Hydrazinecarboximidamide, 2-[(2-hydroxyphenyl)methylene]-, reaction products with 2-undecanone

Endpoint summary

Description of key information

Acute Toxicity - Oral LD50 >2000 mg/kg for rat (OECD TG 401)

Acute Toxicity - Dermal LD50 >10,000 mg/kg for rat (OECD TG 402)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 April 1997 - 12 June 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: ExxonMobil Chemical Company (Edison, NJ) Lot# C96302.01,2
- Expiration date of the lot/batch: 31 October 2001
- Purity test date: not specified

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under test conditions: stable through duration of test
- Solubility and stability of the test substance in the solvent/vehicle: not applicable
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not applicable

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Inc. (Portage, MI; Hollister, CA)
- Females (if applicable) nulliparous and non-pregnant: not specified
- Age at study initiation: 6 to 12 weeks of age
- Weight at study initiation: 224 to 261 g
- Fasting period before study: 17 to 20 hours
- Housing: Animals were separated by sex and group housed in suspended screen-bottom stainless steel cages.
- Diet (e.g. ad libitum): Laboratory Rodent Diet #5001 (PMI Foods Inc.)
- Water (e.g. ad libitum): water periodically analyzed for contaminants
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C to 25°C
- Humidity (%): 50% ± 20%
- Air changes (per hr): not spepcified
- Photoperiod (hrs dark / hrs light): 12 hour dark/light

IN-LIFE DATES: From: 16 April 1997 To: 30 April 1997

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

An individual dose of the undiluted test material was calculated for each animal based on its fasted body weight and administered as a single gavage dose. The test material was administered at a volume of 2.04 mL/kg of body weight based on an average bulk density of 0.98 g/mL.

Doses:

2.0 g/kg

No. of animals per sex per dose:

5 males; 5 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality checks were conducted twice a day (morning and afternoon) for 13 days after test material administration and again the morning of Day 14. Body weights were determined before test material adminstration (Day 0) at Day 7, and at termination of the in-life phase (Day 14).

Statistics:

No statistical analyses were required by the protocol

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed during the study.

Clinical signs:

other: One male animal appeared normal throughout the entire study. All other animals exhibited a red-stained face within 2.5 hours after test material administration. Two of five females were noted with a wet urogenital area on the day of treatment. All animals

Gross pathology:

No lesions were observed at the gross necropsy examination.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 for Hydrazine Carboximidamide, 2-((2-hydroxyphenyl)methylene)-, reaction products with 2 undecanone following oral intubation was established at >2000 mg/kg for males and females. This finding does not warrant classification of Hydrazine Carboximidamide, 2-((2-hydroxyphenyl)methylene)-, reaction products with 2 undecanone as an acute oral 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 oral intubation to 5 female and 5 male Crl:CD(SD) rats at 2.0 g/kg to assess the acute oral toxicity. Animals were observed daily for 14 days post dosing. No overt signs of toxicity were apparent and mortality was not observed at the dose level tested; all animals were free of abnormalities at postmortem examination. All animals 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 these data was established at >2000 mg/kg for males and females. This finding does not warrant classification of Hydrazine Carboximidamide, 2-((2-hydroxyphenyl)methylene)-, reaction products with 2 undecanone as an acute oral toxicant under the Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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

Qualifier:

equivalent or similar to guideline

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

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

Species:

rabbit

Strain:

New Zealand White

Sex:

not specified

Details on test animals or test system and environmental conditions:

Details on test animals and environmental conditions not specified

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

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:

other: 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

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%

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).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

10 000 mg/kg bw

Justification for classification or non-classification

Hydrazine Carboximidamide, 2-((2-hydroxyphenyl)methylene)-, reaction products with 2 undecanone is minimally toxic via ingestion where the LD50 is >2000 mg/kg and via dermal exposure where the LD50 is >10,000 mg/kg.  These findings do not warrant classification of Hydrazine Carboximidamide, 2-((2-hydroxyphenyl)methylene)-, reaction products with 2 undecanone as an acute toxicant under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).