Reaction mass of 2-hydroxyethyl laurate and ethylene dilaurate

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

Effects on developmental toxicity

Description of key information

Oral (Read-across, OECD 414): NOAEL F1 rat, developmental = 900 mg/kg bw/day

Oral (Read-across, OECD 414): NOAEL P0 female, systemic = 900 mg/kg bw/day

The hazard assessment is based on the data currently available. New studies with the registered substance and/or other member substances of the glycol esters category will be conducted in the future. The finalised studies will be included in the technical dossier as soon as they become available and the hazard assessment will be re-evaluated accordingly.

For further details, please refer to the category concept document attached to the category object (linked under IUCLID section 0.2) showing an overview of the strategy for all substances within the glycol esters category.

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Remarks:

Summary of available data used for the endpoint assessment of the target substance

Adequacy of study:

key study

Justification for type of information:

Refer to analogue justification provided in IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Species:

rat

Key result

Dose descriptor:

NOAEL

Effect level:

>= 900 mg/kg bw/day (actual dose received)

Based on:

test mat.

Remarks on result:

other: Source: CAS 91031-31-1

Key result

Abnormalities:

no effects observed

Key result

Dose descriptor:

NOAEL

Effect level:

>= 900 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Remarks on result:

other: Source: CAS 91031-31-1

Key result

Abnormalities:

no effects observed

Key result

Developmental effects observed:

no

Data from the source substance Fatty acids, C16-18, esters with ethylene glycol (CAS 91031-31-1) was selected as key results for reasons of structural similarity and data reliability. Additional data from the two source substances fatty acids, C6-12, esters with propylene glycol (CAS 85583-73-4) and decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) is given. In both of the latter studies conducted according to OECD guideline 414 the NOAEL for maternal toxicity and the NOAEL for embryotoxicity / teratogenicity was found to be 1000 mg/kg bw/day.

Conclusions:

The read across approach is justified in the analogue justification. The target and source substances are considered unlikely to differ in their reproduction toxicity potential. Developmental toxicity data was provided for three source substances. In a study with the source substance fatty acids, C16-18, esters with ethylene glycol (CAS 91031-31-1) the highest tested dose of 900 mg/kg bw/day was found to be the NOAEL for maternal animals and their offspring. No relevant hazard with regard to developmental toxicity is expected for the target substance and therefore a NOAEL for maternal toxicity and for embryotoxicity / teratogenicity of 900 mg/kg bw/day is considered for the target substance reaction mass of 2-hydroxyethyl laurate and ethylene dilaurate.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

900 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises adequate and reliable (Klimisch score 2) studies from reference substances with a common mode of action. Read-across is justified based on different compounds having the same type of effect(s) as described in scenario 2 of the Read-Across Assessment Framework (Read-Across Assessment Framework (RAAF), European Chemicals Agency, Helsinki, Finland, 2017), (please refer to the Analogue Justification for further details provided in IUCLID section 13).The selected studies are thus sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

The hazard assessment is based on the data currently available. New studies with the registered substance and/or other member substances of the glycol esters category will be conducted in the future. The finalised studies will be included in the technical dossier as soon as they become available and the hazard assessment will be re-evaluated accordingly.

For further details, please refer to the category concept document attached to the category object (linked under IUCLID section 0.2) showing an overview of the strategy for all substances within the glycol esters category.

Developmental toxicity

CAS 91031-31-1

Fatty acids, C16-18, esters with ethylene glycol was tested in an oral prenatal developmental toxicity study according to OECD guideline 414 under GLP conditions (key study, 1997).

Groups of 24 or 25 female rats per dose were dosed with the respective test substance via gavage from Gestation Day 6-15. Concurrent negative control groups receiving the vehicle alone were included.

Animals were dosed via gavage with 100, 300 and 900 mg/kg bw/day of Fatty acids, C16-18, esters with ethylene glycol. No mortality in maternal animals and no treatment -related symptoms were observed in the treatment groups. In addition, body weight and body weight gains were within the expected ranges. At scheduled necropsy no macroscopic changes were noted in the dams of the treatment groups. Furthermore, pre-implantation loss, post-implantation loss, mean number of resorptions, embryonic deaths, and total foetuses were not affected by treatment with the test substance in any treatment group. The mean foetal placental and uterus weights were similar in the control and treatment groups. The foetal sex ratio was comparable in all groups and no treatment-related foetal abnormalities were found at necropsy. The mean body weight of live male and female foetuses in the mid-dose group was significantly increased, whereas the body weights of live foetuses of the other treatment groups owed no significant differences, compared with the control group. The effect observed in the mid-dose group is considered to be incidental. The examined foetuses showed no treatment-related visceral malformations or variations in the test groups, compared with the control group . The examination of foetuses for skeletal malformation and variation showed no treatment-related deviations; any findings, all without dose-relationship, were considered to be incidental.

