Estimates of levels of exposure to boron posing minimal risk to humans (MRLs) have been made. These are discussed in Section 2.2 and were based on data believed to be reliable for the most sensitive noncancer effect for each route and exposure duration. No data were located on effects of acute-duration inhalation exposure in humans or animals nor on intermediate-duration inhalation exposure to boron in humans. Available information on intermediate-duration inhalation exposure in animals and chronic-duration inhalation exposure in humans do not reliably identify the most sensitive target organ. No data on effects of acute-duration oral exposure to boron in humans or animals nor on intermediate exposure in humans were located. In animals, prenatal exposure of mice (79 mg boron/kg/day as boric acid) and rats (13.6 mg boron/kg/day as boric acid) during gestation days 0-17 and 0-20 caused developmental effects consisting of reduced fetal body weight or minor skeletal changes and possibly delay in maturation (Heindel et al. 1991). There was degeneration of the seminiferous tubules and impaired spermatogenesis in mice exposed to dose levels of 111 mg boron/kg/day as boric acid for 2 generations (NIEHS 1990). In other studies involving intermediate-duration exposure, gonadal damage, primarily in the testes, was evident at dose levels from 26 to 288 mg/kg/day (NTP, 1987; Weir and Fisher 1972), but not at dose levels of 0.6 and 25 mg/kg/day (Dixon et al. 1976). Exposure of dogs to boron (as boric acid or borax) in the diet for 38 weeks caused testicular atrophy and spermatogenic arrest at dose levels of 29 mg boron/kg/day (Weir and Fisher 1972). Based on a LOAEL value of 13.6 mg boron/kg/day for developmental toxicity, an intermediate oral MRL of 0.01 mg boron/kg/day was derived using an uncertainty factor of 1,000 (10 for use of a LOAEL, 10 for extrapolation from animals to humans and 10 for human variability). However, testicular effects were reversible within 25 days after compound treatment ceased. No effects were observed in rats fed diets containing doses up to 8.75 mg boron/kg/day) for 2 years (Weir and Fisher 1972). Because developmental toxicity occurred at dose levels less than those for reproductive toxicity, the intermediate MRL based on developmental toxicity should be protective against reproductive toxicity following chronic exposure. No data were located on effects of chronic-duration oral exposure in humans. A chronic MRL was not derived. Acute-duration, intermediate-duration, and chronic-duration dermal MRLs were not derived for boron due to the lack of an appropriate methodology for the development of dermal MRLs.
No studies have been found regarding immunological effects of boron and compounds in humans or animals.
Death. Human studies have shown that boron can be lethal following short-term exposure. The minimal lethal dose of ingested boron (as boric acid) was reported to be 2-3 g in infants, 5-6 g in children and 15-20 g in adults (Locatelli et al. 1987; Wong et al. 1964). No data were found on the potential for boron to cause death in humans after intermediate and chronic inhalation and oral exposures. Liver, kidney, brain damage, and skin lesions have been found in lethal cases following ingestion of boron, but death has been attributable to respiratory failure. In other studies, chronic dermal exposure to boron in neonates was fatal (Litovitz et al. 1988). There appears to be a differential susceptibility with regard to death in adults. It has been postulated that increased competence of the adult kidney accounts for adult tolerance to boron. Based on these findings, lethality may be an area of concern following neonate exposure to boron.
Animal studies support human findings. Boron was lethal after ingestion for acute, intermediate, and chronic duration exposures (NTP 1987; Smyth et al. 1969; Weir and Fisher 1972).
Respiratory Effects. Symptoms of acute irritation of the upper airway were observed at borax and boric acid levels of 4 mg/m or greater (Garabrant et al. 1984, 1985). No adverse respiratory effects were observed in humans following intermediate inhalation exposures. Chronic inhalation exposure caused irritation of the upper respiratory tract (Garabrant et al. 1984, 1985). There were no changes in the FEV1 and FVC in borax workers (Wegman et al. 1991). Intermediate inhalation exposure in animals caused irritation of the nose (Wilding et al. 1959).
Gastrointestinal Effects. Boron or boron compounds can result in gastrointestinal disorders in humans following acute and intermediate oral exposures. Most of the studies focused on clinical symptoms including vomiting and diarrhea. No data were found on biochemical changes and limited data were provided on histopathological effects. Infants appear to be particularly susceptible to boron toxicity, possibly due to the fact that their detoxifying enzyme systems are immature and there is greater gastrointestinal absorption.
No studies were located in animals regarding gastrointestinal effects following boron exposure.
Hepatic Effects. No adverse hepatic effects have been reported in humans or animals following inhalation or dermal exposure to boron or boron compounds. Acute oral exposure in humans caused congestion, fatty changes, and parenchymatous degeneration (Wong et al. 1964). No data were available on biochemical changes. It is not clear how boron affects the liver; however, limited animal data suggest impaired electron transfer and macrometabolism. In studies with rats, boron interfered with flavin metabolism in flavoprotein-dependent pathways (Settimi et al. 1982). It is not clear if similar effects will occur in humans.
