Postnatal Effects of Gestational and Lactational Gavage Exposure to Boric Acid in the Developing Sprague Dawley Rat

Abstract

Human exposure to boron occurs primarily through diet and drinking water sources. Animal studies have found that reduced fetal weight following gestational exposure to boron (as boric acid) is the most sensitive toxicological effect. However, recent studies suggest that newborns in areas with elevated boron in drinking water may receive levels of exposure that exceed the U.S. EPA oral reference dose for B. Currently, there are no data to inform a boron risk assessment accounting for this developmental window. To address this knowledge gap, the National Toxicology Program evaluated developmental toxicity following pre- and postnatal boron exposure. Time-mated female Sprague Dawley (Hsd: Sprague Dawley SD) rats were administered 0-20 mg B/kg/day (as boric acid) via gavage from gestation day 6 to 21; offspring were dosed via gavage at the same respective dose level from postnatal day (PND) 1 to 28. There were no dose-related effects on dam bodyweight, bodyweight gain, or feed consumption. Clinical findings were limited to low incidences of umbilical hernia in the 20 mg B/kg pups which resolved by study completion. Pup plasma boron concentrations increased in dose-proportional manner and were similar between PND 4 and PND 28. Postnatal weight gain was significantly reduced at 20 mg B/kg, with male and female pups weighing 23% less than the controls on PND 28. These findings demonstrate that postnatal growth in the Sprague Dawley rat is sensitive to boron exposure and highlights the importance of evaluating the potential toxicity of agents with known human exposures during early life stages.

Keywords: boric acid; boron; postnatal; prenatal; umbilical hernia.

Figure 1.

Maternal growth curves for pregnant rats during gestation and lactation. Body weights are shown as mean ± SEM for each treatment group (N = 6–7 dams/treatment group). Nonpregnant dams were excluded from statistical analysis of gestational weights. No statistically significant pairwise changes were observed with administration of boric acid.

Figure 2.

Postnatal growth of F1 offspring administered 0, 5, 10, and 20 mg B/kg/day. Mean of litter means for absolute (A) and relative weights (% of control) (B) are shown for males and females combined, males only, and females only. Pup weights were adjusted for litter size and statistical analyses were performed using mixed models with the dam as the random effect and Dunnett-Hsu adjustment for multiple comparisons. Asterisks in (A) denote a significant pairwise difference in mean pup weight per litter in the 20 mg B/kg group when compared with the vehicle control (*p ≤ .05, **p ≤ .01).

Figure 3.

Postnatal weights of individual pups with umbilical hernia (20A–K) compared with the control and 20 mg B/kg group means. No outliers were detected among individuals when compared with the control or 20 mg B/kg group means.