α-chlorotoluene

Immunotoxicity

Administrative data

Endpoint:

immunotoxicity: acute inhalation

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented and based on generally well accepted scientific principles. Klimisch 2.e study.

Data source

Reference

Reference Type:

publication

Title:

The Effects Of Inhalation Of Organic Chemical Air Contaminants On Murine Lung Host Defenses

Author:

Aranyi C., O'Shea W., Graham J. A. and Miller F.

Year:

1986

Bibliographic source:

Fundam. Appl. Toxicol., 6, 713-720.

Materials and methods

Principles of method if other than guideline:

Female CD1 mice were exposed to various concentrations of vapors of benzyl chloride and then challenged by an infectious aerosol or checked for their pulmonary bactericidal activity.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

α-chlorotoluene

EC Number:

202-853-6

EC Name:

α-chlorotoluene

Cas Number:

100-44-7

Molecular formula:

C7H7Cl

IUPAC Name:

(chloromethyl)benzene

Constituent 2

Reference substance name:

Chloromethylbenzene

IUPAC Name:

Chloromethylbenzene

Details on test material:

- Name of test material (as cited in study report): benzyl chloride
- Stability under test conditions: yes monitored by GC-FID and not much than 10 % degradation over the exposure period
No further information

Test animals

Species:

mouse

Strain:

CD-1

Sex:

female

Administration / exposure

Route of administration:

inhalation: vapour

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

3h hours a day

Frequency of treatment:

Once or during five days

Doses / concentrations

Remarks:

Doses / Concentrations:
1 ppm +/- 0.1 ppm
Basis:
analytical conc.

No. of animals per sex per dose:

- Single dose exposure experiment: 270 mice
- Five days repeated dose experiment: 135 mice

Control animals:

yes

Results and discussion

Effect levels

1

Dose descriptor:

other: percentage of dead mice

Effect level:

16.7 other: %

Sex:

female

Basis for effect level:

other: single exposure at 1 ppm

2

Dose descriptor:

other: Percentage of bacteria killed in 3 h after the 5 th exposure

Effect level:

10.4 other: %

Sex:

female

Basis for effect level:

other: repeated exposure at 1 ppm

3

Dose descriptor:

other: Percentage of bacteria killed in 3 h

Effect level:

89.9 other: %

Sex:

female

Basis for effect level:

other: Single exposure at 1 ppm

4

Dose descriptor:

other: Percentage of bacteria killed in 3 h after the 5 th exposure

Effect level:

94.4 other: %

Sex:

female

Basis for effect level:

other: repeated exposure at 1 ppm

Applicant's summary and conclusion

Conclusions:

In the test conditions, the authors did not found a statistical difference between the treated mice and the controls in the infectious aerosol challenge. However, in the pulmonary bactericidal activity, the authors found a significant difference between the treated and the control mice when exposed to a single exposure session. These results prove that benzyl chloride may be considered as a potent immuno-modulator.

Executive summary:

The authors tested the impact of benzyl chloride (CAS n° 100 -44 -7) inhalation on the murine host defense system.Female CD1 mice were exposed to saturated vapors of benzyl chloride in individual cages for three hours or daily during three hours for five days. Mice exposed were challenged by pathogens to assess the viability of their immune system.

The first experiment consisted in an infectious aerosol challenge experiment: The streptococus infectivity model was used to determine the effect of the inhaled organic vapors on succeptibility to respiratory infection. Mice exposed to the vapors were simultaneously challenged with an aerosol of viable Streptococcus zooepidemicus (group C). Ensuing deaths were recorded daily over a 14 -day observation period.

The second experiment consisted in a pulmonary bactericidal activity test. 35S- Klebsiella pneumonia (noncapsulated) disseminated with a Retec X-70 disposable nebulizer were used for determination of the in vivo bactericidal activity of alveolar macrophages. Bactericidal clearance was determined in the lungs of individual animals from both treated and control mice that simultaneously inhaled aerosols of the viable radiolabeled bacteria. The ratio of the viable bacterial counts to the radioactive counts in each animal's lungs provides an estimate of the rate at which bacteria are destroyed 3 hr after infection.

In the test conditions, the authors did not found a statistical difference between the treated mice and the controls in the infectious aerosol challenge. However, in the pulmonary bactericidal activity, the authors found a significant difference (p<0.01) between the treated and the control mice when exposed to a single exposure session. However, these results were not similar with the repeated dose inhalation. These results prove that benzyl chloride may be considered as a potent immuno-modulator and further testing would be required to clarify the situation. Also, other test system should be tested.

This study is well documented and based on generally accepted scientific principles.It then should be considered as reliable with restrictions, a Klimisch 2.e study.