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Administrative data

Description of key information

1,3-propanediol dicaprylate is considered to non toxic upon ingestion. The predicted LD50 for rats is >2000 mg/kg bw. This weight-of-evidence assessment is based on experimental data on the metabolites propane-1,3-diol and caprylic acid as well as on experimental data on structurally related esters.
1,3-propanediol dicaprylate is considered to non toxic upon dermal application. The predicted LD50 for rats is > 2000 mg/kg bw. This weight-of-evidence assessment is based on modeling of skin permeability, skin metabolism, and experimental data for oral toxicity on the metabolites propane-1,3-diol and octanoic acid as well as on experimental data on structurally related esters.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Oral Assessment

The only functional group contained in the main product of 1,3-propanediol dicaprylate is the ester bond. Ester bonds are stable to acidic hydrolysis and so 1,3-propanediol dicaprylate is expected to enter the intestine unchanged. It is likely that lipases produced by the bile will initiate ester hydrolysis in the small intestine. Any intact 1,3-propanediol dicaprylate ester that is absorbed will be rapidly cleaved by esterases in the blood. Aliphatic esters consisting only of carbon, hydrogen and oxygen are not associated with any specific toxicity. Therefore, it is acceptable to include the data on 1,3-propanediol and octanoic acid for hazard assessment. In addition, other esters of octanoic acid can serve as analogues because of the rapid ester bond hydrolysis.

 

Dermal Assessment

According to the model by Fitzpatrick (Fitzpatrick, 2004), skin permeability of 1,3-propanediol dicaprylate is moderate. Therefore, systemic effects need to be considered. The only functional group contained in the main product of 1,3-propanediol dicaprylate is the ester bond. This may be hydrolyzed by bacteria on the skin or by enzymes in the skin (Oesch, 2007). Any intact 1,3-propanediol dicaprylate ester that is absorbed will be rapidly cleaved by esterases in the blood (Testa, 2003). Aliphatic esters consisting only of carbon, hydrogen and oxygen are not associated with any specific toxicity. Therefore, it is acceptable to include the data on 1,3-propanediol and octanoic acid for hazard assessment. In addition, other esters of octanoic acid can serve as analogues because of the rapid ester bond hydrolysis.

 

Inhalation Assessment

According to Annex VIII (8.5.2, column 2) of REACH regulation the study doesn't need to be conducted because inhalation of the substance is of no relevance due to the low vapour pressure (7.91x10 -4 Pa at 20°C) and inhalation of the substance is unlikely.

 

Acute toxicity information:

1,2-Propanediol, diester with mixed fatty acids (C8 - C10) (Planchette, 1985)

LD50(oral, mice) > 5 ml /kg bw; no mortality and no clinical signs observed. The report of 1985 is a one-page summary stating that the procedure followed OECD 401 and was performed on 5 female and 5 male mice with an initial body weight of 20 and 22 g, respectively.

 

1,3-Propanediol (Spanjers, 1979)

LD50(oral, rat) = 15800 mg/kg bw

Groups of each five female and male Wistar rats were treated by gavage with single doses of 9, 10.8, 13, 15.6 or 18.7 ml/kg bw. Animals were observed for 14 days. The test design is similar to OECD 423.

 

1,3-Propanediol (Krauser, 1995)

LD50(oral, mice) > 3160 mg/kg bw

This value is derived from the dose-range finder of a micronucleus test in mice. Limited information is given: At 4640 mg/kg bw both males and females showed clinical signs of severe intoxication and mortality occurred. At 3160 mg/kg bw, distinct symptoms of toxicity, but no mortality was noted. At 2150 mg/kg bw, no clinical symptoms and no mortality occurred. In the actual micronucleus test, each 14 male and female mice were given a single dose of 2150 mg/kg bw and animals were sacrified 24 and 48h after treatment. The procedure followed the OECD testing guideline for the microncleus test and therefore deviates in post-observation time and post-mortem investigation from the guideline for acute oral toxicity. This well-reported, GLP-compliant study is suitable as supporting evidence

 

Caprylic acid (octanoic acid, CAS no. 124-07-2)

LD50(oral, rat) > 2000 mg/kg bw.

This study is described as performed according to OECD guideline 401 and under GLP at NOTOX on behalf of Unichema Chemie GmbH in 1987. The information is taken from the ESIS IUCLID4-file of 2000; the full study report was not available for review.

