Fatty acids, montan-wax, stearyl esters

Endpoint summary

Description of key information

Oral: NOAEL m/f rat ≥ 1000 mg/kg bw/day

Read-across from structural analogue source substance docosyl docosanoate (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

Remarks on result:

other: Source: CAS 17671-27-1

Key result

Critical effects observed:

no

In addition, two further supporting studies regarding repeated dose toxicity following oral administration are available with the source substances 2 -octyldodecyl isooctadecanoate (CAS 93803-87-3) and tetradecyl oleate (CAS 22393-85-7). In both studies, no treatment-related and adverse effects were observed up to and including the highest dose level of 1000 mg/kg bw/day.

Conclusions:

The available oral repeated dose toxicity study with the suitable source substance docosyl docosanoate (CAS 17671-27-1) did not show any adverse effect in rats after repeated oral administration and resulted in a systemic NOAEL greater than 1000 mg/kg bw/day. Applying the read-across approach, similar results are expected for the target substance Fatty acids, montan-wax, stearyl esters.

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) studies from reference substances with similar 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. 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 on the repeated dose toxicity of Fatty acids, montan-wax, stearyl esters (CAS 68308-30-5). 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).

CAS 17671-27-1

A combined repeated dose toxicity and reproduction/developmental toxicity screening GLP study was performed with docosyl docosanoate (CAS 17671-27-1) according to OECD 422 (Harlan, 2014). Ten rats/dose/day 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 substance-related premature death was noted. No test substance-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.

 

CAS 22393-85-7

A combined repeated dose toxicity and reproduction/developmental toxicity screening GLP study was performed according to OECD 422 (RTC, 2014) with tetradecyl oleate (CAS 22393-85-7). 10 rats/sex/dose were administered 0, 100, 300 and 1000 mg/kg bw/day once daily for 28-29 days (males) and up to 54 days (females) via oral gavage. The application started two weeks before mating on test day one and ended on the day of or one day before sacrifice. Day of sacrifice was on test day 29 or 30 for the male rats and on lactation day 3 or shortly thereafter for the female rats. There was no mortality during the study period. No toxicologically relevant clinical signs were observed. The body weight, body weight gain and food consumption was comparable between the control and treatment groups. There were no toxicologically relevant effects on organ weights. The statistically significant differences in haematological parameters between control and treated animals (erythrocytes, mean corpuscular haemoglobin and leucocytes in males, haemoglobin, haematocrit and platelets in females) were of low magnitude and/or not dose-related, and therefore considered incidental. Statistically significant fluctuations of some biochemical parameters, compared with the control groups, were recorded in both sexes. An increase in glucose levels in males administered 100 and 1000 mg/kg bw/day (48% for both doses), and an increase in urea in males receiving 100 mg/kg bw/day (19%) was observed. In females in the 300 mg/kg bw/day group, an increase in aspartate aminotransferase level (35%) was noted, while for females administered 1000 mg/kg bw/day, a decrease in bilirubin levels (81%) and an increase in potassium levels (10%) was observed. Due to the lack of dose- and/or sex-consistency, and due to the absence of other relevant findings, these changes are not considered to be toxicologically relevant. There was no significant difference between control and treatment groups during the observational and neurological screenings. 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.

 

CAS 93803-87-3

A 28-day oral repeated dose toxicity GLP study was performed with octyldodecyl isooctadecanoate (CAS 93803-87-3) according to OECD 407 (Notox, 1998). 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 have toxicological relevance. In males of the high-dose group, the level of calcium and chloride was significantly increased. 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 to 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.

 

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 Fatty acids, montan-wax, stearyl esters (CAS 68308-30-5) 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 physico-chemical, 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 Fatty acids, montan-wax, stearyl esters (CAS 68308-30-5), data will be generated from data for 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) No. 1272/2008 and are therefore conclusive but not sufficient for classification.