(4-chlorophenyl)hydrazine

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Limited documentation

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Toxicity of phenylhydrazine in inhalatory exposure

Author:

Pham KC

Year:

1979

Bibliographic source:

Gigiena Truda i Professional'nye Zabolevaniya, 3:45-47; cited in BUA (1995) Phenylhydrazine. Stuttgart, S. Hirzel, Wissenschaftliche Verlagsgesellschaft (Report No. 120; ISBN 3-7776-0691-X).

Reference 2

Reference Type:

publication

Title:

Toxicity of phenylhydrazine in inhalatory exposure

Author:

Pham KC

Year:

1979

Bibliographic source:

Gigiena Truda i Professional'nye Zabolevaniya, 3:45-47; cited in WHO 2000, Phenylhydrazine. CICAD 19, Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, ISBN 92 4 153019 7; ISSN 1020-6167.

Reference 3

Reference Type:

secondary source

Title:

Unnamed

Year:

1994

Reference 4

Reference Type:

secondary source

Title:

Concise International Assessment Document 19: Phenylhydrazine

Author:

WHO

Year:

2000

Bibliographic source:

Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, ISBN 92 4 153019 7; ISSN 1020-6167

Materials and methods

Principles of method if other than guideline:

Animals were exposed to phenylhydrazine vapour at different concentrations. Group size, duration of exposure, and exposure regime were not reported, although it can be expected that some animals were exposed for at least 6 month.

GLP compliance:

no

Limit test:

no

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

- Name of test material (as cited in study report): phenylhydrazine

Test animals

Species:

other: rats, mice, guinea pigs and rabbits

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

- albino rats

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: no data

Remarks on MMAD:

MMAD / GSD: no data

Details on inhalation exposure:

no data

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no data

Duration of treatment / exposure:

up to 6 month

Frequency of treatment:

no data

Doses / concentrations

Remarks:

Doses / Concentrations:
0; 0.1; 15.8; 22.5; or 225 mg/m³ (0; 0.03; 3.5; 5 or 50 ppm)
Basis:

No. of animals per sex per dose:

no data

Control animals:

yes

Details on study design:

no data

Positive control:

no data

Examinations

Observations and examinations performed and frequency:

no data

Sacrifice and pathology:

no data

Other examinations:

no data

Statistics:

no data

Results and discussion

Results of examinations

Details on results:

CLINICAL SIGNS AND MORTALITY
Death were reported to occur in animals exposed to 50 ppm/0.21 +/- 0.015 mg/L (species not specified)

BODY WEIGHT AND WEIGHT GAIN
• 50 ppm corresponding to 0.21 +/- 0.015 mg/L (original data):
Severe weight loss.
• 5 ppm corresponding to 0.021 +/- 0.005 mg/L (original data):
10 % reduction in body weight (p<0.05)

HAEMATOLOGY
• 50 ppm corresponding to 0.21 +/- 0.015 mg/L (original data):
unspecified haematological changes, haemolysis.
• 5 ppm corresponding to 0.021 +/- 0.005 mg/L (original data):
Reduction in erythrocyte concentration of 48% (p<0.001);
Decrease of hemoglobin content of about 20 % (p<0.001);
Increased number of reticulocytes compared to the control (4 fold);
From the 4th month on increase of methemoglobin of about 3 to 3.9-fold compared to the control (p<0.001).

• 3.5 ppm corresponding to 0.0015 +/- 0.006 mg/L (original data):
Reduction in erythrocyte concentration of 21 % (p<0.02);
Decrease of hemoglobin content of about 14 % (p<0.05);
Increased number of reticulocytes compared to the control of about 66 % ((p<0.01);
Increase of methemoglobin of about 96 % compared to the control (p<0.01).

CLINICAL CHEMISTRY
• 5 ppm corresponding to 0.021 +/- 0.005 mg/L (original data):
Increased activity of catalase (blood) and cytochrome oxidase (liver, brain, kidney, up to 3 fold).
Transient increase of cholinesterase, transaminase, glucose-6-phosphate dehydrogenase (blood).
Decrease of ß-lipoprotein, cholesterin (serum) and glycogen (liver) of about 28 %.

• 3.5 ppm corresponding to 0.0015 +/- 0.006 mg/L (original data):
Transient increased activity of cholinesterase (blood) of about 37 % (p<0.05) and of catalase of about 52 % (p<0.002).

ORGAN WEIGHTS
• 5 ppm corresponding to 0.021 +/- 0.005 mg/L (original data):
Increased spleen weight (78 %, p<0.001) and liver weight (14 %, p<0.002).

OTHERS
• 50 ppm corresponding to 0.21 +/- 0.015 mg/L (original data):
There were dystrophic changes in the liver, spleen, and cerebrum.

Effect levels

Dose descriptor:

NOAEL

Effect level:

0.01 mg/m³ air

Sex:

not specified

Basis for effect level:

other: Almost no evidence to pathological changes were reported at 0.1 mg/m³.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Almost no evidence to pathological changes were reported at 0.1 mg/m³.

Additionally, it is not clear if there were lung effects at any of the exposure concentrations.