α,α,α-trichlorotoluene

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is sufficiently documented, meets generally accepted scientific principles and is acceptable for assesment, thus klimisch 2e

Data source

Reference

Reference Type:

publication

Title:

Über das Auftreten von Krebs bei Mäusen nach Inhalation von Benzotrichlorid und Benzoylchlorid

Author:

Yoshimura H., Takemoto K.; Fukuda K. and Matsushita H.

Year:

1986

Bibliographic source:

Japanese Journal of Industrial health, 28: 352-359

Materials and methods

Principles of method if other than guideline:

Carcinogenicity induced by repeated inhalation
(For details on methodology see section examinations)

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): BTC (benzotrichlorid)

No more data available

Test animals

Species:

mouse

Strain:

ICR

Sex:

male

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

other: unchanged (no vehicle)

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

Experiment 1: 5 months
Experiment 2: 10 months

Frequency of treatment:

Experiment 1 & 2: twice weekly for 30 minutes

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
6.7 +/- 1.66 ppm (Experiment 1)
Basis:
analytical conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
1.62 +/- 0.43 ppm (Experiment 2)
Basis:
analytical conc.

No. of animals per sex per dose:

Experiment 1: 33 (32 were evaluated)
Experiment 1: 38 (37 were evaluated)

Control animals:

yes

Results and discussion

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Experiment 1:

- Death rate:

Twelwe exposed animals died within the 2nd and 5th month (36.4%) of exposure, a further 4 in the first month after exposure and a single mice until the 10th month. The remaining animals were in poor health conditions since the 9th month, therefore the experiment was terminated after the 10th month.

- Pulmonar lesions:

Almost all animals showed severe bronchitis and bronchial pneumonia.

- Cutaneous lesions:

Beginning with the 3rd month of exposure hair-loss, skin hardening as well as ulcerous lesions on ventral and dorsal skin were observed.

- Gross pathology:

At necropsy many animals showed inflammatory lesions associated with hypertrophy of organs such as thymus, lymph nodes, and spleen.

Experiment 2:

- Death rate:

After 8 month of exposure first treated animals died. During the 10th month their number increased to 10/38 animals. At this time exposure was stopped. After 13 month animals started to die again (8 animals between month 12 and 15), therefore the experiment was terminated by the end of the 15th month (9 animals remaining). Ten animals were euthanized after month 12 and examined.

- Pulmonar lesions:

Almost all animals examined after the 15th month were found to have proliferation of the trachea, bronchial, and terminal bronchiolar epithelia.

- Cutaneous lesions:

Beginning with the 8th month neoplastic alterations of the skin were noticed.

- Gross pathology:

At necropsy many animals showed inflammation of organs such as thymus, lymph nodes, and spleen. No metastasis of primary lung or dermal neoplasia was observed. Mild keratosis and hyperplasia of the gastric mucosa was seen.

Applicant's summary and conclusion

Conclusions:

The authors tested the toxicity of benzotrichloride after repeated dose exposure via inhalation of vaporized test substance using two experiments. The authors observed deaths during the exposure period in both experiments. In both experiments pulmonary and cutaneous lesions were observed. The gross pathology of animals from experiment 1 at necropsy showed inflammatory lesions associated with hypertrophy of organs such as thymus, lymph nodes, and spleen. At necropsy many animals from experiment 2 showed inflammation of organs such as thymus, lymph nodes, and spleen, but no metastasis of primary lung or dermal neoplasia. Mild keratosis and hyperplasia of the gastric mucosa was also seen.

Executive summary:

The authors tested the toxicity of benzotrichloride (CAS n° 98-07-7)after repeated dose exposure via inhalation of vaporized test substance. Two experiments were performed usingICR male mice. In experiment 1, 33 mice were exposed to 6.7 (+/- 1.66) ppm of benzotrichloride vaporized at 50°C twice weekly for 30 minutes during 5 months. Afterwards they were observed for another 1 to 5 months. In the second experiment 38 mice were exposed to 1.62 (+/- 0.43) ppm of benzotrichloride vaporized at room temperature twice weekly for 30 minutes during 10 months. Afterwards they were observed for another 2 to 5 months. Pathological changes in the respiratory system and skin were noted as well as mortality and gross pathology.

 

In experiment 1, 12 treated mice (36.4%) died during the exposure period (2^ndto 5^thmonth). Afterwards 4 treated animals died in the first month after exposure and a single mice died between this time point and the 10th month. The treated animals were in poor health conditions since the 9th month, therefore the experiment was terminated after the 10th month. Beginning with the 3rd month of exposure hair-loss, skin hardenings as well as ulcerous lesions on ventral and dorsal skin were observed. Furthermore almost all animals showed severe bronchitis and bronchial pneumonia. Finally at necropsy many animals showed inflammatory lesions associated with hypertrophy of organs such as thymus, lymph nodes, and spleen.

In experiment 2, the first treated animals died after 8 month of exposure and during the 10th month their number increased to 10/38 animals. At this time exposure was stopped. After 13 month animals started to die again (8 animals between month 12 and 15), therefore the experiment was terminated by the end of the 15th month (9 animals remaining). Ten animals were euthanized after month 12 and examined.Beginning with the 8th month neoplastic alterations of the skin were noticed. After the 15th month almost all animals examined were found to have proliferation of the trachea, bronchial, and terminal bronchiolar epithelia.Finally, at necropsy many animals showed inflammation of organs such as thymus, lymph nodes, and spleen, and mild keratosis and hyperplasia of the gastric mucosa was seen. No metastasis of primary lung or dermal neoplasia was observed.

 

The GLP status of the study is unknown. Although the study would benefit from a more elaborate description of clinical signs, gross pathology and weight development, it is nevertheless sufficiently documented, meets generally accepted scientific principles and is acceptable for assessment. Thus the study is reliable with restrictions,Klimisch 2e.