Registration Dossier

Using the read-across appraoch, according to the Annex XI item 1.5, of Regulation (EC) No 1907/2006, all available acute oral toxicity studies within the category resulted in an acute oral LD50 values higher than 2000 mg/kg bw for oral administration and dermal application, and LC50 was defined to be higher than 5 mg/L for inhalation. Hence, according to CLP criteria and REACh regualtion, the target substance ethyl decanoate is not classified for acute hazard and STOT-SE.

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 "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 of the key studies performed on the source substances of the category

Common name	CAS	Fatty acids chain length	Type of alcohol	MW	Appareance	Acute oral Toxicity
Ethyl decanoate	110-38-3	C10	ethanol	200.32	Liquid	No data
Ethyl undecylenate	692-86-4	C11	ethanol	212.33	liquid	No data
Isopropyl laurate	10233-13-3	C12	Isopropanol	242,41	Liquid	Experimental result: LD50 > 5000 mg/kgbw
Octyl octanoate	2306-88-9	C8	octanol(C8)	256,42	Liquid	Experimental result: LD50 > 5000 mg/kgbw
Isopropyl myristate	110-27-0	C14	Isopropanol	270,46	Liquid	Experimental result: LD50 > 2000 mg/kg bw
Dodecanoic hexyl ester	34316-64-8	C12	Hexanol(C6)	284,49	Liquid	Experimental result: LD50 > 4300 mg/kg bw
Ethyl linoleate	544-35-4	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
2-ethylhexyl laurate	20292-08-4	C12	2 -ethylhexanol	312,53	Liquid	Experimental result: LD50 > 2000 mg/kgbw
Fatty acids, coco, 2-ethylhexyl esters	92044-87-6	C12-14	2-ethylhexanol	312.53 – 340.60	liquid	Experimental result: LD50 > 2000 mg/kgbw

All the category substance are fatty acid esters. After oral ingestion, it is expected that substances are hydrolyzed by pancreatic lipases. The degradation products are free fatty acids and free alcohol which could be distributed in organism through systemic circulation. They are expected to be metabolized in common energetic pathways or excreted.

All the substances were evaluated for potential acute oral toxicity (expect the target substance and ethyl undecylenate). These experimental studies were performed according to or equivalent to OECD TG 401. Rats or mice were used as model. The LD50 oral were determined as higher than 2000 mg/kg bw to 5000 mg/kg bw.

These experimental studies are consistent with the low toxicity expected for these substances.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the available experimental studies performed on the source substances of the category, none of these showed adverse effect for acute oral 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 decanoate CAS 110-38-3.

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 metabolized or excreted in same way when orally administered in organism.

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

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Reference

Endpoint:

acute toxicity: inhalation

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:

LC50

Effect level:

> 5 mg/L air

Based on:

test mat.

Exp. duration:

4 h

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

Common name	CAS	Fatty acids chain length	Type of alcohol	MW	Appareance	Acute inhalation Toxicity
Ethyl decanoate	110-38-3	C10	ethanol	200.32	Liquid	No data
Ethyl undecylenate	692-86-4	C11	ethanol	212.33	liquid	Experimental result : LC50 > 5,7 mg/L
Isopropyl laurate	10233-13-3	C12	Isopropanol	242,41	Liquid	Experimental result: LC50 > 5 mg/L
Octyl octanoate	2306-88-9	C8	octanol(C8)	256,42	Liquid	no data
Isopropyl myristate	110-27-0	C14	Isopropanol	270,46	Liquid	no data
Dodecanoic hexylester	34316-64-8	C12	Hexanol(C6)	284,49	Liquid	no data
Ethyl linoleate	544-35-4	C18:2	ethanol	308,5	Liquid	no data
Ethyl oleate	111-62-6	C18:1	ethanol	310.52	Liquid	no data
2-ethylhexyl laurate	20292-08-4	C12	2-Ethyl-Hexanol	312,53	Liquid	no data
Fatty acids, coco, 2-ethylhexyl esters	92044-87-6	C12-14	2-ethylhexanol	312.53 – 340.60	liquid	No data

All the category substance are fatty acid esters. After inhalation, it is expected that substances are hydrolyzed by lipases. Substances that are absorbed through the pulmonary alveolar membrane could enter the systemic circulation directly before joining the liver where hydrolysis basically takes place. They are expected to be metabolized in common energetic pathways or excreted.

Ethyl undecylenate and isopropyl myristate were evaluated for acute inhalation toxicity. The studies were performed, respectively, according to OECD TG 403 (limit test) and 436 methods (acute toxic class method – limit test). Rats were exposed for 4 hours in nose-only. The LD50 were defined to be higher than 5 mg/L.

These experimental studies are consistent with the low toxicity expected for these substances.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the available experimental studies performed on the source substances of the category, none of these showed adverse effect for acute inhalation 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 decanoate CAS 110-38-3.

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 metabolized or excreted in same way when inhaled.

