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Description of key information

Oral (OECD 401), rat: LD50 > 5000 mg/kg bw
Dermal (OECD 402), rat: LD50 > 5000 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:
01 - 23 May 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
No information on purity was given.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
Deviations:
yes
Remarks:
no information on purity
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: approx. 4 - 6 weeks
- Weight at study initiation: 120 - 152 g (males), 107 - 137 g (females)
- Fasting period before study: overnight prior to dosing until approx. 2 h after dosing
- Housing: 5 animals of the same sex per cage in polypropylene cages on sawdust
- Diet: Rat & Mouse Expanded Diet No. 1 (Special Diet Services Limited, Witham, UK), ad libitum
- Water: mains tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5 ± 2.5
- Humidity (%): 45 - 60
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
A range-finding study was carried out to establish a dosing regimen for the main study.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
Range-finding study: 25, 200, 2000 and 5000 mg/kg bw
Main study: 5000 mg/kg bw
No. of animals per sex per dose:
Range-finding study: 2
Main study: 5
Control animals:
no
Details on study design:
Range-finding study:
- Duration of observation period following administration: 7 days
- Frequency of observations: Animals were observed 0.5, 1 and 4 h after administration and subsequently once daily for 7 days.

Main study:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 0.5, 1, 2, 3, 4 and 5 h after administration and subsequently once daily for 14 days. Individual body weights were determined on Days 0, 7 and 14.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period of the range-finding study and the main study.
Clinical signs:
Range-finding study:
Abnormal body carriage (hunched posture) and pilo-erection were observed in all rats at all dose levels. Lethargy and ataxia were seen in rats at the 2000 mg/kg bw dose level and above while ptosis and a decreased respiratory rate were recorded at the 5000 mg/kg bw dose level only. Recovery of all animals at the 25 and 200 mg/kg bw dose levels, as judged by external appearance and behaviour, was apparently complete 4 h following dosing. All animals at the 2000 and 5000 mg/kg bw dose levels had recovered by Day 1 with the exception of one male rat, at the higher dose level, in which symptoms persisted until Day 1
but had resolved completely by Day 2.

Main study:
Signs of reaction to treatment observed shortly after dosing in all rats consisted of an abnormal body carriage (hunched posture), pilo-erection and ataxia. Other signs of overt toxicity seen in some rats consisted of lethargy, ptosis and a decreased respiratory rate. Recovery of all animals, as judged by external appearance and behaviour was apparently complete by Day 2.
Body weight:
Body weight development was unremarkable. All animals gained weight during the observation period.
Gross pathology:
Post mortem examination of all rats killed at Day 14 revealed congestion of the lungs in two rats only. No macroscopic abnormalities were observed in any of the remaining animals.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute oral toxicity study a LD50 value > 5000 mg/kg bw in male and female rats was derived.
Executive summary:

An acute oral toxicity study was performed with male and female rats according to OECD 401 under GLP conditions. After a range-finding study with the dose levels 25, 200, 2000 and 5000 mg/kg bw, a main study with 5000 mg/kg bw was performed. No mortality occurred during the study period of the range-finding study and the main study.

In this acute oral toxicity study a LD50 value > 5000 mg/kg bw in male and female rats was derived.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 2), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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:
22 May - 17 June 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
No information on purity was given.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
No information on purity was given.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: approx. 10 - 12 weeks
- Weight at study initiation: 262 - 285 g (males), 237 - 264 g (females)
- Housing: individually during the 24 h exposure period and subsequently up to 5 animals of the same sex per cage in polypropylene cages on sawdust
- Diet: Rat and Mouse Expanded Diet No.1 (Special Diets Services Limited, Witham, UK), ad libitum
- Water: mains tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 ± 2.5
- Humidity (%): 45 - 66
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: skin of the dorsal, lateral and ventral regions (6 cm x 12 cm)
- % coverage: 10%
- Type of wrap if used: The treated skin was covered with a surgical gauze patch (7 cm x 4 cm) which was held in place with a strip of elastic adhesive bandage (7.5 cm wide and 25-30 cm long) wrapped around the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing: The skin and surrounding hair were sponged thoroughly with warm water, rinsed and dried using absorbant paper.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amounts applied: 0.06, 0.46, 2.29 and 5.71 mL/kg bw (range-finding study); 5.71 mL/kg bw (main study)
- Constant concentration used: yes
Duration of exposure:
24 h
Doses:
Range-finding study: 50, 400, 2000 and 5000 mg/kg bw
Main study: 5000 mg/kg bw
No. of animals per sex per dose:
Range-finding study: 2
Main study: 5
Control animals:
not required
Details on study design:
Range-finding study:
- Duration of observation period following administration: 7 days
- Frequency of observations: Animals were observed 30 min and 1 and 4 h after administration and subsequently once daily for 7 days.

Main study:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 30 min and 1, 2, 3, 4 and 5 h after administration and subsequently at least once daily for 14 days. Individual body weights were determined on Days 0, 7 and 14.
- Necropsy of survivors performed: yes
Preliminary study:
No deaths or clinical signs of toxicity were noted up to the highest concentration tested throughout the 7-day observation period. The dose level selected for the main study was therefore 5000 mg/kg bw.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No signs of systemic toxicity were noted until the end of the observation period.
Body weight:
Body weight development was unremarkable. All animals gained weight during the observation period.
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute dermal toxicity study a LD50 value > 5000 mg/kg bw in male and female rats was derived.
Executive summary:

An acute dermal toxicity study was performed with male and female rats according to OECD 402 under GLP conditions. After a range-finding study with the dose levels 50, 400, 2000 and 5000 mg/kg bw, a main study with 5000 mg/kg bw was performed. No mortality occurred during the study period of the range-finding study and the main study.

In this acute dermal toxicity study a LD50 value > 5000 mg/kg bw in male and female rats was derived.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 2). This study is not a standard information requirement set out in Annex VII of Regulation (EC) No 1907/2006 and is thus considered as additional information.

Additional information

Acute oral toxicity

The acute oral toxicity of the test substance was assessed in a study according to OECD Guideline 401 and in compliance with GLP (1985). Based on a preliminary study, groups of 5 male and female rats were given a dose level of 5000 mg/kg bw via gavage. No mortality occurred during the study period up to concentrations of 5000 mg/kg bw. Signs of toxicity were observed in all rats treated with the test substance shortly after dosing, completely recovered by Day 2. Thus, a LD50 > 5000 mg/kg bw for male and female rats was determined.

Acute dermal toxicity

The acute dermal toxicity of the test substance was assessed in a study according to OECD Guideline 402 and in compliance with GLP (1985). Based on a preliminary study, groups of 5 male and female rats were treated with the test substance at a concentration of 5000 mg/kg bw. No mortality or signs of toxicity occurred during the study period. Thus, a dermal LD50 > 5000 mg/kg bw for male and female rats was determined.

Justification for classification or non-classification

The available data on acute oral and dermal toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.