Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02 March 1978 - 12 April 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
- Principle of test: The method of testing the dermal toxicity of the test substance is a patch-test technique on the abraded and intact skin of the New Zealand White rabbit, clipped free of hair.
- Short description of test conditions: Twelve New Zealand White Rabbits were clipped free of abdominal hair. Epidermal abrasions were made longitudinally every 2 to 3 cm over the exposed area on even numbered rabbits. The abrasions were sufficiently deep to penetrate the stratum corneum but not deep enought to produce bleeding. The area was covered with gauze and the trunk was wrapped with impervious material for 24 hours. At 24 hours, the rabbits were cleansed and dermal reactions were evaluated by the Draize technique.
- Parameters analysed / observed: The animals were observed daily for 14 days for clinical signs of toxicity and mortality, and once on Day 1
for skin reactions. Animals which died during the study were examined for gross pathology
GLP compliance:
no
Remarks:
Study predates GLP
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Specific details on test material used for the study:
- Source and lot/batch No. of test material: Mobil Chemical Company (Edison, NJ) Lot # 1086
- Expiration date of the lot/batch: not specified
- Purity test date: not specified

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
not specified
Details on test animals and environmental conditions:
Details on test animals and environmental conditions not specified

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 2- 3 cm
- % coverage: not specified
- Type of wrap if used: impervious

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5.0 g/kg and 10.0 g/kg
- Concentration (if solution): not applicable
- Constant volume or concentration used: no
- For solids, paste formed: not applicable
Duration of exposure:
Epidermal abrasions were made longitudinally every 2 to 3 cm over the exposed area on even numbered rabbits. The abrasions were sufficiently deep to penetrate the stratum corneum but not deep enough to produce bleeding. The area was covered with gauze and the trunk was wrapped with impervious material for 24 hours.
Doses:
5.0 g/kg and 10.0 g/kg
No. of animals per sex per dose:
5.0 g/kg - 4 rabbits; 10.0 g/kg - 8 rabbits
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were recorded daily, Weight was recorded at Day 0 and Day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, and gross necropsy on animals dying during observation period

Results and discussion

Effect levels
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Mortality:
At 5.0 g/kg one rabbit died on Day 9; At 10.0 g/kg one rabbit dies on Day 12
Clinical signs:
At 5.0 g/kg, the rabbit which died displayed signs of prostration, chromorhinorrhea, ataxia and dyspnea on Days 7 and 8. Of the surviving rabbits, one displayed diarrhea on days 1, 2, 5, and 7 through 14. The other two appeared normal throughout study.
At 10.0 g/kg, the rabbit which died displayed signs of diarrhea, alopecia, and lethargy on Days 10 and 11. Of the surviving rabbits, one rabbit was observed to have a bloated abdomen, diarrhea, and yellow discharge from the nose and one other rabbit had diarrhea and was considered to be emaciated on Days 1, 2, 13 and 14. All other animals appeared normal throughout test.
Body weight:
At 5.0 g/kg all surviving rabbits gained wieght through duration of study. At 10.0 g/kg all surviving rabbits but one gained weight through duration of study.
Gross pathology:
For the one mortality at 5.0 g/kg yellow exudate of the nose and mouth, red and bloated areas of the intestines, dark areas of the liver and lungs and a mottled spleen were reported.
For the one mortality at 10.0 g/kg yellow exudate of the nose and mouth, red areas of the intestines, dark areas of the liver, a mottled spleen, and mild skin redness and edema were reported.
Other findings:
Esitmate of remaining material 5.0 g/kg - 90%; 10.0 g/kg- 90- 95%

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 for Hydrazine Carboximidamide, 2-((2-hydroxyphenyl)methylene)-, reaction products with 2 undecanone following dermal exposure was established at >10000 mg/kg. This finding does not warrant classification of Hydrazine Carboximidamide, 2-((2-hydroxyphenyl)methylene)-, reaction products with 2 undecanone as an acute dermal toxicant under the Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).



Executive summary:

Hydrazine Carboximidamide, 2-((2-hydroxyphenyl)methylene)-, reaction products with 2 undecanone was administered via dermal patch to New Zealand White Rabbits at 5000 mg/kg and 10,000 mg/kg to assess the acute dermal toxicity.  Animals were observed daily for 14 days post dosing. Overt signs of toxicity were apparent at both dose levels and mortality was observed in 1/4 rabbits at 5000 mg/kg and 1/8 rabbits at 10000 mg/kg. All surviving animals but one displayed increases in body weight over their day 0 values. The LD50 for Hydrazine Carboximidamide, 2-((2-hydroxyphenyl)methylene)-, reaction products with 2 undecanone based on this data was established at > 10000 mg/kg bw. This finding does not warrant classification of Hydrazine Carboximidamide, 2-((2-hydroxyphenyl)methylene)-, reaction products with 2 undecanone as an acute dermal toxicant under the Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).