Fatty acids, C16-18 and C18-unsatd., Me esters, epoxidized

Endpoint summary

Description of key information

No information on acute oral toxicity is available for the substance itself. Regarding acute oral toxicity the substance is evaluated based on information on other substances of subgroup 1 of the category (CAS 97553-05-4, 8013-07-8).The LD50 > 2000 mg/kg bw.

The substance was subjected to an acute dermal toxicity test. In this study, according to EU method B.3 and OECD Guideline 402. The obtained discriminating dose-value was 2000 mg/kg bw

 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

(adopted 1981)

Deviations:

yes

Remarks:

Use of 2000 mg/kg bw as limit dose. Use of 2 animals per sex.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- in the study report the old CAS 68082-34-8 number is given
- Name of test material (as cited in study report): Edenol B35 (neu)
- Chemical name: 2-Ethylhexyl-Epoxystearate
- Physical state: liquid, light yellow
- Analytical purity: 100%
- Lot/batch No.: 273

Species:

rat

Strain:

Wistar

Remarks:

TNO

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen (district Paderborn)
- Age at study initiation: 152 g (females), 174 g (males)
- Weight at study initiation: at least 6 weeks
- Fasting period before study: 15 hours before treatment until 3 hours post-treatment
- Housing: 2 rats per Makrolon cage (type III)
- Diet: Altromin 1324 pellets, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23
- Humidity (%): 50-70
- Photoperiod: 12 hrs dark / 12 hrs light

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

2%

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg

MAXIMUM DOSE VOLUME APPLIED:
10 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations for mortality and symptoms: Several times at the day of application, twice daily afterwards.
- Frequency of weighing: Day -1 before fasting, day of application as well as 48 hours, 1 week, and 2 weeks after application.
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Directly after application: piloerection, lethargy Day 2-3: lethargy

Gross pathology:

No findings.

Table 1: Development of body weights of rats during the acute oral toxicity study.

Animal No.	Sex	Day -1	Day of application	Day 2	Day 7	Day 14
1	Male	182	173	184	203	236
2	Male	190	175	186	208	228
1	Female	155	149	157	164	166
2	Female	164	154	160	156	169

 

Interpretation of results:

GHS criteria not met

Conclusions:

No mortality occurred and no gross pathology findings were observed.

Executive summary:

In an acute oral toxicity study equivalent to OECD TG 401 (adopted 1981, no GLP), the test substance was administered by oral gavage to two Wistar rats of each sex at 2000 mg/kg bw as a limit dose. All animals were weighed prior to dosing and at termination. They were observed frequently on the day of dosing and daily for a total of 15 days. Clinical signs of toxicity, body weights as well as gross pathological findings were recorded. Directly after application piloerection and lethargy were observed as clinical signs. Lethargy was present at day 2 and 3 after administration. No animals died on account of the treatment nor did they show severe signs of toxicosis in the 14 observation period. The oral LD50 value of the test substance in Wistar rats was established as greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Comparable to guideline study with acceptable restrictions

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

In accordance with column 2 of REACH Annex VIII, testing of the acute toxicity by inhalation is not appropriate as the substance is a liquid with a low vapour pressure (0.0000013 hPa at 20 °C) and inhalation of the substance is unlikely. Therefore, testing of the dermal route is more appropriate.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-07-16 to 2012-09-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted February 24, 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

of 30 May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August 1998

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nosan No. 8147

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Bioassay Labor für biologische Analytik GmbH 69120 Heidelberg

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Name of test material: Sovermol 1055
- Substance type: organic
- Physical state: Liquid / colourless, clear
- Analytical purity: The test item is a mixture of several single compounds. The composition of the substance was verified by GC analysis
- Lot/batch No.: CE80580015
- Expiration date of the lot/batch: February 27, 2013
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions: The test item was stable under storage conditions.
- Storage condition of test material: Room temperature
- The CAS RN cited in the test report is 91051-90-0 (chemical name: Fatty acids, tallow, Me esters, epoxidized). However, after the finalization of the study, it became evident that the test material is better described by CAS RN 158318-67-3 (Fatty acids, C16-18 and C18-unsatd., Me esters, epoxidized).

