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There is a large database of accidental or intentional poisoning incidents for humans. In the literature, the human oral lethal dose is regularly quoted as 2-3 g boric acid for infants, 5-6 g boric acid for children and 15-30 g boric acid for adults. This data is largely unsubstantiated. In most cases it is difficult to make a good quantitative judgment particularly since medical intervention occurred in most cases and there were often other unrelated medical conditions (Culver and Hubbard, 1996).
While boron has been shown to adversely affect male reproduction in laboratory animals, there is 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). There is also 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). However, studies of human developmental effects are not as robust as the studies of male reproduction because of developmental ascertainment issues.

Additional information

Acute oral:

There is a large database of accidental or intentional poisoning incidents for humans. In the literature, the human oral lethal dose is regularly quoted as 2-3 g boric acid for infants, 5-6 g boric acid for children and 15-30 g boric acid for adults. This data is largely unsubstantiated. In most cases it is difficult to make a good quantitative judgment particularly since medical intervention occurred in most cases and there were often other unrelated medical conditions (Culver and Hubbard, 1996). Of more recent reports of accidental ingestion, none were reported as fatal and 88.3 % were asymptomatic. The estimated dose range was 10 mg to 88.8 g (Litovitz et al, 1988). Symptoms of acute effects may include nausea, vomiting, gastric discomfort, skin flushing, excitation, convulsions, depression and vascular collapse.

Acute dermal:

Several poisoning cases have been reported in humans. In pharmaceutical preparations boric acid has been used in the past as skin and mucosa antiseptic. Such medical uses are now obsolete, but have led to poisoning in the past when skin integrity was compromised (Kliegel, 1980; Wong et al. 1964, Litovitz et al, 1988; Goldbloom and Goldbloom, 1953; Valdes-Dapena and Arey, 1962).

Irritant effects:

No respiratory irritation studies dipotassium tetraborate have been conducted. Acute irritant effects have been documented in human workers exposed to sodium borates (Garabrant 1984, 1985; Wegman 1991 and, Woskie, 1998).

A survey of 113 workers exposed (214 unexposed) to boron oxide and boric acid in a borax mining and refining plant was conducted by Garabrant et al. (1984). The mean total dust exposure was 4.1 mg/m3(10.25Institute of Occupational Medicine air sampler (IOM)) equivalent boron oxide or 4.1 mg/m3(10.25 IOM) boric acid equivalent to 1.3 and 0.7 mg B/m3, (3.25 and 1.75 mg B/m3 IOM equivalent) respectively. All measured of exposure were made at various times (days to weeks) prior to the interview of the study participants and study participants were asked to remember what symptoms they experienced at the time when the exposures were measured. Significant associations were found for respiratory symptoms. Symptoms were eye irritation, dryness of mouth, nose or throat, sore throat, and productive cough. Boron oxide reacts exothermically with water to form boric acid suggesting a possible mechanism for boron oxide irritancy. It is believed that these irritant effects are caused by the exothermic hydration of boron oxide to boric acid. This study did not distinguish which of the two exposures was associated with reported symptoms. In a more detailed analysis acute symptoms showing a significant linear trend in order of decreasing frequency were dryness of mouth, nose and throat, eye irritation, dry cough, nosebleeds, sore throat, productive cough, shortness of breath, and chest tightness (Garabrant et al. 1985). Due to several limitations of this study it cannot be used for DNEL derivations, however, the results are useful for the weight of evidence approach.

