Registration Dossier

Administrative data

Description of key information

All available acute oral toxicity studies within this category resulted in an acute oral LD50 > 2000 mg/kg bw. 
All available acute dermal toxicity studies within the category resulted in acute dermal LD50 > 2000 mg/kg bw.
All available acute inhalation toxicity studies within the category resulted in acute inhalation LC50 > 5.0 mg/L air.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for grouping of substances and read-across

The long-chain aliphatic ester (LCAE) category covers mono-esters of a fatty acid and a fatty alcohol. The category contains both mono-constituent and UVCB substances. The fatty acid carbon chain lengths range is C8 - C22 (even and uneven numbered, including saturated, unsaturated, branched and linear chains) esterified with fatty alcohols with chain lengths from C8 - C22 (even and uneven numbered, including saturated, unsaturated, branched and linear) in varying proportions to mono-esters.

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 and 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 for 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.

Overview of acute toxicity

CAS

Acute toxicity Oral

Acute toxicity inhalation

Acute toxicity dermal

20292-08-4 (b)

Experimental result:

LD50 > 2000 mg/kg bw

--

--

91031-48-0

Experimental result:

LD50 > 4300 mg/kg bw

--

--

26399-02-0

Experimental result:

LD50 > 5000 mg/kg bw

Experimental result:

LC50 > 5.7 mg/L air

--

3687-46-5

Experimental result:

LD50 > 2000 mg/kg bw

RA: CAS 26399-02-0

Experimental result:

LD50 > 2000 mg/kg bw

59231-34-4 (a)

RA: CAS 3234-85-3,

3687-46-5, 72576-80-8

RA: CAS 26399-02-0

RA: CAS 3687-46-5, 93803-87-3

36078-10-1

RA: CAS 3234-85-3,

3687-46-5, 72576-80-8

RA: CAS 26399-02-0

RA: CAS 3687-46-5, 93803-87-3

95912-86-0

Experimental result:

LD50 > 5000 mg/kg bw

RA: CAS 26399-02-0

RA: CAS 3687-46-5, 93803-87-3

95912-87-1

RA: CAS 3234-85-3,

3687-46-5, 72576-80-8

RA: CAS 26399-02-0

RA: CAS 3687-46-5, 93803-87-3

91031-91-3

RA: CAS 3234-85-3,

3687-46-5, 72576-80-8

RA: CAS 26399-02-0

RA: CAS 3687-46-5, 93803-87-3

85116-88-7

RA: CAS 3234-85-3,

3687-46-5, 72576-80-8

RA: CAS 26399-02-0

RA: CAS 3687-46-5, 93803-87-3

95912-88-2

RA: CAS 3687-46-5, 95912-87-1

RA: CAS 26399-02-0

RA: CAS 3687-46-5, 93803-87-3

3234-85-3

Experimental result:

LD50 > 5000 mg/kg bw

RA: CAS 26399-02-0

RA: CAS 3687-46-5, 93803-87-3

22393-85-7

RA: CAS 3234-85-3,

3687-46-5, 72576-80-8

RA: CAS 26399-02-0

RA: CAS 3687-46-5, 93803-87-3

101227-09-2

RA: CAS 3234-85-3,

3687-46-5, 72576-80-8

RA: CAS 26399-02-0

RA: CAS 3687-46-5, 93803-87-3

97404-33-6

RA: CAS 3687-46-5, 95912-87-1

RA: CAS 26399-02-0

RA: CAS 3687-46-5, 93803-87-3

Former CAS 97404-33-6

RA: CAS 3687-46-5, 95912-87-1

RA: CAS 26399-02-0

RA: CAS 3687-46-5, 93803-87-3

72576-80-8

Experimental result:

LD50 > 2000 mg/kg bw

RA: CAS 26399-02-0

RA: CAS 3687-46-5, 93803-87-3

3687-45-4

RA: CAS 3234-85-3,

3687-46-5, 72576-80-8

RA: CAS 26399-02-0

RA: CAS 3687-46-5, 93803-87-3

17673-56-2

RA: CAS 3234-85-3,

3687-46-5, 72576-80-8

RA: CAS 26399-02-0

RA: CAS 3687-46-5, 93803-87-3

96690-38-9

RA: CAS 3234-85-3,

3687-46-5, 72576-80-8

RA: CAS 26399-02-0

RA: CAS 3687-46-5, 93803-87-3

93803-87-3

RA: CAS 3234-85-3,

3687-46-5, 72576-80-8

RA: CAS 26399-02-0

Experimental result:

LD50 > 2000 mg/kg bw

17671-27-1

RA: CAS 3234-85-3,

3687-46-5, 72576-80-8

RA: CAS 26399-02-0

RA: CAS 3687-46-5, 93803-87-3

111937-03-2 (c)

Experimental result:

LD50 > 5000 mg/kg bw

--

--

(a) Category members subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font.

(b) Substances that are either already registered under REACh or not subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in normal font.

(c) 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.

For all category members registered under REACh a full data set for each endpoint is provided. For substances not subject to the current REACh Phase-in registration, lack of data for a given endpoint is indicated by "--".

