A study of the teratogenic potential of caffeine ingested in drinking-water

Caffeine dissolved in drinking-water was available ad lib. to Osborne Mendel rats at dose levels of 0, 0.007, 0.018, 0.036, 0.07, 0.10, 0.15 or 0.20% during days 0–20 of gestation. The corresponding daily caffeine intakes were 0, 10.1, 27.4, 50.7, 86.6, 115.8, 160.9 and 204.5 mg/kg body weight. Dosages of 160.9 and 204.5 mg/kg were associated with decreased implantation efficiency, increased resorptions and decreased mean numbers of viable foetuses. Numbers of runts were significantly increased after dosages of 115.8–204.5 mg/kg/day. Foetal body weight and length were decreased and oedematous foetuses were increased at dosages of 86.6–204.5 mg/kg/day. Contrary to results seen after gavage studies, caffeine available ad lib. in drinking-water produced no dose-related gross anomalies. Only two animals with missing or hypoplastic nails were produced, both in the 160.9-mg/kg group. Sternebral ossification deficiencies were increased at all dose levels except 10.1 mg/kg/day. Skeletal ossification deficiencies were increased in a dose-related manner at the four highest dose levels. Caffeine given by water bottle produced ossification deficiencies similar to those seen after intubation, but at higher dosages.