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

A waiver for the requirement to perform an extended one-generation reproduction toxicity study (standard configuration or with additional modules) was included, as the study is not scientifically necessary and, considering concerns regarding the use of vertebrate animals for experimental purposes, unjustified.


Short description of key information:
No data available

Justification for selection of Effect on fertility via oral route:
No study is required. Based on the available information from several independent sources, and based on the general toxicological profile derived from the data, members of the Polyol category are considered to exhibit no or low potential for toxicity to reproduction (fertility). No hazard for reproductive toxicity was identified.

Justification for selection of Effect on fertility via inhalation route:
No study is required. Based on the available information from several independent sources, and based on the general toxicological profile derived from the data, members of the Polyol category are considered to exhibit no or low potential for toxicity to reproduction (fertility). No hazard for reproductive toxicity was identified.

Justification for selection of Effect on fertility via dermal route:
No study is required. Based on the available information from several independent sources, and based on the general toxicological profile derived from the data, members of the Polyol category are considered to exhibit no or low potential for toxicity to reproduction (fertility). No hazard for reproductive toxicity was identified.

Effects on developmental toxicity

Description of key information
Two prenatal developmental toxicity (dermal) studies are available. One study result  in NOAEL of 2000 mg/kg bw and the second one in a NOAEL < 800 mg/kg bw.
One prenatal developmental toxicity (oral) is available, which results in NOAEL of 1000 mg/kg bw.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
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
Additional information

Justification for grouping of substances and read-across

The polyol esters category comprises of 51 aliphatic esters of polyfunctional alcohols containing two to six reactive hydroxyl groups and one to six fatty acid chains. The category contains mono constituent, multi-constituent and UVCB substances with fatty acid carbon chain lengths ranging from C5 - C28, which are mainly saturated but also mono unsaturated C16 and C18, polyunsaturated C18, branched C5 and C9,branched C14 – C22 building mono-, di-, tri-, and tetra esters with an alcohol (i.e.polyol).

The available data allows for an accurate hazard and risk assessment of the category and the category concept is applied for the assessment of environmental fate and environmental and human health hazards. Thus, where applicable, environmental and human health effects are predicted from adequate and reliable data for source substance(s) within the group by interpolation to the target substances in the group (read-across approach) applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006. In particular, for each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Section 7.1 and 13) and within Chapter 5.1 of the CSR.

Data matrix for developmental toxicity

CAS

Developmental toxicity

NPG esters

68855-18-5

RA: CAS 11138-60-6

31335-74-7

RA: CAS 11138-60-6

70693-32-2

RA: CAS 11138-60-6

former CAS 85186-86-3

RA: CAS 11138-60-6

85186-86-3

RA: CAS 11138-60-6

85186-95-4

RA: CAS 11138-60-6

85116-81-0

RA: CAS 11138-60-6

91031-27-5

RA: CAS 11138-60-6

42222-50-4

RA: CAS 11138-60-6

85005-25-0

RA: CAS 11138-60-6

TMP esters

78-16-0

RA: CAS 11138-60-6

RA: CAS 67762-53-2

91050-88-3

RA: CAS 11138-60-6

11138-60-6

NOAEL = 2000 mg/kg bw

91050-89-4

RA: CAS 11138-60-6

RA: CAS 67762-53-2

85566-29-6

RA: CAS 11138-60-6

(Formerly 85186-89-6)

RA: CAS 11138-60-6

68002-79-9

RA: CAS 11138-60-6

 (Formerly 85005-23-8)

EC 931-531-4

RA: CAS 11138-60-6

68002-78-8

RA: CAS 11138-60-6

RA: CAS 67762-53-2

 (Formerly 57675-44-2)

EC 931-461-4

RA: CAS 11138-60-6

85186-92-1

RA: CAS 11138-60-6

68541-50-4

RA: CAS 11138-60-6

RA: CAS 67762-53-2

PE esters

15834-04-5

RA: CAS 11138-60-6

RA: CAS 67762-53-2

85116-93-4

RA: CAS 189200-42-8

85711-45-1

RA: CAS 189200-42-8

25151-96-6

RA: CAS 189200-42-8
RA: CAS 11138-60-6

67762-53-2

NOAEL < 800 mg/kg bw

(Formerly 68441-94-1)

RA: CAS 11138-60-6

RA: CAS 189200-42-8

RA: CAS 67762-53-2

(Formerly 68424-30-6)

RA: CAS 11138-60-6

RA: CAS 189200-42-8

RA: CAS 67762-53-2

68424-31-7 (c)