 

Discussion

Acute toxicity endpoint

Acute oral toxicity

CAS 3687-46-5

An acute oral toxicity study (limit test) was performed with decyl oleate (CAS 3687-46-5), according to a protocol similar to OECD 401 (Dufour, 1994). 5 female NMRI EOPS mice received a single dose of 2000 mg/kg bw by gavage. There were no mortalities. No signs of clinical toxicity were reported during the 6-day study period and there was no effect on the body weights. No necropsy was performed. The acute oral LD50 in mice was found to be > 2000 mg/kg bw.

A study was performed by Gloxhuber (1967) according to a protocol similar to OECD 401, and reported in a summary with limited information. 10 male rats received approximately 17000 mg/kg bw (19.9 mL/kg bw) decyl oleate by gavage (Gloxhuber, 1967). No mortality occurred during the 14-day observation period. Increased respiratory rate, ruffled fur and light diarrhoea were observed in the animals after dosing, for an unknown length of time. The body weight was not affected. The LD50 is considered to be > 17000 mg/kg bw. 

In a non-guideline study, 10 male rats were administered app. 8660 mg/kg bw (10 mL/kg bw) by gavage (Potokar, 1970). The results were summarily reported. No mortalities occurred and no signs of clinical toxicity were observed.

 

CAS 59231-34-4

In a review publication by the Cosmetic Ingredient Review, an acute oral toxicity study was briefly summarised (CIR Expert Panel, 1982). 2-3 rats/sex/dose were administered 2.5, 5, 10, 20 and 40 mL/kg bw isodecyl oleate (CAS 59231-34-4) by gavage, equivalent to approximately 2.2, 4.3, 8.6, 17.2, 34.4 g/kg bw. 1/5 animals in the highest dose level died. Due to the lack of original data and limited documentation, this study was considered insufficient for assessment.

 

CAS 95912-86-0

In a non-guideline study, 5 female mice were administered 5000 mg/kg bw fatty acids, C8-10, C12-18 alkyl esters (CAS 95912-86-0) via the oral route (Dufour, 1991). The study report contained limited information. No mortality occurred and no clinical signs were reported during the 6-day observation period. There were no effects on body weight. The oral LD50 is considered to be > 5000 mg/kg bw.

A non-guideline study was performed by Potokar (1970) and reported in a summary with very limited information. 10 male rats were administered 20 mL/kg bw (approximately 17200 mg/kg bw) of the substance by gavage. No mortality occurred and no clinical signs were reported during the 8-day observation period. The oral LD50 was set at > 17200 mg/kg bw.

 

CAS 95912-87-1

A non-guideline study was performed by Kästner (1977), using two batches of Fatty acids, C16-18, C12-18 alkyl esters (CAS 95912-87-1) and reported in a brief summary. 10 male rats were administered 30 mL/kg bw of a 16.7% solution in water (approximately 5000 mg/kg bw) by gavage. The results were the same for both batches; no mortality occurred and no clinical signs were reported during the 8-day observation period. No gross pathology was performed. The oral LD50 is considered to be > 5000 mg/kg bw.

 

CAS 95912-88-2

In a non-guideline study, 10 male mice/dose were administered 5000 and 10000 mg/kg bw Fatty acids, C16-18, isotridecyl esters (CAS 95912-88-2) by gavage (Gloxhuber and Potokar, 1977). The results were summarily reported. No mortalities occurred and no signs of clinical toxicity were reported during the 8-day study period. The acute oral LD50 in rat was found to be > 10 g/kg bw.

 

CAS 3234-85-3

A study was performed by Cade (1976) according to a protocol similar to OECD 401, and reported in a summary with limited information. 5 rats/sex/dose were administered 5000 mg/kg bw tetradecanoic acid, tetradecyl ester (CAS 3234-85-3) as a 50% solution in corn oil by gavage. One male died on Day 4 of an undisclosed cause. No clinical signs were observed during the 14-day observation period and the body weight gain was within the expected range for this strain and study type. No unusual findings were reported during the macroscopic examination. The oral LD50 is considered to be > 5000 mg/kg bw.

In a non-guideline study, 2 rats/sex/dose were administered 2000 mg/kg bw tetradecanoic acid, tetradecyl ester in a heated oil by gavage (Potokar, 1983). No mortality occurred and no clinical signs were reported during the 14-day observation period. There were no effects on body weight and no substance-related findings were reported during the macroscopic examination. The oral LD50 is considered to be > 2000 mg/kg bw.

A study was performed by Planchette (1985), according to a protocol similar to OECD 401, and reported in a summary with very limited information. 5 mice/sex/dose were administered 5000 mg/kg bw (20mL/kg bw) tetradecanoic acid, tetradecyl ester in corn oil by gavage. No mortality occurred and no clinical signs were reported during the 14-day observation period. The oral LD50 is set at > 5000 mg/kg bw.

In a review publication by the Cosmetic Ingredient Review, two studies using rats were briefly summarised (CIR Expert Panel, 1982). The results lead to the same conclusion as the available study reports; no LD50 was determined.

