Ethyl palmitate

Endpoint summary

Description of key information

Based on the available studies for repeated toxicity assessment and according to the category approach, the NOAEL for the target substance was defined to be higher than 1000 mg/kg bw/day. No adverse effect or mortality was observed in the studies. Hence, according to the CLP criteria, the ethyl palmitate was not classified for STOT-RE.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Justification for type of information:

See attached document in section 0 Category or section 13 Assessment report for justification and rationale of the category approach.

Key result

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: overall observations

Critical effects observed:

no

Table 1: Results from key studies performed on the source substances of the category

Common name	CAS	Fatty acid chain length	Type of alcohol	MW	Appareance	Repeated dose toxicity
Isopropyl myristate	110-27-0	C14	Isopropanol	270,46	Liquid	Experimental result: NOAEL (m,f): 1000 mg/kg bw/day
Isopropyl palmitate	142-91-6	C16	Isopropanol	298.51	Liquid	no data
Ethyl linoleate	544-53-4	C18:2	ethanol	308,5	Liquid	no data
Ethyl oleate	111-62-6	C18:1	ethanol	310.52	Liquid	Experimental result: NOAEL (m,f): 5500 mg/kg bw/day
Fatty acids, C16-18, butyl esters	85408-76-0	C16-18	Butanol	312.53 – 340.58	Paste	no data
Fatty acids, C16-18 and C18-unsatured, isobutyl esters	84988-79-4	C16-18, C18:1	Isobutanol	312.53 – 340.58	Liquid	no data
Isopropyl isostearate	68171-33-5	C18iso	Isopropanol	326.56	Liquid	no data

 

 

All category members are subject to enzymatic hydrolysis by pancreatic lipases resulting in free acids and alcohol. Based on current literature, when absorbed from intestines and carried through blood stream, fatty acids are oxidized by beta-oxydation pathwayin order to provide energy for cell and stored as glycerides esters in fat deposit. The alcohols are primarily metabolized in the liver.

Hence, it can be stated that the members of the category have the same toxicity due to the same metabolic pathways when absorbed in the organisms.

 

Several studies were performed on source substances of the category:

-Isopropyl myristate

-Ethyl oleate

 

Two studies were performed in vivo on rats according to OECD 407 guideline method for repeated short term oral exposure toxicity. None of these studies showed adverse effect or mortality. Hence the target substance ethyl palmitate was not classified for STOT-RE.

Executive summary:

According to the Regulation (EC) NO. 1907/2006, Annex XI, 1.5, A Read-Across Category was performed in order to provide informations on the Ethyl Palmitate.

This category was based on common and shared physico-chemical and structural properties as:

- common functional group,

- common precursors and the likehood of common impurities as well as common breakdown products via biological processes, which are chemically structurally similar, and

- constant pattern in the changing of the potency of the properties across the category.

The fatty acids linked with esters have a common metabolic fate in organisms as glycolytic and fatty acid pathways after first hydrolysis step which led in breakdown products. The common toxicokinetic properties and behavior are expected due to the constant pattern (esters and the fatty acid chain). The toxicological profiles between the members of the category are expected to be the same in organism.

Based on the available studies on the source substances for repeated dose toxicity assessment, none of these susbtances induced mortality or adverse effect when administered 5 days per week. According to physic-chemical similarities betsween source substances and target substance, it can be stated that the ethyl palmitate showed same toxicological profile. Hence, no classification for STOT-RE was made for the ethyl palmitate according to CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

reliability 2

System:

other: no adverse effect observed.

Organ:

not specified

Additional information

The category group covers alcohol linked with fatty acid chains unsatured and satured. This category includes monoconstituent chemicals and UVCB substances varying acid chain length (C14 to C18) and based on alcohol function type (including ethanol, butanol and isopropanol). This approach was performed in order to provide sufficient information for physicochemical, ecotoxicological and toxicological characterizations of the ethyl palmitate. Based on structural and physic-chemicals similarities, available experimental studies from source chemicals could be used for the target substance ethyl palmitate.

This category group includes:

-       Isopropyl myristate                                                 CAS 110-27-0

-       Isopropyl palmitate                                                 CAS 142-91-6

-       Ethyl linoleate                                                         CAS 544-35-4

-       Ethyl oleate                                                            CAS 111 -62-6

-       Fatty acids, C16 -18, butyl esters                          CAS 85408-76-0

-       Fatty acids, C16 -18 and C18-unsatured isobutyl esters              CAS 84988-79-4

-       Isopropyl isostearate                                                                     CAS 68171-33-5

-       Target substance : Ethyl palmitate                                                  CAS 628-97-7

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, environmental fate and ecotoxicity, 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)”. Therefore, the available experimental data were collected and evaluated according to Annex XI requirements.

Summary of the available studies for skin sensitization assessment.

Isopropyl myristate CAS 110 -27 -0

One key study was available. The method was similar to OECD 407 guideline. Wistar rats were exposed for 28 days orally, 5 days per week to test item at 0, 100, 500 and 1000 mg/kg bw/day in olive oil as vehicle. 10 animals were used per group (including vehicle control). Animals were observed daily for clinical effect and bodyweight. Clinical biochemistry and heamatology were performed. At the end of exposure period, animals were sacrified and gross necropsy was performed followed by histopathology. Organs were weighed. No adverse effect or abnormalities were observed until the end of exposure period and at necropsy analysis. The NOAEL was defined to be higher than 1000 mg.kg bw/day.

Ethyl oleate CAS 111-62-6

One key study was performed with a method equivalent to OECD TG 408 guideline method with GLP compliance. Sprague-Dawley rats were treated orally with test item in food, which is provided ad libitum during 91 days. The doses applied were 2.0, 3.9 and 6.1 g/kg bw/day (females) and 1.8, 3.6, 5.5 g/kg bw/day (males). 20 animals were used per condition. The animals were checked for clinical signs, body weight, ophtalmoscopic examinations and neurobehavioural examinations during the study. Clinical chemistry and heamatology analysis were performed at the day 30, 60 and at the sacrifice. At the end of the exposure period, the animals were euthanazied, gross pathology and histopathology analysis were performed. No adverse effect were related to treatment. Hence the NOAEL was defined at the high dose level, 5500 mg/kg bw/day.

Justification for classification or non-classification

Based on the available studies for repeated toxicity assessment and according to the category approach, the NOAEL for the target substance was defined to be higher than 1000 mg/kg bw/day. No adverse effect or mortality was observed up to the high dose level in the studies. Hence, according to the CLP criteria, the ethyl palmitate was not classified for STOT-RE.