A study of the teratogenic potential of caffeine given by oral intubation to rats

A study was made to resolve questions about the fetotoxic and teratogenic potential of the alkaloid caffeine, 1,3,7-trimethylxanthine. Caffeine in aqueous solution was orally intubated to Osborne-Mendel rats as dose levels of 6, 12, 40, 80, or 125 mg/kg during Days 0–19 of gestation; 61 rats were randomly assigned to each dose level. Concurrent control rats were intubated with distilled water on the same days. Six females died at the highest caffeine dose level. The experimental animals gained less weight during gestation than did the controls. Food consumption decreased primarily during the first week of gestation. Two litters were totally resorbed at 80 mg/kg and four litters at 125 mg/kg. Resorptions increased at the dose levels 80 and 125 mg/kg. These were significant decreases in fetal weight and crown-rump lengths in both males and females at 80 and 125 mg/kg, and in female weight and crownrump length at 40 mg/kg. Ectrodactyly was seen only at the dose levels 80 and 125 mg/kg, along with assorted skeletal ossification problems such as misshapen centra, missing centra, reduced dorsal arch, reduced pubis, missing hind phalanges, reduced metacarpals, and reduced metatarsals. In addition, delayed ossification of the sternebrae was seen at all dose levels. No soft tissue variations appeared related to caffeine intake.