Alcohols, C8-10, ethoxylated

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Reproductive / developmental screening test (oral, rat): NOAEL (systemic toxicity) ≥ 1000 mg/kg bw/day, NOAEL (reproductive toxicity) ≥ 1000 mg/kg bw/day

Read-across based on grouping of substances (category approach) considering all available data on reproductive / developmental toxicity on screening level in the 'linear' subgroup of the Alcohol Ethoxylates (AE) category.

An extended one-generation reproductive toxicity study (EOGRTS, OECD 443) is not required for alcohols C8-10, ethoxylated < 2.5 EO (CAS No. 71060-57-6, EC No. 615-247-5) as the requirements given in Annex IX, Section 8.7.3, Column 1, of the REACH Regulation (EC) No. 1907/2006 are not met.

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Justification for type of information:

Please refer to the category justification provided in the category object.

Key result

Dose descriptor:

NOAEL

Effect level:

>= 1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No toxicologically relevant effects observed

Key result

Critical effects observed:

no

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

>= 1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No toxicologically relevant effects observed

Key result

Critical effects observed:

no

Key result

Reproductive effects observed:

no

For a detailed assessment of the reproductive / developmental toxicity of the Alcohol Ethoxylates (AE) category, please refer to the category justification attached to the category object.

Conclusions:

Applying read-across based on grouping of substances (category approach), no toxicologically relevant effects in relation to reproductive / developmental toxicity and a NOAEL for reproductive toxicity ≥ 1000 mg/kg bw/day are predicted for the target substance.

Executive summary:

The available data on reproductive / developmental toxicity in the 'linear' subgroup of the Alcohol Ethoxylates (AE) category indicate no toxicologically relevant effects for the target substance. As explained in the category justification, the differences in molecular structure and composition between the target substance and the members of the AE category are unlikely to lead to differences with respect to reproductive / developmental toxicity.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises adequate and reliable (Klimisch score 1) studies from various source substances in the Alcohol Ethoxylates (AE) category with similar structures and intrinsic properties. Read-across is justified based on common toxicokinetic behaviour and consistent trends in environmental fate, ecotoxicological and toxicological properties of the category member substances. The data pool of the AE category is thus sufficient to fulfil the standard information requirements set out in Annexes VIII - X, Section 8.7, in accordance with Annex XI, Section 1.5, of the REACH Regulation (EC) No. 1907/2006.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Reproductive / developmental toxicity screening

No data on reproductive toxicity on screening level of alcohols C8-10, ethoxylated < 2.5 EO (CAS No. 71060-57-6, EC No. 615-247-5) are available. In order to assess reproductive toxicity, studies in the data pool of the Alcohol Ethoxylates (AE) category are considered in a read-across approach. Due to differences in systemic toxicity between AE substances containing only linear constituents and those containing linear and branched constituents, as observed in studies with repeated dose administration, only data obtained with AE substances in the 'linear' subgroup of the category are used to read-across systemic endpoints, incl. reproductive toxicity, to AE substances containing only linear constituents. Adequate and reliable studies are available for the following linear AE members:

- Alcohols, C10, ethoxylated, < 2.5 EO (CAS No. 26183-52-8, EC No. 500-046-6): (OECD 422) NOAEL (reproductive toxicity) ≥ 1000 mg/kg bw/day

- Alcohols, C12-14, ethoxylated, < 2.5 EO (CAS No. 68439-50-9, EC No. 500-213-3): (OECD 422) NOAEL (reproductive toxicity) ≥ 1000 mg/kg bw/day

- Hexadecan-1-ol, ethoxylated, < 2.5 EO (CAS No. 9004-95-9, EC No. 500-014-1): (OECD 422) NOAEL (reproductive toxicity) ≥ 1000 mg/kg bw/day

- Alcohols, C16-18 (even numbered), ethoxylated, < 2.5 EO (CAS No. 68439-49-6, EC No. 939-518-5): (OECD 422) NOAEL (reproductive toxicity) ≥ 1000 mg/kg bw/day

- (Z)-9-Octadecen-1-ol, ethoxylated, < 2.5 EO (CAS No. 9004-98-2, EC No. 500-016-2): (OECD 422) NOAEL (reproductive toxicity) ≥ 1000 mg/kg bw/day

Conclusion

All available study results indicate a lack of reproductive toxicity, thus demonstrating the similarity of the linear AE substances with respect to toxicological properties. Treatment did not cause any toxicologically relevant changes in relation to mating and fertility indices, precoital time, number of implantation sites, gestation index and duration, parturition and maternal care. Sporadically occurring irregular cycles, variations in precoital time and the number of not pregnant females were not considered treatment-related due to their incidental nature and/or absence of a dose relationship. Therefore, a NOAEL ≥ 1000 mg/kg bw/day for reproductive toxicity is used for the hazard assessment and classification and labelling of the linear AE substances, incl. alcohols C8-10, ethoxylated < 2.5 EO (CAS No. 71060-57-6, EC No. 615-247-5). For a detailed assessment of the reproductive and developmental toxicity of the linear member substances of the AE category, please refer to the category justification documentation attached to the category object.