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: Young adult animals (male animals approx. 8 weeks, female animals approx. 12 weeks)
- Weight at study initiation: male mean weight: 239.0 g ± 7.31 g; female mean weight: 205.6 g ± 7.16 g
- Fasting period before study:
- Housing: Makrolon cage, type III
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany)
- Water: Tap water ad libitum
- Acclimation period: Acclimatization period of at least 5 days before the beginning of the experimental phase; during the acclimatization period, the animals were accustomed to the environmental conditions of the study and to the diet.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 30 – 70%
- Air changes (per hr): Approx. 10
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: About 40 cm²
- % coverage: at least 10% of the body surface
- Type of wrap if used: The test item was covered with an air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing: rinsing of the application site with warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 2.20 mL/kg bw
- Concentration: undiluted
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 male and 5 female animals per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes
- Other examinations performed: Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals. A check for any dead or moribund animals was made atleast once each workday. Necropsy with gross-pathology examination on the last day of the observation period after sacrifice with CO2 in a chamber with increasing concentrations over time.

Statistics:

Calculations were performed using Microsoft Excel 2003 and checked with a calculator.

Key result

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No systemic clinical signs were observed during clinical examination. In four male animals very slight erythema (grade 1), noted on study day 1, increased to well-defined erythema (grade 2) on study day 2 in all animals and persisted in one animal until s

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and guideline compliant study.

Additional information

No acute oral toxicity studies are available for the substance itself. The acute oral toxicity is derived from available studies on other substances of the subgroup of the EFAE category. The summaries of these studies are provided below.

Data on acute dermal toxicity is available for the test substance itself.

 

Acute toxicity, oral (CAS# 97553-05-4):

In an acute oral toxicity study equivalent to OECD TG 401 (adopted 1981, no GLP), the test substance was administered by oral gavage to two Wistar rats of each sex at 2000 mg/kg bw as a limit dose. All animals were weighed prior to dosing and at termination. They were observed frequently on the day of dosing and daily for a total of 15 days. All gross and visible toxic or pharmacological effects were recorded. Directly after application piloerection and lethargy were observed as clinical signs. Lethargy was present at day 2 and 3 after administration. No animals died on account of the treatment nor did they show severe signs of toxicosis in the 14 observation period. The oral LD50 value of the test substance in Wistar rats was established as greater than 2000 mg/kg bw (Henkel 1983).

 

Acute toxicity, oral (CAS# 8013-07-8):

The acute oral LD50 of the test item in rats of both sexes observed over a period of 14 days is greater than 5000 mg/kg. The test material is therefore practically non toxic to the rat by this route of administration. According to Directive 67/548/EEC, no classification is warranted. According to Regulation (EC) No. 1272/2008, no classification is warranted.

 

Acute toxicity, dermal

In an acute dermal toxicity study according to OECD 402, the test substance was administered (single 24-hour dermal application) to five CRL (WI) BR Wistar rats of each sex at 2000 mg/kg bw. All animals were weighed prior to dosing and at termination. They were observed frequently on the day of dosing and daily for a total of 14 days. None of these animals died. Clinical signs or dermal symptoms were not observed during the 14 days post-treatment observation period. No effects on mean body weight and body weight gain were noted. Specific macroscopic alterations related to the toxic effect of the test substance were not found. The dermal discriminating dose value of the test substance in Wistar rats was estimated to be 2000 mg/kg bw (Bioassay 2012).

Justification for classification or non-classification

Based on the LD50 >2000 mg/kg bw in both the oral and dermal acute toxicity studies, classification and labelling is not warranted in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. (EC) 1272/2008.