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 inhalation toxicity studies within the category resulted in acute inhalation LC50 > 5.0 mg/L air.
While no reliable acute dermal toxicity studies are available., the picture of all available data is consistent supporting also a low level of dermal toxicity for the category of fatty acid methyl esters.

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 study available

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 Acute toxicity

CAS

 

Acute Oral

Acute Inhalation

Acute Dermal

106-70-7 (a)

Experimental result: LD50 (rat) > 2000 mg/kg bw

Experimental result: LC50 (rat) > 14,000 mg/m³

RA: 111-82-0 and 85586-21-6

--

111-11-5

Experimental result: LD50 (rat) > 2000 mg/kg bw

RA: 111-82-0 and 106-70-7

--

110-42-9

Experimental result: LD50 (rat) > 14,000 mg/kg bw

RA: 111-82-0 and 106-70-7

--

111-82-0

Experimental result: LD50 (rat) > 2000 mg/kg bw

4 h LC50 (rat) > 5 mg/L (aerosol)

--

112-39-0

Experimental result: LD50 (rat) > 2000 mg/kg bw

RA: 111-82-0 and 85586-21-6

--

112-63-0 (b)

Experimental result: LD50 (rat) > 2000 mg/kg bw

--

--

112-61-8

Experimental result: LD50 (rat) > 2000 mg/kg bw

RA: 111-82-0

--

85566-26-3

RA: 111-11-5

RA: 111-82-0

--

308065-15-8

RA: 111-82-0 and 112-39-0

 

RA: 111-82-0

--

1234694-02-0

RA: 112-61-8, 111-82-0 and 112-63-0

RA: 111-82-0 and 85586-21-6

--

67762-26-9

Experimental result: LD50 (rat) > 2000 mg/kg bw

--

--

85586-21-6

RA: 112-61-8 and 112-39-0

Study report not yet available

--

 

(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) 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. Lack of data for a given endpoint is indicated by “--“.

Discussion

Acute oral toxicity

CAS 111-11-5

For methyl octanoate (CAS 111-11-5), an acute oral toxicity study according to EU Method B.1 (Potokar, 1988) was performed. Groups of 5 male and 5 female Wistar rats received doses of 2000 mg methyl octanoate /kg bw in arachis oil by oral gavage. The animals were observed for 14 days. All animals survived. No signs of systemic toxicity were observed and no abnormalities during gross necropsy were seen. Thus, the acute oral LD 50 in rats was found to be greater than 2000 mg/kg bw.

CAS 110-42-9

For decanoic acid, methyl ester (CAS 110-42-9), a study similar to OECD guideline 401 (Michael, 1965) was performed. 10 rats were orally exposed to a single dose of 14,000 mg/kg bw by gavage. The animals were observed for 14 days. No mortality occurred during the study period. Slight gasping, salivation, abdominal griping, diarrhea and decrease in motor activity were reported during the first day following dosing. The oral LD 50 in rats was found to be greater than 14,000 mg/kg bw.

CAS 111-82-0

Two reliable studies investigating the acute toxicity via the oral route of methyl laurate are available (CAS 111-82-0). An acute oral toxicity study was performed with methyl laurate (CAS 111-82-0) according to OECD Guideline 401 (Sterzel, 1990). Groups of 5 male and 5 female Wistar rats received doses of 2000 mg methyl laurate /kg bw in arachis oil by oral gavage. The animals were observed for 14 days. All animals survived. No signs of systemic toxicity occurred. With exception for one female animal with a strong hydrometra no abnormalities were observed during gross necropsy. Thus, the acute oral LD 50 in rats was found to be greater than 2000 mg/kg bw.

In another study methyl laurate (CAS 111-82-0) was administered to groups of 5 male and 5 female Sprague-Dawley rats at a dose of 20,000 mg/kg bw by oral gavage (Bjorkquist, 1982). The animals were observed for 14 days. All animals survived. Diarrhoea occurred in 4m/4f and 3m/3f (male/female) animals at days 1 and 2 after dosing. No other clinical signs of systemic toxicity were the observed. In this study the acute oral LD50 in rats was found to be greater than 20 g/kg bw. 

CAS 112-39-0

An acute oral toxicity study was performed with methyl palmitate (CAS 112-39-0) according to OECD Guideline 401 (Pittermann, 1992). Groups of 5 male and 5 female Wistar rats received doses of 2000 mg methyl palmitate /kg bw in arachis oil by oral gavage. The animals were observed for 14 days. All animals survived. No signs of systemic toxicity were observed and no abnormalities during gross necropsy were seen. Under the conditions used in this study, it was concluded that the test substance has no toxic effect when administered to the rat at a level of 2000 mg/kg bw. The acute oral LD50 for methyl palmitate in male and female rats was found to be greater than 2000 mg/kg bw.