Based on the lack of adverse effects in this study, the NOAEL for maternal toxicity and developmental toxicity for rats was considered to be 900 mg/kg bw/day.

 

CAS 68583-51-7

One study with Decanoic acid, mixed diesters with octanoic acid and propylene glycol is available. The oral prenatal developmental toxicity study was conducted according to OECD guideline 414 under GLP conditions (supporting study, 1994).

Groups of 24 female Sprague Dawley rats per dose level were dosed with 100, 300 and 1000 mg/kg bw/day by gavage on Day 6-15 of gestation. A concurrent negative control group receiving the vehicle (arachis oil) only was included. No maternal mortality occurred and no substance-related clinical signs of toxicity were observed. The maternal body weight profiles were similar in all groups. Furthermore, at scheduled necropsy no macroscopic changes were noted in the maternal animals.

No treatment -related differences were observed in pre-and post-implantation loss, in utero deaths, mean numbers of resorptions and total number of foetuses in the test groups in comparison with the control group. Mean foetal placental and uterus weights showed no significant differences between the treatment and control groups. The body weights of live foetus and the foetal sex ratio was not affected by treatment. No treatment-related foetal external malformations were found at necropsy. The incidence of skeletal and visceral malformations and variations in the treatment and control groups were considered to be comparable. In the low- and high-dose treatment groups one foetus each with incompletely ossified skull bones and additionally one foetus in the high-dose group with non-ossified skull bones were reported. In the control group, 12 foetuses showed incompletely ossified skull bones and 6 foetuses showed non-ossified skull bones. The number of incomplete- and non-ossified skull bones was decreased in the treatment groups in comparison to the control group and the findings were considered to be identical.

Therefore, due to the lack of adverse effects in this study, the NOAEL for maternal systemic toxicity was considered to be 1000 mg/kg bw/day , and the NOAEL developmental toxicity /teratogenicity for offspring was considered to be 1000 mg/kg bw/day in the rat.

 

CAS 85883-73-4

Fatty acids, C6-12, ester with propylene glycol was tested in an oral prenatal developmental toxicity study performed according to OECD guideline 414 in compliance with GLP (supporting study, 2007). Fatty acids, C6-12, ester with propylene glycol was administered to groups of 25 female rats at dose levels of 500, 1500 and 2500 mg/kg bw/day. No mortality occurred in maternal animals during the study period. In the mid- and high-dose group, treatment -related salivation was noted in 8/25 and 6/25 females, respectively. Further findings noted in the treated groups included hair loss, scabbing and red material on various body surfaces as well as rales and soft stool. These findings occurred infrequently and were not dose-related. Mean maternal body weights, body weight gains, net body weights, net body weight gains and gravid uterine weights were unaffected by the substance administration. A Slightly lower food consumption observed in the high-dose group was not considered to be adverse based on the lack of an effect on mean body weights. Post-implantation loss, live litter size, mean foetal body weights, foetal sex ratios, mean numbers of corpora luteae and implantation sites and the mean litter proportions of pre-implantation loss were similar across all groups. There were no external developmental variations for any foetuses and no visceral and no skeletal malformations or variations which were considered to be test substance-related were noted . Foetal malformations and developmental variations, when observed in treatment groups, occurred infrequently or at a frequency similar to that in the control group and did not occur in a dose-related manner or were within the historical control data ranges.

As no adverse effects in the maternal animals and the offspring were observed, a NOAEL of 1000 mg/kg bw/day for maternal systemic toxicity and a NOAEL for developmental toxicity/teratogenicity in the offspring of 1000 mg/kg bw/day was derived.

 

Overall conclusion for developmental toxicity/teratogenicity

Based on the available data for source substances and following the analogue approach, no hazard for developmental toxicity was identified for the target substance Reaction mass of 2-hydroxyethyl laurate and ethylene dilaurate.

Mode of Action Analysis / Human Relevance Framework

Not applicable

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 analogue concept is applied to Reaction mass of 2-hydroxyethyl laurate and ethylene dilaurate data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis. Based on the analogue read-across approach, the available data on toxicity to reproduction do not indicate any hazard for developmental toxicity.