LD50(dermal, rabbit) > 5000 mg/kg bw.

This information is taken from the Material Safety datasheet by Merck, dated April 29, 2004. No study report was available for review.

Caprylic acid occurs in food and is therefore part of the daily diet. In the USA, it has GRAS-status and is listed as a direct additive to food.

 

Capric acid (decanoic acid, CAS 334-48-5)

The following information was found in publications, but due to the limited details given, their validity cannot be assessed.

LD50(oral, rat) = 3320 mg/kg bw (Leung, 1990)

LD50(oral, rat) > 10000 mg/kg bw (Briggs, 1976)

 

Octanoic acid, methyl ester (CAS no. 111-11-5)

The following two LD50-values were taken from standard health hazard books that are recommended in the ECHA guidance on REACH endpoints of May 2008:

LD50(oral, rat) = 10800 mg/kg bw (Lewis, 1996)

LD50(oral, rat) = 20500 mg/kg bw (Clayton, 1993)

 

1,3-Propanediol

LD50(dermal, rabbit) > 4200 mg/kg bw (4 ml/kg bw)

The following information is taken from the Health and Environmental Data Summary of DuPont Tate & Lyle Bio products; no study report was available for review. Undiluted 1,3-propanediol was applied at 1, 2 or 4 ml/kg bw to the shaved dorso-lumbar skin of male and female Wistrar rats (2 per sex and group). An occlusive patch was applied and removed 24h later. After washing of the area, animals were observed for 9 days. There were no deaths at the highest dose group.

 

1,3-Propanediol (van Beek, 1979)

LD50(dermal, rabbit) > 525 mg/kg bw (0.5 ml/kg bw).

This data is extracted from the report on skin irritation potential of 1,3-propanediol. An amount of 0.5 ml is brought onto the shaved intact or abraded skin under a surgical patch measuring 1 square inch. Six rabbits are treated on the intact skin, six other rabbits on the abraded skin. After 24 hours of exposure, the patches are removed. Another observation is made 48 hours later. 1,3-Propanediol caused very slight or well-defined erythema on the skin, and the treatment was survived by all animals.

The post-observation period and the dose are shorter and lower than the tests for acute dermal toxicity require. However, this study can be used in a weight-of-evidence assessment.

 

Subchronic oral toxicity study with 1,3-Propanediol (Gingel, 2000)

The subchronic toxicity study was performed according to GLP and the EPA Toxic Substances Control Act Health Effects Testing Guidelines. 1,3-Propanediol was given by gavage to groups of each ten male and female rats at doses of 0, 100, 300 or 1000 mg/kg bw per day. The no-observed-effect-level was 1000 mg/kg bw.

 

 

Overall Assessment

All the information listed above shows that neither 1,3-propanediol nor octanoic acid is associated with a hazard for acute oral toxicity and that the structurally related esters with 1,2-propanediol or methanol are also of low acute oral toxicity. The identified impurities in 1,3-propanediol dicaprylate are also non hazardous because they also consist of esters with acids that are part of the daily diet. Since the metabolites after oral and dermal application are the same, read-across from the oral to the dermal route is justified. Bioavailability is expected to be in a similar range for both oral and dermal route. Therefore, it is concluded that the acute oral toxicity of 1,3-propanediol dicaprylate is higher than 2000 mg/kg bw and that performing the animal study to assess acute oral toxicity is not necessary.

Justification for classification or non-classification

1,3-propanediol dicaprylate is considered to be non toxic upon ingestion. The predicted LD50 for rats is >2000 mg/kg bw. This weight-of-evidence assessment is based on experimental data on the metabolites propane-1,3-diol and caprylic acid as well as on experimental data on structurally related esters.

 

1,3-propanediol dicaprylate is considered to be non toxic upon dermal application. The predicted LD50 for rats is > 2000 mg/kg bw. This weight-of-evidence assessment is based on modeling of skin permeability, skin metabolism, and experimental data for oral toxicity on the metabolites propane-1,3-diol and octanoic acid as well as on experimental data on structurally related esters.

 

The results are conclusive but not sufficient for the classification of 1,3-propanediol dicaprylate with regard to acute toxicity (by oral and dermal route).