Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Acute oral toxicity: OECD TG 401: > 5000 mg/kg bw.
Acute inhalation toxicity derived from acute oral toxicity: > 13000 mg/m3

Acute dermal toxicity: OECD TG 402: >2000 mg/kg bw

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:
October 22, 1979 - November 5, 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Reliability 2 is assigned because the study is conducted similar to OECD TG 401 in compliance with GLP, with deviations that influence the quality of the results.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
No details on test material, no purity, no details on environmental conditions.
Principles of method if other than guideline:
E.C. Hagan, "Acute Toxicity", Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (The Association of Food and Drug Officials of the United States, 1975), pp. 17 - 25.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Wistar-strain albino
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Suitable licensed dealer
- Age at study initiation: approx. 6 to 8 weeks
- Weight at study initiation: 200 - 238 g
- Fasting period before study: approx. 18 hours
- Housing: Animals were housed in galvanized cages with indirect bedding
- Diet: Free access to diet consisted of a growth and maintenance ration from a commercial producer
- Water: Free access to water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature controlled
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Individual doses, calculated on the basis of bodyweight, were administered using a stainless steel intragastric feeding needle.
Doses:
5000 mg/kg bodyweight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: The animals were observed for signs of pharmacologic activity and drug toxicity at 1, 3, 6 and 24 hours after application and thereafter daily.
- Necropsy of survivors performed: yes, at the end of the observation period the animals were killed, necropsied and subjected to complete gross necropsy, with all findings noted.
- Body weights: Individual body weights were recorded immediately before treatment and then on the 14th day of the observation period.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred.
Clinical signs:
Slight depression was oberserved among all animals at 3, 6 and 24 hours after application of the substance.
Body weight:
Normal bodyweight increases were observed on the 14th day of the observation period.
Gross pathology:
No gross changes were observed.
Interpretation of results:
other: not acutely orally toxic
Remarks:
according to CLP criteria 1272/2008 and its amendments
Conclusions:
The acute oral toxicity test showed an LD50 of >5000 mg/kg bw
Executive summary:

In this study performed equivalent to OECD TG 401 guideline and GLP principles, 10 rats (5 males and 5 females) were administered to the substance at a dose level of 5000 mg/kg bw. No deaths occurred. Slight depression was oberserved among all animals at 3, 6 and 24 hours after application of the substance. Normal bodyweight increases were observed on the 14th day of the observation period. No gross changes were observed. The acute oral LD50 for the substance in male and female rats was determined to be >5000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The acute oral toxicity result is of sufficient quality and adequate for this dossier.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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:
27 February, 2001 - 13 March, 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Reliability 1 is assigned because the study is conducted according to OECD TG 402 in compliance with GLP, without deviations that influence the quality of the results.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1987)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Sprague-Dawley CD (Crl: CD® ( SD) IGS BR)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: males: 288 - 309 g; females: 233 - 259 g
- Housing: The animals were housed in suspended polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet: Free access to food (Rat and Mouse SQC Expanded Diet No. 1, Special Diets Services Limited, Witham, Essex, UK)
- Water: Free access to drinking water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): set to maintain 19 - 25
- Humidity (%): set to maintain 30 - 70
- Air changes (per hr): At least 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: area of shorn skin
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of selfadhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: The treated skin and surrounding hair was wiped with cotton wool moistened with distilled water to remove any residual test material.
- Time after start of exposure: 24 hours
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations:
Mortality and clinical signs: The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. After removal of the dressings and subsequently once daily for 14 days, the test sites were examined for evidence of primary irritation and scored for skin reactions.
Bodyweights: Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded.
Statistics:
Not performed.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred.
Clinical signs:
There were no signs of systemic toxicity.
Body weight:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
No abnorrnalities were noted at necropsy.
Other findings:
There were no signs of dermal irritation.
Interpretation of results:
other: not acute dermally toxic
Remarks:
according to CLP 1272/2008 and its amendments
Conclusions:
The acute dermal toxicity of the substance was >2000 mg/kg bw.
Executive summary:

In this study performed to OECD TG 402 guideline and GLP principles, 10 rats (5 males and 5 females) were administered to the substance at a dose level of 2000 mg/kg bw. No deaths occurred and there were no signs of systemic toxicity. All animals showed expected gains in bodyweight over the study period. There were no signs of dermal irritation and no abnorrnalities were noted at necropsy. The acute dermal LD50 for the substance in male and female rats was determined to be >2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The acute dermal toxicity result is of sufficient quality and adequate for this dossier.

Additional information

Acute oral: In this study performed equivalent to OECD TG 401 guideline and GLP principles, 10 rats (5 males and 5 females) were administered to the substance at a dose level of 5000 mg/kg bw. No deaths occurred. Slight depression was observed among all animals at 3, 6 and 24 hours after application of the substance. Normal bodyweight increases were observed on the 14th day of the observation period. No gross changes were observed. The acute oral LD50 for the substance in male and female rats was determined to be >5000 mg/kg bw.

Acute dermal: In this study performed to OECD TG 402 guideline and GLP principles, 10 rats (5 males and 5 females) were administered to the substance at a dose level of 2000 mg/kg bw. No deaths occurred and there were no signs of systemic toxicity. All animals showed expected gains in bodyweight over the study period. There were no signs of dermal irritation and no abnormalities were noted at necropsy. The acute dermal LD50 for the substance in male and female rats was determined to be >2000 mg/kg bw.

Acute inhalation: Acute inhalation is predicted based on the acute oral toxicity in accordance with the CLP guidance document (2015, page 255). The acute inhalation is predicted to be 13000 mg/m3 and the saturated vapour pressure is 43 mg/m3. This means that the acute inhalation concentration cannot be reached and therefore no acute inhalation is anticipated.

(Calculation: =>5000 mg/kg bw x 0.0052 mg/l (x 1000 conversion to m3) after 4 h exposure x 50/100% oral versus inhalation absorption. Saturated vapour pressure calculation mg/m3: (MW g/mol*VP (Pa) / 8.3*293)*1000)).

Justification for classification or non-classification

According to the CLP criteria 1272/2008 and its amendments, the substance does not have to be classified for acute toxicity by the oral, dermal and inhalation route.

Categories Display