2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate)

Endpoint summary

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

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 esterswith 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.

Discussion

In accordance with Regulation (EC) No. 1907/2006, Annex X, 8.7.3 Column 1, an extended one-generation reproduction toxicity study (EORGTS, OECD 443, standard configuration) is required, using the most appropriate route of administration, and having regard to the likely route of human exposure.

 

In accordance with Regulation (EC) No. 1907/2006, Annex XI, ‘a registrant may adapt the standard testing regime in accordance with the general rules set out in Section 1 of this Annex’; where Section 1 addresses circumstances under which ‘testing does not appear scientifically necessary’. Annex XI, Section 1.2 covers the ‘weight of evidence’ principle that may be applied using ‘several independent sources of information’ to justify adapting the standard testing regime.

Within the Polyol Ester category, information from several independent sources is available addressing toxicity to reproduction (fertility).

 

The polyol esters category covers 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 polyhydroxy alcohol (e.g., neopentylglycol (NPG), trimethylolpropane (TMP), pentaerythritol (PE) Di-Penta).Due to the structural similarities and consistent trend in physico-chemical, toxicological, ecotoxicological properties and toxicokinetic behaviour (described in thecategory justification in Section 13 ‘Assessment reports’), the members of the Polyol group can be considered as a category of substances, according to Regulation (EC) No. 1907/2006, Annex XI, 1.5.

The toxicological properties show that the category members have similar toxicokinetic behaviour and that the constant pattern consists in a lack of potency change of properties across the category, explained by the common metabolic fate of Polyols independently of the fatty acid chain length and the polyhydroxy alcohol (see Toxicokinetic statement in Section 7.1 ‘Toxicokinetics, metabolism and distribution’ and the category justification in Section 13 ‘Assessment reports’).

After oral ingestion, esters of the respective polyol and fatty acids will undergo stepwise chemical changes in the gastro-intestinal fluids as a result of enzymatic hydrolysis. In general, the hydrolysis rate of fatty acid esters and polyol esters in particular depends on fatty acids/ alcohol combinations and number of ester function groups (Mattson and Volpenhein, 1969; Mattson and Volpenhein, 1972a,b). For example, the speed of hydrolysis of C2-C18 fatty acids with C1-18 primary alcohols by the carboxylic acid esterase pancreatic lipase is influenced by acyl and alkyl chain (Mattson and Volpenhein, 1969). With respect to the fatty acid component, esters of dodecanoic acid usually split at the most rapid rate (Mattson and Volpenhein, 1969). Esters of butyric acid show the next most susceptible effect (attributed to enzyme-substrate specificity). With regard to the alcohol component, e.g. esters of heptyl alcohol are most rapidly hydrolysed (3.2-8.2 µeq/min/mg enzyme). Thus, the relative rate of hydrolysis was influenced by the alcohol components orienting the ester molecule at the oil/water interface (Mattson and Volpenhein, 1969)

The result of the pancreatic digestion of one NPG ester (diester) category member (Heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol, CAS 68855-18-5) shows a degradation of the ester of almost 90% within 4 hours (Oßberger, 2012). With regard to other polyol esters decreased rates of enzymatic hydrolysis in the GIT were shown for compounds with more than three ester groups (Mattson and Volpenhein, 1972a, b). For example, in vitro hydrolysis rate of pentaerythritol ester was 1.1 µmol/min/mL, which is measured in 2100 µmoles FFA/min/mL (Mattson and Volpenhein, 1972a,b).

 

Based on this, polyol esters are capable of being enzymatically hydrolysed to generate alcohol and the corresponding fatty acids. NPG, TMP and PE esters may show different rates of enzymatic hydrolysis depending on the number of ester bonds and the alcohol involved. Nevertheless, the metabolic fate of the substances is considered to be the same, as all polyol ester substances will be hydrolyzed over a period of time.

The resulting products are subsequently absorbed into the bloodstream. The fatty acids, as potential cleavage products on the one hand, are stepwise degraded via beta–oxidation in the mitochondria. Even numbered fatty acids are degraded via beta-oxidation to carbon dioxide and acetyl-CoA, with release of biochemical energy. In contrast, the metabolism of the uneven fatty acids results in carbon dioxide and an activated C3-unit, which undergoes a conversion into succinyl-CoA before entering the citric acid cycle (Stryer, 1994). The alpha- and omega-oxidation, alternative pathways for oxidation, can be found in the liver and the brain, respectively (CIR, 1987).

Polyols (NPG, TMP and PE) are - due to their physical-chemical properties (low molecular weight, low log Pow, and solubility in water) - easily absorbed and can either remain unchanged (PE) or are expected to be further metabolised or conjugated (e.g. glucuronides, sulfates, etc.) into polar products that are excreted via urine (OECD SIDS, Di Carlo et al., 1965).

As supported by the available data on toxicokinetics, no long-term exposure with the test substance is expected, even if applied in repeated doses.

A 90-day oral feeding toxicity study with Fatty acids, C16-18 and C18-unsatd., branched and linear ester with trimethylolpropane (CAS 403507-18-6) was performed comparable to OECD Guideline 408 and under GLP conditions (McRae, 2004). Observations and examinations of the animals included clinical sings, body weight, food consumption, haematology, clinical chemistry, organ weights, neurobehaviour, gross necropsy and histopathology. The daily oral administration of the test substance was tolerated without any adverse effects up to the high dose of 1000 mg/kg bw/day. Therefore, a 90-day oral NOAEL of 1000 mg/kg bw/day was found for Fatty acids, C16-18 and C18-unsatd., branched and linear ester with trimethylolpropane in male and female rats.

