Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

There is sufficient weight of evidence from several independent sources of information leading to the conclusion that the target substance is not expected to cause any toxicity.

- In-vitro metabolism study using porcine pancreas lipase and in-vivo metabolism study of the read-across supporting substance polygylcerol polyricinoleate (PGPR) in rats indicated that metabolism of the target chemical occurs initially via enzymatic hydrolysis, leading to polyglycerols and the corresponding fatty acids. No metabolite is identified as reproduction/developmental toxicant. The information on metabolism covers two mammalian species. The metabolism was also analyzed by Meteor Nexus (v.2.0.2) and no species variation was identified in mouse, rat, dog and human.

- Findings on acute toxicity revealed the target chemical to be of low toxicity with an LD50 oral greater 5000 mg/kg body weight. No study on acute dermal toxicity is available for the target chemical, but absorption via dermal exposure of the test substance is unlikely.Even when absorbed through the skin, due to the demonstrated low systemic toxicity of the source substance it would be of no concern. Further, the target chemical is not a skin irritant or sensitizer. The acute oral toxicity in several species showed that PGPR (source chemical) was pharmaceutically inactive.Inhalation of registered substance is unlikely due to the following reason: The vapour pressure of the registered substance is low with less than 0.001 Pa (at 20°C). During manufacturing and processing inhalation exposure is unlikely due to efficient control measures in place.

- Findings in genetic toxicity revealed the target chemical to be not mutagenic. The target chemical was considered to be not point mutagenic in a reverse mutation assay according to the OECD 471. Further, in an in vitro Mammalian Cell Gene Mutation Test (HPRT-Locus) in Chinese Hamster V79 Cells (OECD 476) withReaction products resulting from the esterification of C18 unsaturated fatty acid with glycerol oligomersno relevant increase in mutants was found. Additionally in an in vitro chromosomal aberration test (OECD 473)Reaction products resulting from the esterification of C18 unsaturated fatty acid with glycerol oligomerswas not clastogenic. Based on these results obtained in three in vitro assays, no significant carcinogenic potential can be reliably derived. This is in line with results of two carcinogenicity studies performed in rats and mice with the source substance (Smith et al., 1998) where the substance did not reveal adverse effects.

- The source substance does not induce any systemic adverse effect with respect to the endpoints acute toxicity, genotoxicity, repeated toxicity and carcinogenicity. The animals species used for these endpoints included mouse, rat and human. Any species difference was not noted.

- No fertility or teratogenic effects are expected based on analogue approach using PGPR as a read-across supporting substance. It can be concluded with sufficient certainty that the target substance will not cause developmental toxicity in rats and other mammals.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

There is sufficient weight of evidence from several independent sources of information leading to the conclusion that the target substance is not expected to cause any toxicity.

- In-vitro metabolism study using porcine pancreas lipase and in-vivo metabolism study of the read-across supporting substance polygylcerol polyricinoleate (PGPR) in rats indicated that metabolism of the target chemical occurs initially via enzymatic hydrolysis, leading to polyglycerols and the corresponding fatty acids. No metabolite is identified as reproduction/developmental toxicant. The information on metabolism covers two mammalian species. The metabolism was also analyzed by Meteor Nexus (v.2.0.2) and no species variation was identified in mouse, rat, dog and human.

- Findings on acute toxicity revealed the target chemical to be of low toxicity with an LD50 oral greater 5000 mg/kg body weight. No study on acute dermal toxicity is available for the target chemical, but absorption via dermal exposure of the test substance is unlikely.Even when absorbed through the skin, due to the demonstrated low systemic toxicity of the source substance it would be of no concern. Further, the target chemical is not a skin irritant or sensitizer. The acute oral toxicity in several species showed that PGPR (source chemical) was pharmaceutically inactive.Inhalation of registered substance is unlikely due to the following reason: The vapour pressure of the registered substance is low with less than 0.001 Pa (at 20°C). During manufacturing and processing inhalation exposure is unlikely due to efficient control measures in place.

- Findings in genetic toxicity revealed the target chemical to be not mutagenic. The target chemical was considered to be not point mutagenic in a reverse mutation assay according to the OECD 471. Further, in an in vitro Mammalian Cell Gene Mutation Test (HPRT-Locus) in Chinese Hamster V79 Cells (OECD 476) withReaction products resulting from the esterification of C18 unsaturated fatty acid with glycerol oligomersno relevant increase in mutants was found. Additionally in an in vitro chromosomal aberration test (OECD 473)Reaction products resulting from the esterification of C18 unsaturated fatty acid with glycerol oligomerswas not clastogenic. Based on these results obtained in three in vitro assays, no significant carcinogenic potential can be reliably derived. This is in line with results of two carcinogenicity studies performed in rats and mice with the source substance (Smith et al., 1998) where the substance did not reveal adverse effects.

- The source substance does not induce any systemic adverse effect with respect to the endpoints acute toxicity, genotoxicity, repeated toxicity and carcinogenicity. The animals species used for these endpoints included mouse, rat and human. Any species difference was not noted.

- No fertility or teratogenic effects are expected based on analogue approach using PGPR as a read-across supporting substance. It can be concluded with sufficient certainty that the target substance will not cause developmental toxicity in rats and other mammals.