RA: CAS 11138-60-6

RA: CAS 189200-42-8

RA: CAS 67762-53-2

68424-31-7 (d)

RA: CAS 11138-60-6

RA: CAS 189200-42-8

RA: CAS 67762-53-2

68424-31-7 (e)

RA: CAS 11138-60-6

RA: CAS 189200-42-8

RA: CAS 67762-53-2

71010-76-9

RA: CAS 189200-42-8
RA: CAS 67762-53-2

85586-24-9

RA: CAS 11138-60-6

85049-33-8

RA: CAS 11138-60-6

RA: CAS 189200-42-8

RA: CAS 67762-53-2

91050-82-7

RA: CAS 189200-42-8

19321-40-5

RA: CAS 189200-42-8
RA: CAS 11138-60-6

68604-44-4

RA: CAS 189200-42-8

62125-22-8

RA: CAS 189200-42-8

68440-09-5

RA: CAS 189200-42-8
RA: CAS 11138-60-6

189200-42-8

NOAEL = 1000 mg/kg bw

(a) Category members subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font.

(b) Substances that are either already registered under REACh or not subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in normal font.

For all category members registered under REACh a full data set for each endpoint is provided. For substances not subject to the current REACh Phase-in registration, lack of data for a given endpoint is indicated by "--".

 (c) CAS 68434-31-7 – Lead registrant

(d) Separate registration of CAS 68434-31-7

(e) Separate registration of CAS 68434-31-7 (2-ethylhexanoic acid)

Discussion

Developmental toxicity

There are three studies available within the polyol esters category to assess the potential to induce developmental effects.

CAS 11138-60-6

Fatty acids, 8-10 (even numbered), di- and triesters with propylidynetrimethanol (CAS 11138-60-6) was tested in a prenatal developmental toxicity study comparable 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. There were no differences from control 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 fetus 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 fetuses with levocardia, although no hearth malformations have been detected. Furthermore levocardia was observed in vehicle control foetuses (Smith et al. 1988) and in the control foetuses conducted in 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.

CAS 189200-42-8

The developmental toxicity of Fatty acids C8-10, mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS 189200-42-8) was investigated according to OECD Guideline 414 (prenatal developmental toxicity study) and under GLP conditions (Trimmer, 1995). 50 male Sprague-Dawley rats were mated with females to achieve groups of 25 pregnant Sprague-Dawley rats which then received daily oral gavage doses of the test substance at concentrations of 100, 500 and 1000 mg/kg bw/day during gestational days 6 to 15. Control animals received the vehicle polyethylene glycol (PEG 400). On day 21 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 1000 mg/kg bw/day. Examination of fetus litter size and weights, offspring viability (number alive and number dead), sex ratio, grossly visible abnormalities, external, head, soft tissue and skeletal abnormalities showed only incidental malformations in two high dose females. The NOAEL for embryo-/fetotoxicity and teratogenicity in rats for Fatty acids C8-10, mixed esteres with dipentaerythritol, isooctanoic acid, pentaerythritol and tridipentaerythritol was found to be 1000 mg/kg bw/day.

Conclusion for developmental toxicity

There are three studies available from the Polyol PE and TMP esters which were used to assess the developmental toxicity/teratogenic potential of the polyol esters category members.

The prenatal developmental toxicity study with Fatty acids, C5-9, tetraesters with pentaerythritol (CAS 67762-53-2) using Sprague-Dawley rats resulted in a NOAEL lower than 800 mg/kg bw/day since levocardia was found in the pups of both treated groups, although not internal heart malformation was detected. However, prenatal developmental toxicity studies conducted with Fatty acids, 8-10 (even numbered), di- and triesters with propylidynetrimethanol (CAS11138-60-6) and PE ester Fatty acids C8-10, mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS 189200-42-8) did not show any developmental toxic effects. The NOAELs are 2000 mg/kg bw/day and 1000 mg/kg bw/day, respectively. Therefore, the members of the polyol esters category were not considered to have a potential for developmental toxicity.

A waiver for the requirement to perform a prenatal developmental toxicity study in a 2nd species was included, as this requirement is considered not to add new information for hazard assessment and therefore is scientifically and, considering concerns regarding the use of vertebrate animals for experimental purposes, unjustified.

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within CSR.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint".

Since the category concept is applied to the polyol esters, data gaps will be filled by interpolation, as part of a read across approach from a representative category member(s) to avoid unnecessary animal testing. Additionally, once the category concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the group concept, all available data on toxicity to reproduction do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.