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Toxicological information

Toxicity to reproduction: other studies

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Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
No data
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Does not meet important study design or analytical criteria.

Data source

Reference
Reference Type:
publication
Title:
Effect of acute exposure to boric acid on the male reproductive system of the rat.
Author:
Linder RE, Strader LF & Rehnberg GL.
Year:
1990
Bibliographic source:
J. Toxicol. Environ. Health 31: 133 - 146.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
In a time-response study, groups of Sprague-Dawley adult male rats (6 rats per group) were exposed by gavage to boric acid at doses of 0 (control) and 2,000 mg boric acid/kg bw (the dose was administered in two volumes on the same day). These doses corresponded to 0 and 350 mg B/kg bw, respectively. Rats were killed at 2, 14, 28 and 57 days post-exposure.
In a second study, groups of Sprague-Dawley adult male rats (8 rats per group) were exposed by gavage to boric acid at doses of 0, 250, 500, 1,000 and 2,000 mg boric acid/kg bw (the dose was administered in two volumes on the same day). These doses correspond approximately to 0, 44, 88, 175 and 350 mg B/kg bw. All animals in the dose-response study were killed 14 days post exposure since this was identified as the interval at which maximum testicular damage was observed in the corresponding time-response study.
GLP compliance:
no
Type of method:
in vivo

Test material

Constituent 1
Chemical structure
Reference substance name:
Boric acid
EC Number:
233-139-2
EC Name:
Boric acid
Cas Number:
10043-35-3
Molecular formula:
H3BO3
IUPAC Name:
Boric acid
Details on test material:
- Name of test material: Boric acid.
- Analytical purity: 99 %
- Lot/batch No.: 95F-0275

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Raleigh, NC.
- Age at study initiation: 105 days
- Housing: Two per cage
- Acclimation period: 2 weeks
- Diet: Ad libitum
- Water: Ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 72 ± 2 °C
- Humidity (%): 50 ± 10 % relative humidity
- Photoperiod (hrs dark / hrs light): 12h light/12 h dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
The boric acid solutions (5 % in water) were administered in a dose volume of 20 mL/kg. The solubility of boric acid in cold water is approxximately 5.6 % therefore 2000 mg/kg was maximum practical dosage that could be given as an aqueous solution on a single day.
Groups of 6 control and 6 boric acid-treated rats were killed at 2 and 14 day post-treatment. Four additional groups of 6 rats each were treated as described but killed at 28 and 57 d post-treatment.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Single dose divided into two volumes administered on the same day
Frequency of treatment:
Single dose divided into two volumes administered on the same day
Duration of test:
57 days
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Remarks:
Study 1 and Study 2
Dose / conc.:
2 000 mg/kg bw/day (nominal)
Remarks:
Study 1
Dose / conc.:
250 mg/kg bw/day (nominal)
Remarks:
44 mg B/kg bw; Study 2
Dose / conc.:
500 mg/kg bw/day (nominal)
Remarks:
88 mg B/kg bw; Study 2
Dose / conc.:
1 000 mg/kg bw/day (nominal)
Remarks:
175 mg B/kg bw; Study 2
Dose / conc.:
2 000 mg/kg bw/day (nominal)
Remarks:
350 mg B/kg bw; Study 2
No. of animals per sex per dose:
Study 1: 6 males
Study 2: 8 males
Control animals:
yes
Details on study design:
Dose-response study: Unanaesthetised animals were decapitated and blood was collected for serum hormone assays. The testes, epididymides, prostate and seminal vesicles were excised and weighed. The ends (approximately 2 - 3 mm) of one testis were removed and this testis and the ipsilateral epididymis were immersed in Bouin's solution for 24 h then washed with 70 % ethanol saturated with lithin carbonat. Tissues were processed for light microscopy. The tissues were embedded in paraffin and transverse sections of hte testis and longitudinal sections of hte epididmysi were stained with hematoxylin and eosin, or periodic-Schff reagent and counterstained with hematoxylin. The contralateral testis was frozen for dtermination of sonication-resistant sperm heads. The contralateral epididymis was used for determination of cauda sperm motility, caput and cauda sperm morphology and caput and cauda sperm reserves.
Statistics:
Sperm counts, body weights and serum hormones were analysed by analysis of variance and Duncan's multiple range test. Organ weights were subjected to analysis of covariance using the final body weight as the covariant; equality of the group least-square means was compared with a t-test. Wilcoxon scores and Kruskal-Wallis test were used to evaluate sperm motility and sperm morphology.

Results and discussion

Effect levels

open allclose all
Dose descriptor:
LOAEL
Effect level:
2 000 mg/kg bw/day
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Study 1: Sporadic but statistically significant differences (p < 0.05) in reproductive organ weights were noted when compared to controls.
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day
Based on:
test mat.
Sex:
male
Dose descriptor:
LOAEL
Effect level:
350 mg/kg bw/day
Based on:
element
Sex:
male
Basis for effect level:
other: Study 1: Sporadic but statistically significant differences (p < 0.05) in reproductive organ weights were noted when compared to controls.
Dose descriptor:
NOAEL
Effect level:
88 mg/kg bw/day
Based on:
element
Sex:
male

Observed effects

In study one, at 2000 mg boric acid (350 mg B)/kg bw sporadic but statistically significant differences (p < 0.05) in reproductive organ weights were noted when compared to controls. The authors stated that these differences were slight and of questionable biological significance. Histopathological changes in the testis and epididymis appeared from day 14 after exposure. These changes consisted of disturbed sperm maturation in the tubules and testicular debris in the epididymides. Recovery occurred from day 28 onwards but was not quite complete at termination of the recovery period (Day 57 post exposure) since 2 out of 6 animals still had some retention of spermatids in the tubules. Abnormalities in sperm heads and tails and in sperm head counts were also observed from Day 14 and changes in spermatozoa motility were noted. By Day 57, all sperm parameters had returned to control levels confirming that the observed effects on sperm parameters were reversible at the dose level tested.

In the second study reported in the same publication, no effect on reproductive organ weights was observed at any exposure level when compared to controls. Histopathological changes in the testes as well as changes in sperm parameters consistent with the time-response study were observed in animals exposed to 1000 mg boric acid (175 mg B) and 2000 mg boric acid (350 mg B)/kg bw. No significant effect on serum hormones was found at any exposure level.

Applicant's summary and conclusion

Conclusions:
Aacute exposure to boric acid could adversely affect the testis (spermiation) and sperm quality in the adult male rat at dosages of 1000 mg boric acid (175 mg B)/kg bw and above. These effects were reversible at the dose level tested in the time response study (2000 mg boric acid (350 mg B)/kg bw) since by Day 57 post exposure, only minimal testicular changes remained. Based on the non-detection of the above effects, the authors concluded that the no observed effect level for acute exposure of the rat to boric acid was 500 mg boric acid (88 mg B)/kg.