Wegman et al (1991, 1994) conducted a study to examine for work-related acute irritative effects and chronic pulmonary function abnormalities in mining and processing plant workers exposed to boron-containing dust. This approach was reported more fully by Hu et al. 1992 and Woskie et al (1994, 1998). However, this study did not evaluate worker exposure to boric acid. Average daily exposure (6 h time weighted average) for the exposed group was 5.72 mg/m3of total dust (0.44 mg B/m3B). The mean total boron value of 0.44 mg B/m3from Wegman et al. 1991 as reported in the text of the report is incorrect since it appears that it includes the background or comparison group exposure level of 0.02 mg/m3, which when included in the calculation of the mean, gives a lower exposure value than the true exposure level of the exposed group. The background or comparison group included non-office hourly employees who had no routine exposure to borate particulate matter, other than background (Wegman et al. 1991). When the background value is excluded from the calculation, the mean total boron value of all exposed groups is 0.52 mg B/m3. When this value is corrected by 2.5 for under sampling bias (Vincent 2007) that occurs with total dust sampling the mean total boron exposure for the exposed group is 1.3 mg B/m3. 

The exposure – response trends were statistically significant (p < 0.05), except for eye irritation. The most striking difference was for nasal irritation where 23 % of the exposed group reported at least two incident symptoms as compared to none of the unexposed. Despite some drawbacks of this study a concentration response curve can be derived. The number of workers investigated and the evaluated exposure intervals was high, the exposure was representative for the workplace situation and the protocol of the observations is adequate. The investigators considered these findings to be compatible with an OEL of 10 mg/m3 TWA (Total Dust) without a STEL (short-team exposure limit) for all the sodium borates (Wegman et al 1991). It is therefore used as a supporting study for deriving a DNELacute, inhalation, local for sodium borates. A bench mark dose analysis BMDL05 value of 0.95 mg B/m3 (Based on Total Dust sampler) was calculated using data from Wegman et al. 1991 (See appendix A).

The total dust samples used for the studies by Garabrant (1984, 1985) and Wegman et al. (1991) were collected by personal samplers consisting of a 37 mm, 5-µm PVC filter in a closed-face cassette attached to a personal sampling pump set at a flow rate of 2 L/min as described by NIOSH Method 0500. This method is defined as collecting total aerosol mass or total dust. Wegman et al. (1991) used a closed-face 37 mm cassette attached in-line to a MINIRAM operated at 2 L/min. Since dust particles of different sizes deposit selectively in different parts of the respiratory tree, size selective dust sampling has replaced the total dust method. Because the most sensitive effect of borate exposure in the workplace is irritation of the nose and throatand to a lesser extent, eyes, current air sampling for borates is most frequently done with samplers designed to collect the inhalable particulate fraction (IOM sampler), the particle fraction that deposits in the upper respiratory tract. The relationship between total dust and inhalable dust air sampling results for borates becomes important when comparing measures of past exposures with current exposures. The samplers designed for the inhalable fraction collect larger dust particles more efficiently than do the total dust samplers so that in dust environments containing large particles the inhalable dust sampler will collect larger proportions of the airborne mass than the total dust sampler. Several studies have demonstrated that the 37-mm total dust sampler equipment under-samples suspended particles by factors ranging from 1.2 to 4.0 compared to the IOM sampler (Shen et al. 1991; Culver et al. 1994; Tsai et al. 1995; Werner et al. 1996; Katchen et al. 1998; Teikari et al. 2003; Vincent 2007). The dust particles associated with borate mining and processing typically have mass median aerodynamic diameters of 10-15 µm and in this environment the IOM sampler collects between 2 and 3 times more mass per unit volume of air than the total dust sampler (Culver et al. 1994; Katchen et al. 1998). A conversion factor of 2.5 has been suggested for converting “total” personal exposure measures from industries similar to the borate mining and processing facility to equivalent inhalable aerosol exposures (Werner et al. 1996; Vincent 2007) further supported by paired 37 mm closed face cassette and 25 mm IOM sampling at a borate processing facility in France (Shen et al. 1991).

Woskie et al. (1998) further analyzed the Wegman et al. 1991 data and concluded that those who may appear most susceptible to borate exposure, because of greater reactivity, were the healthy non-smoking workers not using nasal sprays/drops, not reporting allergies or colds on the test day or any history of bronchitis. To examine possible biologic mechanisms for the irritant response, a toxicokinetic dose model was used to calculate nasal osmolarity during symptom intervals. The estimated levels suggested that osmolar activation of mast cells to release histamine and other mediators is a plausible mechanism by which these workers may experience nasal irritation. The study cannot be used for DNEL derivation, but helps to interpret the data generated by Wegman et al. (1991).

