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Toxicological information

Repeated dose toxicity: inhalation

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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

Referenceopen allclose all

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 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 Type:
secondary source
Title:
Unnamed
Year:
1994
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 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.

Applicant's summary and conclusion