Extended one-generation reproductive toxicity study

According to Annex IX, Section 8.7.3, Column 1, of the REACH Regulation (EC) No. 1907/2006 an extended one-generation reproductive toxicity study (EOGRTS, OECD 443) must be performed if the available repeated dose toxicity studies (e.g. 28-day or 90-day studies, OECD 421 or 422 screening studies) indicate adverse effects on reproductive organs or tissues or reveal other concerns in relation to reproductive toxicity. The repeated dose toxicity as well as reproductive / developmental data available for various members of the AE category do not provide any concern in relation to reproductive toxicity. No toxicologically relevant effects were noted in reproductive organs and tissues. Please refer to the category justification attached to the category object for details on studies and the grouping and read-across approach in the AE category.

It is, therefore, concluded that the requirements given in Annex IX, Section 8.7.3, Column 1, of the REACH Regulation are not met and an EOGRTS is not required for alcohols C8-10, ethoxylated < 2.5 EO (CAS No. 71060-57-6, EC No. 615-247-5). However, pursuant to compliance check final decision for a number of substances in the AE category, several subchronic (OECD 408) and prenatal developmental toxicity studies (OECD 414, in first and/or second species) are currently ongoing. The evaluation whether an EOGRTS study is required will be reassessed once all experimental results will be available.

Effects on developmental toxicity

Description of key information

Reproductive / developmental screening test (oral, rat): NOAEL (developmental toxicity) ≥ 1000 mg/kg bw/day, not teratogenic

Read-across based on grouping of substances (category approach) considering all available data on reproductive / developmental toxicity on screening level in the 'linear' subgroup of the Alcohol Ethoxylates (AE) category.

Developmental toxicity (oral, rat): NOAEL (developmental toxicity) ≥ 1000 mg/kg bw/day, not teratogenic

Read-across based on grouping of substances (category approach) considering all available data on combined subacute repeated dose toxicity studies with the reproductive / developmental toxicity screening test (OECD 422) conducted with members of the 'linear' subgroup of the AE category.

Pursuant to compliance check final decision for a number of substances in the AE category, several prenatal developmental toxicity studies according to OECD guideline 414 are currently ongoing. The NOAEL for developmental toxicity will be re-evaluated once the results of the OECD 414 studies are available.

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Justification for type of information:

Please refer to the category justification provided in the category object.

Key result

Dose descriptor:

NOAEL

Effect level:

>= 1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: no toxicologically relevant effects observed

Key result

Abnormalities:

no effects observed

Key result

Dose descriptor:

NOAEL

Effect level:

>= 1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no toxicologically relevant effects observed

Key result

Abnormalities:

no effects observed

Key result

Developmental effects observed:

no

For a detailed assessment of the developmental toxicity of the Alcohol Ethoxylates (AE) category, please refer to the category justification attached to the category object.

Conclusions:

Applying read-across based on grouping of substances (category approach), no toxicologically relevant effects in relation to developmental toxicity / teratogenicity and a NOAEL for developmental toxicity ≥ 1000 mg/kg bw/day are predicted for the target substance.


are predicted for the registered substance.

Executive summary:

The available data on developmental toxicity in the 'linear' subgroup of the Alcohol Ethoxylates (AE) category indicates no toxicologically relevant effects for the target substance. As explained in the category justification, the differences in molecular structure and composition between the target substance and the members of the AE category are unlikely to lead to differences with respect to developmental toxicity.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises adequate and reliable (Klimisch score 1) studies from various source substances in the Alcohol Ethoxylates (AE) category with similar structures and intrinsic properties. Read-across is justified based on common toxicokinetic behaviour and consistent trends in environmental fate, ecotoxicological and toxicological properties of the category member substances. The data pool of the AE category is thus sufficient to fulfil the standard information requirements set out in Annexes VIII - X, Section 8.7, in accordance with Annex XI, Section 1.5, of the REACH 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

