Developmental Toxicity of Disinfection Byproducts in F344 Rats: Effects on Pregnancy Maintenance and Eye Development

ABSTRACT Background Epidemiological studies report associations of drinking water disinfection byproducts (DBPs) with adverse health outcomes, including birth defects. Here, we used a rat model susceptible to pregnancy loss (full‐litter resorption; FLR) and eye malformations (anophthalmia, microphthalmia) to test 11 DBPs, including trihalomethanes, haloacetic acids (HAAs), and nitrogen‐containing DBPs (N‐DBPs). Methods Timed‐pregnant F344 rats received gavage doses of chloroform, chlorodibromomethane, iodoform, chloroacetic acid, bromoacetic acid, dibromoacetic acid (DBA), diiodoacetic acid (DIA), trichloroacetic acid (TCA), dibromonitromethane, and iodoacetonitrile on gestation days (GD) 6–10. Bromonitromethane and TCA were administered via drinking water on GD 6–11. Litters were examined on postnatal days 1 and 6. Results All trihalomethanes tested caused FLR. The di‐ and tri‐halogenated HAAs, but not the mono‐HAAs, caused eye malformations. N‐DBPs caused neither effect at the dosages tested. TCA by gavage caused both FLR and eye defects, whereas drinking water exposure only caused eye defects. Potency rankings for causing FLR were chloroform ≥ iodoform > chlorodibromomethane and the rankings for causing eye defects were DIA > TCA = DBA. Conclusion We confirmed that trihalomethanes caused pregnancy loss and that di‐ and tri‐HAAs were teratogenic. The N‐DBPs induced neither effect. Potency rankings were inconsistent with rankings seen in vitro.