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EC number: 215-575-5
CAS number: 1332-77-0
A number of sub-chronic and chronic studies on boric acid and disodium tetraborate decahydrate were carried out in rats, mice and dogs. In some cases, these studies are research studies (Weir and Fisher, 1972; Dixon et al, 1976; Seal and Weeth, 1980; Lee et al., 1978; Treinen and Chapin, 1991; Ku et al., 1993), but most support that boron can cause adverse haematological effects and that the main target organ of boron toxicity is the testis. The NOAEL for fertility effects is equivalent to 17.5 mg B/kg bw/day (Weir, 1966) that corresponds to a NOAEL of 94.6 mg dipotassium tetraborate/kg bw (anhydrous, and 123.7 mg dipotassium tetraborate tetrahydrate/kg bw).
Based on the sub-acute inhalation study on boron oxide conducted in rats (Wilding, 1960), the NOAEC for systemic effects is equivalent to 146 mg B/m3 that corresponds to a NOAEC of 789 mg dipotassium tetraborate/m3 (anhydrous, and 1032 mg dipotassium tetraborate tetrahydrate/m3).
number of animals examined
Mortality at 104 weeks
body weight gain
0-104 weeks (g)
at week 52 (g/kg/day)
at 26 weeks
testes weight (g)
at 104 weeks
Testes atrophy at 24 months
Summary of haematological data from 2 year
rat study boric acid:
Cell Volume (%)
Hb Value (g/100 mL)
WBC Count (x103/cm2)
RBC Count (x103/cm2)
* Significantly different from controls
Missing data not thought to be significant
according to the summary of the study
Table 1. Exposure animals to aerosols of boron oxide
Duration of exposure
Particle size, MMD
Table 2. The pH, volume and creatinine coefficient for urine of control and of exposed rats (concentration 77 mg/m³)
Weeks of exposure
Table 3. Chemical analyses of the blood of rats exposed to aerosols of boron oxide
Time of exposure
Females exposed to 470 mg/m³
Males exposed to 77 mg/m³
Male controls (13 samples)
Table 4. Boron content of urine control rats and of rats exposed to aerosols of boron oxide
Urinary boron content*
* When the urine of the rats was analyzed a week after the end of the period of exposure, the boron content in the urine of the control rats and exposed rats was 0.3 mg/kg/day. After a 2-week interval, the boron content in the urine of the control rats wae 0.5 mgjkglday; in the urine of the exposed rats, it was 0.9 mg/kg/day.
Table 5. Fragility of femurs of control rats and rats exposed to an aerosol of boron dioxide
* Arerages of groups that had been exposed for 6 and 10 weeks to a concentraam of 470 mg/m³
Groups of albino rats and dogs were exposed to aerosols of boron oxide in dynamic chambers. The rats were individually caged in racks, 10 cages each, which were randomly changed for each exposure. The animals were exposed for 6 hours a day for 5 days a week. 70 rats were exposed for 24 weeks (77 mg/m³), 4 rats were exposued for 12 weeks (175 mg/m³), 20 rats were exposed for 10 weeks (470 mg/m³) and 3 dogs were exposed for 23 weeks to 57 mg/m³. The test concentrations were verified analytically and mass median diameters (MMAD) were derived.
No toxic signs were evident in any of the animals. All groups of rats exposed to concentrations of 77 and 470 mg/m³ gained weight at about the same rate as their controls. Chemical analyses of dog and rat blood, and urine showed no changes from control values, except for an increased urinary excretion of creatinine in the rats, and lower pH, increased volume, and increased boron content in the rat urine. No changes were found as a result of aerosol exposures in the following:
1. rat tissues and organs
2. bone fragility
3. roentgenograms of rat bones
4. hematology of dog blood
5. sulfobromophthalein retention
6. rat organ weight.
A number of studies on boric acid or disodium tetraborate decahydrate in diet or via drinking water for periods of 30 days to two years in rats, mice and dogs are available, however, the majority of these studies do not comply with current test guidelines, and they lack essential information regarding e. g. histological descriptions and statistical evaluations of the results. Most studies support that boron can cause adverse haematological effects and that the main target organ of boron toxicity is the testis. Other effects observed at high doses include rapid respiration, hunched position, bloody nasal discharge; urine stains on the abdomen, inflamed bleeding eyes, desquamation and swollen paws and tail, reduced food consumption and body weight gain. Treatment with boric acid and disodium tetraborate decahydrate disrupted spermiation, induced degeneration of testicular tubules and caused testicular atrophy. For effects on the blood system extramedullary haematopoiesis, reduced red cell volume and haemoglobin values and deposition of haemosiderin in spleen, liver and proximal tubules of the kidney were described. Several cases of anaemia have been observed in human poisoning cases. However, although doses in these poisoning cases are difficult to define, the effects occurred generally at relatively high concentrations.
