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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented publication

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Toxicity of hydroxylamine sulfate following dermal exposure: variability with exposure method and species.
Author:
Derelanko
Year:
1987
Bibliographic source:
Fundamental and applied toxicology, 8:583–594.
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

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Phenylhydrazine hydrochloride (PHZ)
- Physical state: no data
- Analytical purity: 97 %

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 162 - 182 g
- Housing: individually in single unit, suspended steel cages
- Diet: Purina Rodent Chow 5001, ad libitum
- Water: ad libitum
- Acclimation period: 2 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 °C
- Humidity (%): 50 %
- Photoperiod (hrs dark / hrs light): 12h/12h

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Type of wrap if used: The test material was held in contact with the skin by wrapping the torso of the rat with Elastoplast elastic bandage lined with polyethylene. The rats were unable to reach the wrappings in a sufficient manner to remove them and for this reason a restraining device was not used.

REMOVAL OF TEST SUBSTANCE
- Washing: After removal of the wrappings, the exposure site was wiped with gauze soaked with distilled water to remove residual test material.
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5; 0.1 and 0.01 g/kg bw (only with occlusive conditions);
- For solids, paste formed: yes
Duration of exposure:
24 hrs
Doses:
0.5, 0.1 and 0.01 g/kg bw
No. of animals per sex per dose:
10 per group
Control animals:
yes, concurrent vehicle
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed closely at least twice each day for gross signs of toxicity.
Body weights were recorded on days -1, 0, 1, 4, 7, 11, and 14 (day 0 being the day of application of the test material)
- Necropsy of survivors performed: Spleen and liver were weighed and gross appearance was recorded.
- Other examinations performed:
• Blood samples were collected from rats via intraorbital puncture under light ether anesthesia from randomly selected animals (5/group) on day 2. Blood samples were collected from the remaining 5 rats from each group on Day 4 and from all 10 rats in each group on Day 14.
• Methemoglobin determinations were performed on the day 2 blood samples using an IL-282 Co-oximeter.
• Erythrocyte, leukocyte, platelet, and reticulocyte counts, as well as determinations of total hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration, were determined from Day 4 and 14 blood samples.
• Platelet counts were performed using an Ultra-Flow 100 counter.
• Reticulocyte counts were obtained from new methylene blue-stained blood smears. The remaining parameters were measured with a HEMAC automated hematology analyzer.
Statistics:
Statistical analysis was based on a decision-tree scheme for selecting statistical procedures as described by Gad and Weil (1984, in: Principle and Methods of Toxicology (A. W. Hayes, Ed.), pp. 273-320. Raven Press, New York). Quantitative continuous variables were intercompared for test versus control groups by employing the following statistical tests: Bartlett's homogeneity of variance, ANOVA, and Duncan's multiple range test. In cases where heterogeneous variance was indicated or where data was suspected to be nonparametric, the Kruskal-Wallis nonparametric ANOVA and Wilcoxon rank sum test were utilized.

Results and discussion

Effect levels
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 500 mg/kg bw
Remarks on result:
other: No mortality
Mortality:
No mortality occurred in rats exposed at any of the dose levels tested.
Clinical signs:
• Skin irritation from topically applied PHZ occurred at a high incidence and was evident within 24 hours of initial contact and persisted as long as 7 days. Necrosis was evident on only a small number of PHZ-exposed rats.
• Paleness was not visible in PHZ exposed rats until 48 hours post exposure and was observed as long as 11 days posttreatment.
• Cyanosis occurred in some of the PHZ-exposed animals at all dose levels beginning 48 hours following initial application of the test material and lasting approximately 2 days.
• Other gross signs of toxicity observed in rats exposed to PHZ included staining of the nares, mouth, and forepaws with brown material, yellow staining of the anal-genital area, and lacrimation.
• A dose-related, statistically significant increase in methemoglobin at 48 hours post-exposure was observed. There was a statistically significant reduction in erythrocyte count, measured on day 4 and 14 in the mid and high dose group. Reticulocyte numbers were significantly elevated on day 14 post-exposure.
Body weight:
Rats treated with PHZ at the higher dose levels (0.1 and 0.5 g/kg) gained weight at a statistically slower rate than controls during the first week of the study.
Gross pathology:
At necropsy, the spleens appeared enlarged and dark in color. Mean relative spleen weight was statistically significant increased with topical exposure at dose levels of 0.1 and 0.5 g/kg. A slight but statistically significant increase was noted in liver weight in rats at a dose of 0.5 g/kg.

Applicant's summary and conclusion