Ethyl palmitate

Endpoint summary

Description of key information

Based on the available studies performed on the source substances of the category, the LD50 was defined to be higher than 2000 mg/kg bw for the target substance, ethyl palmitate. Hence, the substance was not classified for Acute Toxicity according to CLP criteria.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute 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 report for category rationale and justification

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

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	Acute oral Toxicity
Isopropyl myristate	110-27-0	C14	Isopropanol	270,46	Liquid	Experimental result: LD50 > 2000 mg/kgbw
Isopropyl palmitate	142-91-6	C16	Isopropanol	298.51	Liquid	Experimental result: LD50 > 5000 mg/kgbw
Ethyl linoleate	544-53-4	C18:2	ethanol	308,5	Liquid	Experimental result: LD50 >2000 mg/kgbw
Ethyl oleate	111-62-6	C18:1	ethanol	310.52	Liquid	Experimental result: LD50 > 4360mg/kgbw
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	Experimental result: LD50 > 2000 mg/kgbw
Isopropyl isostearate	68171-33-5	C18iso	Isopropanol	326.56	Liquid	Experimental result: LD50 > 2000 mg/kgbw

 

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-oxydationpathway in 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 in members of the category for acute oral toxicity. For acute oral toxicity studies, results showed an LD50 value greater than 2000 mg/kgbw.

Interpretation of results:

GHS criteria not met

Conclusions:

According to the results of the key studies on the source substances of the category, the LD50 value for the ethyl palmitate was defined to be higher than 2000 mg/kg bw. Hence, the target substance was not classified according to CLP regulation.

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 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.

Several reliable studies were available (GLP, accordingly to OECD 401 guideline method). The experimental studies were performed in rodents (rat and mouse) which were treated orally (gavage) by

single dose. Lethal Dose 50 (LD50 ) values were found to be greater than 2000 mg/kg bw, or 5000 mg/ kg bw in the differents test performed.

According to the results from experimental study performed on the substances of the category, the LD50 value for the Ethyl Palmitate was defined higher than 2000 mg/kg bw. Hence, according to the CLP criteria and the category approach, the registered substance was not classified for Acute Oral Hazard.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

key studies on source substances of the category

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

See "Assessment reports" section 13 or "Categories" section for the justification and rationale document for category approach.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

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	Acute dermal Toxicity
Isopropyl myristate	110-27-0	C14	Isopropanol	270,46	Liquid	no data
Isopropyl palmitate	142-91-6	C16	Isopropanol	298.51	Liquid	no data
Ethyl linoleate	544-53-4	C18:2	ethanol	308,5	Liquid	Experimental result: LD50 > 2000 mg/kgbw
Ethyl oleate	111-62-6	C18:1	ethanol	310.52	Liquid	no data
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

 

According to the current literature, esterase enzymes were present into the skin of different mammalian species (as human, rodents orminpigs). These enzymes, as carboxylesterase, hydrolyzed different substrates as xenobiotic or different ester as fatty acids esters (C. Jewell, 2007; J.J.Prusakiewicz, 2006). Based on this principle, when applied on skin, the source and the target substances are expected to be substrates of these carboxylesterase. They are hydrolyzed into fatty acids and alcohols. In the case that the products of hydrolysis could across the dermal barrier to reach systemic system, they have the same behavior as oral ingestion. The potential toxicity should bebringby these hydrolyzed products.They are expected to be metabolized in common energetic pathways or excreted.

One dermal acute study was performed for the ethyl linoleate, according to OECD 402 method. Rats were exposed and the LD50 was defined to be higher than 2000 mg/kgbw.

 The experimental study is consistent with the experimental studies performed for skin irritation. No toxicity was observed when the substances were applied dermally. Hence, no acute dermal toxicity is expected. 

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the available experimental study performed on one source substance of the category, none of these showed adverse effect for acute dermal toxicity on rodents. Hence, no classification is required for category substances according to REACh regulation and the category approach.

Executive summary:

According to the Regulation (EC) NO. 1907/2006, Annex XI, 1.5, A read-across category for short chain fatty acid was performed in order to provide informations on 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 category substances are fatty acid esters covering chain length C8 to C18 satured or unsatured linked to alcohol including ethanol, isopropanol, octanol, hexanol and 2-ethylhexanol. These substances showed similar physico-chemical properties as very low solubility in water, not volatile, ready biodegradable and high log Kow. The substances are expected to have same toxicity behavior according to the common structural and physico-chemical similarities. Indeed, they are expected to be hydrolyzed in same way when applied dermally.

As expected, none of the acute dermal toxicity tests performed showed adverse effect. Hence, the category substances are not classified for acute dermal hazard according to CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

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 acute oral toxicity

Isopropyl Myristate CAS 110 -27 -0

Three studies were available for acute oral toxicity assessment. The key study was performed according to 401 OECD Guideline, EU Method B.1 and GLP compliance. Wistar rats were exposed orally to 2000 mg/kg bw of the susbtance. No effect was observed. Hence, the LD50 was defined to be higher than 2000 mg/kg bw.

Two additional supporting studies were performed. In one study, rats were exposed to 4300 mg/kg bw and to 5000 mg/kg bw in the second. None of the treated animals died and no adverse effect were observed.

Isopropyl palmitate CAS 142 -91 -6

The key study was performed in mice which were exposed to 5000 mg/kg bw with a method similar to OECD 401. None of the treated animals died and no adverse effect were observed. The LD50 was defined to be higher than 5000 mg/kg bw.

Isopropyl isostearate CAS 68171-33-5

The key study was performed in Sprague-Dawley rats which were exposed to 2000 mg/kg according to OECD 401 limit test method. None of the treated animals died and no adverse effect were observed. None of the two treated animals died and no adverse effect were observed. The LD50 was defined to be higher than 2000 mg/kg bw.

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

The key study was performed in Wistar rats which were exposed by gavage to 2000 mg/kg similarly to OECD 401 Guideline and GLP compliance. None of the two treated animals died and no adverse effect were observed. The LD50 was defined to be higher than 2000 mg/kg bw.

Ethyl oleate CAS 111-62 -6

The key study was performed with a method similar to the OECD TG 401 limit test method. NMRI female mice were orally treated with test item ethyl oleate at 5 mL/kg bw (equivalent to 4360 mg/kg bw calculated with a density of 0.872 g/mL for ethyl oleate). No mortality and clinicals signs occured during the study period. Hence, the LD50 was defined to be higher than 4360 mg/kg bw.

Ethyl linoleate CAS 544-35-4

One study was performed which was quoted as key study. Five Swiss female mice were treated in single administration at 2000 mg/kg bw with the ethyl linoleate according to OECD TG 401 limit test method. No mortality occured during the study period. Hence, the LD50 was defined to be higher than 2000 mg/kg bw. Another dermal acute study was conducted for the ethyl linoleate, according to OECD 402 method. Rats were exposed at 2000 mg/kg bw by dermal route. The LD50 was defined to be higher than 2000 mg/kg bw.

Based on the 9 avalaible studies on source chemicals of the category, it can be stated that the target substance Ethyl Palmitate did not induced acute oral toxicity and dermal toxitcity with a LD50 value higher than 2000 mg/kg bw.

Justification for classification or non-classification

Based on the available studies performed on the source substances of the category, the LD50 was defined to be higher than 2000 mg/kg bw for the target substance, ethyl palmitate. Hence, the substance was not classified for Acute Toxicity according to CLP criteria.