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Administrative data

Description of key information

Acute oral toxicity: LD50 > 2000 mg/kg bw (OECD 401; GLP; male and female rats)

Acute dermal toxicity: LD50 > 2000 mg/kg bw (OECD 402; GLP; male and female rats)

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:
1992-09-01 to 1992-09-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987-02-24
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
1984
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 1992-06-11
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: test material was ground to a fine powder using a mortar and pestle
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: approx. five to eight weeks old
- Weight at study initiation: males: 122 - 138 g; females: 121 - 134 g
- Fasting period before study: overnight fast immediately before dosing and for approximately two hours after dosing
- Housing: housed in groups of five by sex in solid-floor polypropylene cages with sawdust bedding.
- Diet (ad libitum, except of fasting period): Rat and Mouse Expanded Diet No. 1
- Water (ad libitum, except of fasting period): mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 21 °C
- Relative humidity: 42 - 68 %
- Air changes: approx. 15 changes/hour
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
arachis oil
Remarks:
B.P.
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
The volume administered to each animal was calculated according to its fasted body weight at the time of dosing.

DOSAGE PREPARATION: test material was freshly prepared as a suspension at the appropriate concentrations in the vehicle

Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males / 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
death and overt signs of toxicity: 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days
individual bodyweights: prior to dosing on Day 0 and on Days 7 and 14

- Necropsy of survivors performed: yes, at the end of the study the animals were sacrificed and subjected to gross pathological examination.
Statistics:
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.
Preliminary study:
A range-finding study was conducted in rats (1 male / 1 female) at a dose level of 2000 mg/kg. Deaths and overt signs of toxicity were recorded 0.5, 1, 2, and 4 hours after dosing and then daily for five days. Individual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed.
There were no deaths. Common signs of systemic toxicity noted were lethargy and ataxia.
Based on this result, a dose level of 2000 mg/kg bw was selected for the main study.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
Common signs of systemic toxicity noted were lethargy and ataxia with isolated incidents of hunched posture. Animals recovered one day after dosing except for one female which appeared normal throughout the study.
Body weight:
All animals showed expected gain in bodyweight during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
LD50 (male and female rats) > 2000 mg/kg bw
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is not acutely toxic via the oral route.
Executive summary:

The acute oral toxicity of the substance was investigated according to the OECD guideline 401 (1987). Five male and five female Sprague-Dawley rats received a single dose of 2000 mg/kg bw in arachis oil B.P. by gavage. Clinical signs, mortality, and body weight were recorded. All animals were subjected to gross necropsy.

Mortality or abnormalities at necropsy were not observed during the study. Common signs of systemic toxicity noted were lethargy and ataxia with isolated incidents of hunched posture. Animals recovered one day after dosing except for one female which appeared normal throughout the study. Lastly, all animals gained the expected weight during the observation period.

Thus, the LD50 was considered to be greater than 2000 mg/kg bw for male and female rats. According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is not acute toxic via the oral route.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

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 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:
1992-09-8 to 1992-09-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1981-05-12
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
1984
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 1992-06-11
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: approx. ten to fourteen weeks old
- Weight at study initiation: males: 209 - 225 g; females: 215 - 223 g
- Housing: individually in suspended polypropylene cages furnished with softwood sawdust, during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet (ad libitum): Rat and Mouse Expanded Diet No. 1
- Water (ad libitum): mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 22 °C
- Relative humidity: 50 - 75%
- Air changes: approx. 15 changes/hour
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
arachis oil
Remarks:
B.P.
Details on dermal exposure:
TEST SITE
- Area of exposure: back and flanks were clipped free of hair (approx. 5 cm x 4 cm)
- % coverage: approx. 10 % of the total body surface area was treated with the test substance, which has previously been moistened with the vehicle
- Type of wrap: piece of 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: treated skin and surrounding hair wiped with cotton wool moistened with arachis oil to remove any residual test material
- Time after start of exposure: 24 hours
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males / 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
death and overt signs of toxicity: 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days (adverse dermal reactions were also noted)
individual body weights: prior to application on Day 0 and on Days 7 and 14

- Necropsy of survivors performed: yes, at the end of the study the animals were sacrificed and subjected to gross pathological examination.
Statistics:
Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test material was made.
Preliminary study:
not applicable
Key result
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.
Moderate erythema was noted at the treatment sites of all females two and three days after dosing. Desquamation was also noted at the treatment site of one female three to five days after dosing.
No signs of skin irritation were noted in males during the study.
Body weight:
All animals showed expected gain in bodyweight during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
LD50 (male and female rats) > 2000 mg/kg bw
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is not acutely toxic via the dermal route.
Executive summary:

The acute dermal toxicity of the substance was investigated according to the OECD guideline 402 (1981). The substance was applied to clipped skin of five male and five female Sprague-Dawley rats at a dose level of 2000 mg/kg bw and covered with a semi-occlusive dressing. The application site had been moistened with arachis oil B.P. before application.The application site was exposed for 24 hours and the test sites were cleaned using a cotton wool moistened with arachis oil to remove any residual test substance. Clinical signs, mortality, adverse dermal reactions and body weight were recorded during the 14 day observation period. All animals were subjected to necropsy at the end of the study.

No mortality occurred and no signs of systemic toxicity were noted during the study. Moderate erythema was noted at the treatment sites of all females two and three days after dosing. Desquamation was also noted at the treatment site of one female three to five days after dosing. No signs of skin irritation were noted in males during the study. Furthermore, all animals showed expected gain in bodyweight during the study and no abnormalities were noted at necropsy.

Thus, the LD50 was considered to be greater than 2000 mg/kg bw for male and female rats. According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the test item is not acutely toxic via the dermal route.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

Justification for classification or non-classification

Acute oral toxicity

The substance is not acutely toxic via the oral route based on an acute oral toxicity test (OECD 401) and does not require classification according to Regulation (EC) No 1272/2008 and subsequent adaptations.

Specific target organ toxicant (STOT) - single exposure: oral

Reversible or irreversible adverse health effects were not observed immediately or after exposure in an acute oral toxicity test (OECD 401).Thus, the classification criteria as specific target organ toxicant (STOT) – single exposure, oral are not met and the substance does not require classification according to Regulation (EC) No 1272/2008 and subsequent adaptations.

Acute dermal toxicity

The substance is not acutely toxic via the dermal route based on an acute dermal toxicity test (OECD 402) and does not require classification according to Regulation (EC) No 1272/2008 and subsequent adaptations.

Specific target organ toxicant (STOT) - single exposure: dermal

Reversible or irreversible adverse health effects were not observed immediately or after exposure in an acute dermal toxicity test (OECD 402).Thus, the classification criteria as specific target organ toxicant (STOT) – single exposure, dermal are not met and the substance does not require classification according to Regulation (EC) No 1272/2008 and subsequent adaptations.