The reproductive toxicity of boric acid.

Abstract

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)

Oral (Drinking Water) Two-Generation Reproductive Toxicity Study of Dibromoacetic Acid (DBA) in Rats

“…Retention of step 19 spermatids is a well-described nding that has been reported as a exposure-related lesion, with a range of different toxicants, as well as with hormone disruption. Boric acid is one of the best known chemicals to produce this nding (Chapin and Ku 1994;Linder, Strader, and Rehnberg 1990). The nding is normally characterized by the presence of a prominent layer of step 19 spermatids overlying the newly elongating sper-…”

Effects of Chronic Boron Exposure on Semen Profile

“…It has been reported that boron compounds at high doses cause formation of testicular atrophy, as observed after feeding F344 rats with 6,000 ppm boric acid for 9 weeks or 9,000 ppm boric acid for 6 weeks [2,3]. Nevertheless, the presence of similar effects has not been proven in humans, albeit with only limited epidemiological data [4][5][6].…”

Boron Workers in China

“…In a follow-up study, Sayli (2003) did not replicate the 1998 finding of a slightly lower percentage of male births to boron-exposed couples in Turkey, but reported a male-to-female birth ratio of 1.00 and a ratio of less than 1.05 for Turkey overall. In animal toxicology studies, delayed release of sperm into the lumen of the seminiferous tubule and retention of residual cytoplasm in maturing sperm cells are the initial effects of boron toxicity (Chapin & Ku, 1994;Ku, Chapin, Wine, & Gladen, 1993), but to date, none of these animal studies have published changes in sex ratios. It may be that variations in expected sex ratios were seen but not reported, or that humans' susceptibility in relation to boron toxicology differs from that of animals.…”