CAS 106-70-7

For methyl hexanoate (CAS No. 106-70-7), an acute oral toxicity study was performed according to OECD Guideline 401 under GLP conditions (Pittermann, 1992). Groups of 5 male and 5 female Wistar rats received doses of 2000 mg methyl hexanoate/kg bw in water by oral gavage. The animals were observed for 14 days. All animals survived. During the observation period no signs of systemic toxicity occurred and no abnormalities during gross necropsy were seen. Thus, the acute oral LD 50 for methyl hexanoate in rats was found to be greater than 2000 mg/kg bw.

CAS 112-61-8

Another acute oral toxicity study was performed with methyl stearate (CAS No. 112-61-8) according to OECD Guideline 401 (Pittermann, 1992). Groups of 5 male and 5 female Wistar rats received doses of 2000 mg methyl stearate /kg bw in arachis oil by oral gavage. The animals were observed for 14 days. All animals survived. No signs of systemic toxicity were observed and no abnormalities during gross necropsy were seen. The acute oral LD50 for methyl stearate in rats was found to greater than 2000 mg/kg bw.

CAS 67762-26-9

For fatty acids, C14-18 and C16-18-unsatd., Methyl esters (CAS No. 67762-26-9) an acute oral toxicity study was performed according to EU Method B.1 (Potokar, 1988). Groups of 5 male and 5 female Wistar rats received doses of 2000 mg /kg bw in arachis oil by oral gavage. The animals were observed for 14 days. All animals survived. During the observation period no signs of systemic toxicity occurred and no abnormalities during gross necropsy were seen. Thus, the acute oral LD 50 for Fatty acids, C14-18 and C16-18-unsatd., Methyl esters in male and female Wistar rats was found to be greater than 2000 mg/kg bw.

CAS 112-63-0

An acute oral toxicity study was performed with methyl linoleate (CAS No. 112-63-0) according to OECD Guideline 401 (Pittermann, 1992). Groups of 5 male and 5 female Wistar rats received doses of 2000 mg methyl linoleate/kg bw in arachis oil by oral gavage. The animals were observed for 14 days. All animals survived. During the observation period no signs of systemic toxicity occurred and no abnormalities during gross necropsy were seen. Thus, the acute oral LD 50 for methyl linoleate in male and female rats was found to be greater than 2000 mg/kg bw.

 

Acute inhalation toxicity

CAS 111-82-0

An acute inhalation toxicity study was performed with methyl laurate (CAS No. 111 -82 -0) according to OECD guideline 436 (Huygevoort, 2010). Three Crl:WI (Han) rats per sex were exposed (head/nose only) to an aerosol of the test material with an actual concentration of 5.6 ± 0.5 mg/L air (nominal concentration was 7.1 mg/L) for a exposure duration of four hours. No mortality occurred. Lethargy, hunched posture and/or laboured respiration were noted among all animals at 1 hour after exposure, with hunched posture persisting until Day 2 after exposure. No clinical signs were noted during exposure. Body weight gain in males and females were within the range expected for rats of this strain and age used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals. Thus, the LC 50 after acute inhalation of methyl laurate in male and female rats was found to be greater than 5.6 mg/L air.

 

CAS 106-70-7

In a publication by the Centre of International Projects Moscow, mice were exposed by inhalation (Izmerov, 1982). The results were summarily reported. No mortalities occurred. Thus, the LC 50 of methyl hexanoate in mice was found to be greater than 14,000 mg/m³ air.

CAS 85586-21-6

Testing according to OECD GUIDELINE 403 is still ongoing. The dossier will be updated as soon as possible and the Chemical Safety Assessment according to Annex I of Regulation (EC) No 1907/2006 will be re-evaluated based on the outcome of this new study.

 

Acute dermal toxicity

Reliable studies on the acute dermal toxicity are not available for the members of the SCAE methyl esters. Testing via dermal route is not necessary as dermal uptake of the category members is negligible due to Dermwin v2.0 QSAR predictions and appropriate data for oral and inhalation route suggesting a low level of toxicity is available.

Conclusions:

In summary, several studies are available studying the acute oral toxicity of SCAE Me category members resulting in oral LD50 values greater than 2000 mg/kg bw. For acute inhalation toxicity two studies are available within the SCAE Me category. From these studies a LC50 value of > 5.6 mg/L air was determined. While reliable studies on the acute dermal toxicity are not available for the members of the SCAE methyl esters, the coherent picture of low acute oral and inhalation toxicity of SCAE Me category members paired with the estimated low level of dermal penetration suggests also low toxicity of the SCAE Me category members via the dermal route.

Thus, the available data indicate no acute toxicity for the category members and thus no hazard for acute oral, dermal and inhalative toxicity was identified.

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 representative reference substance(s) within the category to avoid unnecessary animal testing. Additionally, once the group concept is applied, substances will be classified and labeled 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.