Docosyl docosanoate

Endpoint summary

Description of key information

Short-term (28-day) repeated dose toxicity (OECD 422): NOAEL = 1000 mg/kg bw/day

Study performed with the analogue source substance fatty acids C20-22 (even numbered), C18-22 (even numbered) alkyl esters (EC 701-233-7)

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Remarks:

combined repeated dose and reproduction / developmental screening

Type of information:

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

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

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

Remarks on result:

other: Source: EC 701-233-7, Lasem, 2014

Key result

Critical effects observed:

no

Conclusions:

A reliable combined short-term (28-day) repeated dose toxicity study with the reproduction/developmental toxicity screening test conducted in accordance with OECD guideline 422 and GLP found no toxicologically relevant and test substance-related effects in rats. The No-Observed-Adverse-Effect-Level (NOAEL) for general toxicity in male and female rats was determined to be 1000 mg/kg bw/day.

Executive summary:

The short-term (28-day) repeated dose toxicity of the target substance docosyl docosanoate (CAS 17671-27-1) is estimated based on an adequate and reliable in vivo study with an analogue source substance. In this study the test substance did not induce any toxicologically relevant test substance-related effects. The No-Observed-Adverse-Effect-Level (NOAEL) for general toxicity in male and female rats was determined to be 1000 mg/kg bw/day. Therefore, also for the target substance a NOAEL of 1000 mg/kg bw/day is taken forward to the hazard assessment and for the determination of the classification. As explained in the Analogue Justification, the differences in molecular structure between the target and the source substances are unlikely to lead to differences in the repeated dose toxicity.

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 an adequate and reliable (Klimisch score 1) study from a source substance with similar structures and intrinsic properties. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, Item 8.6, in accordance with Annex XI, Item 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

No data on subacute repeated dose toxicity are available for docosyl docosanoate (CAS 17671-27-1). An adequate and reliable study performed with an analogue source substance is, therefore, used to assess the endpoint of repeated dose toxicity.

A combined repeated dose toxicity and reproduction/developmental toxicity screening study (according to OECD 422 under GLP conditions) was performed with fatty acids C20-22 (even numbered), C18-22 (even numbered) alkyl esters (EC 701-233-7) (Lasem, 2014). 10 rats/dose were administered 0, 100, 300 and 1000 mg/kg bw/day test substance once daily via gavage. Males were treated from 2 weeks before mating for at least 49 days and females were treated from 2 weeks before mating until day 4 postpartum (females). The treatment ended one day before sacrifice. No test item-related premature death was noted. Only a lower locomotor activity was recorded in males at 100 mg/kg bw/day and in females at 300 and 1000 mg/kg bw/day. No other test item-related signs of toxicity were noted during the observational and neurological screenings. A test item-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 changes were noted for the haematological parameters, while bilirubin values tended to increase at 300 and 1000 mg/kg bw/day in both sexes. No further changes of the clinical chemistry parameters were noted. The macroscopic inspection at autopsy did not show test item-related changes. No test item-related changes were noted during the histopathological examination. The NOAEL for systemic toxicity of fatty acids C20-22 (even numbered), C18-22 (even numbered) alkyl esters was determined to be 1000 mg/kg bw/day in this study.

Justification for classification or non-classification

The available data on subacute repreated dose toxicity for an adequate analogue source substance do not meet the criteria for classification according to Regulation (EC) No. 1272/2008 (CLP). Data are conclusive but not sufficient for classification. Based on an analogue read-across approach, the target substance docosyl docosanoate (CAS 17671-27-1) is, therefore, also not classified for repeated dose toxicity (STOT RE).