 

CAS 101227-09-2

A study was performed with fatty acids, C16-18, 2-hexyldecyl esters (CAS 101227-09-2), according to a protocol similar to OECD 401 (Kästner, 1984). Only a summary report with very limited information was available. 5 male rats were administered 5 mL/kg bw test substance (approximately 4350 mg/kg bw) by gavage. No mortality occurred. The animals had piloerection and were lethargic 1 hour after dosing; no other clinical signs were noted during the 14-day observation period. The gross pathology did not show substance-related effects. The oral LD50 is considered to be > 5 mL/kg bw (app. 4350 mg/kg bw).

 

CAS 72576-80-8

An acute oral toxicity study was performed with hexadecanoic acid, isooctadecyl ester (CAS 72576-80-8) similar to OECD 401 (Bouffechoux, 1999). 5 rats/sex were administered 2000 mg/kg bw of the test substance by gavage. No mortality occurred. No clinical signs were observed during the 14-day observation period and the body weights were comparable between the control group and treatment group. The gross pathology examination was not performed. The oral LD50 is considered to be > 2000 mg/kg bw.   

 

CAS 93803-87-3

The results of an acute oral toxicity study with 2-octyldodecyl isooctadecanoate (CAS 93803-87-3) were briefly summarised in a report published by the National Industrial Chemicals Notification and Assessment Scheme (NICNAS) of Australia in 1999. 5 rats/sex were administered 2000 mg/kg bw 2-octyldodecyl isooctadecanoate by gavage in a study reported to be OECD 401-compliant. No mortality occurred and no clinical signs were reported during the 14-day observation period. No toxicologically relevant findings were noted during the gross pathology.

 

Acute inhalation toxicity

CAS 26399-02-0

The acute inhalation toxicity of 2-ethylhexyl oleate (CAS 26399-02-0) was assessed in a study performed according to OECD 436 (Van Huygevoort, 2010). 3 rats/sex were administered 5.7 ± 0.4 mg/L (actual concentration) of the test substance as an aerosol via nose-only exposure for 4 hours. The nominal concentration was 15.4 mg/L and the MMAD was 2.1-2.5 µm. No mortality occurred. The animals had a hunched posture on Day 2; no further clinical signs were observed during the 14-day study period. The body weight gain was within the range that is normal for this strain and study type. No findings were reported during the macroscopic examination. The LC50 is considered to be > 5 mg/L.  

 

Acute dermal toxicity

CAS 3687-46-5

An acute dermal toxicity study (limit test) was performed with decyl oleate (CAS 3687-46-5) according to OECD Guideline 402 (Beerens-Heijnen, 2010). 2000 mg/kg bw of the test substance was applied to the skin of 5 Wistar rats/sex/dose under an occlusive dressing for 24 hours. No mortality occurred. Piloerection and/or chromodacryorrhoea were noted in all males on Day 1 and/or 2. No clinical signs were noted in females. The body weight increases were within the range expected for rats used in this type of study and no treatment-related findings were reported during the necropsy and histopathological examination. Erythema was observed on the treated skin for up to 4 days during the first week in 3/5 females. Scales or scabs were noted on the treated skin area in 5/5 females and 3/5 males for up to 9 days during Day 7-15 of the observation period. The LD50 is considered to be > 2000 mg/kg bw.

 

CAS 3234-85-3

An acute dermal toxicity study was briefly summarised in a review publication by the Cosmetic Ingredient Review, (CIR Expert Panel, 1982). 2000 mg/kg bw tetradecanoic acid, tetradecyl ester (CAS 3234-85-3) was applied to the skin of 10 albino rabbits of unknown sex for 24 hours. The type of coverage was not specified. No mortality occurred and no clinical signs were reported. Some skin irritation was noted at the application site, with maximum skin irritation scores of well-defined erythema (grade 2 of 4) and very slight edema (grade 1 of 4).

 

CAS 93803-87-3

The potential acute dermal toxicity of 2-octyldodecyl isooctadecanoate (CAS 93803-87-3) was assessed in a study (limit test) performed according to a protocol similar to OECD Guideline 402 (Busschers, 1998). 2000 mg/kg bw of the test substance was applied to the skin of 5 Wistar rats/sex/dose under an occlusive dressing for 24 hours. No mortality occurred. No toxicologically relevant clinical signs were noted during the 14-day observation period. The body weight increases were within the range expected for rats used in this type of study and no treatment-related findings were reported during the necropsy and histopathological examination. The LD50 is considered to be > 2000 mg/kg bw.

 

Overall conclusion for acute toxicity

A total of 13 oral toxicity studies of acceptable quality and reliability are available within the LCAE category, although some are summarily reported (e.g. Bouffechoux, 1999; Cade, 1976; Dufour, 1994). The conclusions of these studies are similar; no mortality was observed at doses from 2000 mg/kg bw and above. No mortality was observed in the acute inhalation study, leading to an LC50 of > 5 mg/L (Van Huygevoort, 2010). The available acute dermal toxicity data for category members consistently showed no mortality and no treatment-related effects (Beerens-Heijnen, 2010; Busschers, 1998). The overall LD50 dermal is therefore set at > 2000 mg/kg bw.

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