Reaction product of mixed inorganic base and acid resulting in dipotassium hydroxytetrafluoro triborontrioxide, dipotassium tetrahydroxy tetraboronpentaoxide dehydrate, potassium fluoride, potassium tetrafluroborate, water in paste form

Epidemiological data

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:

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 simillar 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.
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.