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Administrative data

Description of key information

Acute oral Toxicity: 

The acute oral toxicity dose (LD50) for target chemical (+)-Neomenthol (CAS no: 2216-52-6) was estimated based on QSAR prediction done using the Danish (Q)SAR Database. The LD50 values were estimated to be 2800 mg/kg bw in rats and 3000 mg/kg bw in mice. The study concluded that the LD50 value is >2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, (+)-Neomenthol cannot be classified for acute oral toxicity. 

Acute Inhalation Toxicity:

The acute inhalation toxicity study need not be conducted because exposure of humans via inhalation route is not likely taking into account due to the low vapour pressure of the substance (+)-Neomenthol (CAS no: 2216-52-6), which is reported to be 7.67E-03 mmHg. Thus, exposure to inhalable dust, mist and vapour of the chemical (+)-Neomenthol is highly unlikely. Therefore this study is considered for waiver.

 

Acute dermal Toxicity: 

The acute dermal toxicity dose (LD50) for (+)-Neomenthol (CAS no: 2216-52-6) was considered based on data available for the structurally and functionally similar read across chemicals. The LD50 value is >5000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, (+)-Neomenthol cannot be classified for acute dermal toxicity. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
calculation (if not (Q)SAR)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
Data is from Danish QSAR.
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: Predicted data
Principles of method if other than guideline:
Prediction is done by using Danish QSAR
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
- IUPAC Name: (+)-Neomenthol- InChI: 1S/C10H20O/c1-7(2)9-5-4-8(3)6-10(9) 11/h7-11H,4-6H2,1-3H3/t8-,9+,10+/m1/s1- Smiles: C[C@@H]1CC[C@H]([C@H](C1)O)C(C)C- Name of test material :d-Neomenthol- Molecular formula:C10H20O- Molecular weight :156.267 g/mol- Substance type:Organic
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
not specified
Doses:
2800 mg/kg bw
No. of animals per sex per dose:
not specified
Control animals:
not specified
Details on study design:
not specified
Statistics:
not specified
Preliminary study:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
2 800 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality observed
Mortality:
not specified
Clinical signs:
not specified
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified
Interpretation of results:
other: Not classified
Conclusions:
LD50 was estimated to be 2800 mg/kg bw, when rats were treated with (+)-Neomenthol (CAS no: 2216-52-6) via oral route.
Executive summary:

Based on the QSAR prediction done using the Danish (Q)SAR Database, the acute oral toxicity was estimated for (+)-Neomenthol (CAS no: 2216-52-6). The LD50 was estimated to be 2800 mg/kg bw with Reliability Index 0.88 (>0.75 = high prediction quality), when rats were treated with (+)-Neomenthol via oral route.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 800 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from Danish QSAR.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Quality of whole database:
Waiver

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
Experimental data of read across substances
Justification for type of information:
Data for the target chemical is summarized based on the structurally and functionally similar read across chemicals.
Reason / purpose:
read-across source
Related information:
Composition 1
Reason / purpose:
read-across source
Related information:
Composition 1
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
WoE report is based on two acute dermal toxicity studies as- WoE 2.and WoE 3. Acute dermal toxicity test was carried out to study the effects of the test chemicals on rodents
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
- IUPAC Name: (+)-Neomenthol- InChI: 1S/C10H20O/c1-7(2)9-5-4-8(3)6-10(9) 11/h7-11H,4-6H2,1-3H3/t8-,9+,10+/m1/s1- Smiles: C[C@@H]1CC[C@H]([C@H](C1)O)C(C)C- Name of test material :d-Neomenthol- Molecular formula:C10H20O- Molecular weight :156.267 g/mol- Substance type:Organic
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
1. not specified2. not specified
Type of coverage:
other: 1. Dermal 2. Dermal
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
1. not specified2. not specified
Duration of exposure:
1. not specified2. not specified
Doses:
1. 5000 mg/kg bw 2. 5000 mg/kg bw
No. of animals per sex per dose:
1. not specified2. not specified
Control animals:
not specified
Details on study design:
1. not specified2. not specified
Statistics:
1. not specified2. not specified
Preliminary study:
1. not specified2. not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed
Mortality:
1. No mortality was observed in treated rabbits at 5000 mg/kg bw 2. No mortality was observed in treated rabbits at 5000 mg/kg bw
Clinical signs:
1. not specified2. not specified
Body weight:
1. not specified2. not specified
Gross pathology:
1. not specified2. not specified
Other findings:
1. not specified2. not specified
Interpretation of results:
other: Not classified
Conclusions:
According to CLP regulation, the test chemical (+)-Neomenthol (CAS no: 2216-52-6) cannot be classified for acute dermal toxicity, as the LD50 value is >2000 mg/kg bw
Executive summary:

Data available for the structurally similar read across chemicals has been reviewed to determine the acute dermal toxicity of the test chemical (+)-Neomenthol (CAS no: 2216-52-6). The studies are as mentioned below:

1. The acute dermal toxicity study was conducted by using test chemical in rabbits at the dose concentration of 5000 mg/kg bw. No mortality was observed in treated rabbits at 5000 mg/kg bw. Therefore, LD50 was considered to be >5000 mg/kg bw, when rabbits were treated with test chemical by dermal application.

2. The acute dermal toxicity study was conducted by using test chemical in rabbits at the dose concentration of 5000 mg/kg bw. No mortality was observed in treated rabbits at 5000 mg/kg bw. Therefore, LD50 was considered to be >5000 mg/kg bw, when rabbits were treated with test chemical by dermal application.

