Icosyl acrylate

Endpoint summary

Description of key information

Oral

In two combined repeated oral dose and reproductive / developmental toxicity screening studies (OECD 422) in rats the structural analogues 2-Propenoic acid, C12-14-alkyl esters and 2-Propenoic acid, C18-22-alkyl esters showed no toxicity up to the highest administered dose of 1000 mg/kg bw/day (see table 1).

 

Table 1. Data on repeated oral dose toxicity

Ester	Method	Species	NOAEL	Reference
2-Propenoic acid, C12-14-alkyl esters [84238-60-8]	OECD TG 422	Rats	1000 mg/kg bw/day (highest dose tested)	BASF SE 2013
2-Propenoic acid, C18-22-alkyl esters [85085-17-2]	OECD TG 422	Rats	1000 mg/kg bw/day (highest dose tested)	BASF SE 2013

 

The available data from the group of long-chain acrylate esters for repeated dose toxicity cover the shortest and longest chain lengths present in the category. They are consistent and sufficient to enable an assessment for this endpoint.

 

Inhalation

The inhalation route is not of relevance due to the very low vapour pressure of the substances (see chapter on Toxicokinetics).

 

Dermal

The experimental repeated dose oral toxicity data demonstrated in accordance with acute dermal and oral tests the low toxicity of the long-chain alkyl esters. In addition, the characteristics of skin penetration and metabolism in the skin show the limited bioavailability of the esters via the dermal route (see chapter on Toxicokinetics). Therefore, the potential for repeated dermal dose toxicity can be considered low.

 

Conclusion

In conclusion, the long-chain alkyl acrylate esters (C12 – C22) showed no oral toxicity after repeated application. Studies available are considered to be reliable and suitable to cover the endpoint repeated dose toxicity and fulfil the REACH information requirements of Annex VIII / IX, section 8.6.

 

The variable part of the category approach is the length and/or configuration of the side chain of the parent ester and the alcohol metabolite, as well as their impacts on physico-chemical properties and consequent biological properties. Despite these variations, the available data support a lack of systemic toxicity for all the category members, since data is availablefor the shortest and longest chain lengths present in the category. These repeated dose toxicity studies have also reported a similar and common profile of target organs (i.e. a lack of systemic toxicity). Thus, the results of the collection of these studies conducted on these substances are consistent and can be regarded as offering a true picture of repeated dose toxicity for the category. In order to fill the data-gap for the mono-constituents, a category based read-across is applied to the repeated dose toxicity studies available for oral route. Overall, the read-across approach is applied with a high level of confidence.

 

A confirmatory sub-chronic toxicity test with 2-propenoic acid, C12-14 alkylesters (CAS 84238-60-8) is proposed to strengthen the read across.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The mixture 2-Propenoic acid, C12-14-alkyl esters was administered orally via gavage to groups of 10 male and 10 female Wistar rats (F0 animals) at dose levels of 0 mg/kg bw/day (test group 0), 100 mg/kg bw/day (test group 1), 300 mg/kg bw/day (test group 2) and 1000 mg/kg bw/day (test group 3). The objective of the study was to detect possible effects of the test substance on the integrity and performance of male and female reproductive systems including gonadal function, mating behavior, conception, gestation and parturition. Furthermore, it was intended to obtain information about the general toxicological profile including target organs and the no observed adverse effect level (NOAEL) after repeated oral administration. The duration of treatment covered a 2-week pre-mating and mating period in both sexes, approximately 1 week post-mating in males, and the entire gestation period as well as 4 days of lactation and two weeks thereafter in females. The parents’ and the pups’ state of health was checked each day, and parental animals were examined for their mating and reproductive performances. After 2 weeks of premating treatment the F0 animals were mated to produce F1 generation pups. Mating pairs were from the same test group. Mating was discontinued as soon as sperm was detected in the vaginal smear. F0 animals were examined for their reproductive performance including determinations of the number of implantations and the calculation of the postimplantation loss in all F0 females. A detailed clinical observation (DCO) was performed in all animals before initial test substance administration and, as a rule, thereafter at weekly intervals. Food consumption of the F0 parents was determined once weekly during premating. In dams food consumption was determined for gestation days 0 – 7, 7 – 14, 14 – 20 and lactation days 1 – 4. Body weights of F0 parents were determined once a week, in males throughout the study and in females during premating and mating. During gestation and lactation period, F0 females were weighed on gestation days (GD) 0, 7, 14 and 20, on the day of parturition (postnatal day [PND] 0) and on PND 4. The pups were sexed and examined for macroscopically evident changes on PND 0. They were weighed on PND 1 and on PND 4. Their viability was recorded. At necropsy on PND 4, all pups were sacrificed under isoflurane anesthesia with CO2and examined macroscopically for external and visceral findings. Clinical chemistry and hematological examinations as well as urinanalysis were performed in 5 animals per sex and group towards the end of the administration period. Towards the end of the administration period a functional observational battery was performed and motor activity was measured in 5 animals per sex and test group. All F0 parental animals were sacrificed by decapitation, under isoflurane anesthesia, and were assessed by gross pathology. Weights of selected organs were recorded and a histopathological examination was performed. The various analyses confirmed the stability of the test substance in corn oil at room temperature over a period of 7 days and the correctness of the prepared concentrations of the test substance preparations in corn oil. No test substance-related, adverse findings were noted in neither F0 parental animals nor in F1 pups in all test groups. Therefore, the NOAEL for general, systemic toxicity was determined to be 1000 mg/kg bw/day in rats (BASF SE, 2013).

