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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: Spermhead morphology assay (reproductive function)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Test method was not according to any guideline. It provides information on the observed effects on the spermhead morphology. No data on GLP.

Data source

Reference
Reference Type:
publication
Title:
Genotoxicity Studies of Sodium Dichloroacetate and Sodium Trichloroacetate.
Author:
Meier JR, Stewart BE, Blazak WF
Year:
1997
Bibliographic source:
Environmental Sciences, 5, 2, 095-108.

Materials and methods

Principles of method if other than guideline:
A spermhead morphology assay was performed in mice with sodium trichloroacetate. B6C3F1 mice (24/group) were given 0, 625, 1250, or 2500 mg/kg bw/day of test substance for five consecutive days by oral gavage. Twelve mice per treatment group were sacrificed at 21 and 35 days after the first treatment. These sacrifice times correspond to treatment of cells at the late spermatogonial and primary spermatocyte periods, respectively, assuming no treatment-related delays in sperm development. Body weights were recorded for each animal during the dosing phase and at sacrifice, and testes and cauda epididymidal weights were recorded at sacrifice. Ten animals from each treatment/sacrifice group were randomly selected to be evaluated for sperm count and morphology. The types and frequencies of spermhead abnormalities were based on the scoring of 500 sperm per animal.
GLP compliance:
not specified
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): TCA
- Analytical purity: > 99 %

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Simonsen Laboratories, lnc., Gilroy, CA, USA.
- Age at study initiation: Eleven-week-old
- Weight at study initiation: 20-30 g
- Housing: The animals were housed six per cage with wood shavings used for bedding, and beddings were changed weekly.
- Diet (e.g. ad libitum): Certified Purina Lab Chow, #5002C, ad libitum.
- Water (e.g. ad libitum): Recirculated, deionized, UV -treated water was available to the animals throughout the study.
- Acclimation period: min. 5 days

ENVIRONMENTAL CONDITIONS
- Photoperiod: 12 hrs dark / 12 hrs light.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
A forty percent (w/v) solution of the acid as its sodium salt was prepared by dissolving sodium trichloroacetate in distilled water and titrating the pH to 7.0 with NaOH.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
5 days
Frequency of treatment:
Daily
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
625 mg/kg bw/day
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
1250 mg/kg bw/day
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
2500 mg/kg bw/day
Basis:
nominal conc.
No. of animals per sex per dose:
24 male mice per group were used.
Control animals:
yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:
Twelve mice per treatment group were sacrificed at 21 and 35 days after the first treatment. These sacrifice times correspond to treatment of cells at the late spermatogonial and primary spermatocyte periods, respectively, assuming no treatment-related delays in sperm development.
Body weights were recorded for each animal during the dosing phase and at sacrifice, and testes and cauda epididymidal weights were recorded at sacrifice.
Sperm parameters (parental animals):
Ten animals from each treatment/sacrifice group were randomly selected to be evaluated for sperm count and morphology.
The types and frequencies of spermhead abnormalities were based on the scoring of 500 sperm per animal.
Statistics:
Initial and sacrifice body weights, testes and cauda epididymal weights, testes to final body weight ratios, and sperm concentration/mg of cauda epididymis were analyzed by one-way analysis of variance (ANOVA) at a significance level of p < 0.05. When significant differences were found, Dunnett's test was applied to compare the different treatment group means with the negative control means. The numbers of morphologically abnormal sperm were analyzed by the Kruskall-Wallis and Mann-Whitney U tests, with differences considered significant at the p < 0.05 level. These latter tests are nonparametric alternatives to ANOVA and Dunnett's test, respectively.

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
not examined

Details on results (P0)

The testes-to-final-body weight ratio, the number of sperm per milligram of cauda epididymis, and the percentage of abnormal spermheads were unaffected in the treated animals either at 21 or 35 days following oral gavage administration.

Effect levels (P0)

Dose descriptor:
NOEL
Effect level:
>= 2 500 mg/kg bw/day
Sex:
male
Basis for effect level:
other: overall effects
Remarks on result:
other: Generation not specified (migrated information)

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

The NOEL value at 21 and at 35 days wqas equal or greater than 2500 mg/kg bw/day.

Applicant's summary and conclusion

Conclusions:
The NOEC value at 21 and at 35 days was equal or greater than 2500 mg/kg bw/day.
Executive summary:

A spermhead morphology assay was performed in mice with sodium trichloroacetate. B6C3F1 mice (24/group) were given 0, 625, 1250, or 2500 mg/kg bw/day of test substance for five consecutive days by oral gavage. Twelve mice per treatment group were sacrificed at 21 and 35 days after the first treatment. These sacrifice times correspond to treatment of cells at the late spermatogonial and primary spermatocyte periods, respectively, assuming no treatment-related delays in sperm development. Body weights were recorded for each animal during the dosing phase and at sacrifice, and testes and cauda epididymidal weights were recorded at sacrifice. Ten animals from each treatment/sacrifice group were randomly selected to be evaluated for sperm count and morphology. The types and frequencies of spermhead abnormalities were based on the scoring of 500 sperm per animal. Initial and sacrifice body weights, testes and cauda epididymal weights, testes to final body weight ratios, and sperm concentration/mg of cauda epididymis were analyzed by one-way analysis of variance (ANOVA) at a significance level of p < 0.05. When significant differences were found, Dunnett's test was applied to compare the different treatment group means with the negative control means. The numbers of morphologically abnormal sperm were analyzed by the Kruskall-Wallis and Mann-Whitney U tests, with differences considered significant at the p < 0.05 level. These latter tests are nonparametric alternatives to ANOVA and Dunnett's test, respectively.

The testes-to-final-body weight ratio, the number of sperm per milligram of cauda epididymis, and the percentage of abnormal spermheads were unaffected in the treated animals either at 21 or 35 days following oral gavage administration.

The NOEL value at 21 and at 35 days was equal or greater than 2500 mg/kg bw/day.