Cain et al. (2008) investigated the sensory irritation and perception of dusts of boric acid, sodium tetraborate pentahydrate, calcium sulphate, and calcium oxide in human volunteers. Cain et al. (2008) reported a NOAEL for irritation among human volunteers inhaling boric acid of 1.75 mg B/m3(10 mg/m3of boric acid), the highest exposure evaluated for boric acid. The exposures of 2, 5 and 10 mg/m3evaluated in Cain et al. did not reach a level defined by the investigators as being irritating. Furthermore, for any given point in exposure time the dose-response curve had a very low slope, not characteristic of an irritant.

No respiratory irritation studies dipotassium tetraborate have been conducted. Dipotassium tetraborate was not evaluated in the studies by Garabrant et al., Wegman et al. or Cain et al.

 

Chronic irritation - inhalation:

Garabrant et al. 1984 indicated that boron oxide and boric acid dusts caused upper respiratory tract and eye irritation at concentrations less than 10 mg/m3 (total dust). The mean exposures of 4.1 mg/m3 total dust (10.25 mg/m3 IOM equivalent) with a range of 1.2 mg/m3 to 8.5 mg/m3.

An investigation into work-related chronic abnormality in pulmonary function associated with exposure to boron dust in mining and processing operationsevaluated by Garabrant et al. (1984, 1985) was assessed by Wegman et al. (1991). This study relied on the availability of a 1981 survey by Garabrant et al (1984, 1985) which provided standardized measurements of pulmonary function and respiratory tract symptoms. Pulmonary function at the beginning and end of a 7-year study period was examined. Reduction of forced expiratory volume 1 sec (FEV1) was observed among smokers who had heavy cumulative sodium borate exposure (≥80 mg/m3-year), but not among less-exposed smokers and non-smokers. Change in pulmonary function over the 7 years was found unrelated to the estimate of cumulative exposure during that interval. The analysis of the relationship of sodium borate exposures in the workplace to chronic effects on pulmonary function was examined by evaluating annual, functional decline in relation to exposure between 1981 and 1988. In this analysis, no association was found between FEV1 and exposure accumulated between surveys. The expected smoking-related abnormalities were observed. Thus, it appears that the 7-year exposure to dust in the work environment examined is not associated with long-term health effects. Approximately 50 % of subjects were lost to follow-up therefore conclusions that can be made regarding chronic respiratory effects of borate exposure are limited.

Sensitisation:

The data indicate that these borates are not sensitisers. No evidence of skin sensitisation in humans exposed occupationally to borates has been reported (Bruze et al., 1995).

Repeat dose toxicity:

Generally, it can be stated that chronic boric acid intoxication may have a mode of presentation quite different from that of the acute form (Gordon et al, 1973) and single large doses (~250-300 mg B/adult) are often less dangerous than repeated smaller doses (Jordon & Crissey, 1956). Since boric acid is principally eliminated by the kidney, impaired renal function may account for the high blood levels observed in some patients (Jordon & Crissey, 1956) and this might also be an explanation for differences in human responses.

Oral:

In humans multiple exposures to boric acid and borax result in various symptoms which may appear singly or together and include dermatitis, desquamation of the skin, alopecia, loss of appetite, nausea, vomiting, diarrhoea, menstruation disorders, anaemia and focal or generalized central nervous system irritation or convulsions. Much data comes from the mid 1800s to around 1940, when borates were used systematically for a variety of medical conditions including amenorrhea, malaria, epilepsy, urinary tract infection and exudative pleuritis (Kliegel, 1980).

