Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

In accordance with Regulation (EC) No 1907/2006, Annex VIII, 8.7.1 column 1, a reproductive toxicity test in one species is required if there is no evidence from available information on structurally related substances, from (Q)SAR estimates or from in vitro methods that the substance may be a developmental toxicant. However, according to Annex VIII, 8.7.1 column 2, the study does not need to be conducted if a pre-natal developmental toxicity study or a two-generation study is available. Thus, in accordance to the information provided in colum 2, no reproductive toxicity data are required as developmental toxicity tests according to OECD 414 are included in the dossier for the structural analogues Fatty acids, 8-10 (even numbered), di- and triesters with trimethylolpropane (CAS 11138-60-6) and Fatty acids, C5-9 tetraesters with pentaerythritol (CAS 67762-53-2) and considered for hazard assessment.

Effects on developmental toxicity

Description of key information
Two prenatal developmental toxicity (dermal) studies are available. One study resulted in a NOAEL of 2000 mg/kg bw/day and the second study in a NOAEL < 800 mg/kg bw/day.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable studies (Klimisch score 2) from reference substances with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to endpoint discussion for further details). The selected studies are thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.
Additional information

Justification for grouping of substances and read-across

There are no data available for developmental toxicity of the substance 1,3-Propanediol, 2,2-dimethyl-, C5-9 carboxylates (CAS 85711-80-4). In order to fulfil the standard information requirements set out in Annex VIII, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across to structurally related substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met. In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests", which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby toxicological properties may be predicted from data for the reference substance(s) on the basis of structural similarity, the substance Fatty acids, 8-10 (even numbered), di- and triesters with propylidynetrimethanol (CAS 11138-60-6) and Fatty acids, C5-9, tetraesters with pentaerythritol (CAS 67762-53-2) are selected as source substances for hazard assessment.

Discussion

CAS 11138-60-6

Fatty acids, 8-10 (even numbered), di- and triesters with trimethylolpropane (CAS 11138-60-6) were tested in a prenatal developmental toxicity study similar to OECD Guideline 414 (Azuka and Daston, 2004). The test substance was percutaneously applied to Sprague-Dawley rats for 6 h/day under occlusive conditions. 25 animals per sex per dose were treated with 200, 600 or 2000 mg/kg bw/day in corn oil on Days 6-15 of gestation. Control animals (25 per sex per dose) received the vehicle. The middle and the high dose levels caused some local irritation at the site of application, but no decreases in maternal weight gain or food consumption were observed. No differences between control and test animals were detected in any of the developmental parameters measured, including embryo/fetal viability, fetal weight, malformations, or variations. Therefore, a NOAEL of 2000 mg/kg bw/day was derived for prenatal development and for systemic maternal toxicity. Due to the irritation effects on skin, the local maternal NOAEL was found to be 200 mg/kg bw/day.

CAS 67762-53-2

The developmental toxicity of Fatty acids, C5-9, tetraesters with pentaerythritol (CAS 67762-53-2) was investigated comparable to OECD Guideline 414 (prenatal developmental toxicity study) (Feusten, 1988). Groups of 15 presumed pregnant female Sprague-Dawley rats received daily dermal doses of the test substance at concentrations of 800 and 2000 mg/kg bw/day during gestational days 0 to 19. Control animals remained untreated. On day 20 of gestation the animals were euthanized and examined for maternal and fetal parameters. There were no adverse effects found for all parameters examined in maternal animals. Based on the number of implantations, number of total litter losses by resorption, mortality, clinical signs, body weight, gross pathology and organ weights of maternal animals the NOAEL for maternal toxicity was found to be 2000 mg/kg bw/day. Examination of foetus litter size and weights, offspring viability (number alive and number dead), sex ratio, grossly visible abnormalities, external, head, soft tissue and skeletal abnormalities revealed no differences to controls and thus no indication for teratogenic effects. The only effect found was a dose-dependently increased number of foetuses with levocardia (3.2 and 10.1% of fetuses exposed to 800 and 200 mg/kg bw/day), although no heart malformations have been detected. Furthermore levocardia was observed in vehicle control foetuses in another study (Smith et al. 1988) and in control foetuses of the test laboratory. Since levocardia was observed in both treated groups, the NOAEL for embryo-/fetotoxicity and teratogenicity in rats Fatty acids, C5-9, tetraesters with pentaerythritol was found to be < 800 mg/kg bw/day and the LOAEL = 800 mg/kg bw/day.

Conclusion for developmental toxicity

There are two studies available on structurally related substances which were used to assess the developmental toxicity/teratogenic potential of 1,3-Propanediol, 2,2-dimethyl-, C5-9 carboxylates (CAS 85711-80-4).

The prenatal developmental toxicity study performed with Fatty acids, C5-9, tetraesters with pentaerythritol (CAS 67762-53-2) resulted in a NOAEL lower than 800 mg/kg bw/day since levocardia was found in the pups of both treated groups, although no internal heart malformations were detected. However, the prenatal developmental toxicity study conducted with the structural related substance Fatty acids, 8-10 (even numbered), di- and triesters with propylidynetrimethanol (CAS 11138-60-6) did not show any developmental toxic effects and hence, a NOAEL of 2000 mg/kg bw/day was derived.

Following a weight-of-evidence approach based on both structural analogue substances and considering the fact that levocardia 1) was not correlated to heart malformations, 2) was also observed in vehicle control foetuses of another study (Smith et al. 1988) and in control foetuses of the test laboratory, the finding of levocardia in foetuses after in utero exposure to Fatty acids, C5-9, tetraesters with pentaerythritol (CAS 67762-53-2) is not considered as sufficient to justify a classification as developmental toxicant. Therefore, following a weight-of-evidence approach, 1,3-Propanediol, 2,2-dimethyl-, C5-9 carboxylates is not considered as hazardous for in utero development.


Justification for selection of Effect on developmental toxicity: via dermal route:
Hazard assessment is conducted by means of read-across from structural analogues. The studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

Based on read-across from structurally similar substances, the available data on toxicity to reproduction/developmental toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.