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Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

Oral: OECD 422, rat, NOAEL reproduction ≥ 1000 mg/kg bw/day

Oral: OECD 422, rat, NOAEL systemic ≥ 1000 mg/kg bw/day

Read-across from analogue source substance docosyl docosanoate (CAS 17671-27-1, key)

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
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
Key result
Dose descriptor:
NOAEL
Remarks:
systemic
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 were observed up to and including the highest tested dose level
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 were observed up to and including the highest tested dose level
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 were observed up to and including the highest tested dose level
Key result
Critical effects observed:
no
Reproductive effects observed:
no

In addition, a supporting screening for reproductive / developmental toxicity study is available with the source substance tetradecyl oleate (CAS 22393-85-7). In this study, no adverse effects on reproductive performance or in utero development in rats following oral administration was noted, therefore the NOAEL was greater than 1000 mg/kg bw/day for reproduction and the offspring.

Conclusions:
The available screening for reproductive / developmental toxicity study with the suitable source substance docosyl docosanoate (CAS 17671-27-1) did not show any adverse effects on reproduction performance or in utero development and resulted in a NOAEL greater than 1000 mg/kg bw/day for reproduction and the offspring. Applying the read-across approach, similar results are expected for the target substance Fatty acids, montan-wax, stearyl esters.
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 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 (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, 8.7, in accordance with Annex XI, 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

Justification for read-across

There are no data available regarding the reproduction toxicity of the target substance Fatty acids, montan-wax, stearyl esters (CAS 68308-30-5). The assessment was therefore based on studies conducted with analogue source 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 grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Section 13).

CAS 17671-27-1

A combined repeated dose toxicity study with a reproduction/developmental toxicity screening test was performed according to OECD 422 under GLP conditions (Harlan, 2014). 10 rats/ sex/dose were administered 0, 100, 300 and 1000 mg/kg bw/day docosyl docosanoate once daily, via gavage. Males were exposed for 28-29 days, from two weeks before mating on test day one until after mating. Females were exposed for 54 days (during 2 weeks prior to mating, during mating, during post-coitum, and during 3 days of lactation). No treatment-related parental effects were seen on viability, clinical signs, body weight (gain), food consumption, clinical chemistry parameters, during observational screening, and during macroscopic and microscopic examinations. In females, an increase in bilirubin, cholesterol and triglyceride levels was recorded at 300 and 1000 mg/kg. As this was only observed in one sex and no other hepatic changes were observed, this is not considered to be toxicologically relevant. Lower locomotor activity was recorded in males at 100 mg/kg and in females at 300 and 1000 mg/kg. As no effects were noted on other neurological parameters, this is not considered to be toxicologically relevant. Therefore, the NOAEL for parental systemic toxicity was ≥ 1000 mg/kg bw/day. In parental animals, no effects on reproductive function (qualitative sperm staging, oestrus cycle) or performance (male and female mating and fertility indices, conception index, precoital interval, and number of corpora lutea and implantation sites, gestation length) were observed, compared with the control animals. One female from the control group had a 100% postimplantation loss, which is considered to be incidental. The testis weight, epididymis weight, and histological examination of the testes in males as well as the weight and histological examination of the uterus and ovaries in females did not reveal any substance-related effects in the parental animals. Therefore, a NOAEL for parental fertility of ≥1000 mg/kg bw/day was derived for male and female rats.

CAS 22393-85-7

A combined repeated dose toxicity study with a reproduction/developmental toxicity screening test was performed according to OECD 422 under GLP conditions (RTC, 2014). 10 rats/sex/dose were administered 0, 100, 300 and 1000 mg/kg bw/day tetradecyl oleate (CAS 22393-85-7) once daily, via oral gavage. Males were exposed for 28-29 days, from two weeks before mating on test day one until after mating.Females were exposed for 54 days (during 2 weeks prior to mating, during mating, during post-coitum, and during 3 days of lactation). No treatment-related parental effects were seen on viability, clinical signs, body weight (gain), food consumption, haematological parameters, clinical chemistry parameters, during observational and neurological screening, and during macroscopic and microscopic examinations. Therefore the NOAEL for parental systemic toxicity was ≥ 1000 mg/kg bw/day. In parental animals, no effects on reproductive function (qualitative sperm staging, oestrus cycle) or performance (male and female mating and fertility indices, conception index, pre-coital interval, and number of corpora luteae and implantation sites, gestation length) were observed, compared with the control animals.The testis weight, epididymis weight, and histological examination of the testes in males as well as the weight and histological examination of the uterus and ovaries in females did not reveal any substance-related effects in the parental animals. All the pregnant females gave birth to live pups with the exception of one high dose female which had a total litter loss on day 3 post-partum. This female and two females in the control group had unilateral implantation, which is not considered to be treatment-related. Therefore, a NOAEL for parental fertility of≥ 1000 mg/kg bw/day was derived for male and female rats.

Effects on developmental toxicity

Description of key information

Oral: OECD 422, rat, NOAEL developmental ≥ 1000 mg/kg bw/day

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 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 (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, 8.7, in accordance with Annex XI, 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

Justification for read-across

There are no data available regarding developmental toxicity of the target substance Fatty acids, montan-wax, stearyl esters (CAS 68308-30-5). The assessment was therefore based on studies conducted with analogue source 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 grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Section 13).

CAS 17671-27-1

A combined repeated dose toxicity study with a reproduction/developmental toxicity screening test was performed according to OECD 422 under GLP conditions (Harlan, 2014) with docosyl docosanoate (CAS 17671-27-1). No toxicologically relevant treatment related adverse effects were seen regarding viability, body weight, gross pathology, sex ratio, feeding, morphological examinations including behaviour observations of F1 offspring.Postural reflexes were determined on Day 1 postpartum in the pups. A significantly lower percentage of foetuses with positive response in the surface-righting reflex (righting reflex) at 1000 mg/kg bw was recorded compared to the control group. There were no treatment-related differences compared to the control animals at 100 or 300 mg/kg bw. The clinical relevance of this parameter remained unclear. Righting reflex was only assessed on Day 1 postpartum. The study report did not contain exact age matching of pups, nor considered biologically possible range of gestation length. No follow up behavioural testing at later time points during development of pups was done. Testing of righting reflex is not required following OECD GL 422.Therefore, a developmental NOAEL of ≥ 1000 mg/kg was determined based on the absence of toxicologically relevant effects.

CAS 22393-85-7

A combined repeated dose toxicity study with a reproduction/developmental toxicity screening test was performed according to OECD 422 under GLP conditions (RTC, 2014) with tetradecyl oleate (CAS 22393-85-7). No toxicologically relevant treatment related adverse effects were seen on viability, clinical signs, body weight, sex ratio, and gross pathology of F1 offspring. Based on these results, a developmental NOAEL of ≥ 1000 mg/kg was determined.

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 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.

Based on the analogue read-across approach, the available data on developmental toxicity do not meet the classification criteria according to Regulation (EC) No. 1272/2008. However, as no subchronic repeated dose toxicity and/or no reproduction toxicity study is available, the conclusion for classification is ‘data lacking’.

Additional information