Reproductive / developmental toxicity screening

No data on developmental toxicity of alcohols C8-10, ethoxylated < 2.5 EO (CAS No. 71060-57-6, EC No. 615-247-5) are available. In order to assess developmental toxicity, studies in the data pool of the Alcohol Ethoxylates (AE) category are considered in a read-across approach. Due to differences in systemic toxicity between AE substances containing only linear constituents and those containing linear and branched constituents, as observed in studies with repeated dose administration, only data obtained with AE substances in the 'linear' subgroup of the category are used to read-across systemic endpoints, incl. developmental toxicity, to AE substances containing only linear constituents. Adequate and reliable studies investigating developmental toxicity on screening level are available for the following linear AE members:

- Alcohols, C10, ethoxylated, < 2.5 EO (CAS No. 26183-52-8, EC No. 500-046-6): (OECD 422) NOAEL (developmental toxicity) ≥ 1000 mg/kg bw/day, not teratogenic

- Alcohols, C12-14, ethoxylated, < 2.5 EO (CAS No. 68439-50-9, EC No. 500-213-3): (OECD 422) NOAEL (developmental toxicity) ≥ 1000 mg/kg bw/day, not teratogenic

- Hexadecan-1-ol, ethoxylated, < 2.5 EO (CAS No. 9004-95-9, EC No. 500-014-1): (OECD 422) NOAEL (developmental toxicity) ≥ 1000 mg/kg bw/day, not teratogenic

- Alcohols, C16-18 (even numbered), ethoxylated, < 2.5 EO (CAS No. 68439-49-6, EC No. 939-518-5): (OECD 422) NOAEL (developmental toxicity) ≥ 1000 mg/kg bw/day, not teratogenic

- (Z)-9-Octadecen-1-ol, ethoxylated, < 2.5 EO (CAS No. 9004-98-2, EC No. 500-016-2): (OECD 422) NOAEL (developmental toxicity) ≥ 1000 mg/kg bw/day, not teratogenic

Conclusion

All available study results indicate a lack of developmental toxicity and the absence of any teratogenic effect, thus demonstrating the similarity of the linear AE substances with respect to in utero and early-life development. Treatment did not cause any toxicologically relevant changes in relation to sex ratio and early postnatal pup development, i.e. mortality, clinical signs, body weights, sex, anogenital distance, areola/nipple retention and macroscopy, measurement of thyroid hormone T4 (post-natal day (PND) 14-16). Sporadically pups were found dead at first litter check or pups were missing on PND 4. These incidences were not considered of toxicological relevance since the mortality incidence did not show dose-related trends. Moreover, variations and retardations observed remained within the range considered normal for pups of this age in all studies. Therefore, a NOAEL ≥ 1000 mg/kg bw/day for developmental toxicity and a lack of any teratogenic effect are considered for the hazard assessment and classification and labelling of the linear AE substances, incl. alcohols C8-10, ethoxylated < 2.5 EO (CAS No. 71060-57-6, EC No. 615-247-5). For a detailed assessment of the reproductive and developmental toxicity of the linear member substances of the AE category, please refer to the category justification attached to the category object.

Prenatal developmental toxicity in a first species

No data on prenatal developmental toxicity of alcohols C8-10, ethoxylated < 2.5 EO (CAS No. 71060-57-6, EC No. 615-247-5) are available. In order to assess this endpoint, studies in the data pool of the AE category will be considered. Pursuant to final compliance check decision for a number of linear AE substances, several prenatal developmental toxicity studies according to OECD guideline 414 are currently ongoing. Until results of these studies will be available, a NOAEL of ≥ 1000 mg/kg bw/day for developmental toxicity as determined in the reproductive / developmental toxicity screening tests with the linear AE substances listed above is considered as the NOAEL for prenatal development for the hazard assessment and the evaluation of classification and labelling of the linear AE substances. The NOAEL for developmental toxicity established for the linear AE substances will be re-evaluated once the results of the OECD 414 studies are available. For a detailed assessment of the developmental toxicity of the AE category, please refer to the category justification attached to the category object.

Justification for classification or non-classification

The available data on reproductive and developmental toxicity obtained with members of the 'linear' subgroup of the Alcohol Ethoxylates (AE) category do not meet the criteria for classification according to the CLP Regulation (EC) No. 1272/2008 and are therefore conclusive but not sufficient for classification. Based on grouping of substances (category approach), alcohols C8-10, ethoxylated < 2.5 EO (CAS No. 71060-57-6, EC No. 615-247-5) is predicted not to fulfil the classification criteria and is consequently not classified for reproductive and developmental toxicity.