α,2-dichlorotoluene

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

publication

Title:

Orthochlorobenzylchloride 28-day Inhalation Toxicity Study in Rats with Cover Letter (Product code: OTS0526421)

Author:

Occidental Chemical Corporation

Year:

1990

Bibliographic source:

Orthochlorobenzylchloride 28-day inhalation toxicity study in rats with cover letter, EPA Doc# 88-900000192, NTIS/OTS0526421

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

α,2-dichlorotoluene

EC Number:

210-258-8

EC Name:

α,2-dichlorotoluene

Cas Number:

611-19-8

Molecular formula:

C7H6Cl2

IUPAC Name:

1-chloro-2-(chloromethyl)benzene

Details on test material:

Source: Occidental Chemical Corporation-Batch No.:20-50253 00/S-2359- Purity: 99%

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

inhalation

Duration of treatment / exposure:

28 days

Frequency of treatment:

6 hours a day, five consecutive days a week (Monday to Friday) for 4 consecutive weeks

Doses / concentrations

Remarks:

Doses / Concentrations:
0.01, 0.03, 0.10 mg/l
Basis:

Control animals:

yes

Results and discussion

Effect levels

Dose descriptor:

NOAEL

Effect level:

0.03 other: mg/l

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

No animals were dead. At the highest exposure level only,
there were several observations indicative of an adverse
effect of the test substance. During exposure, there were
clinical signs indicative of an irritation of the
respiratory tract. These included eyes shut/half-shut,
adoption of a prone/hunched posture, rubbing of the chin on
the mesh floor of the exposure chamber with licking of the
inside of the mouth, red ears, agitated grooming and short
periods of head shaking, and rale was noted in one male rat
of highest dose group during the latter half of Week 4.
Weight gain, food consumption and water consumption were
reduced during the 4 weeks of exposure. The laboratory
investigations performed at the end of the exposure period
showed increased packed cell volume, hemoglobin and

red cell count and  production of a reduced volume of urine.

The ratio of myeloid: erythroid  cells was also increased.

The gross necropsy revealed enlarged tracheobronchial lymph

nodes and elevated lung weights. The histopathological

examination showed damage to the nasal mucosa, trachea

and bronchi (epithelial degeneration and hyperplasia of

the nasal mucosa  and the bronchiolar epitherium, squamous

metaplasia of the bronchiolar  epitherium) consistent with

inhalation of an irritant vapour. The tracheobronchial

lymph nodes of some of the rats showed lymphoid hyperplasia.

There were no changes that were considered to be treatment-related

 in male and female rats exposed at 0.01 or 0.03 mg/l.

The no observed adverse effect level(NOAEL)in this study

was considered to be 0.03 mg/l.

Table 1. Effects of OCBC observed in the lungs
=====================================================
Dose (mg/l)             0       0.01    0.03    0.10
-----------------------------------------------------
[Male]
No. of animals          5       5       5       5
Body weight (g)         392     384     380     306
Weight gain (g)         131     127     127     52**
Lung weight (g)         1.37    1.37    1.38    1.47
Enlarged tracheo-bronchial lymph nodes
                        0       0       0       4
Lymphoid hyperplasia in tracheo-bronchial lymph node
                        0       0       0       3
-------------------------------------------------------
[Female]
No. of animals          5       5       5       5
Body weight (g)         244     231     234     224
Weight gain (g)         61      53      50      33**
Lung weight (g)         1.04    1.07    1.05    1.25**
Enlarged tracheo-bronchial lymph nodes
                        0       0       0       1
Lymphoid hyperplasia in tracheo-bronchial lymph node
                        0       0       0       1
=======================================================
**, P<0.01 compared with control data using Williams' test