Renal Effects. No adverse renal effects have been reported in humans or animals following inhalation of boron oxide, boric acid dust, or boron oxide aerosol. Similarly, dermal exposure to boric acid in humans or animals did not adversely affect the kidneys. Renal tubular damage has been observed, and there was reduced urine output in infants who consumed 505 mg boron/kg in infant formula for 3-5 days (Wong et al. 1964). Since renal effects occurred in only a few cases and there is no confirming evidence in animals, the potential for boron to cause renal effects cannot be conclusively established.
Dermal/Ocular Effects. Human occupational exposure to boron oxide and boric acid dusts in workplace air irritated the eyes (Garabrant et al. 1984). Ingestion of large amounts of boron (505 mg boron/kg as boric acid) caused extensive exfoliative dermatitis in humans (Wong et al. 1964). The application of boric acid on the forearm of human subjects did not affect the skin (Draize and Kelley 1959). Rabbits developed erythema when boron oxide dust was applied to the skin and conjunctivitis was observed following contact with boron oxide dust (Wilding et al. 1959).
Immunological Effects. No studies were located regarding the effects of boron on the immune system in humans or animals after inhalation, oral, or dermal exposure. In the absence of effects on target organs and direct tests on immune function, the potential for boron to cause immunological effects in humans cannot be conclusively evaluated.
Neurological Effects. No adverse neurological effects have been observed in humans or animals following inhalation or dermal exposure. Acute and intermediate oral exposures to boron and boron compounds caused various neurological responses in humans. Degenerative changes in brain neurons which may have been an agonal effect were reported in one infant who consumed 505 mg boron/kg as boric acid for 3 days (Wong et al. 1964). At a higher dose (765 mg boron/kg), there was extensive vascular congestion, widespread perivascular hemorrhage, and intravascular thrombosis in another infant who ingested infant formula containing boric acid for 5 days (Wong et al. 1964). Biochemical changes have also been found. Cerebral succinate dehydrogenase activity was increased in rats that ingested borate in drinking water for 10-14 weeks, suggesting alteration in electron-transfer in the mitochondrial respiratory chain (Settimi et al. 1982). Increased RNA concentration and increased acid proteinase activity in the brain also occurred (Settimi et al. 1982). Altered metabolism and brain tissue redox state suggest changes in protein metabolism.
Based on these considerations, neurological damage is an area of concern following exposure to boron at toxic levels.
Developmental Effects. Developmental changes in rats and mice have been observed in offspring of dams exposed to 28.4 mg boron/kg/day and 175.3 mg boron/kg/day, respectively (Heindel et al. 1991). These effects have been observed at dose levels in the same range as those producing changes in spermatogenesis. No epidemiological studies were located regarding the effects of boron on the developing fetus. Although human data are lacking and there are no direct quantitative studies regarding placental transfer of boron, positive responses in two animal species suggest that developmental toxicity may be an area of concern in humans following exposure to boron. The LOAEL value of 13.6 mg boron/kg/day (Heindel et al. 1991) was used to calculate an intermediate oral MRL of 0.01 mg/kg/day as described in the footnote in Table 2-2.
Reproductive Effects. A study of 28 male workers exposed to borate aerosols during the production of boric acid revealed low sperm counts in six of these workers (Tarasenko et al. 1972). The authors reported exposure concentrations ranging from 22 to 80 mg/m . The overall reliability of these data is reduced due to the small study group. It should also be noted that low sperm count is a naturally occurring phenomenon. No studies were located regarding reproductive effects in humans after oral or dermal exposure.
In animals, boron affects gonads in dogs, rats, and mice. The testes are particularly susceptible after intermediate ingestion (44 and 29 mg boron/kg/day, respectively) (Seal and Weeth 1980; Weir and Fisher 1972). Following chronic oral exposure, no effects were observed at a dose of 8.75 mg boron/kg/day (Weir and Fisher 1972). In spite of the absence of reliable human data, limited evidence of reproductive effects in animals suggest that reproductive toxicity may be an area of concern following boron exposure in humans.
Genotoxic Effects. No studies were located regarding genotoxic effects of boron by inhalation, oral, or dermal exposure in humans and animals. Results were negative in bacterial assays and in the in vitro (Table 2-4) mammalian assays, including tests for chromosomal aberrations and gene mutation. Existing data suggest that genotoxicity is not an area of concern following exposure to boron in humans.
Cancer. No epidemiological studies were located associating ancer and boron exposure. In mice fed boron (as boric acid) for 103 weeks, the number of tumors observed did not differ significantly from untreated control levels (NTP 1987). In the absence of human data and studies from other animal species, and the lack of evidence of mutagenic activity, the carcinogenic potential of boron in humans cannot be determined conclusively.
TABLE 2-4. Genotoxicity of Boron In Vitro
Species (test system) End point
Prokaryotic organisms: Salmonella typhi muri um
S ._typhi muri um
Eschsrinhia noli S ._typhi muri um
Gene mutation Gene mutai ton Gene mutation Gene mutation
Mouse lymphoma Gene mutation
Chinese hamster ovary Chromosomal aberrati on
= negative result
With Without activation activation
Haworth et al. 1984 Benson et al. 1951 Demerec et al. 1951 NTP 19787
NTP 1987 NTP 1987
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