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Administrative data

Description of key information

Acute toxicity: oral: LD50 > 5000 mg/kg bw (in 2 studies; similar to OECD 401 in rats; rel.2, WoE)

Acute toxicity: dermal: LD50 > 5000 mg/kg bw/day (similar to OECD 402 in rabbits, rel.2, S)

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
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Basic data given: comparable to standard guideline OECD 401. No details on test item purity, form or batch number, on test animals, environmental conditions of animal room and body weight.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
No details on test animals, environmental conditions of animal room and body weight.
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No data
Route of administration:
oral: unspecified
Vehicle:
unchanged (no vehicle)
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
10 animals/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for toxicity and clinical signs daily for 14 days.
- Necropsy of survivors performed: Yes
Statistics:
No data
Preliminary study:
Not applicable
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
No clinical signs were observed.
Body weight:
No data
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the oral LD50 for the test substance is higher than 5000 mg/kg bw in rats therefore it is not classified according to the Annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In an acute oral toxicity study (limit test), performed similarly to OECD Guideline No. 401, groups of rats (10/dose) were administered a single oral dose of test material at 5000 mg/kg bw. Animals were then observed for mortality and clinical signs daily for 14 days.

 

No mortality or clinical signs were observed at 5000 mg/kg bw. No abnormalities were noted at necropsy. 

Rat Oral LD50 = 5000 mg/kg bw

 

Under the test conditions, test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS. 

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1997
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:
no details of diet and water to test animals reported; No justification for solvent used.
Principles of method if other than guideline:
Test substance was orally administered to rats by gavage at dose level of 5000 mg/kg bw. The animals were observed for mortality, clinical signs and body weight for 14 days and then necropsied for macroscopic observations.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Source: Cho Seon Pharm. & Trading Co., Ltd.
- Physical state: Colourless liquid
- Impurities (identity and concentrations): no data
- Lot/batch No.: Pilot 3, 96.11.27
- Expiration date of the lot/batch: no data
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Japan
- Housing: 5 animals/sex were housed in polycarbonate cages

ENVIRONMENTAL CONDITIONS
- Temperature: 23 ± 3 °C
- Humidity: 50 ± 10%
- Photoperiod: 12 h light/12 h dark
Route of administration:
oral: gavage
Vehicle:
other: 0.1% Tween 80 solution
Details on oral exposure:
DOSAGE PREPARATION
- The dose was calculated for each individual animal based on the body weight on the day of administration by using the ratio 0.9221/kg bw. For preparation of the test substance, the calculated amount of l-muscone was mixed with 0.1% Tween 80 solution to obtain a final concentration of 500 mg/mL, which was mixed completely with a stirrer and then gavaged to rats using a feeding needling.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Animals were monitored and recorded for any clinical signs every hour up to 6 h followed by additional checking in a day at fixed interval for 14 days. The observation was made on changes in general conditions, appearance of toxic symptoms, animal death, and symptoms that might appear to be caused by test substance administration.
- Frequency of weighing: Body weights of all animals were measured twice a week during the experimental period before administration of the test substance and at the time of autopsy.
- Necropsy of survivors performed: Yes; dead animals were immediately autopsied and subjected to macroscopic examination. All surviving animals were subjected to gross necropsy.
Statistics:
Median lethal dose (LD50) values for the test material were calculated using the Litchfield and Wilcoxon method, and statistical analysis of data obtained from the main test including the body weight was performed to evaluate the significance of the difference between the control and treated groups using the Student’s t-test.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
No clinical signs were observed.
Body weight:
Test substance treated group showed a significant weight loss from the day of administration of test substance to autopsy day. However, females in this group showed a significant weight loss only during the first 2 days after administration of test substance (p < 0.01) and gradually recovered thereafter, resulting in no significant weight changes.
Gross pathology:
- No abnormalities were noted at necropsy.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the oral LD50 for the substance is higher than 5000 mg/kg bw in rats therefore it is not classified according to the Annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In an acute oral toxicity study (limit test), a groups (5/sex/dose) of Sprague-Dawley rats were given a single oral (gavage) dose of test substance at 5000 mg/kg bw in 0.1% Tween 80 solution. A similar group of rats was administrated 0.1% Tween 80 solution. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.  

No mortality or clinical signs was observed. Test substance treated group showed a significant weight loss from the day of administration of test substance to autopsy day. However, females in this group showed a significant weight loss only during the first 2 days after administration of test substance and gradually recovered thereafter, resulting in no significant weight changes. No abnormalities were noted at necropsy of animals that were killed at the end of the study. 

Oral LD50 Combined > 5000 mg/kg bw. 

