Effects of cefonicid and other cephalosporin antibiotics on male sexual development in rats.
The purpose of this study was to determine whether cefonicid, a cephalosporin antibiotic with a modified N-methylthiotetrazole (MTT) side chain, caused testicular toxicity when subcutaneously administered to Sprague-Dawley male rats from days 6 to 36 postpartum at doses of 50 to 1,000 mg/kg per day. Moxalactam (a cephamycin antibiotic which will be referred to as a cephalosporin for convenience throughout), which contains the MTT side chain, was used as a positive control and was administered at 100 to 1,000 mg/kg per day, and cephalothin, which lacks an MTT side chain, was used as the negative control at 1,000 mg/kg per day. Moxalactam caused a significant reduction in testicular and seminal vesicle weights in 37-day-old animals, and histological examination revealed bilateral multifocal atrophy of the seminiferous tubules at all dose levels. Animals reared to reproductive maturity had significant deficits in fertility, and histological examination revealed multifocal or diffuse atrophy of the seminiferous tubules at all doses with a severity greater than that observed in the 37-day-old animals. The histological findings were confirmed by marked reductions in testicular sperm production rates and cauda epididymal sperm numbers. Cephalothin and cefonicid had no treatment-related adverse effects on the sexual maturation of prepubertal, juvenile, or adult males. The absence (in cephalothin) or modification (in cefonicid) of the MTT side chain was not associated with adverse reproductive effects. The relevance of these findings to humans in prenatal and prepubertal stages of life cannot be determined at this time.
Manson
J M
JM
Reproductive and Developmental Toxicology Department, Smith Kline and French Laboratories, Philadelphia, Pennsylvania 19101.
Zolna
L E
LE
Kang
Y J
YJ
Johnson
C M
CM
D000367:Age Factors; D000818:Animals; D002435:Cefamandole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D015790:Cefonicid; D002512:Cephalothin / Q000633:toxicity*; D055598:Chemical Phenomena; D002621:Chemistry; D003307:Copulation / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects; D007279:Injections, Subcutaneous; D008297:Male; D009070:Moxalactam / Q000633:toxicity*; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D012671:Seminiferous Tubules / Q000187:drug effects; D012741:Sexual Maturation / Q000187:drug effects*; D013076:Sperm Count / Q000187:drug effects; D013737:Testis / Q000187:drug effects*
D002435:Cefamandole; D015790:Cefonicid; D002512:Cephalothin; D009070:Moxalactam