 

In another study, the mixture 2-Propenoic acid, C18-22-alkyl esters was administered orally via gavage to groups of 10 female Wistar rats (F0 animals) at dose levels of 0 mg/kg bw/day (test group 0), 100 mg/kg bw/day (test group 1), 300 mg/kg bw/day (test group 2) and 1000 mg/kg bw/day (test group 3). The objective of the study was to detect possible effects of the test substance on the integrity and performance of male and female reproductive systems including gonadal function, mating behavior, conception, gestation and parturition. Furthermore, it was intended to obtain information about the general toxicological profile including target organs and the no observed adverse effect level (NOAEL) after repeated oral administration. The duration of treatment covered a 2-week pre-mating and mating period in both sexes, approximately 1 week post-mating in males, and the entire gestation period as well as 4 days of lactation and two weeks thereafter in females. After 2 weeks of premating treatment the F0 animals were mated to produce F1 generation pups. Mating pairs were from the same test group. Mating was discontinued as soon as sperm was detected in the vaginal smear. A detailed clinical observation (DCO) was performed in all animals before initial test substance administration and, as a rule, thereafter at weekly intervals. Food consumption of the F0 parents was determined once weekly during premating. In dams food consumption was determined for gestation and lactation period, F0 females were weighed on gestation days (GD) 0, 7, 14 and 20, at the day of parturition (postnatal day [PND] 0) and on PND 4. The pups were sexed and examined for macroscopically evident changes on PND 0. They were weighed on PND 1 and on PND 4. Their viability was recorded. At necropsy on PND 4, all pups were sacrificed under isoflurane anesthesia with CO2and examined macroscopically for external and visceral findings. Clinicochemical and hematological examinations as well as urinanalyses were performed in 5 animals per sex and group towards the end of the administration period. Towards the end of the administration period a functional observational battery was performed and motor activity was measured in 5 animals per sex and test group. All F0 parental animals were sacrificed by decapitation, under isoflurane anesthesia, and were assessed by gross pathology. Weights of selected organs were recorded and a histopathological examination was performed. The various analyses demonstrated the stability of the test substance in corn oil over a period of 7 days at room temperature and confirmed the overall accuracy of the prepared concentrations. No test substance-related adverse findings were observed in neither F0 parental animals nor in F1 pups in all test groups. Thus, under the conditions of this study the NOAEL for general, systemic toxicity was determined to be 1000 mg/kg bw/day in rats (BASF SE, 2013).

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data of the structural related substances are reliable and suitable for classification purposes under Regulation 1272/2008. There were no significant toxic effects at doses of 1000 mg/kg bw/day upon subacute oral exposure in rats. As a result the substance is not classified for repeated dose toxicity under Regulation (EC) No. 1272/2008, as amended fpr the tenth time in Regulation (EC) No. 2017/776.