The most frequently reported symptoms in poisoning cases between 113 mg – 500 mg B/day (equivalent to 646 – 1857 mg boric acid or 1000 – 4425 mg borax) are nausea, emesis, diarrhoea, skin rash, erythema, desquamation and alopecia, but it is important to note that in about half of these cases no vomiting was induced (Kliegel, 1980).

Dermal:

Several poisoning cases after treatment of burned or abraded skin have been described. Exact doses are difficult to derive for dermal application, but the described effects are the same as for oral exposure (Kliegel, 1980).

Inhalation:

One poisoning case via the inhalation route was described in a 50 year old man who was exposed to borax dust occupationally. The induced effects were alopecia, insomnia, headache, erythema and desquamation with verification of boron in the urine (Tan, 1970). The sole long-term (7-year) follow-up study failed to identify any long-term health effects, although a healthy worker effect cannot be entirely ruled out, given the rate of attrition (47 %) (Wegman et al. 1991; Wegman et al., 1994).

Fertility:

The potential reproductive effects of inorganic borate exposure to a population of workers at a large mining and production facility was assessed using the Standardised Birth Ratio (SBR), a measure of the ratio of observed to expected births. The average exposure for the highest exposure group was 28.4 mg B/day (approximately 0.4 mg B/kg bw/day) for two or more years. The average duration of exposure was 16 years. The number of offspring indicated no adverse effects on reproduction in these workers (Whorton et al., 1994). Exposure data used in this study was the same as reported by Wegman et al. 1991, and was collected using the total dust sampler. The IOM equivalent exposure would be 71 mg B/day.

In a study of a highly exposed population in, where exposure comes mainly from naturally high levels of B in drinking water (up to 29 mg B/L) as well as from mining and production, no adverse effect has been reported on fertility over three generations (Sayli, 1998; 2001).

Boron treatment of rats, mice and dogs has been associated with testicular toxicity, characterised by inhibited spermiation at lower dose levels and a reduction in epididymal sperm count at higher dose levels. Studies in human workers and populations have not identified adverse effects of boron exposure on fertility (Robbins et al. 2010, Scialli et al. 2010).

Chinese workers were studied by a research team from the Beijing University of Science and Technology and the China National Environmental Monitoring Centre in collaboration with University of California at Los Angeles (Robbins et al. 2010). Boron exposure/dose measures in workplace inhalable dust, dietary food/fluids, blood semen and urine were collected from boron workers and two comparison worker groups (n = 192) over three months and correlations between boron and semen parameters. Parameters for total sperm count, sperm concentration, motility and morphology were not significantly different across the three boron exposure comparison groups. Continuous measures of boron in workers' post-work shift urine and blood were correlated with percent normal morphology but this did not remain statistically significant after controlling for age, abstinence interval, smoking, alcohol intake, pesticide exposure and mg blood levels. No other significant correlations between boron levels and conventional semen parameters were found. DNA strand breakage and percent apoptotic cells were similar cross the exposure groups and not correlated with boron levels in post-work shift urine or blood (p > 0.05). Sperm aneuploidy and diploidy did not differ by exposure group or boron levels (Robbins, 2010).

Scialli et al (2010) reviewed and summarized the papers of the study of Chinese workers that described the reproductive effects of boron exposure, particularly in North Eastern China. This study was reported in a series of publications, some of which were in Chinese and some in English. Boron workers (n = 75) had a mean daily boron intake of 31.3 mg B/day, and a subset of 16 of these men, employed at a plant where there was heavy boron contamination of the water supply, had an estimated mean daily boron intake of 125 mg B/day. Estimates of mean daily boron intake in local community and remote background controls were 4.25 mg B/day and 1.40 mg/day, respectively. Three categories of endpoints were identified: Semen analysis, reproductive outcome and sperm X: Y ratio. There were no statistically significant differences in semen characteristics between exposure groups including in the highly exposed subset, except that sperm X: Y ratio was reduced in boron workers. Within exposure groups the X: Y ratio did not correlate with the boron concentration in blood, semen and urine. 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 (Scialli et al. 2010). 

