The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings were not evaluated in accordance with the levels of evidence for reproductive or developmental criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
The potential reproductive toxicity of boric acid (BA) in CD- l (Swiss) mice was evaluated using the Reproductive Assessment by Continuous Breeding (RACB) Protocol. Male and female Swiss (CD-l) mice were exposed to BA at concentrations of 0, 1000, 4500, or 9000 ppm in the feed; this produced estimated consumption levels of approximately 152, 636, and 1262 mg/kg body weight.
During 14 weeks of cohabitation with continuous access to a BA-containing diet, no litters of dead or live pups were produced by 9000 ppm cohabited pairs. Among the litters born to pairs fed BA at 4500 ppm, live litter size and pup body weight were significantly reduced in comparison to controls. All aspects of fertility were unaffected at 1000 ppm BA.
A crossover mating trial (Task 3) at the end of the continuous cohabitation phase, using the middle dose group, confirmed the male as the affected sex, with observed fertility rates of: 0 ppm male x 0 ppm female, 74%; 4500 ppm male x 0 ppm female, 5%; and 0 ppm male x 4500 ppm female, 65%. The mating index was 79%, 30%. and 70% for the same groups. Additionally, adjusted body weights, for pups born from the mating of control male x 4500 ppm female, were significantly decreased from controls (P less than O.Ol), indicating that the female and/or pup are also affected by BA.
At sacrifice, after 27 weeks of BA exposure, the F0 males fed 9000 ppm BA had significantly lower body weight and reproductive organ weights (testes, combined caput and corpus epididymis. and cauda epididymis) and significantly fewer spermatozoa in the cauda epididymis. Males fed 4500 ppm BA also had significantly lower testes, epididymis, prostate weight. and fewer spermatozoa in the cauda epididymis. Organ weights were unaffected at 1000 ppm BA for the F0 males.
The germinal epithelium of F0 males in the 9000 ppm group was atrophied and consisted mostly of Sertoli cells with occasional spermatogonia. The 4500 ppm group had fewer spermatids than in the controls; multinucleate giant cells were observed.
Sperm concentration per mg cauda was dramatically reduced in 9000 ppm males (2.8±1.7 x 103) compared to controls (519±36 x 103). Motility was difficult to quantify due to extremely low sperm concentrations. In 4500 ppm males, both sperm concentration (146.9±26.5 x 103) and sperm motility (53.3± 8.2%) were lower than in controls (519±36 x 103 sperm with 78.1±3.0% motility). Males fed 1000 ppm BA had normal sperm concentrations with reduced motility (69.0±4.5%).
At necropsy, F0 female body weight was significantly decreased in the high dose group. The F0 females in the 4500 ppm group had significantly decreased kidney/adrenals and liver weights.
The F1 mice exposed to dietary BA (0 and 1000 ppm), beginning at conception, had normal fertility. The adjusted mean body weight of F2 pups was decreased. However. the number of live pups per litter, the proportion of pups born alive, sex of pups born alive, and unadjusted weights of pups born alive, were not significantly changed by BA exposure. At necropsy, F1 males had normal reproductive organ weights and sperm motility. However. BA treatment decreased sperm concentrations in F1 males (585.6±32.5 x 103 in controls vs. 442.6±51.2 x 103). Female F1 mice had significantly greater uterus and kidney/adrenal weights than controls.
This study confirms that BA is a reproductive toxicant in mice, primarily through an effect in the male. The 1000 ppm dose approached a No Observed Adverse Effects Level (NOAEL) for the adult reproductive system, as well as for the developing reproductive system.
NTIS # PB90253808