Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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

Mode of Action Analysis / Human Relevance Framework

Additional information

Justification for grouping of substances and read-across

The short chain methyl esters category (SCAE Me) covers fatty acid esters of methanol. The category contains both mono-constituent substances, with fatty acid C-chain lengths ranging from C6 to C18 and UVCB substances, composed of single methyl esters in variable proportions.

The available data allows for an accurate hazard and risk assessment of the category and the category concept is applied for the assessment of environmental fate, environmental and human health hazards. Thus where applicable, environmental and human health effects are predicted from adequate and reliable data for source substance(s) within the group by interpolation to the target substances in the group (read-across approach) applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006. In particular, 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 Sections 7.1 and 13) and within Chapter 5.1 of the CSR.

Table: Endpoint repeated dose toxicity

CAS No.

NOAEL [mg/kg bw/day]

111-82-0 (a)

1000 (m,f)

111-62-6 (b)

5500 (m,f)

123-95-5

6000 (m,f)

 

(a) Category members subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font. Only for these substances a full set of experimental results and/or read-across is given.

(b) Surrogate substances are either chemicals forming part of a related category of structurally similar fatty acid esters or precursors/breakdown products of category members (i.e. alcohol and fatty acid moieties). Available data on these substances are used for assessment of (eco )toxicological properties by read-across on the same basis of structural similarity and/or mechanistic reasoning as described below for the present category.

 

CAS 111-82-0

Methyl laurate (CAS 111-82-0) was tested for oral toxicity in rats in an OECD 422 combined repeated dose and reproductive toxicity screening test under GLP conditions (MHLW, 2000). 12 male and female Crj:CD (SD) rats per dose were administered doses of 0, 250, 500 and 1000 mg/kg/day by gavage. The animals were mated. The test material was administered to females from 14 days before mating until day 3 of lactation and to males for 45 days. Terminal kill was on day 45 for males and on day 4 of lactation for females. The test substance showed no general toxicological effects in either sex. There were no clinical observations attributable to the administration of test substance and there was no mortality in any of the groups. No effects were observed in terms of body weights, food consumption, haematology, blood chemistry, organ weight, necropsy or histopathological findings. Therefore, under the experimental conditions of the study the NO(A)EL for methyl laurate for repeated dose toxicity after oral administration is 1000 mg/kg bw/day in both sexes.

 

CAS 111-62-6

Ethyl ester - Repeated dose toxicity:

oral subchronic NOAEL for rats: 5500 mg/kg bw/day

 

A subchronic oral feeding study (Bookstaff, 2004) was performed with ethyl oleate (CAS 111-62-6) according to the 1993 FDA draft "Redbook II" guidelines (Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food). The study was performed equivalent to OECD Guideline 408. The purpose of the study was to determine the safety of ethyl oleate (EO) in a subchronic feeding study in Sprague-Dawley rats. EO was mixed into AIN-93G purified diet at levels of 0, 3.3, 6.7, and 10% by weight (approx. 0, 1900, 3800 and 6000 mg/kg bw/day). All diets were calorie- and fat-matched using high oleic safflower oil (HOSO) as the control fat. There were 20 male and 20 female rats per group. EO in the diet was well tolerated and there were no toxicologically significant findings in any of the measured parameters (clinical observations, body weight gains, appearance of the faeces, ophthalmic examinations, haematology, clinical chemistry, urinalysis, organ weights, histopathology, or male and female reproductive assessments). The subchronic oral NOAEL was determined to be 10% ethyl oleate, which corresponds to approximately 5500 mg/kg bw/day when administered by daily feeding to rats for 91-days.

 

 

CAS 123-95-5

Butyl ester - Repeated dose toxicity:

2 -year NOAEL for rats: 6000 mg/kg bw/day

A 2-year feeding study was performed with butyl stearate (CAS 123-95-5) comparable to OECD Guideline 452 (Smith, 1953, summarized by Elder, 1985). Groups of 16 male Sprague-Dawley rats received daily doses of 0, 0.01, 0.05, 0.25, 1.25 and 6.25% in the diet. Based on absence of abnormalities in clinical signs, mortality, body weight, food consumption, haematology, clinical chemistry, gross pathology, organ weights and histopathology the chronic NOAEL was found to be 6000 mg/kg bw/day.

 

There are no data available on the repeated dose toxicity after dermal application and inhalation of the category members.

 

Conclusions:

In summary, all available data do not indicate any toxicological hazard after repeated exposure via the oral route.

There are no reliable data available on the repeated dose toxicity after dermal application and inhalation of the category members.

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within CSR.

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 physicochemical, 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 group concept is applied to the members of the SCAE Me category, data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the group concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the group concept, the available data on repeated dose toxicity 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.