Boric acid, zinc salt

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

other: worker reproductive toxicity study

Adequacy of study:

key study

Study period:

No data

Reliability:

other: Not applicable

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Acceptable well documented publication which meets basic scientific principles Read-across is justified on the following basis: The family of zinc borates that include Zinc Borate 500, Zinc Borate 2335 and Zinc Borate 415 (also known as Zinc Borate 411). Zinc borate 500 is anhydrous Zinc Borate 2335 and Zinc Borate 415 has different zinc to boron ratio. Zinc borate 2335 (in common with other zinc borates such as Zinc borate 415 and 500) breaks down to Zinc Hydroxide (via Zinc oxide) and Boric Acid, therefore the family of zinc borates shares the same toxicological properties. Zinc borates are sparingly soluble salts. Hydrolysis under high dilution conditions leads to zinc hydroxide via zinc oxide and boric acid formation. Zinc hydroxide and zinc oxide solubility is low under neutral and basic conditions. This leads to a situation where zinc borate hydrolyses to zinc hydroxide, zinc oxide and boric acid at neutral pH quicker than it solubilises. Therefore, it can be assumed that at physiological conditions and neutral and lower pH zinc borate will be hydrolysed to boric acid, zinc oxide and zinc hydroxide. Hydrolysis and the rate of hydrolysis depend on the initial loading and time. At a loading of 5% (5g/100ml) zinc borate hydrolysis equilibrium may take 1-2 months, while at 1 g/l hydrolysis is complete after 5 days. At 50 mg/l hydrolysis and solubility is complete (Schubert et al., 2003). At pH 4 hydrolysis is complete. Zinc Borate 2335 breaks down as follows: 2ZnO • 3B2O3 •3.5H2O + 3.5H2O + 4H+ ↔ 6H3BO3 + 2Zn2+ 2Zn2+ + 4OH- ↔ 2Zn(OH)2 ____________________________________________________________ Overall equation 2ZnO • 3B2O3 •3.5H2O + 7.5H2O ↔ 2Zn(OH)2 + 6H3BO3 The relative zinc oxide and boric oxide % are as follows: Zinc borate 2335:zinc oxide = 37.45% (30.09% Zn) B2O3 = 48.05% (14.94% B) Water 14.5% Zinc borate 415: zinc oxide = 78.79%; (63.31% Zn) B2O3 = 16.85% (5.23% B) Water 4.36% Zinc borate, anhydrous: Zinc oxide = 45 % B2O3= 55% (17.1 % B)

Data source

Reference

Reference Type:

publication

Title:

Chronic boron exposure and human semen parameters.

Author:

Robbins WA, Xun L, Jia J, Kennedy N, Elashoff DA & Ping L.

Year:

2010

Bibliographic source:

Reproductive Toxicology 29: 184 - 190.

Materials and methods

Study type:

other: worker reproductive toxcity study

Endpoint addressed:

toxicity to reproduction / fertility

Test guideline

Qualifier:

according to guideline

Guideline:

other: No data

Deviations:

not specified

Principles of method if other than guideline:

Boron exposure/dose measures in workplace inhalable dust, dietary food/fluids, blood semen and urine were collected from born workers and two comparison worker groups (n = 192) over three months and correlations between boron and semen parameters, namely total sperm count, sperm concentration, motility, morphology, DNA breakace, apoptosis and aneuploidy were determined.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

borates

IUPAC Name:

borates

Details on test material:

- Name of test material: Borates

Method

Details on study design:

METHOD OF DATA COLLECTION
- Type: Interview and sampling
- Details: Data was collected using a 51 item questionnaire developed during phase 1 in collaboration with a Community Advisory Board familiar with local industry and customs. Inter-rater reliability of this instrument demonstrated an error rate of less than 0.8 %. Consistency of data reported by subjects over the repeated sampling interval was > 95 %. Domains included work, general health, reproductive health, diet and lifestyle.
Boron exposure through inhalable dust was assessed using full workshift breathing zone air samples collected using inhalable particulate mass lapel filter cassettes and personal air monitoring pumps. Each pump was calibrated pre- and post-shift.
Boron exposure through food and fluids was assessed by collecting 24 h duplicate food and fluids for all men during the exposure assessment phase in 2003 and a subset of volunteers (15 per exposure group) in 2004. A composite of total daily exposure was generated by adding exposure through work place inhalable dust, food and fluid intake and this was shown to be highly correlated with post-workshift urine. Post-workshift urine was then used to predict total exposure for the study period. Post-shift urine ranged from 1.3 - 217.0 mg/L in boron workers; 0.7 - 121.3 mg/L in the community comparison group and 0.7 - 6.0 mg/L in the control comparison group.

STUDY PERIOD: 3 months

STUDY POPULATION
- Selection criteria: Employed at the same work place for at least the previous year, not currently under treatment for chronic disease and no history of vasectomy.
- Total number of subjects participating in study: Boron workers n = 74
- Sex/age/race: 18 - 40 years of age,


COMPARISON POPULATION
- Type: Control group:
- Details: A comparison control group (n = 70) enrolled from a region with very little boron in ground water and soil ~30 miles away. A second comparison group (n = 60) was enrolled to assess effects of environmental exposure to boron through food and water due to living in the area of boron industry with high environmental boron but not working in the boron industry, referred to as the community comparison group.

HEALTH EFFECTS STUDIED
- health effects: Semen parameters

Exposure assessment:

measured

Results and discussion

Results:

Based on interview data, the three comparison groups did not differ significantly on history of infertility, having prior semen analysis, history of radiation or surgery or injury to the genital tract, exposure to other known reproductive toxicants, use of contraception, years of marriage, spontaneous pregnancy loss, stillbirths or birth defects in offspring (p >0.05). The means for self-reported abstinence interval were not statistically significant across groups (p > 0.05). The median abstinence interval was three days for each group, however several men reported extended abstinence intervals that varied across the exposure groups. Evaluating the data with and without the men reporting extended abstinence intervals gave similar results overall. Because of the importance of abstinence interval to interpretation of semen parameters, especially total sperm count it was included as a covariant in the final analyses. The groups differed on boron measures in blood, semen and post-work shift urine. Boron workers had the highest levels of boron in blood, urine and semen with the community comparison group falling between the boron worker group and the group from the area of low environmental boron. Each participant contributed three semen samples, one a month spanning approximately three months. Comparisons across the three samples showed them not to differ significantly on semen parameters, except for morphology "percent natural forms" (p = 0.04) and sperm head defects (p = 0.004). Averaging the three samples and using the mean for statistical testing gave the same conclusions overall. Because the third sample was most representative of a complete cycle of spermatogenesis for which continuous exposure data was available, analyses presented were based on the third semen sample.

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.

Confounding factors:

No data

Strengths and weaknesses:

No data

Applicant's summary and conclusion

Conclusions:

Blood boron averaged 499.2 ppb for boron workers, 96.1 and 47.6 ppb for workers from high and low environmental boron areas (p < 0.0001). Boron concentrated in seminal fluid. No significant correlations were found betwen blood or urine boron and adverse semen parameters.