Methyl 12-hydroxyoctadecanoate

Endpoint summary

Description of key information

Not acutely toxic

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Methyl Dodecanoate, purity 99.2%; lot/batch # GD01

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Japan, Inc.
- Females (if applicable) nulliparous and non-pregnant: no
- Age at study initiation: 5 wk
- Weight at study initiation: 154 - 167 g for males and 130 - 141 g for females, at dosing
- Fasting period before study: yes; fasting period for 16 hrs before administration to 3 hrs after administration
- Housing: 5/cage, stainless steel mesh
- Diet (e.g. ad libitum): Ad libitum, solid feed MF manufactured by the Oriental Yeast Co., Ltd (Chuo-ku, Tokyo). Analysis of the contaminants in the feed and water were implemented by request of Oriental Yeast Co., Ltd to the Japan Food Product Analysis Center Foundation (Shibuya-ku, Tokyo).
- Water (e.g. ad libitum): ad libitum, tap water via automatic water supply nozzle.
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 2
- Humidity (%): 55 +/- 10
- Air changes (per hr): 20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 40% w/v%
- Amount of vehicle (if gavage):
- Justification for choice of vehicle:
- Lot/batch no. (if required):
- Purity:

MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg bw

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes

Statistics:

Verification was performed using statistical methods (not specified)

Preliminary study:

Preliminary results in 3 animals per sex at 2000 mg/kg bw showed no lethality at this dose. This dose was used in the main study

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

0 of 10

Clinical signs:

Soft stool in males and females up to 3 h after administration.

Body weight:

All animals gained weight during the study.

Gross pathology:

No abnormalities observed during necropsies.

Interpretation of results:

GHS criteria not met

Conclusions:

An OECD 401 Acute Toxicity assay in rats was undertaken with the test material at a limit dose of 2000 mg/kg bw in corn oil by oral gavage. No deaths or adverse effects were observed in any animal within the 14 days of the study. The substance is not classified for acute oral toxicity effects.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

The analogue approach is used for the hazard assessment of toxicological, eco-toxicological and environmental fate endpoints for the registration of 12-hydroxstearate methyl ester (CAS 141-23- 1). The hypothesis is that data can be read-across between this ester and its structural analogues, based on structural similarity and which cause the same type of effect(s) in physical and biological systems (Scenario 2 of the Read-Across Assessment Framework (RAAF, ECHA, 2015). The primary fatty acids in this read-across are lauric acid (C12) and myristic acid (C14), as these are well studied with high-quality experimental data. Supplemental analogues are used which contribute understanding of the effects of other structural features not contained in the two primary analogues.

There are no GHS classifications for 12-hydroxstearate methyl ester for endpoints which are reliant on read-across. There is a high degree of confidence that hazards for these endpoints are not underestimated, based on a strong weight of evidence from multiple data sources.

Read-across data, all evaluated as reliable according to Klimisch scores of 1 or 2, to estimate the toxicity of the registered substance is used for fulfilling the data requirements of the REACH registration and classifying potential hazards. This read-across approach is adequate for the purposes of risk assessment and classification and labeling.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Methyl Dodecanoate, purity 99.2%; lot/batch # GD01

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Japan, Inc.
- Females (if applicable) nulliparous and non-pregnant: no
- Age at study initiation: 5 wk
- Weight at study initiation: 154 - 167 g for males and 130 - 141 g for females, at dosing
- Fasting period before study: yes; fasting period for 16 hrs before administration to 3 hrs after administration
- Housing: 5/cage, stainless steel mesh
- Diet (e.g. ad libitum): Ad libitum, solid feed MF manufactured by the Oriental Yeast Co., Ltd (Chuo-ku, Tokyo). Analysis of the contaminants in the feed and water were implemented by request of Oriental Yeast Co., Ltd to the Japan Food Product Analysis Center Foundation (Shibuya-ku, Tokyo).
- Water (e.g. ad libitum): ad libitum, tap water via automatic water supply nozzle.
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 2
- Humidity (%): 55 +/- 10
- Air changes (per hr): 20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 40% w/v%
- Amount of vehicle (if gavage):
- Justification for choice of vehicle:
- Lot/batch no. (if required):
- Purity:

MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg bw

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes

Statistics:

Verification was performed using statistical methods (not specified)

Preliminary study:

Preliminary results in 3 animals per sex at 2000 mg/kg bw showed no lethality at this dose. This dose was used in the main study

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

0 of 10

Clinical signs:

Soft stool in males and females up to 3 h after administration.

Body weight:

All animals gained weight during the study.

Gross pathology:

No abnormalities observed during necropsies.

Interpretation of results:

GHS criteria not met

Conclusions:

An OECD 401 Acute Toxicity assay in rats was undertaken with the test material at a limit dose of 2000 mg/kg bw in corn oil by oral gavage. No deaths or adverse effects were observed in any animal within the 14 days of the study. The substance is not classified for acute oral toxicity effects.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study waived due to provisions of other regulation

Justification for data waiving:

other:

Justification for type of information:

According to Annex VIII, Section 8.5, Column 2, of Regulation EC No. 1907/2006, a toxicity study, in addition to the acute oral toxicity study, under 8.5.2 to 8.5.3 shall be provided for at least one other route. Commission Regulation (EU) 2016/863 amends this data requirement, stating that substances that are not toxic via the oral route may be expected with high certainty to be also non-toxic via the dermal route. The risk of acute toxicity by the dermal route has been addressed in light of an acute oral toxicity study with a LD50 > 2000 and no systemic toxicity observed in other in vivo studies. It is determined that testing for acute dermal toxicity is not scientifically indicated. The criteria for satisfaction of Sections 8.5.2 and 8.5.3 are met and the data requirement for an acute toxicity study by a third route, inhalation, is waived.

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study waived due to provisions of other regulation

Justification for data waiving:

the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)

Justification for type of information:

According to Commission Regulation (EU) 2016/863 amending Regulation EC No. 1907/2006, acute testing by the dermal route does not need to be conducted if the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route, and no systemic effects have been observed in in vivo studies with dermal exposure. The test material displayed an acute oral LD50 > 2000 mg/kg bw in rats, is not classified as STOT SE, and no systemic toxicity or local irritation was observed in a LLNA study in mice. Therefore the substance meets the criteria for waiving the testing requirements for acute dermal toxicity.

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The LD50 of an acute oral toxicity study is greater than 5000 mg/kg bw. No other studies are needed when the substance is not classified for oral toxicity.

Justification for classification or non-classification

The substance shows no acute oral toxicity at 5000 mg/kg bw. This does not meet the criteria for classification for acute toxicity, according to Regulation EC No. 1272/2006. Furthermore, it is not classified as STOT SE, and shows no systemic toxicity or local irritation. Therefore the substance meets the criteria for waiving the testing requirements for acute dermal toxicity according to Commission Regulation (EU) 2016/863 amending Regulation EC No. 1907/2006.