Fatty acids, C16-18 and C18-unsatd., Et esters

Endpoint summary

Description of key information

Acute toxicity: Oral LD50 (rat, m/f): > 4360 mg/kg bw (OECD 401, analogue approach)
Acute toxicity: Dermal LD50 (rat, m/f): > 2000 mg/kg bw (OECD 402, analogue approach)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

; only female animals tested; lack of details on test substance and methodological details

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

mouse

Strain:

NMRI

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Weight at study initiation: 20 g

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg bw

Doses:

5 mL/kg bw equivalent to 4360 mg/kg bw calculated with a density of 0.872 g/mL for ethyl oleate

No. of animals per sex per dose:

5

Control animals:

no

Sex:

female

Dose descriptor:

LD50

Effect level:

> 4 360 mg/kg bw

Based on:

test mat.

Remarks on result:

other: converted from 5 mL/kg bw based on a density of 0.872 g/mL

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: No clinical signs occurred during the study period.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent trends in the toxicological profile (refer to endpoint discussion for further details).

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

16 Jun - 30 Jun 2010

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP guideline study, tested with the source substance CAS 544-35-4. According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (Dec 2012)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Wistar, Crl:WI (Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: approx. 10 weeks old
- Mean Bodyweight at study initiation: Males: 294 g, Females: 205 g. Body weight variation did not exceed +/- 20% of the sex mean.
- Housing: individually in Makrolon cages (MIII type, height 18 cm), containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet: pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany), ad libitum.
- Water: tap water, ad libitum.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0 (actual range: 19.9 - 21.5)
- Humidity (%): 40-70 (actual range: 39 - 75)
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back skin, clipped one day before exposure
- % coverage: approx. 10% of the total body surface (are of approx. 25 cm² for males and 18 cm² for females)
- Type of wrap if used: The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch, successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing: dressings were removed and the skin cleaned of residual test substance using tap water

TEST MATERIAL
- Amount(s) applied: 2000 mg/kg (2.27 mL/kg) body weight. Dose volume calculated as dose level (g/kg) /density (g/mL).
In order to obtain homogeneity, the test substance (formulations) were heated in a water bath with a maximum temperature of 39.5 ºC for a maximum of approximately 10 minutes.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Mortality/Viability: Twice daily;
Body weights Days 1 (pre-administration), 8 and 15;
Clinical signs at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes, at the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Chromodacryorrhoea was shown by two animals on Day 1. Other clinical signs were not noted in any of the animals. The application site did not display any signs of skin irritation.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent trends in the toxicological profile (refer to endpoint discussion for further details).

Additional information

Justification for grouping of substances and read-across

There are no data available for the acute toxicity of Fatty acids, C16-18 and C18-unsatd., ethyl esters (CAS 85049-36-1). In order to fulfil the standard information requirements set out in Annex IX, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, a read-across from structurally related substances was conducted.

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, 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).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

Overview of acute toxicity

CAS #	Acute oral	Acute inhalation	Acute dermal
85049-36-1 Target substance	RA: 544-35-4 RA: 111-62-6	waiving	RA: 544-35-4
111-62-6	LD50 > 4360 mg/kg bw	--	--
544-35-4	LD50 > 2000 mg/kg bw	--	LD50 > 2000 mg/kg bw

The above mentioned substance is considered to be similar on the basis of structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the same endpoints for Fatty acids, C16-18 and C18-unsatd., ethyl esters (CAS 85049-36-1).

A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Acute oral toxicity:

CAS 111 -62 -6

An acute oral toxicity study (limit test) with ethyl oleate (CAS No. 111 -62 -6) similar to OECD Guideline 401 was performed (Masson, 1986). A group of 5 female NMRI EOPS mice received single oral doses of 5 mL/kg bw (equivalent to 4360 mg/kg bw calculated with a density of 0.872 g/mL for ethyl oleate). No mortalities were observed during the study period. No signs of clinical toxicity were reported. All animals showed the expected gain in bodyweight. The acute oral LD50 in mice was found to be greater than 5 mL/kg bw (equivalent to 4360 mg/kg bw calculated with a density of 0.872 g/mL).

CAS 544 -35 -4

Ethyl linoleate (CAS 544 -35 -4) was tested for acute oral toxicity similarly to OECD guideline 401 (Bouffechoux, 1995). Five male and female Swiss mice received single oral gavage doses of the test substance at a dose level of 2000 mg/kg bw. No mortality, abnormal clinical signs occurred within the observation period. Thus, the acute oral LD50 was found to be greater than 2000 mg/kg bw in mice.

Acute dermal toxicity:

CAS 544-35-4

An acute dermal toxicity (limit test) was performed on ethyl linoleate (CAS 544-35-4) according to OECD Guideline 402 (Otterdijk, 2010). 5 male and female Wistar rats were exposed to 2000 mg test substance /kg bodyweight for 24 hours on the back skin under occlusive conditions. The observation period was 14 days. Besides chromodacryorrhoea shown by two animals on Day 1, no other clinical signs of systemic toxicity were noted in any animal. Body weight gain and necropsy at study termination revealed no abnormalities. Thus, the acute dermal LD50 in rats for ethyl linoleate was found to be greater than 2000 mg/kg bw.

Conclusion:

Two studies from structural analogue substances are available investigating the acute oral toxicity of ethyl oleate (CAS 111-62-6) and ethyl linoleate (CAS 544-35-4) resulting in oral LD50 values greater than 2000 mg/kg bw. Acute dermal toxicity data from ethyl linoleate (CAS 544-35-4) showed no effects at the limit dose of 2000 mg/kg bw. Fatty acids, C16-18 and C18-unsatd., ethyl esters is a liquid with calculated vapour pressures below 0.00383 Pa at 20 °C. Therefore, exposure via the inhalation route can be considered negligible. Thus, the available data indicate no hazard for acute toxicity for Fatty acids, C16-18 and C18-unsatd., ethyl esters and thus no hazard for acute oral, inhalative and dermal toxicity was identified.

Justification for selection of acute toxicity – oral endpoint
Hazard assessment is conducted by means of read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – dermal endpoint
Hazard assessment is conducted by means of read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

Based on read-across from structurally similar substances, the available data on oral and dermal 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.