Groups of albino rats and dogs were exposed to aerosols of boron oxide for periods up to 24 weeks, 6 hours a day for 5 days a week. The highest concentration rats were exposed was 470 mg/cu m for a period of 10 weeks. There were no significant changes in tissues from rats or in chemical analyses of rats and dogs blood. No changes or toxic signs were noted in the mature female dogs exposed for 23 weeks to a concentration of 57 mg/cu m (Wilding et al. 1959; 1960).
Boric acid, the main species present under physiological conditions, acts as a Lewis acid and as such owns the ability to complex with hydroxyl, amino and thiol groups from diverse biomolecules, like e. g. carbohydrates and proteins (BfR, 2006). Such a mechanism could be involved in effects of boron on different enzyme activities (Huel et al., 2004).
A NOAEL for effects on testes and the blood system of 17.5 mg B/kg bw/day can be derived (with a LOAEL of 58.5 mg B/kg bw/day) from two 2-year studies in rats on boric acid and disodium tetraborate decahydrate (Weir, 1966a, b).
Please also refer to the read-across statement attached to section 13.
Boric acid and disodium tetraborate are classified under the 1stATP to CLP as Repr. 1B; H360FD.
However, text of the 30th ATP as published in the EU Official Journal, 15 September 2008 stated that “The classification and labelling of the substances listed in this Directive should be reviewed if new scientific knowledge becomes available. In this respect, considering recent preliminary, partial and not peer-reviewed information submitted by industry, special attention should be paid to further results of epidemiological studies on the Borates concerned by this Directive including the ongoing study conducted in…”
While boron has been shown to adversely affect male reproduction in laboratory animals, there was no clear evidence of male reproductive effects attributable to boron in studies of highly exposed workers (Whorton et al. 1994; Sayli 1998, 2001; Robbins et al. 2010; Scialli et al. 2010). Not only are these the most exposed workers, but the Chinese worker study is the most sensitive study that has been carried out as semen analysis was performed, a very sensitive detection system for testicular damage. There is no evidence of developmental effects in humans attributable to boron in studies of populations with high exposures to boron (Tuccar et al. 1998; Col et al. 2000; Chang et al. 2006).
A weight of evidence approach was used in evaluating numerous independent studies on the determination of the hazard of boric acid to humans. Information that was considered together included results of in vitro tests, animal data, occupational exposure data, epidemiological studies and mechanistic data.
Extensive evaluations of sperm parameters in highly exposed workers in Turkey and China have demonstrated no effects on male fertility. No evidence of developmental effects in humans attributable to boron (B) has been observed in studies of populations with high exposures to boron. Although the epidemiological studies have methodological deficiencies, collectively these studies consistently show an absence of effects in highly exposed populations.
Workers in boron mining and processing industries represent the maximum possible human exposure. However, a comparison of blood, semen and target organ boron levels in studies of laboratory animals and human studies shows that boron industry worker exposures are lower than untreated control rats.
Mechanistic data provide possible explanations for the absence of developmental and reproductive effects in humans exposed to high levels of boron. Recent studies provide evidence that boric acid may act by similar mechanisms in causing developmental effects in mice as sodium salicylate (the natural deacetylated form of aspirin and a rodent teratogen) including effects on Hox gene expression and inhibition of embryonic histone deacetylases. Although aspirin is known to cause developmental effects in laboratory animals, controlled human studies have not demonstrated developmental effects in humans. Similar mechanisms of action of boric acid and aspirin, and the absence of developmental effects in humans ingesting aspirin suggest that boric acid related developmental effects in humans are unlikely.
Additionally, zinc levels in soft tissue in humans is over 2 times greater than in comparative tissues in rats (King et al. 2000; Yamaguchi et al. 1996), which explain in part the absence of fertility and developmental effects in humans. Zinc has been shown to protect against testicular toxicity of cobalt and cadmium (Anderson et al. 1993), and the developmental effects of cadmium (Fernandez et al. 2003). There is evidence that zinc interacts with boric acid in the body reducing the toxicity of boric acid. The interaction of zinc and boric acid is evident by the low acute toxicity of zinc borate (absorbed as boric acid and zinc) with a LD50 value greater than 10,000 mg/kg-body weight in rats (Daniels 1969) compared to disodium tetraborate pentahydrate (similar % boron composition as zinc borate) with a LD50 value of 3300 mg/kg-body weight. Furthermore, no toxic effects were observed in the testes of males (a target organ of boric acid) administered 1000 mg zinc borate/kg/day in a 28-day repeated dose oral gavage toxicity study, equivalent dose of boron of 50 mg B/kg bodyweight (Wragg et al. 1996). The LOAEL for testicular effects is 26 mg B/kg body weight.
Based on the total weight of evidence, the data show that it is improbable that boric acid or dipotassium tetraborate will cause reproductive or developmental effects in humans.
Therefore, based on a total weight of evidence, Category 2 H361d: suspected human reproductive toxicant, suspected of damaging the unborn child is considered the appropriate classification. Extensive evaluations of sperm parameters in highly exposed workers have demonstrated no effects on male fertility. While no developmental effects have been seen in highly exposed populations, epidemiological studies of developmental effects are not as robust as the fertility studies, warranting the Category 2 H361d.
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