TCA

Repeated dose toxicity: oral

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

Guideline:

OECD Guideline 409 (Repeated Dose 90-Day Oral Toxicity Study in Non-Rodents)

Deviations:

yes

Remarks:

(only three animals of each sex were used per dose).

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

TCA

EC Number:

211-479-2

EC Name:

TCA

Cas Number:

650-51-1

Molecular formula:

C2HCl3O2.Na

IUPAC Name:

trichloroacetic acid

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 or test system 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 / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
500 ppm
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
2000 ppm
Basis:
nominal in diet

Doses / concentrations 3

Remarks:

Doses / Concentrations:
4000 ppm
Basis:
nominal in diet

Doses / concentrations 4

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).