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Description of key information

Both studies were performed in 1985. The reliability of these reports is Klimisch 1 as these studies were performed under GLP.

The calculated acute oral LD50 for male and female rats was determined to be 1569 mg/kg with 95% confidence limits of 1243 to 1980 mg/kg The calculated acute oral LD50 in males was determined to be 1960 mg/kg with 95% confidence limits of 1376 to 2792 mg/kg. The calculated acute oral LD50 in females was determined to be 1231 mg/kg with 95% confidence limits of 860 to 1761 mg/kg.

The acute dermal LD 50 for rabbits was determined to be greater than 8.0 g/kg.

Based upon the observations made in the study, the estimated LD50 of the test material was determined to be greater than 8.0 g/kg. Therefore, the test substance is considered not to be classified according to CLP regulation .

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:
March 14, 1985 -April 2, 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study is well-documented and performed according to generally accepted scientific standards.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 5601-49-1, J-243

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Stability under test conditions: there was no apparent change in the physical state of the test article during administration
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Labs, Wilmington, Mass.
- Females, nulliparous and non-pregnant: yes, and Males
- Weight at study initiation: 180-360 g after fasting, weight variation not to exceed 20% in or between groups.
- Fasting period before study: 18 h
- Housing: standard steel wire mesh cages, individually or in groups by sex.
- Diet (e.g. ad libitum): ad libitum, Wayne Lab Blox
- Water (e.g. ad libitum): ad libitum, fresh tap water, fir for human consumption, using an automatic watering system supplied by Edstrom Industries, Inc., Waterford, Wisconsin.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 °C, +/- 3 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12 hr dark/12 hr light
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
No Vehicle

MAXIMUM DOSE VOLUME APPLIED: 2500 mg/kg

DOSAGE PREPARATION (if unusual): as received

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Based on range finding study
Doses:
1000, 3000, 6300, 10000 mg/kg (dose range finding study)
1000, 1600, 2000, and 2500 mg/kg (main study)
No. of animals per sex per dose:
2 males, 2 females (dose range finding study)
5 males, 5 females (main study)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed immediately after dosing, and at 1 and 4 hours after dosing, then once daily for 14 days. Body weight recorded days 7 and 14.
- Necropsy of survivors performed: yes, sacrified by CO2 inhalation
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
according to the method of Litchfield and Wilcoxon
Preliminary study:
In a dose range finding study, 4 fasted animals, 2 per sex, were dosed with the test substance at 1000, 3000, 6300 and 10000 mg/kg via oral gavage. Signs observed were decreased activity, ptosis, salivation, decreased muscle tone, dyspnea, abnormal gait, abnormal stance, ataxia, discoloration around the mouth and anus and prostration. None of the rats died at 1000 mg/kg. All of the rats died at 3000, 6300, and 10000 mg/kg.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 569 mg/kg bw
Based on:
test mat.
95% CL:
ca. 1 243 - ca. 1 980
Sex:
male
Dose descriptor:
LD50
Effect level:
1 960 mg/kg bw
Based on:
test mat.
95% CL:
ca. 1 376 - ca. 2 792
Sex:
female
Dose descriptor:
LD50
Effect level:
1 231 mg/kg bw
Based on:
test mat.
95% CL:
ca. 860 - ca. 1 761
Mortality:
2 of 10 rats died at 1000 mg/kg, 5 of 10 died at 1600 mg/kg, 7 of 10 died at 2000 mg/kg, and 8 of 10 died at 2500 mg/kg.
Clinical signs:
Decreased activity, dyspnea, decreased muscle tone, salivation, ptosis, nasal discharge, chromodacryorrhea, diarrhea, abnormal stance, abnormal gait, lacrimation and prostration.
Gross pathology:
Necropsy of animals dying during study revealed fluid-filled stomachs and intestines, and multiple lesions in stomach. Terminal necropsy of the suriving animals revealed no visible lesions.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based upon the results, the calculated acute oral LD50 value for male and female rats treated with the test substance was determined to be 1569 mg/kg bw, with a 95% CL of 1243-1980 mg/kg. The test substance is therefore considered classified as acute oral toxicant category 4 according to CLP regulation.
Executive summary:

In the dose-range finding study, four fasted animals per dose level, two per sex, were administered the test article at 1000 / 3000 / 6300 and 10000 mg/kg, orally, by gavage.

Signs observed were decreased, activity, ptosis, salivation, decreased muscle tone, dyspnea, abnormal gait, abnormal stance, ataxia, discoloration around mouth and anus and prostration. None of the rats died at 1000 mg/kg. All of the rats died at the 3000 / 6300 and 10000 mg/kg dose levels.

Four groups of ten rats (five males and five females) were fatsed for eighteen hours and administered the test item at a dose levels of 1000 / 1600 / 2000 and 2500 mg/kg by oral gavage. Signs observed included decreased activity, dyspnea, decreased muscle tone, salivation, ptosis, nasal discharge, chromodacryorrhea, diarrhea, abnormal stance, abnormal gait, lacrimation and prostration. Two of ten rats died at 1000 mg/kg, five died at 1600 mg/kg, seven died at 2000 mg/kg and eight died at 2500 mg/kg. Necropsy of the animals dying on study revealed fluid-filled stomachs and intestines with multiple lesions in the stomach. No visible lesions were observed at terminal necropsy.

