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1061026 
Journal Article 
Abstract 
Effects of bismuth citrate on pregnant rats and rabbits 
Secker, R 
1993 
1 
Teratology
ISSN: 0040-3709
EISSN: 1096-9926 
48 
2 
33A 
English 
BCI:BCI199345105823 
Preparations containing bismuth are used orally for the treatment of a variety of indications including gastric and duodenal ulcers. The bismuth is absorbed to a small and variable extent and accumulates in tissues including the brain. Passage of bismuth into amniotic fluid and the foetus has been reported but information on effects upon foetal development appears limited. In order to establish levels of bismuth which could be tolerated during pregnancy, preliminary studies were performed in pregnant AHA rats and Dutch rabbits. Bismuth citrate was formulated as solutions in aqueous ammonium hydroxide. Dosages of 50, 100 or 200 mg/kg were administered once daily by oral gavage to rabbits from Days 8-20 of pregnancy inclusive (day of mating is Day 1 of pregnancy). Plasma bismuth levels were determined on Days 8 and 20 of pregnancy. On Day 30 the rabbits were subjected to autopsy and foetuses examined for external, visceral and skeletal abnormalities. In contrast, considerably higher dosages of 300, 600, 1200 mg/kg were administered to pregnant rats from Days 7-16 of pregnancy inclusive. Plasma bismuth levels were again determined at the beginning and end of the treatment period. Foetal examination was performed on half the females on Day 21. The remaining half were allowed to litter and post-natal development of the offspring assessed. Results obtained indicated that plasma bismuth levels in the rabbit of up to 420 ng/g were not linearly related to dose and that there was evidence of accumulation. Maximum levels in the rat (495 ng/g) were similar to those of the rabbit while there was more evidence of a linear relationship to dose but with no obvious accumulation. Maternal toxicity, manifest as a marked reduction in body weight, was only apparent in the rabbit. Following a second study in the rat comparing the effects of bismuth citrate and sodium citrate (as trisodium salt dihydrate), it was concluded that no adverse effects upon pre- or post-implantation loss, numbers of viable foetuses or foetal development were apparent in either species. Rat post-natal development was also unaffected. 
Pregnancy; Rabbits; Rats; Animal; Female; Dose-Response Relationship, Drug; Embryo and Fetal Development/DRUG EFFECTS; Organometallic Compounds/TOXICITY; Antacids/TOXICITY; Anti-Ulcer Agents/TOXICITY; 57644-54-9; NO CAS RN; 813-93-4; 6132-04-3