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Administrative data

Endpoint:
epidemiological data
Type of information:
other: worker reproductive toxcity study
Adequacy of study:
key study
Study period:
No data
Reliability:
other: Not applicable
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study is conducted on an analogue substance. Read-across is justified on the following basis: In aqueous solutions at physiological and acidic pH, low concentrations of simple inorganic borates such as boric acid, disodium tetraborate decahydrate, disodium tetraborate pentahydrate, boric oxide and disodium octaborate tetrahydrate will predominantly exist as undissociated boric acid. At about pH 10 the metaborate anion (B(OH)4-) becomes the main species in solution (WHO, 1998). This leads to the conclusion that the main species in the plasma of mammals and in the environment is un-dissociated boric acid. Since other borates dissociate to form boric acid in aqueous solutions, they too can be considered to exist as un-dissociated boric acid under the same conditions. For comparative purposes, exposures to borates are often expressed in terms of boron (B) equivalents based on the fraction of boron in the source substance on a molecular weight basis. Some studies express dose in terms of B, whereas other studies express the dose in units of boric acid. Since the systemic effects and some of the local effects can be traced back to boric acid, results from one substance can be transferred to also evaluate the another substance on the basis of boron equivalents. Therefore data obtained from studies with these borates can be read across in the human health assessment for each individual substance. Conversion factors are given in the table below. Conversion factor for equivalent dose of B Boric acid H3BO3 0.175 Boric Oxide B2O3 0.311 Disodium tetraborate anhydrous Na2B4O7 0.215 Disodium tetraborate pentahydrate Na2B4O7•5H2O 0.148 Disodium tetraborate decahydrate Na2B4O7•10H2O 0.113 Disodium octaborate tetrahydrate Na2B8O13•4H2O 0.210 Sodium metaborate (anhydrous) NaBO2 0.1643 Sodium metaborate (dihydrate) NaBO2•2H2O 0.1062 Sodium metaborate (tetrahydrate) NaBO2•4H2O 0.0784 Sodium pentaborate (anhydrous) NaB5O8 0.2636 Sodium pentaborate (pentahydrate) NaB5O8∙5H2O 0.1832 References: WHO. Guidelines for drinking-water quality, Addendum to Volume 1, 1998.

Data source

Reference
Reference Type:
publication
Title:
An overview of male reproductive studies of boron with an emphasis on studies of highly exposed Chinese workers
Author:
Scialli AR, Bonde JP, Brüske-Hohlfeld, Culver DB, Li Y & Sullivan FM.
Year:
2010
Bibliographic source:
Reproductive Toxicology 29: 10 - 24.

Materials and methods

Study type:
other: worker reproductive toxcity study
Endpoint addressed:
toxicity to reproduction / fertility
Test guideline
Qualifier:
according to
Guideline:
other: No data
Deviations:
not specified
Principles of method if other than guideline:
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, but outcome measures in these studies were relatively insensitive, based on family size and did not include an evaluation of semen endpoints. This review outlines the general outline of boron and its reproductive effects and includes the basic procedures used in a Chinese study. Three categories of endpoints were identified: Semen analysis, reproductive outcome and sperm X:Y ratio.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: Boric acid; Borax

Method

Details on study design:
A review panel reviewed and summarized papers of studies of highly exposed Chinese workers in China. Male workers at one boron mine and four boron processing plants in northeast China were studied. The 5 workplaces were selected based on the location, number of employees and the presence and cooperation of an industrial hygienist at the site. 957 men between 18 and 40 years of age agreed to an interview to provide demographic, exposure, reproductive and general health information. Of the interviews, 945 were considered eligible. Potential subjects were 25 - 35 years of age, married without a history of contact with a number of substances and disorders. In addition to general physical examination, men were evaluated for hair distribution breast tissue size; the size, firmness and location of testes, epididymides and ductus deferens and the presence of variocele of hydrocele.
A comparison group of 251 men were recruited from an area 30 miles away with low background boron exposure levels. Later in the course of the studies, another comparison group was added, consisting of 63 workers without occupational exposure to boron but drawn from the same community as the boron workers and was termed the local community control group.

Boron content of environmental and biological samples was measured. The detection limits and relative standard deviation for boron in different media were: Airborne particulates 0.01 μg/g ± 5.01 %; food 0.0063 μg/g ± 0.63 %; drinking water and urine by ICP-AES 0.0072 ng/mL ± 0.6 %; drinking water and urine by ICP-MS 0.057 μg/mL ± 1.25 %.
Personal measurements were performed in borate processing areas using IOM inhalable dust sampler. Total airborne dust concentrations ranged from 0.3 to 33 mg/m3. The boron concentration in the dust ranged from 1.5 to 4.2 %.
Ingestion was measured from the sum of boron intake from food and drink several times using a duplicate plate method. Boron workers were calculated to ingest a weighted mean of 16.9 mg B/day, while the community comparison group's boron intake was 4.25 mg B/day.
Exposure assessment:
measured

Results and discussion

Results:
Semen analysis:
The data do not indicate that boron exposure under the conditions described impairs testicular function with respect to sperm concentration, motility morphology or chromatin denaturability. The methods used to assess these endpoints were standard methods reliably performed.

Reproductive success:
Evaluation of sex ratio did not show a significant effect of boron exposure.

Sperm X:Y ratio
There were differences in Y:X ratio across the three groups defined by boron exposure. Y:X ratio appeared to be more related to group membership than boron exposure. The within-subject variability of Y:X ratio and possible determinants of Y:X ratio are unknown, except for possible miniscule effects of age, calendar time and race. Y:X ratio is not known to be associated with impaired semen quality, reproductive success or offspring health.

There is no clear evidence of male reproductive effects attributable to boron in studies of highly exposed workers.
Confounding factors:
No data
Strengths and weaknesses:
Semen analysis:
There are questions regarding the selection of subjects for semen analysis and whether bias may have been introduced by subject selection.
The statistical power of the analyses was considered adequate.

Reproductive success:
The methods were not adequate to address the question of whether men exposed occupationally have different reproductive experiences than men not so exposed.
The assessment of sex ratio in China is considered unlikely to be reliable.

Applicant's summary and conclusion

Conclusions:
Reproductive outcomes in the wives of 945 boron workers were not significantly different from outcomes in the wives of 249 background control men after adjustment for potential confounders. 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.
Read-across is justified on the basis detailed in the rationale for reliability above. This study is therefore considered to be of sufficient adequacy and reliability to be used as a supporting study and no further testing is justified.