 

The Chinese semen studies in highly exposed workers are a major source of information as to human reproductive toxicity. Not only are these the most exposed workers, but the Chinese worker study is themost sensitive study that has been carried out as semen analysis was performed, a very sensitive detection system for testicular damage.

Limitations of this research include:

1) The number of workers in the study cohort is limited given the large variation in most semen characteristics.

2) Recruitment procedures of workers for the various study groups are not entirely clear raising a concern with respect to possible selection bias.

3) It is uncertain if results obtained in the Chinese population fully apply to people in other regions of the world.

4) One semen study (presented in several papers) is insufficient to provide strong evidence that a given exposure is not representing a human hazard at the given exposure levels.

5) The highest exposed workers were exposed to about 5mgB/Kg/day, about one third to one quarter of the NOAEL for testis effects in rodents. However, this shows that humans are not significantly more sensitive to this type of toxic effect than rodents.

In an epidemiologic cohort study with 102 exposed workers and 102 control workers, the correlation between combined environmental and occupational exposure to boron and boron levels in blood, urine and semen was analyzed (Duydu et al. 2011). This study was conducted to investigate the reproductive effects of boron exposure in workers employed in a boric acid production plant in Turkey. A high environmental oral exposure via contaminated well water of the central cantina was found for both groups leading to a re-classification of all 204 workers into 4 groups based on their calculated total daily boron exposure (DBE) and their blood boron concentrations. The new control group had blood boron levels below the LOQ of 48.5 ng/g, additionally a low, medium and high exposure group were derived. Average age and average period of employment compared favourably between the groups. While blood and urine levels correlate reasonably well with the calculated exposure, the correlation between blood boron levels and semen boron levels is very weak. Boron is accumulated in semen and the concentration factor is highest at the lowest exposure.

Adverse effects in hormone levels were absent when exposure groups are compared to the new control group. For any of the semen parameters a statistically significant differences was seen between new control group and exposure groups. These facts indicates that boron does not have an adverse effect on the male reproductive system at typical exposure conditions.

 

In addition to the published data additional reprouping of the exposed workers was done based on the urine boron level and the semen boron level into 4 groups respectively. This data is confidential and legal property of ETI MINE SA and therefore only shortly summarised here. It has to be stated that for several parameters the scattering of values within the respective groups are large resulting often in standard deviations that have almost the same magnitude as the average value. In these cases the relative low number of volunteers per group complicates the determination of correlations.

Correlation between semen levels and adverse effects:

For Neck/mid-piece defects (%) a statistically significant difference in the percentage was seen in the pairwise comparison of the low dose with the high dose and the mid dose with the high dose but not the control with the high dose. No clear dose response is seen, and the correlation coefficient of 0.228 is very weak.

Correlation between urine levels and adverse effects:

For FSH (follicle stimulating hormone) the global null hypothesis that all group means are equal wass rejected. The significant pair wise differences are between Control-Medium and Medium-High. Neither a clear dose response nor a significant correlation was found. A statistically significant correlation was seen between urine boron concentrations and LH (lutenising hormone) levels. Nevertheless this correlation is very weak.

Besides the effects stated in the two preceding paragraphs no other statistically significant effects or correlations between boron levels in body fluids and semen parameters or hormone levels were found.

The weak effects, that were seen, are all not indicative for a reproductive toxicity potential of boric acid but are rather most probably incidental. The absence of clear correlations between urine or semen boron levels and adverse effects in semen parameters strengthens the position made in the publication that boron does not have an adverse effect on the male reproductive system at typical exposure conditions.

Developmental: 

While developmental effects of boron have been observed in rodent bioassays that include fetal body weight reduction and minor skeletal variations, 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). Three epidemiological studies evaluating high environmental exposures to boron and developmental effects in humans have been conducted. Epidemiological studies of human developmental effects have shown an absence of effects in exposed borate workers and populations living in areas with high environmental levels of boron. A more detail discussion of these studies is presented in Appendix B.