Thus, based on the above summarised studies, (+)-Neomenthol (CAS no: 2216-52-6) and it’s structurally and functionally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, (+)-Neomenthol cannot be classified for acute dermal toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from authoritative database.

Additional information

Acute oral Toxicity: 

In different studies, (+)-Neomenthol (CAS no: 2216-52-6) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats and mice for (+)-Neomenthol along with the data available for the structurally and functionally similar read across chemicals. The predicted data using Danish (Q)SAR Database has also been compared with the experimental study. The studies are summarized as below –

Based on the QSAR prediction done using the Danish (Q)SAR Database, the acute oral toxicity was estimated for (+)-Neomenthol (CAS no: 2216-52-6). The LD50 was estimated to be 2800 mg/kg bw with Reliability Index 0.88 (>0.75 = high prediction quality), when rats were treated with (+)-Neomenthol via oral route.

The above prediction study is supported by another QSAR prediction study done using the Danish (Q)SAR Database, the acute oral toxicity was estimated for (+)-Neomenthol (CAS no: 2216-52-6). The LD50 was estimated to be 3000 mg/kg bw with Reliability Index 0.84 (>0.75 = high prediction quality), when mice were treated with (+)-Neomenthol via oral route.

Both the above predictions are supported with the experimental study conducted on mice and mentioned in publication for the target chemical (+)-Neomenthol (CAS no: 2216-52-6). The acute oral toxicity study was conducted in mice at the dose concentration of 4000 mg/kg bw. 50% mortality was observed in treated mice. Hence, LD50 value was considered to be 4000 mg/kg bw, when mice were treated with (+)-Neomenthol via oral route.

All the above prediction and experimental studies are supported with the data available for the structurally and functionally similar read across chemical. The acute oral toxicity study was conducted by using test chemical in groups of 10 male and female Osborne-Mendel rats at the dose concentration of 3180 (2790-3620) mg/kg bw. The given test chemical was dissolved in corn oil as 50% w/v concentration and administered via oral gavage route. All animals were maintained under close observation for recording toxic signs and time of death. Such observation was continued until animals appeared normal and showed weight gain. LD50’s were computed by the method of Litchfield & Wilcoxon (1949). Mortality was observed within 4 hour to 3 days of observation. Ataxia and scrawny appearance was observed in animals. Hence, LD50 value was considered to be 3180 mg/kg bw, with 95% confidence limit of 2790-3620 mg/kg bw, when groups of 10 male and female Osborne-Mendel rats were treated with test chemical via oral gavage route.

These studies are further supported with data available for the structurally and functionally similar read across chemical. The acute oral toxicity study was conducted by using test substance in groups of 20 male Wistar rats at the dose concentration of 2000, 4000, and 8000 mg/kg bw. The given test chemical was administered via oral gavage route. All animals were observed for mortality and clinical signs for 48 hours. LD50’s were computed by the Reed-Muench method. Mortality was observed after 48 hours as follows, at 2000 mg/kg – 9/20 animals died; at 4000 mg/kg – 14/20 animals died; and at 8000 mg/kg – 20/20 animals died. Animals exhibited brief stimulation, followed by depression beginning in approximately 15 min. Twitching, spastic convulsions, ataxia with hind limb paralysis, and abdominal contractions, very slow respiration, and loss of righting reflex after 25 min. were all observed. However, the effects were much slower in appearing, taking 45 min. or longer to show the initial stimulation, twitching, and ataxia. Therefore, LD50 value was considered to be 2426 mg/kg bw, when groups of 20 male Wistar rats were treated with test chemical via oral gavage route.

Thus, based on the above summarised studies, (+)-Neomenthol (CAS no: 2216-52-6) and it’s structurally and functionally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, (+)-Neomenthol cannot be classified for acute oral toxicity.

 

Acute Inhalation Toxicity:

The acute inhalation toxicity study need not be conducted because exposure of humans via inhalation route is not likely taking into account due to the low vapour pressure of the substance (+)-Neomenthol (CAS no: 2216-52-6), which is reported to be 7.67E-03 mmHg. Thus, exposure to inhalable dust, mist and vapour of the chemical (+)-Neomenthol is highly unlikely. Therefore this study is considered for waiver.

Acute dermal Toxicity: 

Data available for the structurally similar read across chemicals has been reviewed to determine the acute dermal toxicity of the test chemical (+)-Neomenthol (CAS no: 2216-52-6). The studies are as mentioned below:

1. The acute dermal toxicity study was conducted by using test chemical in rabbits at the dose concentration of 5000 mg/kg bw. No mortality was observed in treated rabbits at 5000 mg/kg bw. Therefore, LD50 was considered to be >5000 mg/kg bw, when rabbits were treated with test chemical by dermal application.

2. The acute dermal toxicity study was conducted by using test chemical in rabbits at the dose concentration of 5000 mg/kg bw. No mortality was observed in treated rabbits at 5000 mg/kg bw. Therefore, LD50 was considered to be >5000 mg/kg bw, when rabbits were treated with test chemical by dermal application.

Thus, based on the above summarised studies, (+)-Neomenthol (CAS no: 2216-52-6) and it’s structurally and functionally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, (+)-Neomenthol cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction, (+)-Neomenthol (CAS no: 2216-52-6) and it’s structurally and functionally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw for acute oral and dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, (+)-Neomenthol cannot be classified for acute oral and dermal toxicity. For acute inhalation toxicity wavier were added so, not possible to classify.