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Administrative data

Description of key information

In an acute oral toxicity study performed similarly to OECD guideline 401 in rats, LD50 = 4500 mg/kg bw.
In an acute dermal toxicity study performed similarly to OECD guideline 402 in rabbits, 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:
1972
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Study conducted similarly to OECD Guideline 401 with deviations: purity of test item not reported; source of animals and environmental conditions not reported; acclimation period not reported; animals were not weighed after dosing; gross pathology not reported
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
purity of test item not reported; source of animals and environmental conditions not reported; acclimation period not reported; animals were not weighed after dosing; gross pathology not reported
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 200-250 g
- Fasting period during the study: Animals were fasted for a minimum of 16 h prior to administration of the test item.
- Diet: Food, ad libitum
- Water: Water, ad libitum
Route of administration:
oral: unspecified
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
- Test material was administered as a concentrate.
Doses:
2560, 4000, 6250 and 9800 mg/kg bw
No. of animals per sex per dose:
10 males/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Observations for mortality were made at 1 and 6 h after dosing and daily thereafter for 14 days.
- Necropsy of survivors performed: Yes; all surviving animals were sacrificed for gross necropsy examination.
Statistics:
None
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
4 500 mg/kg bw
Based on:
test mat.
95% CL:
3 400 - 5 600
Remarks on result:
other: Deaths occurred overnight to two days following administration of test item. 1/10, 4/10, 7/10 and 10/10 animals were died at 2560, 4000, 6250 and 9800 mg/kg bw, respectively.
Mortality:
- Deaths occurred overnight to two days following administration of test item.
- 1/10, 4/10, 7/10 and 10/10 animals were died at 2560, 4000, 6250 and 9800 mg/kg bw, respectively.
Clinical signs:
- Exophthalmia, hyperreflexiveness, restlessness, lethargy and the loss of righting reflex were observed.
Body weight:
- No data
Gross pathology:
- No data
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 for nerol is higher than 2000 mg/kg bw in rats therefore it is not classified according to Directive 67/548/EEC and CLP Regulation (EC) N° 1272/2008.
Executive summary:

In an acute oral toxicity study performed similarly to OECD Guideline 401, groups (10 males/dose) of Wistar rats were given a single oral dose of nerol at 2560, 4000, 6250 and 9800 mg/kg bw. Animals were then observed for mortality and clinical signs for 14 days and all survivors were sacrificed for macroscopic examination.

Exophthalmia, hyperreflexiveness, restlessness, lethargy and the loss of righting reflex were observed. Deaths occurred overnight to two days following administration of test item. 1/10, 4/10, 7/10 and 10/10 animals were died at 2560, 4000, 6250 and 9800 mg/kg bw, respectively. In this study, the oral LD50 of test item was 4500 mg/kg bw with 95 % confidence limits of 3400 -5600 mg/kg bw in male rats.

The oral LD50 for nerol is higher than 2000 mg/kg bw in rats therefore it is not classified according to Directive 67/548/EEC and CLP Regulation (EC) N° 1272 /2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
4 500 mg/kg bw
Quality of whole database:
Study performed similarly to OECD guideline 401 with deviations but considered as appropriate and reliable to complete this endpoint.

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:
1972
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Study conducted similarly to OECD Guideline 402 with deviations: purity of test item not reported; source and sex of animals and environmental conditions not reported; acclimation period not reported; observation period was 7 days instead of 14 days.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
purity of test item not reported; source and sex of animals and environmental conditions not reported; acclimation period not reported; observation period was 7 days instead of 14 days
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.9-2.2 kg
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Clipped abraded abdominal skin
- Type of wrap if used: Animals were wrapped with binders of rubber dam, gauze and adhesive tape.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 mg/kg bw
Duration of exposure:
24 h
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
10 animals
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: Yes; gross necropsy was performed on all animals at the termination of the study.
Statistics:
None
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: One rabbit died on Day 2.
Mortality:
One rabbit died on Day 2.
Clinical signs:
- Slight to moderate erythema and edema were noticed throughout the observation period. Moderate atonia was observed in one animal on Day 1, which was died on Day 2.
Body weight:
Body weight evolution of the animals remained normal throughout the study.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal LD50 of nerol is higher than 2000 mg/kg bw in rabbits therefore it is not classified according to Directive 67/548/EEC and CLP Regulation (EC) N° 1272/2008.
Executive summary:

In an acute dermal toxicity study performed similarly to OECD Guideline 402, a group of New Zealand white rabbits (10 animals/dose) were given a single dermal application of nerol at 5000 mg/kg bw. The test item was applied to the abraded abdominal skin. The test site was then covered by a semi-occlusive dressing for 24 h. Animals were then observed for mortality, clinical signs and bodyweights for 7 days and were all sacrificed for macroscopic examination.

Slight to moderate erythema and edema were noticed throughout the observation period. Moderate atonia was observed in one animal on Day 1, which was died on Day 2. Body weight evolution of the animals remained normal throughout the study. No abnormalities were noted at necropsy. The dermal LD50 of test item was considered to be higher than 5000 mg/kg bw in rabbits.

The acute dermal LD50 of nerol is higher than 2000 mg/kg bw in rabbits therefore it is not classified according to Directive 67/548/EEC and CLP Regulation (EC) N° 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Study performed similarly to OECD guideline 402 with deviations but considered as appropriate and reliable to complete this endpoint.

Additional information

In an acute oral toxicity study performed similarly to OECD Guideline 401, groups (10 males/dose) of Wistar rats were given a single oral dose of nerol at 2560, 4000, 6250 and 9800 mg/kg bw. Animals were then observed for mortality and clinical signs for 14 days and all survivors were sacrificed for macroscopic examination. Exophthalmia, hyperreflexiveness, restlessness, lethargy and the loss of righting reflex were observed. Deaths occurred overnight to two days following administration of test item. 1/10, 4/10, 7/10 and 10/10 animals were died at 2560, 4000, 6250 and 9800 mg/kg bw, respectively. In this study, the oral LD50 of test item was 4500 mg/kg bw with 95 % confidence limits of 3400 -5600 mg/kg bw in male rats.

In an acute dermal toxicity study performed similarly to OECD Guideline 402, a group of New Zealand white rabbits (10 animals/dose) were given a single dermal application of nerol at 5000 mg/kg bw. The test item was applied to the abraded abdominal skin. The test site was then covered by a semi-occlusive dressing for 24 h. Animals were then observed for mortality, clinical signs and bodyweights for 7 days and were all sacrificed for macroscopic examination. Slight to moderate erythema and edema were noticed throughout the observation period. Moderate atonia was observed in one animal on Day 1, which was died on Day 2. Body weight evolution of the animals remained normal throughout the study. No abnormalities were noted at necropsy. The dermal LD50 of nerol was considered to be higher than 5000 mg/kg bw in rabbits.


Justification for selection of acute toxicity – oral endpoint
Only one study available for this endpoint.

Justification for selection of acute toxicity – inhalation endpoint
No study was available and in accordance with column 2 of REACH Annex VIII (§8.5), the acute toxicity by inhalation does not need to be conducted since acute toxicity is already assessed by two different routes of exposure (oral and dermal routes). Also, acute toxicity studies by oral and dermal routes showed very low toxicity, with high LD50 values.

Justification for selection of acute toxicity – dermal endpoint
Only one study available for this endpoint.

Justification for classification or non-classification

Oral and dermal LD50 are higher than 2000 mg/kg bw in rats and rabbits, respectively, therefore nerol does not need to be classified for acute toxicity according to Directive 67/548/EEC and CLP Regulation (EC) No. 1272/2008.