Registration Dossier

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test method was similar to OECD 409 guideline, but only three animals of each sex were used per dose. No GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1970
Report Date:
1970

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 409 (Repeated Dose 90-Day Oral Toxicity in Non-Rodents)
Deviations:
yes
Remarks:
(only three animals of each sex were used per dose).
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): NaTA

Test animals

Species:
dog
Strain:
Beagle
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 13 months old
- Weight at study initiation: Average: 15.8 kg (15.0-17-7 kg)

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90 days
Frequency of treatment:
Daily
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
500 ppm
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
2000 ppm
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
4000 ppm
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
8000 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
3 male and 3 female dogs per group
Control animals:
yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:
During all the test period, general clinical observations were made once a day (signs of morbidity and mortality, food consumption). The body weight was recorded once a week. At the end of the study blood and urine analysis, and the macro- and microscopic examination of the organs were made.
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Haematological findings:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related

Effect levels

Dose descriptor:
NOEL
Effect level:
500 ppm
Sex:
male/female
Basis for effect level:
other: From 2000 ppm upwards effects were observed in mortality, body weights, haematology, urinalysis, gross pathology and histopathology.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

The male animals were significantly more affected by the administration of sodium trichloroacetate than the female. Five male dogs from the two highest dose groups did not survive the experiment and they had to be humanely killed.One female died intercurrently of pleuritis. All dogs in groups from 2000 ppm upwards showed a body weight reduction. With the exception of the 500 ppm dose, all treated animals showed anemia and white cell counts disorders. In groups from 2000 ppm upwards, changes in liver and heart muscles were recorded. From 4000 ppm upwards atrophy of skeletal muscles occurred. It was also observed damage to spermatogenesis in animals from the 2000 ppm group upwards. Urinalysis of the males from the 4000 ppm and 8000 ppm groups killed during the study revealed positive protein and bilirrubin reactions.

Applicant's summary and conclusion

Conclusions:
Based on the results, the no effect level in this study was 500 ppm (approximately 30 mg sodium trichloroacetate/kg bw/day).
Executive summary:

Sodium trichloroacetate was studied in a subchronic toxicity experiment for 90 days. The substance was administered daily in food to three male and three female beagle dogs at four dose levels (500, 2000, 4000 and 8000 ppm). Another group with the same number of animals was used as a control group. The male animals were significantly more affected by the administration of sodium trichloroacetate than the female. Five male dogs from the two highest dose groups did not survive the experiment and they had to be humanely killed. One female died intercurrently of pleuritis. All dogs in groups from 2000 ppm upwards showed a body weight reduction. With the exception of the 500 ppm dose, all treated animals showed anemia and white cell counts disorders. In groups from 2000 ppm upwards, changes in liver and heart muscles were recorded. From 4000 ppm upwards atrophy of skeletal muscles occurred. It was also observed damage to spermatogenesis in animals from the 2000 ppm group upwards. Urinalysis of the males from the 4000 ppm and 8000 ppm groups killed during the study revealed positive protein and bilirrubin reactions. Based on these results, the no-effect-level in this study was 500 ppm (approximately 30 mg sodium trichloroacetate/kg bw/day).