Isooctadecyl isooctadecanoate

Endpoint summary

Description of key information

Oral (OECD 422), rat: NOAEL (systemic):
Females = 300 mg/kg bw/day
Males = ≥ 1000  mg/kg bw/day
Oral (OECD 408), rat: NOAEL (systemic) = ≥ 1000  mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

300 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2 due to read-across) and consistent studies from reference substances with similar structure and intrinsic properties (refer to endpoint discussion for further details). The available studies are sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 8.6, in accordance with Annex VIII, 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

Justification for read-across

There are no data available on the repeated dose toxicity of isooctadecyl isooctadecanoate (CAS 41669-30-1). In order to fulfil the standard information requirements set out in Annex IX, 8.6, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across to avoid the need to test every substance for every endpoint).

 

Overview of repeated dose toxicity

  

CAS	Chemical name	Molecular weight	Repeated dose toxicity: oral
41669-30-1	isooctadecyl isooctadecanoate	536.95	RA: CAS 868839-23-0 + CAS 59231-34-4
868839-23-0	propylheptyl octanoate	284.48	Experimental result (OECD 408): NOAEL = ≥ 1000 mg/kg bw/d
59231-34-4	isodecyl oleate	422.73	Experimental result (OECD 422): NOAEL females = 300 mg/kg bw/d  NOAEL males = ≥ 1000 mg/kg bw/day

 

The above mentioned substances are considered to be similar to each other based on structurally similar properties and/or activities. Therefore, available data on the source substances has been read-across to isooctadecyl isooctadecanoate (CAS 41669-30-1).

The target substance is characterized as an UVCB substance comprised of a branched C18 fatty acid esterified with an aliphatic, but branched C16 and C18 alcohol. The source substances are structurally similar to the target substance. Propylheptyl octanoate (CAS 868839 -23-0) is a mono-constituent substance consisting of stearic acids esterified with propylheptanol. Isodecyl oleate (CAS 59231-34-4) is an UVCB substance consisting of oleic acid esterified with a branched alcohol (decanol). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

 

CAS 868839-23-0

 

A repeated dose toxicity study was performed in rats according to OECD 408, using propylheptyl octanoate (CAS 868839-23-0) (Leuschner, 2006). 10 Wistar rats/sex/dose were administered 100, 300 and 1000 mg/kg bw/day of the test substance in soybean oil by gavage, for 90 consecutive days.

1/10 females in each of the low-, mid- and high dose groups, respectively, died during the laboratory examinations on the last treatment day after blood withdrawal. These deaths are considered to be caused by the ether narcosis and are therefore not treatment-related. No treatment-related clinical signs were observed. No treatment-related effects were noted on body weight, body weight gain, food consumption and water consumption. The ophthalmoscopic examination did not show treatment-related effects on the eyes. No treatment-related effects were observed during the neurobehavioral and observational tests. There were no statistically significant differences in the haematology parameters between the control group and the treatment groups. The albumin and blood urea nitrogen levels were significantly increased in the males in the high-dose group. As no effects were noted on these parameters in the females of the high-dose group, and in the absence of related histopathological findings, these effects are not considered to be toxicologically relevant. A statistically significant decrease in urinary pH value was noted in males in the mid-dose group and in males and females in the high-dose groups. This is considered to be a treatment-related, but not toxicologically relevant, effect as no other effects on urinary parameters or kidney histopathology was noted. The absolute and relative liver weight in high-dose males and females was significantly increased. This is probably an adaptive response to the increased metabolic load due to ingestion of the test substance. As no related effects were noted on liver enzyme levels or liver histopathology, this is not considered to be a toxicologically relevant effect. There were no statistically significant differences in the mean length of the oestrus cycles and the number of complete cycles between the females in the control group and the treatment groups. In males, there were no statistically significant differences between the control group and the treatment groups in the mean number and percentage of ultrasound-resistant spermatids, number of motile spermatozoa in the cauda epididymis, and in the percentage of spermatids with malformations. No treatment-related gross pathological or histopathological effects were observed in organs or tissues.

Based on the lack of toxicologically relevant effects up to and including the highest dose level, the NOAEL is considered to be ≥ 1000 mg/kg bw/day.

 

 

CAS 59231-34-4

A combined repeated dose toxicity and reproduction/developmental toxicity screening study (according to OECD 422 under GLP conditions) was performed with isodecyl oleate (Hansen, 2013). 10 rats/sex/dose were administered 100, 300 and 1000 mg/kg bw/day isodecyl oleate once daily for 28 day (males) and up to 54 days (females) via gavage. The application started two weeks before mating on test Day 1 and ended on the day or one day before sacrifice. Day of sacrifice was on test Day 36 for the male rats and on lactation Day 4 or shortly thereafter for the female rats. No test item-related premature death was noted. No 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) only on lactation Day 4. A test item-related decrease in food consumption was noted for the female animals of the high dose group (1000 mg/kg bw/day) during the lactation/gestation period. No test item-related changes were noted for the haematological parameters and the parameters of clinical chemistry. Macroscopic inspection at autopsy revealed no test item related changes. The histopathological examination revealed no test item-related changes. No other effect was observed in any further group or any parameter. The effects observed at 1000 mg/kg bw/d in the females were considered adverse and leading to maternal toxicity; thus, the NOAEL for systemic toxicity was determined to be 300 mg/kg bw/day in females and 1000 mg/kg bw/d in male rats in this study.

 

Conclusions on repeated dose toxicity

 

Based on the available 90-d and combined repeated dose/reproduction/developmental toxicity screening test studies with the structural analogous substances, propylheptyl octanoate (CAS 868839-23-0) and isodecyl oleate (CAS 59231-34-4), the overall sub-acute and sub-chronic NOAEL, for isooctadecyl isooctadecanoate, is therefore considered to be 300 mg/kg bw/day based on the adverse effects observed in the OECD 422 screening study at a dose level of 1000 mg/kg bw/d (Hansen, 2013).

 

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Hazard assessment is conducted by means of read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between the source and target substances and overall quality assessment (refer to the endpoint discussion for further details). The study with the lowest dose descriptor was chosen for chemical safety assessment.

Justification for classification or non-classification

Based on read-across from structurally similar substances, the available data on repeated dose toxicity via the oral route do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.