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

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 000 mg/m³

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 of the key studies performed on the source substances of the category

Common name	CAS	Fatty acids chain length	Type of alcohol	MW	Appareance	Acute dermal Toxicity
Ethyl decanoate	110-38-3	C10	ethanol	200.32	Liquid	No data
Ethyl undecylenate	692-86-4	C11	ethanol	212.33	liquid	No data
Isopropyl laurate	10233-13-3	C12	Isopropanol	242,41	Liquid	no data
Octyl octanoate	2306-88-9	C8	octanol (C8)	256,42	Liquid	no data
Isopropyl myristate	110-27-0	C14	Isopropanol	270,46	Liquid	no data
Dodecanoic hexyl ester	34316-64-8	C12	Hexanol (C6)	284,49	Liquid	no data
Ethyl linoleate	544-35-4	C18:2	ethanol	308,5	Liquid	Experimental result: LD50 > 2000 mg/kg bw
Ethyl oleate	111-62-6	C18:1	ethanol	310.52	Liquid	no data
2-ethylhexyl laurate	20292-08-4	C12	2-Ethyl-Hexanol	312,53	Liquid	no data
Fatty acids, coco, 2-ethylhexyl esters	92044-87-6	C12-14	2-ethylhexanol	312.53 – 340.60	liquid	No data

All the category substances are fatty acid esters. After dermal exposure, it is expected that substances are hydrolyzed by lipases. Substances that are absorbed through the skin could enter the systemic circulation directly before joining the liver where hydrolysis basically takes place. They are expected to be metabolized in common energetic pathways or excreted.

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

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 decanoate CAS 110-38-3.

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:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

This category groups covers esters (including ethanol, isopropanol, octanol, hexanol and 2-ethylhexanol) linked to fatty acids chain satured and unsatured (C8 to C18). This category includes monoconstituent substances and UVCB substances varying fatty acid chain length and based on the alcohol sources. This category group was made in order to provide sufficient information for physico-chemical, environmental, ecotoxicological and toxicological caracterisation of ethyl decanoate (CAS 110-38-3). This approach covers these endpoints including skin irritation, eye irritation, and in vitro gene mutation study in bacteria for which data on the target substance of the category are available.

This category includes:

- Target substance:

o Ethyl decanoate (CAS 110-38-3)

- Source substances:

o Ethyl undecylenate (CAS 692-86-4)

o Isopropyl laurate (CAS 10233-13-3)

o Octyl octanoate (CAS 2306-88-9)

o Isopropyl myristate (CAS 110-27-0)

o Dodecanoic hexyl ester (CAS 34316-64-8)

o Ethyl linoleate (CAS 544-35-4)

o Ethyl oleate (CAS 111-62-6)

o 2-Ethylhexyl laurate (CAS 20292-08-4)

o Fatty acids, coco, 2-ethylhexyl esters (CAS 92044-87-6)

Summary of available studies for acute oral toxicity

Isopropyl laurate CAS 10233 -13 -3

One study is available. The study was performed with a method equivalent to OECD TG 401 limit test method. NMRI mice were exposed in single administration to 5000 mg/kg bw of test substance. After 6 days of observations, no adverse effect was releved. Hence, the LD50 was defined to be higher than 5000 mg/kg bw.

Octyl octanoate CAS 2306 -88 -9

One study is available. The study was performed with a method equivalent to OECD TG 401. Wistar male rats were exposed in single administration to 1000 and 5000 mg/kg bw of test substance. After 14 days of observations, no adverse effect was releved. Hence, the LD50 was defined to be higher than 5000 mg/kg bw.

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.

Dodecanoic hexyl ester CAS 34316 -64 -8

One study is available. The study was performed with a method equivalent to OECD TG 401 limit test method. Male NMRI mice were exposed in single administration to 5 mL/kg bw of test substance (equivalent to 4360 mg/kg bw). After observation period, no adverse effect was releved. 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 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.

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.

2 -ethylhexyl laurate CAS 20292 -08 -4

One study is available for assessment/ The experimental study was peformed with a method similar to OECD TG 401 limit test method. Female Swiss mice were exposed in single administration to 2000 mg/kg bw. After 14 days of observation period, no adverse effect related to the test substance was observed. Hence, the LD50 was defined to be higher than 2000 mg.kg bw.

Fatty acids, coco, 2 -ethylhexyl esters CAS 92044 -87 -6

Two experimental studies were performed. The key study was performed according to OECD TG 401 method. Wistar rats were treated in single administration to 560, 1400, 1800, 3200 and 5600. No adverse effect was obersed until the end of observation period of 14 days. Hence the oral LD50 was defined to be higher than 5000 mg/kg bw.

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

Summary of available studies for acute inhalation toxicity

Ethyl undecylenate CAS 692 -86 -4

Ethyl undecylenate was evaluated for acute inhalation toxicity. The study was performed, according to OECD TG 403 (limit test). Rats were exposed to the test substance by inhalation at 5.7 mg/L for 4 hours in nose-only. No adverse effect was observed up to the end of observation period. The LC50 were defined to be higher than 5.7 mg/L.

Isopropyl myristate CAS 110 -27 -0

Isopropyl myristate was evaluated for acute inhalation toxicity. The study was performed, according to OECD TG 436 (limit test). Rats were exposed to the test substance by inhalation at 5 mg/L for 4 hours in nose-only. No adverse effect was observed up to the end of observation period. The LC50 were defined to be higher than 5 mg/L.

Summary of available study for acute dermal toxicity

Ethyl linoleate CAS 544 -35 -4

One dermal acute study was performed for 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.

None of the tested substances showed adverse effect at the high dose tested. Hence, the target substance is expected to have same acute toxicity behavior according to the category approach.

Using the read-across appraoch, according to the Annex XI item 1.5, of Regulation (EC) No 1907/2006, all available acute oral toxicity studies within the category resulted in an acute oral LD50 values higher than 2000 mg/kg bw for oral administration and dermal application, and LC50 was defined to be higher than 5 mg/L for inhalation. Hence, according to CLP criteria and REACh regualtion, the target substance ethyl decanoate is not classified for acute hazard and STOT-SE.