Reproductive toxicity of boric acid in Swiss (CD-1) mice: Assessment using the continuous breeding protocol

Fail, Patricia A.

doi:10.1016/0272-0590(91)90215-p

Cited by 73 publications

(32 citation statements)

References 28 publications

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“…Table 1 shows that boric acid effectively inhibited reproduction in mice. The high-dose group (9000 ppm) had no litters at all, while the controls averaged 4.7 litters per cohabiting pair (4). Mean litter size was decreased in the 4500-and 9000-ppm groups.…”

Section: Male Pathogenesis Studymentioning

confidence: 91%

“…Specific methods and results for the Reproductive Assessment by Continuous Breeding (RACB) study may be found in Fail et al (4). Briefly, male and female Swiss CD-1 mice ( 1 weeks of age at start) were fed boric acid in a powdered diet starting 1 week prior to cohabitation.…”

Section: Racb Studymentioning

confidence: 99%

“…They found testicular degeneration and infertility after 60 days of boron consumption. Other studies have reported adverse effects of boron exposure on the male reproductive system (4). These studies raised the issue of the reproductive toxicity of high-level boron exposure.…”

Section: Introductionmentioning

confidence: 99%

“…There was a significant 3% decrease in pup body weight when adjusted for litter size; otherwise, there were no significant effects [data not shown (4)]. …”

Section: Racb Studymentioning

confidence: 99%

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The reproductive toxicity of boric acid.

Chapin

1994

Environ Health Perspect

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Previous studies on the reproductive toxicity of boric acid have indicated that male rodents suffer testicular atrophy after treatment. There were, however, no studies of the potential effects on female fertility or on the neonate. In addition, no study described the development of the testicular lesion, thought to be related to the mechanism of toxicity. A Reproductive Assessment by Continuous Breeding (RACB) study using mice exposed to boric acid at 1000, 4500, and 9000 ppm in the diet indicated that there are probably multiple sites of action, although male fertility appears very sensitive. Possible effects on female fertility cannot be separated from potential developmental toxicity and need additional investigation.Decrements in sperm motility were observed at all exposure levels, and testicular atrophy was confirmed in high-and middle-dose-group males.This was investigated further by timed serial-sacrifice studies using 9000 ppm in the diet of rats, which found that the first lesion seen in the testis was an inhibition of spermiation (release of mature spermatids). With continued dosing, this was followed by a disorganization of the normal ordered layering of the seminiferous epithelium, germ cell sloughing and death, and finally, atrophy. Subsequent studies using additional doses (2000, 3000, 4500, 6000, and 9000 ppm) found that it was possible to observe inhibited spermiation that did not progress to atrophy (4500 ppm and below) within the 9-week exposure period. Also, once atrophic (from 9000-and 6000-ppm exposures), there was no return of spermatogenesis after refeeding of normal diet for 8, 16, 24, or 32 weeks, despite the presence of a normal-sized population of spermatogonia that was seen to divide. No effects were observed in rats treated with 2000 ppm. Testicular boron concentrations remained steady during exposure at the same level as found in blood, and declined to background levels within 72 hr after cessation of exposure. Bone boron levels were greater than those found in blood, and maintained slightly elevated levels even 32 weeks after the cessation of exposure. These studies document the effects of boric acid on functional and structural aspects of the male reproductive system; demonstrate that the tissue concentration of boron, and not total dose, is important for the testicular toxicity; and show that there is a threshold for these effects. These studies also suggest that the potential for recovery from boric acidinduced testicular atrophy should be examined in other species to evaluate the significance of the persistent atrophy seen in the rats. -Environ Health Perspect 102(Suppl 7): 87-91 (1994)

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Section: Male Pathogenesis Studymentioning

confidence: 91%

Section: Racb Studymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…There was a significant 3% decrease in pup body weight when adjusted for litter size; otherwise, there were no significant effects [data not shown (4)]. …”

Section: Racb Studymentioning

confidence: 99%

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The reproductive toxicity of boric acid.

Chapin

1994

Environ Health Perspect

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“…At high concentrations, boric acid is a reproductive toxicant in mice (4) and rats (5)(6)(7). While males appear to be the predominandy affected sex (4), other investigators have shown that pregnancy in mice can also be disrupted by boric acid exposure. A single dose of boric acid (500-3000 mg/kg) to mice on the first day of pregnancy disrupted pregnancy because of failure of blastulation in mice (2).…”

Section: Introductionmentioning

confidence: 99%

The developmental toxicity of boric acid in mice, rats, and rabbits.

