Docosyl stearate

Endpoint summary

Description of key information

Oral (OECD 422): NOAEL m/f rat ≥ 1000 mg/kg bw/day (read-across from CAS 17671-27-1, key)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

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

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 adverse effects observed up to and including the highest tested dose level

Remarks on result:

other: Source: CAS 17671-27-1

Key result

Critical effects observed:

no

Besides the key study, two reliable oral repeated dose toxicity as supporting studies with the suitable source substances CAS 3687-46-5 and CAS 93803-87-3 in rats are available. In both studies, no adverse effects were observed and the NOAEL was considered to be ≥ 1000 mg/kg bw/day.

Conclusions:

No adverse effects were observed in the repeated dose toxicity studies following oral administration with the source substances, all resulting in a NOAEL greater than 1000 mg/kg bw/day. Applying the read-across approach, similar results are expected for the target substance docosyl stearate (CAS 22413-03-2).

Endpoint conclusion

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 and 2) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to the endpoint discussion for further details). The selected studies are thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.6, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

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

Read-across justification

There are no data available on the repeated dose toxicity of docosyl stearate (CAS 22413-03-2). 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 analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Repeated dose toxicity, oral, subacute

CAS 17671-27-1

A combined repeated dose toxicity and reproduction/developmental toxicity screening study was performed with docosyl docosanoate (CAS 17671-27-1) according to OECD 422 and under GLP conditions (Harlan, 2014). Ten rats/sex/dose were administered 0, 100, 300 and 1000 mg/kg bw/day docosyl docosanoate once daily via gavage up to day 49 of treatment (males) or day 4 postpartum (females). The application started two weeks before mating on test day one and ended one day before sacrifice. No test item-related premature death was noted. No test item-related signs of toxicity were noted during the observational and neurological screenings. A treatment-related decrease in body weight was noted for the female animals of the high dose group (1000 mg /kg bw/day) on lactation day 4. No toxicologically relevant effects were observed on the haematological and clinical chemistry parameters. The macroscopic inspection at autopsy and subsequent histopathological examination did not show any treatment-related changes. Based on the absence of adverse effects the NOAEL for systemic toxicity was considered to be ≥ 1000 mg/kg bw/day for male and female rats.

 

CAS 3687-46-5

A 28-day oral repeated dose toxicity study was performed with decyl oleate (CAS 3687-46-5) similar to OECD 407 (Henkel, 1987). Ten Wistar rats per sex and dose and 5 per sex and dose satellite rats were administered once daily (5 days a week) 0, 100, 500 and 1000 mg/kg bw/day by gavage, for 28 consecutive days. There was no mortality and no toxicologically relevant clinical signs were observed during the study period. No significant differences in body weight, body weight gain, food consumption, water consumption and organ weight were noted between the control group and treatment groups. No treatment-related effects on the ophthalmology-, haematology- and clinical biochemistry parameters were observed. No treatment-related changes were noted during the gross pathology and histopathology examinations. Based on the absence of adverse toxic effects the NOAEL for systemic toxicity was ≥ 1000 mg/kg bw/day.

 

CAS 93803-87-3

A 28-day oral repeated dose toxicity study was performed with octyldodecyl isooctadecanoate (CAS 93803-87-3) according to OECD 407 and under GLP conditions (Notox, 1998d). Five Wistar rats/sex/dose were administered 0, 50, 200 and 1000 mg/kg bw/day by gavage, for 28 consecutive days. There was no mortality and no toxicologically relevant clinical signs were observed during the study period. No significant differences in body weight, body weight gain and food consumption between the control group and treatment groups were noted. In females of the high-dose group, a statistically significant increase in relative leucocyte level (approx. 8%) and decrease in relative neutrophil level (approx. 8%) was noted, compared with the control group values. These values are related to each other as a percentage of the total lymphocyte concentration, and a variation in one will necessarily affect one or several other specific lymphocyte values. As the changes were minimal, no effects were seen in males and no other haematological effects were noted, this result is considered not to have toxicological relevance. In males of the high-dose group, the level of calcium and chloride was significantly increased, compared with the control group. These increases were around 5% compared with the control group levels and no similar effects were observed in the female groups. Therefore, they are not considered to have toxicological relevance. No treatment-related effects on neurobehavioral parameters were observed. There were no significant differences in absolute or relative organ weight in the treatment groups, compared with the control group. The macroscopic inspection at autopsy and subsequent histopathological examination did not reveal any treatment-related changes. The NOAEL for systemic toxicity was considered to be ≥ 1000 mg/kg bw/day for male and female rats.

 

Overall conclusion for repeated dose toxicity

The data for the read-across analogue substances showed that no effects were observed up to and including the recommended limit values. Therefore, as the available data did not identify any hazard for repeated dose toxicity, the target substance docosyl stearate (CAS 22413-03-2) is not expected to be hazardous following repeated exposure.

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 docosyl stearate (CAS 22413-03-2), 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.

Therefore, based on the analogue read-across approach, the available data on repeated dose toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.