National Toxicology Program

National Toxicology Program

Abstract for RACB81078 - Caffeine (CASRN 58-08-2)

The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program (NTP). The findings may or may not have been peer reviewed and were not evaluated in accordance with the Explanation of Levels of Evidence for Reproductive Toxicity criteria (see or with the Explanation of Levels of Evidence for Developmental Toxicity criteria (see established by the NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the US Government.

Caffeine (CAS #58-08-2): Reproduction and Fertility Assessment in CD-1 Mice When Administered in the Drinking Water

two dimensional chemical structure

NTP Report # RACB81078


Caffeine, a natural alkaloid drug found in tea, coffee, cocoa, and cola, and a common soft drink additive, was tested for its effects on reproduction and fertility in Swiss CD-1 mice. Caffeine was tested simultaneously at two laboratories, each using a variation on the standard RACB study design. This study used Tasks 1, 2, and 4, while the other study in mice utilized Tasks 1, 2, and 3. Caffeine was among the very first compounds run at these labs using this protocol. Data on body weights, clinical signs, and food and water consumptions were collected during the dose-range-finding phase (Task 1), and used to set exposure concentrations for Task 2 at 0.0, 0.012, 0.025, and 0.05% in drinking water. Water was chosen to mimic the route of human exposure. Water consumption was not affected by addition of caffeine. These levels of caffeine, and measured water consumption and body weights, produced calculated consumption estimates nearly equal to 22, 44, and 88 mg/kg/d.

For the F0 animals, there were no effects on body weight. Alopecia occurred in 55% of the medium dose and 50% of the high dose animals. While there were no exposure-related changes in the number of litters/pair, viability, or adjusted pup weight, the number of live pups per litter, averaged over the 4-5 litters, dropped 15% at the medium dose and 20% for the high dose animals.

No crossover mating trial was conducted, and the offspring from the last litter of control and high dose mice were reared by their dams until weaning, when they were given the same treatment as their parents until mating at 74 ± 10 days of age.

At the second generation mating trial, there were no changes in any reproductive endpoint.

At necropsy, at 0.05% caffeine, male body weight was reduced by 8% while male adjusted liver weight increased by 8%. No change was found in female body or organ weights, or in any sperm endpoint.

In summary, a reduction in the number of live pups/litter for the F0 generation was the only reproductive effect observed in this study. This occurred in the absence of a change in body weights in the F0 parental mice.

Report Date: August 29, 1984

NTIS #PB85101202/AS

Return to Organ Systems Toxicity Abstracts

NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.