Heindel

Price

Schwetz

1994

Environ Health Perspect

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Boric acid (BA) is a naturally occurring agent used in manufacturing processes and numerous consumer products. Because of the potential for both industrial and consumer exposure to boron-containing compounds, and the lack of developmental toxicity data, the National Toxicology Program evaluated the potential for boric acid to cause developmental toxicity in pregnant Swiss (CD-1) mice, Sprague-Dawley rats (n = 26-28/group), and New Zealand rabbits (n = 1 8-23/group). BA was provided in the feed to mice and rats at 0, 0.1, 0.2, or 0.4% throughout gestation to attain steadystate exposure as early as possible during development. Average doses (mg/kg/day) were 248, 452, or 1003 for mice, and 78, 163, or 330 in rats. A separate group of rats received 0.8% BA in the feed, or 539 mg/kg/day only on gestation days (gd) 6 to 15. Rabbits were given BA (0, 62.5, 125, or 250 mg/kg) by gavage administration on gd 6 to 19. Maternal body weight, food and/or water consumption and signs of toxicity were monitored at regular intervals. At termination, gd 17 (mice), 20 (rats), or 30 (rabbits), the uterus was examined to determine the number of resorptions, dead, or live fetuses. Fetuses were weighed and live fetuses were examined for external, visceral, and skeletal defects. Mouse dams exhibited mild renal lesions (.248 mg/kg/day BA), increased water intake and relative kidney weight (1003 mg/kg/day BA), and decreased weight gain during treatment. Maternal rats exhibited increased liver and kidney weights at 2163 mg/kg/day BA, altered water and/or food intake at >163 mg/kg/day BA, and decreased weight gain at >330 mg/kg/day BA. In rabbits, signs of toxicity included decreased food consumption during treatment, and vaginal bleeding associated with pregnancy loss at 250 mg/kg/day. Maternal body weight (gd 9 to 30), weight gain during treatment, and gravid uterine weight decreased at 250 mg/kg/day. Relative maternal kidney weight (but not absolute weight) was increased at 250 mg/kg/day, but microscopic evaluation did not indicate any renal pathology associated with BA exposure. BA is a developmental toxicant in all three species. The lowestobserved-adverse-effect level (LOAEL) for developmental toxicity was 78 mg/kg/day for rats (fetal weight reduction), 250 mg/kg/day for rabbits (prenatal mortality and malformations), and 452 mg/kg/day for mice (fetal weight reduction). The no-observed-adverse-effect levels (NOAELs) for developmental toxicity in these species were <78 mg/kg/day (rats), 125 mg/kg/day (rabbits), and 248 mg/kg/day (mice). With regard to maternal toxicity, the rat was the most sensitive (163 mg/kg/day), while both the mouse and rabbit showed maternal toxicity at 250 mg/kg/day. Thus, developmental toxicity occurred below maternally toxic levels in the rat, and only in the presence of maternal toxicity in mice or rabbits. -Environ Health Perspect 102(Suppl 7): 107-112 (1994)

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Boron

Ball¹

2023

Patty's Toxicology

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Boron is the fifth element of the periodic table and the only electron‐deficient nonmetallic element. Consequently, boron has a high affinity for electronegative atoms such as oxygen and forms strong covalent boron–oxygen bonds in compounds known as borates. Boron is an essential micronutrient in plants and nutritionally important in animals and humans. Boron occurs naturally in all foods; fruits, vegetables, and nuts contain the highest levels. The toxic effects and pharmacokinetics of boron and borates are reviewed. The inorganic boron‐containing materials share many chemical and biological characteristics thought to be due to unique properties of the boron element. This chapter reviews the shared characteristics and the individual inorganic boron‐containing compounds that have a significant use in industry. Some of the more important physical and chemical properties of boron compounds of commercial significance and widespread exposure are listed. Boron has been shown to cause developmental effects and adversely affect male reproduction in laboratory animals. However, there is no clear evidence of male reproductive effects attributable to boron in studies of highly exposed workers or of developmental effects in humans in studies of populations with high exposures to boron.

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Reproductive toxicity of boric acid in Swiss (CD-1) mice: Assessment using the continuous breeding protocol

Cited by 73 publications

References 28 publications

The reproductive toxicity of boric acid.

The reproductive toxicity of boric acid.

The developmental toxicity of boric acid in mice, rats, and rabbits.

Boron

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