α,α,α-trichlorotoluene

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: reliable without restriction 1b comparable to guideline study OECD 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Data source

Reference

Reference Type:

publication

Title:

Toxicity of trichlorotoluene isomers: A 28-day feeding study in the rat

Author:

Chu I., Shen S.Y., Villeneuve D.C. and Secours V.E.

Year:

1984

Bibliographic source:

Journal of Environmental Science and Health, B19(2): 183-191

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

no

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

α,α,α-trichlorotoluene

EC Number:

202-634-5

EC Name:

α,α,α-trichlorotoluene

Cas Number:

98-07-7

Molecular formula:

C7H5Cl3

IUPAC Name:

α,α,α-trichlorotoluene

Constituent 2

Reference substance name:

trichloromethylbenzene

IUPAC Name:

trichloromethylbenzene

Details on test material:

- Name of test material (as cited in study report): alpha, alpha, alpha-trichlorotoluene
- Analytical purity: 98%
- Other:
Supplier: Aldrich Chemical Co.

No more data available

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Vehicle:

corn oil

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

28 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0.5, 5.0, 50.0, 500 ppm (= ca. 0.038, 0.375, 3.75, 37.5 mg/kg bw)
Basis:
nominal in diet

No. of animals per sex per dose:

10 animals/sex per dose

Control animals:

yes

Results and discussion

Effect levels

Dose descriptor:

LOAEL

Effect level:

0.5 ppm

Sex:

male/female

Basis for effect level:

other: clinical signs; mortality; body weight; food consumption; haematology; clinical chemistry; organ weights; histopathology

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Clinical observations:

- No clinical signs of toxicity were observed

- No deaths

- Growth rate and food consumption not affected by treatment

- Based on food consumption data the amount of chemical ingested was 0.048 - 46 mg/kg bw/day for male rats and 0.053 - 53 mg/kg bw/day for female rats

- No gross changes observed

Organ weights:

- Organ weights not affected

Biochemistry:

- Significant increases in sorbitol dehydrogenase (SDH) activities in male rats (5.0 and 50.0 ppm dose group)

- Elevated LDH activities in male rats (500 ppm dose group)

Haematology:

- Hematological parameters and bone marrrow not affected by treatment

Histopathology:

- Mild histopathologic changes in the liver, kidney and thyroid of all the treated rats (even at highest dose levels), male rats more susceptible than female rats

- Histological changes became progressively more severe and more frequent as dose levels increased

- Liver: Hepatocytes had mild anisokaryosis associated with pyknosis and occasionally necrotic hepatocytes were observed. Cytoplasmic vacuolation and increased eosinophilia was seen in portal areas of the hepatic lobe

- Kidney: Renal changes consisted of an accumulation of eosinophilic cytoplasmic inclusions in the epithelium of proximal tubules associated with focal glomerular adhesions and interstitial scarring due to spontaneous ageing process

- Thyroid: reduced follicular size and colloid density. The epithelium cells became columnar and thickened with focal and multifocal angular angular collapse of follicles. Additional changes included focal and multifocal papillary proliferations and focal vacuolations.

- No residual compound was measured in liver and fat (detection limit: 0.1 ppm)

Applicant's summary and conclusion

Conclusions:

The authors tested the subacute oral toxicity of benzotrichloride in a 28-day feeding study with a methodology similar to the OECD guideline 407. In the test conditions, the LOAEL was established at 0.5 ppm. Consequently subacute oral toxicity of benzotrichloride is, for both male and female rats, of a low and similar order.

Executive summary:

The authors tested the subacute oral toxicity of benzotrichloride (CAS n° 98-07-7) in a 28-day feeding study with a methodology similar to the OECD guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents). The test substance was dissolved in corn oil and then mixed to the diet of weanling (ca. 60 g) male and female Sprague-Dawley rats . The doses given to the 10 animals/group/sex were 0.5, 5.0, 50.0, 500 ppm leading to 0.048 - 46 mg/ kg bw/day for male rats and 0.053 - 53 mg/kg bw/day for female rats of test substance finally ingested. A control group was also included.

Clinical observations were made daily, body weight and food consumption were determined weekly and after the 28 day feeding period the animals were lightly anesthetized with ether, exanguined and gross pathologically examined at necropsy. Bone marrow cytology, hematological parameters (hemoglobin concentration, packed cell volume, total and differential leukocyte cell counts), serum analysis and liver, brain, heart, spleen and kidney weights determined and prepared for microscopic inspection.

No deaths occured during the duration of the experiment and also growth rate, food consumption and haematological parameters were not affected by the treatments. Mild serum biochemical changes were observed in male rats, namely significant increases in SDH activities (sorbitol dehydrogenase, indicative for liver injury) (5.0 and 50.0 ppm dose group) and elevated LDH activities (lactate dehydrogenase) (500 ppm dose group). Mild histopathologic changes in the liver, kidney and thyroid of the treated rats were seen and males were more susceptible than females. The observed histological changes became progressively more severe and occurred more frequently as dose levels increased. Hepatocytes had mild anisokaryosis associated with pyknosis and occasionally necrotic hepatocytes were observed. Cytoplasmic vacuolation and increased eosinophilia was seen in portal areas of the hepatic lobe. Renal changes consisted of an accumulation of eosinophilic cytoplasmic inclusions in the epithelium of proximal tubules associated with focal glomerular adhesions and interstitial scarring due to spontaneous ageing process. Thyroids had a reduced follicular size and colloid density. The epithelium cells became columnar and thickened with focal and multifocal angular angular collapse of follicles. Additional changes included focal and multifocal papillary proliferations and focal vacuolations. Finally no detectable residual of the test substance was found in liver and fat (detection limit: 0.1 ppm).

Considering all these results, the LOAEL was established 0.5 ppm. Hence at this level of information the subacute oral toxicity of benzotrichloride is of a low and similar order for both male and female rats.

Although no data is availalbe on the GLP status of this study, it is considered reliable without restriction as it is comparable to the OECD guideline 407 with no deviations (Klimisch 1b).