Submission Number: CHR-4-34-11

Abstract Number: 355

MALE REPRODUCTIVE TOXICITY OF BROMOCHLOROACETIC ACID IN MICE.

J Christopher Luft, J Brian Garges, John R Rockett and David J Dix

Reproductive Toxicology Divison, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC ¹

Abstract:
Haloactetic acids (HAs) are unintended by-products of drinking water disinfection. Bromochloroacetic acid (BCA) is a commonly occurring HA that acts as a reproductive toxicant in adult male rats. To determine if BCA produces male reproductive toxicity in mice, adult C57BL/6 males were dosed via gavage with 0, 8, 24, 72, or 216 mg/kg of BCA once daily for 14 days. Following 14 days of BCA gavage, 5 of 12 animals from each dose-group were harvested and testes, epididymides, and seminal vesicles were weighed and either frozen or prepared for subsequent molecular and histological evaluations, respectively. There were no significant differences between control and BCA treated males in body weight or reproductive organ weights. After dosing, remaining males were used in a 40-day sequential breeding assay to determine if BCA negatively affects reproductive performance by targeting a particular phase of spermatogenesis. Coital plug-positive females were replaced daily and harvested 14 days later. Uteri were dissected to evaluate the number of implantations, resorptions and fetuses which were weighed and examined to identify malformations. Only the first 10 days of the mating assay resulted in significant decreases in: 1) mean number of litters/male (0, 8, 24, 72, and 216 mg/kg BCA were 3, 2.42, 1.85, 1.1*, and 1.1*, respectively (* p<0.05)), 2) percentage of litters/female bred (i.e. plugged females becoming pregnant) 68%, 80%, 57%, 36%*, 30%*, respectively, and 3) total number of fetuses/male (27, 18, 16, 10*, and 9*, respectively). These results indicate that BCA was affecting development of meiotic spermatocytes, spermatids and sperm during this period (14 days dosing and days 1-10 mating). No significant differences between dose groups were seen for: 1) number of coital plugs, 2) number of fetuses/litter, 3) number of resorptions, or 4) number of terata. These data indicate no systemic toxicity (i.e. no reduction in body weight), no behavioral effects (i.e. no decrease in coital plugs), and no gross effects on reproductive organ weight following BCA exposure. However, short-term exposure to BCA causes transient subfertility in mice providing proof-in-principle for investigating mechanisms involved in this outcome. (This is an abstract of a proposed presentation and does not necessarily reflect EPA policy). .

Keywords: bromochloroacetic acid, mice, and spermatogenesis

This abstract is being presented at: 8:00 AM in session:
Toxicology II