Another 90-day oral feeding toxicity study including a 28 d recovery group with Pentaerythritol ester of pentanoic acids and isononanoic acid (CAS 146289-36-3) was performed according to OECD Guideline 408 and under GLP conditions (Müller, 1998). Observations and examinations of the animals included clinical signs, body weight, food consumption, haematology, clinical chemistry, organ weights, neurobehaviour, gross necropsy and histopathology. The daily oral administration of the test substance was tolerated without any adverse effects up to 1000 mg/kg bw/day. An increase in kidney weights in all male animals could be correlated to the formation of hyaline droplets a phenomenon widely accepted to be specific to the male rat and as such considered to have no relevance to man, a 90-day oral NOAEL of 1000 mg/kg bw/day was found for Pentaerythritol ester of pentanoic acids and isononanoic acid in male and female rats.

A 90-day subchronic inhalation toxicity study was performed with Sprague-Dawley rats with Fatty acids, C5-9, tetraesters with pentaerythritol (CAS 67762-53-2) comparable to OECD guideline 413 (Dulbey, 1992). Animals were observed for clinical sings, body weight, haematology, clinical chemistry, organ weights, gross necropsy and histopathological examinations. No substance-related adverse effects were observed for body weight, body weight gain, mortality, clinical biochemistry and haematological parameters. Thus, the NOAEC were found to be 0.5 mg/L.

A 90-day dermal toxicity study with Fatty acids, C5-9, tetraesters with pentaerythritol (CAS 67762-53-2) was performed comparable to OECD Guideline 411 (Cruzan, 1988). Application to the skin was done open without coverage. Animals were observed for clinical signs, body weight, dermal irritation, haematology, clinical chemistry, urinalysis, organ weights, gross necropsy and histopathological examinations. Since no effects of systemic toxicity were identified up to the highest dose tested, the 90-day dermal NOAEL was found to be 2000 mg/kg bw/day for Fatty acids, C5-9, tetraesters with pentaerythritol in Sprague-Dawley rats.

In summary the representative category members Pentaerythritol ester of pentanoic acids and isononanoic acid (CAS 146289-36-3) and Fatty acids, C16-18 and C18-unsatd., branched and linear ester with trimethylolpropane (CAS 403507-18-6) did not show adverse effects on reproductive organs and tissues including testes, epididymides, prostate, seminal vesicle, ovaries, and uterus after oral exposure over 90 days. The daily oral administration of either Polyol ester was tolerated without any adverse effects up to the high dose of 1000 mg/kg bw/day. There were no toxicologically significant effects on body weight, food consumption and clinical condition and mortality up to and including the highest dose level. Both studies were performed according to GLP and the NOAEL for systemic and reproductive effects was considered to be ≥ 1000 mg/kg bw/day in male and female rats. In addition, fatty acids, C5-9, tetraesters with pentaerythritol (CAS 67762-53-2) exerted no adverse effects on reproductive organs and tissues when applied for 90 days via inhalation and dermal route. Moreover, no effects on sperm count and morphology were observed. Thus, the NOAEC respective and NOAEL were ≥ 0.5 mg/L/day and ≥ 2000mg/kg bw/day, respectively in both studies.

  

Further, developmental toxicity studies with structural similar substances including decanoic acid, ester with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol octanoate (CAS 11138-60-6), fatty acids, C5-9 tetraesters with pentaerythritol (CAS 67762-53-2) and Fatty acids, C8-10 mixed esters with dipenaterythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS 189200-42-8) did not show an influence on the observed maternal and developmental parameters up to the highest dose tested.

 

In conclusion, information is available from the physico-chemical characteristics of the category members as well as from the toxicokinetic behaviour, and from repeated dose toxicity studies with polyfunctional alcohols containing two to six reactive hydroxyl groups and one to six fatty acid chains. 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.

 

Therefore, referring to Regulation (EC) No. 1907/2006 and for animal welfare reasons, performing an extended one-generation reproduction toxicity study (standard configuration or with additional modules) is not scientifically necessary 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.

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.

Polyol esters are capable of being enzymatically hydrolysed to generate alcohol and the corresponding fatty acids. NPG, TMP and PE esters may show different rates of enzymatic hydrolysis depending on the number of ester bonds and the alcohol involved. Nevertheless, the metabolic fate of the substances is considered to be the same, as all polyol ester substances will be hydrolyzed over a period of time.They are hydrolysed in rats by esterases that are ubiquitously expressed in mammals and nonspecific. In example the pancreatic triglyceride lipase family is highly conserved across species (Lowe et al., 1989, Payne et al. 1994). These non-specific processes leading to the formation of the constituent alcohols and acids would be expected to occur in a similar manner in rats, rabbits and humans.

Furthermore, the preliminary results of a comparative analysis of data on pharmaceutical compounds suggest that the 2^ndspecies does not add significant information for the assessment of developmental effects. (Theunissen et al. 2014 and 2015)

 

Therefore, referring to Regulation (EC) No. 1907/2006, Annex IX, 8.7.2 Column 2, performing a prenatal developmental toxicity study in a 2^ndspecies is considered not to add new information for hazard assessment and therefore is scientifically 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.