Isooctadecanoic acid, monoester with glycerol

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Analogue justification

Data on the reproduction toxicity of Glycerol monoisostearate (CAS 66085-00-5) are not available. The assessment was therefore based on studies conducted with analogue substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. 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 13) and within Chapter 5.1 of the CSR.

Toxicity to reproduction

CAS No. 111-03-5

A GLP-compliant reproductive toxicity screening study was performed according to OECD 422 with 2,3-dihydroxypropyl oleate at dose levels of 100, 300 and 1000 mg/kg bw/day (Yamaguchi, 2005). Male and female Sprague-Dawley rats (12 per sex and group, except for 1000 mg/kg bw/day: only 7 males) received the test substance in corn oil once daily via gavage. A control group, consisting of 7 males and 12 females, was treated with the vehicle alone. The duration of treatment was 42 days (14 days prior to mating and 28 days thereafter) in males and 42-52 days (from 14 days before mating to day 4 of lactation) in females, respectively. Satellite groups of 5 animals per sex, each for the control and test groups, were used to investigate reversibility of effects during a 14-day post-exposure recovery period. In parental animals, no difference in reproductive function was observed compared to controls. Reproductive performance (copulation, fertility, gestation indices) and offspring viability (delivery, live birth, sex ratio and viability indices) in treated animals were comparable to controls. No substance-related changes in organ weights and histopathology of reproductive organs in males and females were observed. Based on the results of the study, the NOAEL for reproductive toxicity in male and female rats is ≥1000 mg/kg bw/day.

CAS No. 91052-13-0

An oral gavage screening toxicity study was performed according to OECD guideline 422 and under GLP- conditions in Crl:WI(Han) Wistar rats receiving 100, 300 and 1000 mg/kg bw/day (Otterdijk, 2010). Dilutions of the test substance in polyethylene glycol or the vehicle alone were administered once daily to groups of 10 male and 5 female rats (main groups) via gavage. In addition, satellite groups of 5 males and 5 females (recovery animals) each for the control and high dose group were used to investigate the reversibility of effects during a 14-day post-exposure recovery period. Furthermore, 10 females (repro animals) were added to each group for the assessment of reproduction and developmental toxicity. The main and recovery groups were exposed for at least 28 days from start of treatment up to termination or start of recovery. Females used for the assessment of reproduction/developmental toxicity were exposed for 41-49 days (during 2 weeks prior to mating, during mating, during post-coitum, and during at least 4 days of lactation). In parental animals, no effects on reproductive function (spermatogenetic and oestrus cycle) or performance (mating, fertility and conception indices, precoital time, and number of corpora lutea and implantation sites) were observed after treatment compared with the control animals. The testis weight, epididymis weight, and histological examination of the testes in males as well as the histological examination of the uterus epithelium in females did not reveal any substance-related effects in the parental animals. No toxicologically relevant changes in the offspring viability indices were observed. Therefore, a NOAEL for parental reproductive toxicity of ≥1000 mg/kg bw/day was derived for male and female rats.

Overall conclusion for toxicity to reproduction

There are no available studies on the toxicity to reproduction of Glycerol monoisostearate. Therefore analogue read-across from source substances was applied.

The available data on the toxicity to reproduction of the 2 source substances includes several short-term studies in rats via the oral route that were taken into account for assessment. No effects on reproductive parameters/organs were observed in any of these screening studies. NOAEL values for reproduction toxicity were all at or above the currently applied limit dose value of 1000 mg/kg bw/day. Therefore, no hazard to reproduction was identified.

Based on the available data and following the analogue approach, Glycerol monoisostearate is considered to be not toxic to reproduction.

Short description of key information:
The available studies on toxicity to reproduction resulted in a NOAEL ≥ 1000 mg/kg bw/day.

Justification for selection of Effect on fertility via oral route:
No study was selected, as a Weight of Evidence approach was applied.

Effects on developmental toxicity

Description of key information

The available study did not indicate the test substance causes developmental toxicity/teratogenicity at doses up to and including 1000 mg/kg bw/day.

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 study available

Additional information

Analogue justification

Data on the developmental toxicity/teratogenicity of Glycerol monoisostearate (CAS 66085-00-5) are not available. The assessment was therefore based on studies conducted with analogue substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. 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 13) and within Chapter 5.1 of the CSR.

Developmental toxicity/teratogenicity

CAS No. 91052-13-0

An oral gavage screening toxicity study was performed according to OECD guideline 422 and under GLP- conditions in Crl:WI(Han) Wistar rats receiving 100, 300 and 1000 mg/kg bw/day (Otterdijk, 2010). Dilutions of the test substance in polyethylene glycol or the vehicle alone were administered once daily to groups of 10 male and 5 female rats (main groups) via gavage. In addition, satellite groups of 5 males and 5 females (recovery animals) each for the control and high dose group were used to investigate the reversibility of effects during a 14-day post-exposure recovery period. Furthermore, 10 females (repro animals) were added to each group for the assessment of reproduction and developmental toxicity. The main and recovery groups were exposed for at least 28 days. Females used for the assessment of reproduction/developmental toxicity were exposed for 41-49 days (during 2 weeks prior to mating, during mating, during post-coitum, and during at least 4 days of lactation). Limited developmental data is assessed in the study, as pups are observed until Day 4 post-parturition. The viability index (pup mortality), postnatal loss (day 0-4), percentage of live females and males at first litter check were calculated. The pups were observed for clinical signs, and the body weights were examined. In addition, external examination for abnormalities was performed. No treatment-related effects or abnormalities were observed at any dose level. No toxicologically relevant changes in the offspring viability indices were observed.

 

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 Glycerol monoisostearate (CAS No. 66085-00-5), 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 does not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and is therefore conclusive but not sufficient for classification. Under Regulation (EC) No. 1907/2006, Annex VIII,a pre-natal developmental toxicity study is not required if a (screening) study on toxicity to reproduction is available. Under these circumstances, the health hazard ‘reproductive toxicity’ as defined in Section 2.1 GHS and the reason for no classification (conclusive but not sufficient for classification) is considered to cover both the reproduction and developmental toxicity.