Abstract for TER84001

Developmental Toxicity Evaluation of Sulfamethazine in Feed to Fischer 344 Rats

CASRN: 57-68-1
Chemical Formula: C12H14N4O2S
Molecular Weight: 278.3346
Report Date: September 1987


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

This study is a component of the NCTR lifespan and multigeneration studies on sulfamethazine. The conceptuses were from the second litter of the third generation of Fischer 344 rats (F3b) exposed continuously to 0, 600, 1200, or 2400 ppm of sulfamethazine in their feed. Each female was bred to a male that was not the same mate from the first breeding, but was from the same dose group. Sibling matings were avoided.

Dams were weighed on gestational days 0, 7, 14, and 20 (prior to sacrifice) and were observed daily for early delivery, morbidity, or mortality. Mortality did not occur in any group. One animal in the control and two animals in the 1200 ppm group delivered prematurely.

The animals were sacrificed on gestational day 20 and gravid uteri were weighed and examined for number and status of implants (alive, early/late resorbed, or dead). Individual fetal body weights and any fetal malformations (external, internal and skeletal) were recorded.

Examination of gravid uteri at sacrifice revealed no significant differences among treatment groups in the incidence of resorptions, dead or malformed fetuses or in average body weight of live fetuses per litter. Fetal skeletal variations per litter were significantly altered among the experimental groups. No biological significance was attributed to that finding. The total number of implantations/litter and the total number of alive fetuses/litter were significantly reduced across experimental groups in a positive dose-related trend (p < 0.05). The trend may have resulted from an effect on fertility, a preimplantation loss, or a random effect. If corpora lutea had been counted, the existence of a preimplantation loss could have been determined. Since the prevalence between dose groups for post implantation loss was not significantly altered, the trend toward decreased implantations with increased dose was not considered biologically significant in this study.

Exposure of Fischer 344 rats to sulfamethazine prior to and during gestation did not produce developmental toxicity (embryo/fetotoxicity or teratogenic effect) in their fetuses under the conditions of this study.