Docosanoic acid, monoester with glycerol

Endpoint summary

Description of key information

Docosanoic acid, monoester with glycerol (glycerol monobehenate) is a mono constituent substance with a purity of 80-90%.Test data on acute toxicity of docosanoic acid, monoester with glycerol (Glycerol monobehenate) as well as for other glycerol monoesters of fatty acidsare available. The acute toxicity is therefore based on a weight of evidence analysis. Based on the studies available for docosanoic acid, monoester with glycerol (Glycerol monobehenate) and the relevant hydrolysis products, it can be concluded that the substance has low acute oral and dermal toxicity with LD50-values above the highest dose used for classification as acute toxicity (i.e., 2000-5000 mg/kg).Thus, glycerol monobehenate is not to be classified for acute oral and dermal toxicity. Further, inhalation is not considered a relevant exposure route for humans. The available information comprises adequate, reliable studies from reference substances with similar structure and intrinsic properties. The weight-of-evidence approach is justified based on common functional group and common precursors/breakdown products. The information from these independent sources is consistent and provides sufficient weight of evidence leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

other: weight of evidence analysis based on expert evaluated data on hydrolysis products and structural analogues

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: based on expert group reviews

Justification for type of information:

Data are available for docosanoic acid, monoester with glycerol (glycerol monobehenate). Because of the structural and functional similarities, data from other glyceryl monoesters are also included in this weight of evidence assessment as supporting data.

The following expert opinion (attached in section 13) will be used in the weight of evidence approach:

CIR 2016: Cosmetic Ingredient Review. Safety assessment of monoglyceryl monoesters as used in cosmetics. Final amended report, January 15, 2016.





 

Principles of method if other than guideline:

The results are based on a weight of evidence analysis from collection of data extracted from the literature/expert opinions. For more details please refer to the attached weight of evidence document as well as documents attached in section 13 identified as key references.

In relation to the data requirements of REACH Annex VII (1-10 t/y), data on acute oral toxicity must be provided. Limited data on this endpoint is available for docosanoic acid, monoester with glycerol (glycerol monobehenate). Glycerol monobehenate is a mono-constituent substance. The main component is docosanoic acid, monoester with glycerol, the remaining compounds are mainly fatty acids and monoesters of fatty acid and glycerol. Glycerol can also be present in a low concentration. Glyceryl monoesters (monoglycerides) are metabolized to free fatty acids and glycerol, both of which are available for the resynthesis of triglycerides.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Docosanoic acid, monoester with glycerol is a mono-constituent substance. The main component is docosanoic acid monoester with glycerol, the remaining compounds are mainly fatty acids and monoesters of fatty acid and glycerol. The acute oral toxicity was evaluated based on data on docosanoic acid, monoester with glycerol (Glycerol Monobehenate) as well as data from other glycerol monoesters.

The following was concluded from expert opinions:

Nine acute oral toxicity studies are described in the CIR (2016) for glycerol monobehenate and other monoglyceryl monoesters. The acute oral toxicity of monobehenate was reported to be >2 g/kg bw in mice. In the acute oral toxicity study, similar to OECD guideline 401, glycerol monobehenate was administered via gavage to five female Swiss mice at a limit dose of 2 g/kg bw (CIR 2016). No mortalities and no clinical signs were observed in the animals up to the end of the 14-day observation period. No effects on body weights were noted during the study. An oral LD50 value in female Swiss mice was set to> 2 g/kg bw.

For other glycerol monoesters, In two acute oral toxicity studies, glycerol ester of partially hydrogenated gum rosin, neat or in olive oil, was administered via gavage to five Sprague Dawley rats at a limited dose of 2 g/kg bw (CIR 2016). An oral LD50 value in male Sprague Dawley rats was set to > 2 g/kg bw. 

In four acute oral toxicity studies, glyceryl rosinate neat or in different solvents (vaselin oil, corn oil and 0.25% agar and 0.10% Tween 80) was administered via gavage to Sprague Dawley rats at limited doses of 2, 5, or 10 g/kg bw the LD50 were set to >2 g/kg bw, >5 g/kg bw and >10 kg/kg bw respectively.

Finally, in two studies with five mice exposed to glyceryl stearate by oral gavage resulted in no mortality at a dose of 5 g/kg bw (CIR 2016).

To summarize the CIR expert panel concluded based on the oral studies, LD50 values to be >2 g/kg glyceryl behenate, >2 g/kg glyceryl hydrogenated rosin, >5 g/kg glyceryl stearate, and >10 g/kg glyceryl rosinate. Furthermore, monoglyceryl monoesters are considered Generally Recognized as Safe (GRAS) for food use (CIR 2015; 2016).

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the studies available for docosanoic acid, monoester with glycerol (Glycerol monobehenate), the relevant hydrolysis products as well as data from other glycerol monoesters, it can be concluded that glycerol monobehenate has low acute oral toxicity with LD50-values above the highest dose used for classification as acute toxicity (i.e. 2000- 5000 mg/kg). Thus, docosanoic acid, monoester with glycerol (glycerol monobehenate) is not to be classified for acute oral toxicity.

