Docosyl docosanoate

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on fertility

Description of key information

Screening for reproductive / developmental toxicity (OECD 422): NOAEL(reproduction) = 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)

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

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

Immunological findings:

not examined

Key result

Dose descriptor:

NOAEL

Remarks:

reproduction

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 in the study

Remarks on result:

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

Key result

Critical effects observed:

no

Key result

Dose descriptor:

NOAEL

Remarks:

developmental

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 adverse effects observed in the study

Remarks on result:

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

Key result

Critical effects observed:

no

Key result

Reproductive 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 with respect to reproductive performance and developmental toxicity. The No-Observed-Adverse-Effect-Level (NOAEL) for reproduction and the NOAEL for development were determined to be 1000 mg/kg bw/day, respectively.

Executive summary:

The reproductive and developmental 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 adverse toxicologically relevant test substance-related effects with respect to reproductive performance and developmental toxicity. The No-Observed-Adverse-Effect-Level (NOAEL) for reproduction and the NOAEL for development were determined to be 1000 mg/kg bw/day, respectively. Therefore, also for the target substance NOAEL values of 1000 mg/kg bw/day for reproductive and for developmental toxicity, respectively, are 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.

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 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 8.7, in accordance with Annex XI, Item 1.5, of 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

No data on reproductive 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 toxicity to reproduction.

A combined repeated dose toxicity and reproduction/developmental toxicity screening study (according to OECD guideline 422) was performed with fatty acids C20-22 (even numbered), C18-22 (even numbered) alkyl esters (EC 701-233-7) under GLP conditions (Lasem, 2014). The test item was administered orally (gavage) once daily at the doses of 100, 300 and 1000 mg/kg bw/day to 10 rats/sex/group. The male and female rats were treated from two weeks before pairing to Day 4 post-partum for females, and to 5 weeks post coitum for males. Treatment with the test item did not cause signs of paternal toxicity. No mortality was recorded in either sex and there were no relevant differences in food consumption, water consumption or body weight. 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 changes of toxicological relevance were recorded in the clinical pathology analysis. Bilirubin values tended to increase at 300 and 1000 mg/kg bw/day in both sexes. Concerning the differences in organ weights observed in males and females, it cannot be concluded that there is a relationship with the test item given that the differences are not related with any histopathological finding. All macroscopic and microscopic findings recorded were considered to be within the range of normal background lesions that may be seen in rats of this strain and age and under the experimental conditions used in this study. There were no differences between the control and the test substance-treated animals in the type, location, distribution and severity of the histopathological findings recorded. Regarding fertility, no treatment-related effects on the percentage of mated animals, gestation index, fertility index or conception rate were recorded. The mean and median pre-coital time was slightly higher at 300 mg/kg bw/day. It cannot be concluded that there is a relationship with the test item as the differences are not dose-related. One female from this dose group did not mate with the male after 14 days of pairing. Those animals were mated again with a different male of the same group and with a female from a reserve group, respectively, and mating led to pregnancy. No differences in pre- or postimplantation losses or live pups at first check on lactation day 0 were recorded compared to the control group. One female from the control group had 100% post implantation losses. The pregnancy length was similar in all groups. Lower milk production was observed in one female at 1000 mg/kg bw/day that did not nurse her pups. All the pups of this female died or were devoured between Days 0 - 4 post-partum. As a consequence, the postnatal pup losses increased. In conclusion, the NOAEL for systemic toxicity and that for toxicity to reproduction of fatty acids C20-22 (even numbered), C18-22 (even numbered) alkyl esters were considered to be 1000 mg/kg bw/day, respectively, for males and females.

Effects on developmental toxicity

Description of key information

Screening for reproductive / developmental toxicity (OECD 422): NOAEL(development) = 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)

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 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 8.7, in accordance with Annex XI, Item 1.5, of 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

No data on developmental 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 developmental toxicity.

A combined repeated dose toxicity and reproduction/developmental toxicity screening study (according to OECD guideline 422) was performed with fatty acids C20-22 (even numbered), C18-22 (even numbered) alkyl esters (EC 701-233-7) and observing GLP criteria (Lasem, 2014). The test item was administered orally (gavage) once daily at the doses of 100, 300 and 1000 mg/kg bw/day 10 rats/sex/group. The male and female rats were treated from two weeks before pairing to Day 4 post-partum for females and to 5 weeks post coitum for males. Only the effects related to pup development are summarised here. For further details of the OECD guideline 422 study, please refer to 'Additional information' in the 'Effects on fertility' section of this endpoint summary and to the endpoint summary on repeated dose toxicity.

No differences from the control group were recorded for the mean body weight in the F1 generation. Regarding physical development, no differences from the control group were recorded. Regarding motor development, a lower percentage of pups with positive response to the surface righting reflex was recorded at 1000 mg/kg bw/day. The macroscopic findings recorded at necropsy were considered to have no toxicological relevance and to fall within the range of normal background lesions that may be seen in animals of this strain. Therefore, the No-Adverse-Observed-Effect-Level (NOAEL) for developmental toxicity of fatty acids C20-22 (even numbered), C18-22 (even numbered) alkyl esters was determined to be 1000 mg/kg bw/day.

Justification for classification or non-classification

The available data on reproductive and developmental 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 toxicity to reproduction and developmental toxicity.