Based upon the results of the acute oral toxicity study in rats, the calculated acute oral LD50 for male and female rats treated with the test item, was determined to be 1569 mg/kg with 95% confidence limits of 1243 to 1980 mg/kg. The calculated acute oral LD50 in males was determined to be 1960 mg/kg with 95% confidence limits of 1376 to 2792 mg/kg. The calculated acute oral LD50 in females was determined to be 1231 mg/kg with 95% confidence limits of 860 to 1761 mg/kg.

Endpoint conclusion
Dose descriptor:
LD50
Value:
1 569 mg/kg bw
Quality of whole database:
Only this study is 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:
March 24, 1985- April 4, 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
The study is well-documented and performed according to generally accepted scientific standards.
GLP compliance:
yes
Test type:
other: Dose range finding followed by a unique dose application.
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 5601-49-1, J-243

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Stability under test conditions: There was no apparent change in the physical state of the test article during administration
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Sgarlat's rabbitry, Harvey's Lake, Pennsylvania
- Age at study initiation: no data
- Weight at study initiation: 2 - 3 kg
- Fasting period before study: no data
- Housing: rabbits were individually housed in cages sized in accordance with the 'Guide for the Care and Use of Labratory Animals' of the Institute of Laboratory Resources, National Research Council.
- Diet (e.g. ad libitum): ad libitum, Waye Rabbit Ration
- Water (e.g. ad libitum): ad libitum, fresh tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 °C +/- 3 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12h light/12 h dark

IN-LIFE DATES: From: March 21, 1985 To: April 4, 1985
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsal trunk, abraded area.
- % coverage: No less than 20%
- Type of wrap if used: Gauze, followed by a rubber dam and wrapped with an ace bandage to retard evaporation.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Wrappings were removed, no washing done.
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 8.0 g/kg
- Constant volume or concentration used: yes

Duration of exposure:
24 hrs
Doses:
1, 3, 5 and 8 g/kg (dose range finding study)
8 g/kg (main study)
No. of animals per sex per dose:
1 male, 1 female (dose range finding)
5 males, 5 females (main study)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 30 minutes, 2 and 4 hours, and then twice daly through 14 days.
- Necropsy of survivors performed: yes, sacrificed by CO2 inhalation
- Other examinations performed: clinical signs, body weight, organ weights
Preliminary study:
A dose-range-finding study was performed, consisting of 4 groups of two rabbits per group, dosed at 1.0, 3.0, 5.0 and 8.0 g/kg. No mortality was observed.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 8 other: g/kg
Based on:
test mat.
Mortality:
3 out of 10 rabbits died during the study
Clinical signs:
Decreased activity, diarrhea, ptosis, decreased muscle tone, abnormal stance, dypsnea, poor grooming, necrosis and alopecia at the application site, bruxism, red exudate (anal-genital region) and prostration.
Body weight:
All animals showed apparent weight loss over the course of the study.
Gross pathology:
Necropsy of rabbits dying on study revealed hemorrhages of fascia underlying application site, edematous and congested lungs, pale kidneys, cortical necrosis of the kidneys, discolored ureter and fluid-filled bladder. Terminal necropsy of the surviving animals revealed hemorrhage of fascia and necrosis of skin underlying application site.
Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the observations made in the study, the estimated LD50 of the test material was determined to be greater than 8.0 g/kg. Therefore, the test substance is considered not to be classified according to CLP regulation .
Executive summary:

In a dose-range-finding screen, four groups of two abraded rabbits per group (one male and one female) were administered the test article at 1.0 / 3.0 / 5.0 and 8.0 mg/kg. None of the rabbits died in the dose-range-finding study.

In an 8.0 mg/kg limit test, one group of ten rabbits (five males and five females) was dermally administered the test article.

Three of the animals died during the study. Signs observed included: decreased activity, diarrhea, ptosis, decreased muscle tone, abnormal gait, abnormal stance, dyspnea, poor grooming, necrosis and alopecia at the applicatio site, bruxism, red exudate (anal-genital region) and prostration.

Necropsy of the animals dying on study revealed hemorrhages of fascia underlying the application site, edematous and congested lungs, pale kidneys, cortical necrosis of the kidneys, discolored ureter and fluid-filled bladder.

Terminal necropsy of the surviving animals revealed hemorrhage of fascia and necrosis of skin underlying the application site.

Based upon the observations made in the definitive acute dermal toxicity study in rabbits, the estimated LD50 for the test article was determined to be greater than 8.0 mg/kg.

Endpoint conclusion
Dose descriptor:
LD50
Value:
8 000 mg/kg bw
Quality of whole database:
Only this study is available.

Additional information

Justification for classification or non-classification

Based on the above mentioned, the test item Jeffamine EDR 148 does need to be classified as Acute Oral tox. 4 (H302: Harmful if swallowed) and for Acute Dermal tox. does not need to be classified according

to CLP regulation (Regulation EC No.1272/2008) and DSD (Directive 67/548/EEC).