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Description of key information

Acute toxicity oral: Weight of evidence: Test method similar to OECD 401. 2 different experimental sudies are available in which the oral LD50 was determined to be 1179 mg/kg bw and 1560 mg/kg bw in rats, respectively.

Acute toxicity inhalation: Key study: Test method similar to OECD 403. The LC50 was determined to be >4.8 mg/L air after 1h exposure to aerosol in rats.

Acute toxicity dermal: Key study: Test method similar to OECD 402. The LD50 was determined to be greater than 2025 mg/kg bw after 24h dermal exposure to rabbits.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
2 rats per sex and dose / poorly documented
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
Purity of each material was checked in the Organic Chemicals Synthesis Laboratory, AEQI, in Beltsville by gas chromatography: > 98%
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 150-240 g
- Fasting period before study: 16 hr before dosing.
- Housing: Individually in suspended wire-mesh cages.
Route of administration:
other: Directly into the stomachs with a hypodermic syringe that had a ball-tipped intubation needle.
Vehicle:
unchanged (no vehicle)
Doses:
From 600 to 3038 mg/kg bw
No. of animals per sex per dose:
2 rats per sex and dose.
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 179 mg/kg bw
Based on:
test mat.
95% CL:
927.9 - 1 430.1
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The oral LD50 was determined to be 1179 mg/kg bw in rats.
Executive summary:

An acute oral toxicity test was performed in Sprague-Dawley rats. Test item up to 3038 mg/kg bw was administered to two rats per sex and per dose, directly into the stomachs with a hypodermic syringe that had a ball-tipped intubation needle. The animals were observed for 14 days after exposure. The oral LD50 was determined to be 1179 (± 251.1) mg/kg bw in rats.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Method similar to OECD guideline 401, but no information on doses were reported
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
No information on tested doses
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Osborne-Mendel
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: young adults rats
- Fasting period before study: 18 h
- Housing: cages
- Diet (e.g. ad libitum): Food was replaced in cages as soon as animals received their doses.
- Water (e.g. ad libitum): Ad libitum.

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
Not reported
No. of animals per sex per dose:
5 females and 5 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 2 weeks
- Necropsy of survivors performed: no specified
- Other examinations performed: clinical signs, body weight and time of death
Statistics:
LD50 were computed by the method of Litchfield & Wilcoxon (1949).
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 560 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 170 - <= 2 070
Mortality:
Death time: less than 8 hr
Clinical signs:
Coma within 1 hr after treatment.
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
other: Not classified (CLP Regulation EC no. 1272/2008)
Conclusions:
The LD50 of the test item is 1560 mg/kg body weight by oral route in the rat.

Executive summary:

The acute oral toxicity of the test compound was tested following a method similar to OECD Test Guideline 401. Ten young adult Osborne-Mendel rats evenly divided by sex were administered by oral gavage.

Animals were observed for 2 weeks during which time the development of toxic signs was followed and time of death recorded. Animals exposed to methyleugenol showed coma within 1 hr after treatment. The acute oral LD50 of the test item was determined to be 1560 mg/kg bw (95% confidence limits: 1170 -2070 mg/kg bw).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 179 mg/kg bw
Quality of whole database:
Two experimental studies available with klimisch=2.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
1h exposure, poorly documented
GLP compliance:
no
Test type:
traditional method
Limit test:
no
Specific details on test material used for the study:
Purity of each material was checked in the Organic Chemicals Synthesis Laboratory, AEQI, in Beltsville by gas chromatography: > 98%
Species:
rat
Strain:
Sprague-Dawley
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 150-240 g
- Fasting period before study: 16 hr before dosing.
- Housing: Individually in suspended wire-mesh cages.
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Duration of exposure:
1 h
Concentrations:
4.8 mg/L
No. of animals per sex per dose:
10
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
Key result
Sex:
not specified
Dose descriptor:
LC50
Effect level:
> 4.8 mg/L air
Based on:
test mat.
Exp. duration:
1 h
Interpretation of results:
GHS criteria not met
Conclusions:
The LC50 was determined to be >4.8 mg/L air after 1h exposure to aerosol in rats.
Executive summary:

Ten rats, caged separately to minimize filtration of inspired air by animal fur, were exposed for one hour to the aerosol generated from the undiluted test material by a pneumatic nebulizer. The average nominal concentrations of aerosol, the maximum attainable with the experimental equipment, were calculated by dividing the weight lost from the nebulizer by the total volume of air used (in milligrams per liter air) and it results to be 4.8 mg/L air. Following exposure, the animals were observed for 14 days. The LC50 was determined to be >4.8 mg/L air after 1h exposure to aerosol in rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
4.8 mg/m³
Quality of whole database:
Only one key 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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
2 rabbits per sex and dose / poorly documented
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
Purity of each material was checked in the Organic Chemicals Synthesis Laboratory, AEQI, in Beltsville by gas chromatography: > 98%
Species:
rabbit
Strain:
New Zealand White
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.9-3.1 kg
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Back
- % coverage: 30
- Type of wrap if used: The site of application was covered by wrapping the trunk of the animal with plastic sheeting that was taped securely in place, and oral contact with the test material was prevented by fitting each animal with a light-weight flexible plastic collar that was worn throughout the observation period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not specified.
- Time after start of exposure: 24 h.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2025 mg/kg bw
Duration of exposure:
24 hours
Doses:
2025 mg/kg bw
No. of animals per sex per dose:
2 rabbits per sex.
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days- Duration of observation period following administration: 14 days (or other?)
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 025 mg/kg bw
Based on:
test mat.
Mortality:
No deads were observed in the highest dose tested.
Clinical signs:
No untoward behavioral reactions were seen. All the test chemicals caused local skin reactions characterized at the end of the 24-hr contact period by erythema and edema.
Gross pathology:
Necropsies revealed no abnormal findings other than these dermal alterations.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 was determined to be greater than 2025 mg/kg bw after 24h dermal exposure to rabbits.
Executive summary:

An acute dermal toxicity test was performed in Albino rabbits of the New Zealand strain. The backs of the rabbits were shaved with electric clippers; the shaved area on each animal was about 30% of the total body surface. After a 24 h waiting period to allow the stratum corneum to recover from any disturbance accompanying the close-clipping procedure and to permit healing of any microscopic abrasions, the undiluted liquid test material was applied, using two male and two female rabbits at each dose level. All materials were tested at 2025 mg/kg. The site of application was covered by wrapping the trunk of the animal with plastic sheeting that was taped securely in place, and oral contact with the test material was prevented by fitting each animal with a light-weight flexible plastic collar that was worn throughout the observation period. When the test material had been in contact with the skin for 24 h, the plastic sheeting was removed and all residues of test material were washed off, the test sites were examined for local skin reactions, and the animals were returned to their separate cages. Observations were continued for 14 days following the skin applications. Necropsies were conducted on all animals that died during the study and on all animals that survived the observation period. No deads were observed in the highest dose tested. No untoward behavioral reactions were seen. All the test chemicals caused local skin reactions characterized at the end of the 24 h contact period by erythema and edema. Necropsies revealed no abnormal findings other than these dermal alterations. The LD50 was determined to be greater than 2025 mg/kg bw after 24h dermal exposure to rabbits.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 025 mg/kg bw
Quality of whole database:
Only one key study available.

Additional information

Justification for classification or non-classification

Based on available data, the substance is classified for Acute Toxicity Category 4, H302 according to the CLP Regulation (EC) no. 1272/2008.