Comparison of Blood, Semen and Testes Boron Levels in Human and Rat

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. Background boron levels in standard rat chow are high (10-20 ppm), as a result control rats in toxicity studies receive 45 times more boron than background exposure in humans. Blood boron levels in female control rats is about 0.23 µg B/g (Price et al. 1997), approximately equal to the blood levels in boron industry workers in China, Turkey and U.S. of 0.25, 0.22 and 0.26 µg B/g, respectively (Scialli et al. 2010; Culver et al. 1994; Duydu et al. 2011). Plasma and seminal vesicle fluid (the major component of semen) boron levels in untreated male control rats were 1.94 and 2.05 µg B/g, respectively, while boron levels in testes in rats dosed at the rat fertility LOAEL (26 mg B/kg) was 5.6 µg B/g (Ku et al. 1991,1993). Values in male control rats were higher than corresponding boron levels in the highest exposed Chinese boron industry workers with blood boron levels of 1.56 µg B/g and 1.84 µg B/g in semen (Scialli et al. 2010). Blood and semen boron levels in highly exposed Turkish boron workers were also lower than control rats with levels of 0.22 and 1.88 µg B/g, respectively (Duydu et al. 2011). Boron levels in testes of rats dosed at the rat fertility LOAEL was over 3x the blood boron levels in highest exposure group of Chinese boron industry workers. The blood level at the lowest animal LOAEL (13 mg B/kg) was 1.53 µg B/g, about 6 times greater than typical boron industry workers (Price et al. 1997). No adverse effects on sperm were seen in Turkish boron industry workers or in the most highly exposed subgroup of Chinese boron industry workers drinking boron contaminated water (mean blood level 1.52 µg B/g, the human NOAEL). Only under extreme conditions do human levels reach those of the animal LOAEL: the subgroup of Chinese boron workers who also drank contaminated water. Since no boron accumulation occurs in soft tissues (testes) over plasma levels biological monitoring in humans provide direct comparison to test animal target organ boron levels. Workers in boron mining and processing industries represent the maximum possible human exposure however their blood and semen boron levels are less than levels in untreated control rats. This provides an explanation whystudies of highly exposed boron industry workers have shown no adverse effects anddemonstrates that maximal possible exposures in humans are insufficient to cause reproductive toxicity effects.Graphs comparing the rodent and human exposure, blood, semen and tissue boron levels are presented in Appendix C.

Essentiality

A recent review of evidence for the essentiality of dietary boron shows that boron meets the criteria for essentiality in humans (Hunt 2007). A nutritional role for boron has been demonstrated in humans and animals (Nielsen 1994, 1996, 1998; Hunt 1994, 1996, 1998; Penland 1994, 1998; Hunt et al 1997; Nielsen and Penland 1999; Hunt and Idso 1999). The essentiality of dietary boron in humans is suspected but has not been directly proven (NRC 1989; Mertz 1993; Devirian and Volpe 2003). A World Health Organization (WHO) expert committee concluded that boron is “probably essential” (WHO1996). Although the data is not sufficient to confirm essentiality in humans, the U. S. Food and Nutrition Board in 2001 (FNB 2001) published a Tolerable Upper Intake Level (UL) for boron of 20 mg/day. Also, the UK Expert Group on Vitamins and Minerals (EGVM 2003) and the European Food Safety Authority (EFSA 2004) also regarded boron as nutritionally important and determined an acceptable daily intake for boron (0.16 mg /kg/day). More detail discussion of the essentiality and beneficial effects of boron presented in Appendix C.

Weight of Evidence Evaluation

Although reproductive and developmental effects have been demonstrated in laboratory animals exposed to high doses of boric acid in their feed, similar effects have not been observed in highly exposed human populations or workers. 

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 salycilate (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 pentahydrat\e (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 potassium pentaborate will cause reproductive or developmental effects in humans.