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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
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:
Sex dependent toxicity of four chemicals.
Author:
Toth
Year:
1975
Bibliographic source:
Res. Comm. Chem. Path. Pharmacol. 10, 577-580; cited in WHO 2000, Phenylhydrazine. CICAD 19, Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, ISBN 92 4 153019 7; ISSN 1020-6167.
Reference Type:
publication
Title:
Sex dependent toxicity of four chemicals.
Author:
Toth
Year:
1975
Bibliographic source:
Res. Comm. Chem. Path. Pharmacol. 10, 577-580; cited in BUA (1995) Phenylhydrazine. Stuttgart, S. Hirzel, Wissenschaftliche Verlagsgesellschaft (Report No. 120; ISBN 3-7776-0691-X).
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
Reference Type:
secondary source
Title:
Unnamed
Year:
1994

Materials and methods

Principles of method if other than guideline:
Mice were treated with the test compound orally ad libitum in drinking water. Survival rates, water consumption, body weight and histological changes were determined.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): phenylhydrazine HCl (phenylhydrazine hydrochloride; PH)

Test animals

Species:
mouse
Strain:
Swiss
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: from a colony bred randomly in the laboratory of the authors.

ENVIRONMENTAL CONDITIONS
- not reported

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
water
Details on oral 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:
28 days
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0.001 %
Basis:
nominal in water
No. of animals per sex per dose:
4
Control animals:
yes
Details on study design:
no data
Positive control:
no data

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: yes
- Time schedule: at least every 4 days

BODY WEIGHT: Yes
- Time schedule for examinations: no data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: no data
Sacrifice and pathology:
GROSS PATHOLOGY and HISTOPATHOLOGY: Yes
Other examinations:
no data
Statistics:
no data

Results and discussion

Results of examinations

Details on results:
CLINICAL SIGNS AND MORTALITY
Survival rates at four day intervals up to 28 days: see Table 1
Phenylhydrazine, administered daily in drinking water exert a stronger toxic effect in male mice compared to female mice. Whereas no female mice died up to 28 days, male mice died between 4 and 28 days of treatment. Only one male of 4 males survived.

BODY WEIGHT AND WEIGHT GAIN
Decreased substantially; the decrease in body weight was the most pronounced at one week after the application of chemicals followed by a gradual increase.

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study)
In the phenylhydrazine treated groups the animals consumed 30% less than in the corresponding untreated controls.

HISTOPATHOLOGY: NON-NEOPLASTIC
Pheylhydrazine caused congested lungs. In addition, slight fatty degeneration in the liver was observed.


Effect levels

Dose descriptor:
dose level:
Effect level:
0.001 other: %
Sex:
male/female
Basis for effect level:
other: mortality; body weight loss; reduced water consumption, congested lungs, slight fatty degeneration in the liver.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Table 1: Sex dependent toxicity of phenylhydrazine

Chemical

Dose

No

Sex

No of survivors (age in days)

4

8

12

16

20

24

28

Phenylhydrazine

0.001% in

drinking water

4

females

4

4

4

4

4

4

4

4

males

3

3

2

2

2

2

1

Applicant's summary and conclusion