Executive summary:

Detailed study reports on acute oral toxicity is not available for docosanoic acid, monoester with glycerol (glycerol monobehenate), however data on glycerol monobehenate from a CIR expert review (2016) is available. Because of the structural and functional similarities, data from other glyceryl monoesters are also included in this weight of evidence assessment as supporting data.

The LD50 of glycerol monobehenate from acute oral toxicity studies performed in mice was set to >2 g/kg bw. Furthermore, the CIR expert panel concluded, based on the oral studies, LD50 values to be >2 g/kg glyceryl hydrogenated rosin, >5 g/kg glyceryl stearate, and >10 g/kg glyceryl rosinate. In all studies, no mortality is reported. The acute oral toxicity of glycerol monobehenate is therefore considered to have low toxicity and to be above the doses used for classification.

The overall conclusion is therefore that glycerol monobehenate has low acute oral toxicity with a LD50-value above 2000 mg/kg bw. Thus, classification for acute oral toxicity according to (EC) No 1272/2008 is not warranted.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Data are available for docosanoic acid, monoester with glycerol (glycerol monobehenate) from expert opinions. Because of the structural and functional similarities, data from other expert opinions on glyceryl monoesters are also included in this weight of evidence assessment as supporting data.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Inhalation is not considered a relevant exposure route for humans.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

other: Weight of evidence analysis based on expert evaluation data on hydrolysis products and structural analogues

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: based on expert group reviews

Justification for type of information:

Because of the structural and functional similarities, data from other glyceryl monoesters are also included in this weight of evidence assessment as supporting data.
The following expert opinion (attached in section 13) will be used in the weight of evidence approach:
CIR 2016: Cosmetic Ingredient Review. Safety assessment of monoglyceryl monoesters as used in cosmetics. Final amended report, January 15, 2016.

Principles of method if other than guideline:

In relation to the data requirements of REACH Annex VIII (10-100 t/y), data on acute toxicity must be provided. Limited data on this endpoint is available for docosanoic acid, monoester with glycerol (glycerol monobehenate).

Glycerol monobehenate is a mono-constituent substance. The main component is docosanoic acid, monoester with glycerol which is present in the product at a concentration of 80-97%; the remaining compounds are mainly fatty acids and monoesters of fatty acid and glycerol. Glycerol can also be present in a low concentration. Glyceryl monoesters (monoglycerides) are metabolized to free fatty acids and glycerol, both of which are available for the resynthesis of triglycerides.

The acute toxicity of this substance is therefore assessed in the present document as a weight of evidence analysis based on existing data on groups of mono-, di- and triglycerides, fatty acids, which are all components with similar properties. Hereby, data is available for deriving a conclusion on the acute toxicity of the substance.

A weight of evidence approach is used for the assessment of the acute toxicity via oral, inhalation, and dermal route of exposure.

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST MATERIAL
- Concentration (if solution):

Duration of exposure:

24 h

Doses:

5000 mg/kg

No. of animals per sex per dose:

4

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Collection of relevant data, please see attached document

Clinical signs:

other:

Conclusions:

No irritation observed, no acute toxicity at the tested level

Executive summary:

Glycerol monobehenate is a mono-constituent substance. The main component is docosanoic acid, monoester with glycerol which is present in the product at a concentration of 80-90%; the remaining compounds are mainly fatty acids and monoesters of fatty acid and glycerol. Glycerol can also be present in a low concentration. Glyceryl monoesters (monoglycerides) are metabolized to free fatty acids and glycerol, both of which are available for the resynthesis of triglycerides. 

From literature search, no specific data on the acute dermal toxicity of glycerol monobehenate was found. However, three studies conducted on other glycerol monoesters of fatty acids were found in an expert assessment from CIR (2016). 

Glyceryl Rosinate was administered to New Zealand white Rabbits at 5000 mg/kg bw or 10 000 mg/kg bw in water. The report LD50 in the two studies were 5000 and 10 000 mg/kg bw.   

Glycerides, C16-18 and C18-hydroxy mono- and di- was administered neat on Wistar rats at 2000 mg/kg bw. No irritation was observed and the LD50 was set at 2000 mg/kg bw. 

Based on the dermal studies identified in the CIR report, the expert panel concluded that the LD50 for glyceryl rosinate, and glycerides, C16-18 and C18-hydroxy mono- and di- are 10 000 mg/kg bw and 2000 mg/kg bw, respectively.  

The overall conclusion is therefore that monobehenate has low acute dermal toxicity with a LD50-value above 2000 mg/kg bw. Thus, classification for acute dermal toxicity according to (EC) No 1272/2008 is not warranted. 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

No acute dermal toxicity data available for docosanoic acid, monoester with glycerol (glycerol monobehenate) from expert opinions. Because of the structural and functional similarities, data from expert opinions on other glyceryl monoesters has been used in this weight of evidence assessment.

Justification for classification or non-classification

The overall conclusion using a weight of evidence approach is that glycerol monobehenate has low acute oral and dermal toxicity with LD50-values above 2000 mg/kg bw. Exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/nor the possibility of exposure to aerosols, particles or droplets of an inhalable size. Thus, classification for acute oral and dermal toxicity according to (EC) No 1272/2008 is not warranted.