Under the test conditions, the test substance is not classified for acute oral toxicity according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw
Quality of whole database:
The two studies were non-GLP but were of good quality (Klimish score= 2)

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Not required for substances at the REACH Annex VII tonnage level.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Basic data given: comparable to standard guideline. comparable to guideline study with acceptable restrictions Pre-guideline and pre-GLP study. Only basic data given, but considered sufficiently reliable for the purpose of hazard assessment.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
(no details on test animals, environmental condition of animal room, dermal exposure (duration, occlusive-dressing or not, abraded skin or not), body weight)
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No data
Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 mg/kg bw
Duration of exposure:
No data
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
10 animals/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for toxicity and clinical signs daily for 14 days.
- Necropsy of survivors performed: Yes
Statistics:
No data
Preliminary study:
Not applicable
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: One animal died on Day 4.
Mortality:
1 animal died on day 4
Clinical signs:
Moderate redness was observed in 10/10 animals. Slight oedema in 3/10 and Moderate oedema in 7/10.
Body weight:
No data
Gross pathology:
Liver dark, intestine slightly red and fecal matter dried around anal region in the animal which died.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the available data, the substance is not classified according to the Regulation (EC) No. 1272/2008 and to the GHS as the dermal LD50 is greater than 5000 mg/kg bw in rabbits.
Executive summary:

In an acute dermal toxicity study (limit test), the skin of ten rabbits was exposed to test material at dose of 5000 mg/kg bw. Animals were observed for mortality and clinical signs at least daily for 14 days. 1/10 animal died on Day 4 post exposure. Dermal irritation was observed in all the animals.

Rabbit Dermal LD50 > 5000 mg/kg bw

Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for acute dermal toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw
Quality of whole database:
The study was non-GLP but was of good quality (Klimish score= 2)

Additional information

Acute toxicity: oral

A study was identified (MB research laboratories, 1977, rel.2). In this acute oral toxicity study, performed similarly to OECD Guideline No. 401, rats were given a single oral dose of test material at 5000 mg/kg bw. Animals were then observed for mortality and clinical signs for 14 days and at the end of the study the surviving animals were sacrificed for necropsy.

No mortality or clinical signs were observed. No abnormalities were noted at necropsy.

This study gave an oral LD50 (rats) > 5000 mg/kg bw.

An other study was identified (Seung-Min Oh, 1997, Rel.2). In this acute oral toxicity study, also performed similarly to OECD Guideline No. 401, rats were given a single oral dose of test material at 5000 mg/kg bw. Animals were then observed for mortality , clinical signs and body weights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.

No mortality or clinical signs were observed. Test substance treated group showed a significant weight loss from the day of administration of test substance to autopsy day. However, females in this group showed a significant weight loss only during the first 2 days after administration of test substance and gradually recovered thereafter, resulting in no significant weight changes. No abnormalities were noted at necropsy.

This study also gave an oral LD50 (rats) > 5000 mg/kg bw.

A LD50 higher than 2000 mg/kg bw was also found following a single administration of the substance in beagle dogs of both sexes ( 3 animals/sex) with no death observed nor treatment related clinical signs, urinalysis, eye examination, hematology, serum chemistry, organ weight or other findings [You et al., 1997]. This study supports the conclusion that this substance is not acutely toxic.

Acute toxicity: dermal

Not required for substances at the REACH Annex VII tonnage level. However a study was identified (MB research laboratories, 1977, rel.2). In this acute dermal toxicity study (limit test), the skin of 10 rabbits was exposed to test material at dose of 5000 mg/kg bw. Animals were then observed for mortality and clinical signs at least daily for 14 days. 1/10 animal died on Day 4 post exposure. Moderate dermal irritation was observed in all the animals.

This study gave a dermal LD50 (rabbits) > 5000 mg/kg bw.

Reference:

[You et al., 1997] Acute and Subacute Toxicity of l-Muscone in Beagle Dogs. Korean J. Toxicol. Vol. 13, No. 4, pp. 449-460, 1997.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self classification:

Acute toxicity via Oral route:

Based on the available information, the substance is:

- not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the oral LD50 is higher than 5000 mg/kg bw

- not classified according to the GHS as the oral LD50 is higher than 5000 mg/kg bw.

Acute toxicity via Dermal route:

Based on the available information, the substance is:

- not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the dermal LD50 is higher than 5000 mg/kg bw

- not classified according to the GHS as the dermal LD50 is higher than 5000 mg/kg bw.

Acute toxicity (Inhalation):

No data was available. Not required for substances at the REACH Annex VII tonnage level.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Annex VI of the Regulation (EC) No. 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C ≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex VI of the Regulation (EC) No. 1272/2008 are not met since narcotic effects were not observed in the acute oral toxicity study.

Specific target organ toxicity: single exposure (Dermal):

The classification criteria according to the Annex VI of the Regulation (EC) No. 1272/2008 as specific target organ toxicant (STOT) – single exposure, dermal are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (dermal) for a Category 1 classification (C ≤ 300 mg/kg bw) and at the guidance value (dermal) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required.

Specific target organ toxicity: single exposure (Inhalation):

No data was available. Not required for substances at the REACH Annex VII tonnage level.