toxicity*; D004988:Ethers, Cyclic / Q000633:toxicity*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006869:Hydronephrosis / Q000139:chemically induced*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007774:Lactation; D008892:Milk / Q000378:metabolism; D010084:Oxidation-Reduction; D011247:Pregnancy; D011422:Propionates / Q000633:toxicity*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014521:Urethra / Q000187:drug effects
D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D005227:Fatty Acids; D011422:Propionates; D011506:Proteins; C017522:methyl 2-tetradecylglycidate