Cataractogenesis in rats induced by in utero exposure to RG 12915, a 5-HT3 antagonist.

Abstract

RG 12915, a selective 5-HT3 antagonist developed for the treatment of emesis and nausea associated with cancer chemotherapy, was administered by gavage to four groups of pregnant rats from Gestation Day 6 to 17 at doses of 0, 1, 10, and 100 mg/kg/day, as part of a Segment II (developmental toxicity) study. The 100 mg/kg/day dose was maternally toxic as indicated by decreased body weight gain and food consumption during the treatment period. A portion of the rats were allowed to deliver and rear their litters and three pups from two litters in the 100 mg/kg/day group were observed to have lens opacities (visible to the naked eye) at weaning. At a later examination, when the offspring were approximately 4 months old, four additional animals from the same two litters had cataracts. A slight growth retardation was also observed postweaning in the offspring of the 100 mg/kg/day group. To confirm the lens findings and more precisely define the no-effect dose, another study was conducted in which pregnant rats were administered daily RG 12915 doses of 0, 10, 30, 60, or 100 mg/kg/day from Gestation Day 6 to 17. There was a dose-related decrement in maternal body weight gain during the treatment period in the 30, 60, and 100 mg/kg/day groups (12, 28, and 47%, respectively) compared to the control group. A treatment-related incidence of nuclear cataract was observed in the offspring of the 60 and 100 mg/kg/day groups (litter incidence 6 and 45%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: S A Lerman, J L Delongeas, J P Plard, R W Veneziale, R L Clark, L Rubin, J E Sanders
• Journal: Fundamental and applied toxicology : official journal of the Society of Toxicology (Fundam Appl Toxicol) Vol. 27 Issue 2 Pg. 270-6 (Sep 1995) ISSN: 0272-0590 [Print] United States
• PMID: 8529823 (Publication Type: Journal Article)

Chemical References

• Benzofurans
• Bridged Bicyclo Compounds, Heterocyclic
• Serotonin Antagonists
• RG 12915

Topics

• Animals
• Benzofurans (toxicity)
• Body Weight (drug effects)
• Bridged Bicyclo Compounds, Heterocyclic (toxicity)
• Cataract (chemically induced, pathology)
• Female
• Lens, Crystalline (pathology)
• Male
• Pregnancy
• Prenatal Exposure Delayed Effects
• Rats
• Serotonin Antagonists (toxicity)