Registration Dossier

Administrative data

Description of key information

Acute Oral Toxicity: The acute oral LD50 of the test material in the rat was >5000 mg/kg.
Acute Dermal Toxicity: The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be > 2000 mg/kg bodyweight.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl CDBR
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
corn oil
Doses:
Single dose of 5000 mg/kg
No. of animals per sex per dose:
5 males and 5 females at 5000 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical obserbations made over 14 day period. Bodyweight assessed periodically throught study.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities (0/5) in males treated at 5000 mg/kg.
No mortalities (0/5) in females treated at 5000 mg/kh/
Clinical signs:
Signs of toxicity related to dose levels: The only sign of toxicity was soft stool in two females on the day of treatment.
Body weight:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
Effects on organs: At necropsy, the spleen in one male was observed to have two 5 mm in diameter, white areas and the left testis in a second male was observed to be small when compared to the right testis. These were considered incidental findings and unrelated to the test material. There were no visible lesions in any of the remaining animals.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 is >5000 kg/mg in rats of both sexes.
Executive summary:

The study was conducted in accordance with OECD Guideline No. 401.

The test material was administered to 10 Crl:CD BR rats (5 per sex) by oral gavage, at a single dose of 5000 mg/kg in corn oil. Clinical observations were made over a 14 -day period.

No deaths occurred during the observation period. All rats were sacrificed on day 14 and necropsy performed. Bodyweight gains of the treated animals were unaffected by treatment. Clinical signs of toxicity were limited to soft stool in two females on the day of treatment. Necropsy on sacrificed animals revealed no treatment-related macroscopic lesions/

Results of the study indicate an acute oral LD50 of >5000 mg/kg in rats of both sexes for the test material.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
All relevant studies have been assigned a reliability 1.

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 October 1997 to 16 October 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: males: 215 to 243 g; females: 208 to 230 g
- Housing: animals were housed in suspended polypropylene cages furnished with wood flakes. The animals were housed individually during the 24-h exposure period and in groups of 5, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 22 °C
- Humidity (%): 50 to 74 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/ 12
- On one occasion the relative humidity was above the limit specified in the protocol (70 %). This deviation was not considered to affect the purpose or integrity of the study.
Type of coverage:
semiocclusive
Vehicle:
other: moistened with arachis oil BP.
Details on dermal exposure:
TEST SITE
- % coverage: 10 % of the total body surface
- Type of wrap if used: surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage. The bandage was further secured with a piece of Blenderm wrapped around each end.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated skin and surrounding hair was wiped with cotton wool moistened with arachis oil BP to remoe any residual test material.
- Time after start of exposure: 24 h

TEST MATERIAL
- The test material, as received, was applied uniformly to an area of shorn skin which had been previously moistened with arachis oil BP.
Duration of exposure:
24 h
Doses:
2000 mg/kg
No. of animals per sex per dose:
5/ sex/ dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 h after dosing and subsequently once daily for 14 aysd. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: dermal reactions (scored according to the Draize scale).
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the study.
Body weight:
All animals showed an expected gain in bodyweight during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Dermal reactions: No signs of skin irritation were noted.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal toxicity of the test material was assessed according to OECD guideline 402. The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be > 2000 mg/kg bodyweight.
Executive summary:

A study was performed to assess the actue dermal toxicity of the test material in the Sprague-Dawley CD strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 402 "Acute Dermal Toxicity" and Method B3 of Commission Directive 92/69/EEC.

A group of 10 animals (5 males and 5 females) was given a single 24-hour, semi-occluded dermal application to intact skin at a dose level of 2000 mg/kg bodyweight. The animals were observed for 14 days after the day of treatment and were then killed for gross pathological examination.

There were no deaths. No signs of systemic toxicity or skin irritation were noted during the study.

All animals showed an expected gain in bodyweight during the study.

No abnormalities were noted at necropsy.

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be > 2000 mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
All relevant studies have been assigned a reliability 1.

Additional information

Acute toxicity: via oral route:

The study was conducted in accordance with OECD Guideline No. 401.

The test material was administered to 10 Crl:CD BR rats (5 per sex) by oral gavage, at a single dose of 5000 mg/kg in corn oil. Clinical observations were made over a 14 -day period.

No deaths occurred during the observation period. All rats were sacrificed on day 14 and necropsy performed. Bodyweight gains of the treated animals were unaffected by treatment. Clinical signs of toxicity were limited to soft stool in two females on the day of treatment. Necropsy on sacrificed animals revealed no treatment-related macroscopic lesions/

Results of the study indicate an acute oral LD50 of >5000 mg/kg in rats of both sexes for the test material.

Acute toxicity: via dermal route:

A study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley CD strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 402 "Acute Dermal Toxicity" and Method B3 of Commission Directive 92/69/EEC.

A group of 10 animals (5 males and 5 females) was given a single 24-hour, semi-occluded dermal application to intact skin at a dose level of 2000 mg/kg bodyweight. The animals were observed for 14 days after the day of treatment and were then killed for gross pathological examination.

There were no deaths. No signs of systemic toxicity or skin irritation were noted during the study.

All animals showed an expected gain in bodyweight during the study.

No abnormalities were noted at necropsy.

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be > 2000 mg/kg bodyweight.


Justification for selection of acute toxicity – oral endpoint
The study has been conducted according to OECD guideline 401 and GLP. Therefore, the study has been assigned a reliability 1 and is considered suitable for classification and labelling purposes.

Justification for selection of acute toxicity – inhalation endpoint
Refer to acute inhalation data waiver.

Justification for selection of acute toxicity – dermal endpoint
The study has been conducted according to OECD guideline 402 and GLP and is adequately reported. Therefore, the study has been assigned a reliability 1 and is considered suitable for classification and labelling purposes.

Justification for classification or non-classification

Acute toxicity: via oral route: The test material did not meet the criteria for classification as acutely toxic via the oral route according to Regulation 1272/2008 as the LD50 of >5000 mg/kg is above the threshold for classification.

Acute toxicity: via dermal route: The test material did not meet the criteria for classification as acutely toxic via the dermal route according to Regulation 1272/2008 as the LD50 of >2000 mg/kg is above the threshold for classification.