Branched and linear octadecanoic acid, esters with glycerol oligomers

Endpoint summary

Description of key information

Oral (similar to OECD 401, RL2), mice: LD50 > 5000 mg/kg bw (limit test)

Inhalation: no study available

Dermal (according to OECD 402, RL1), rat: LD50 > 2000 mg/kg bw (limit test)

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

Study period:

6 Aug - 20 Aug 1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Remarks:

/ no information on body weights were given

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

24 Feb 1987

Deviations:

yes

Remarks:

/ no information on body weights were given

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

mouse

Strain:

CD-1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Wilmington, USA
- Fasting period before study: animals were fasted for 4 h prior to administration
- Housing: group caged (5 animals per cage, separated regarding sex) in wire mesh cages. The cages and feeders were sanitized every two weeks.
- Diet: Wayne Lab Blox, ad libitum
- Water: tap water, ad libitum (analysis was performed)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/ 12

IN-LIFE DATES: From: 6 Aug To: 20 Aug 1990

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 5.4 mL/kg bw

- Rationale for the selection of the starting dose: as requested from sponsor

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Remarks:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
observation: immediately,1 and 4 h after gavage and thereafter daily for 14 days
weighing: at day 1 and day 14
- Necropsy of survivors performed: yes

Statistics:

No statistical analysis were performed.

Preliminary study:

No preliminary study was performed.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: On Day 1 (4 h /24 h) and Day 2 and 3 decreased activity was observed in one male animal. From Day 4 to Day 14, no clinical signs were observed in any of the animals.

Gross pathology:

Necropsy revealed that one male had a small left testis. The rest of the animals showed no abnormal gross findings in the examined organs and tissues.

Interpretation of results:

other: CLP/ EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable (RL2) key study, and an adequate and reliable (RL2) supporting study with a read-across substance. The information is therefore sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

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:

experimental study

Adequacy of study:

key study

Study period:

24 February - 09 March 2016

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:

24 Feb 1987

Deviations:

yes

Remarks:

(relative humidity value (24%) outside the expected range of 30 - 70%)

GLP compliance:

yes (incl. QA statement)

Remarks:

OGYÉI National Institute of Pharmacy and Nutrition, Budapest, Hungary

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: controlled room temperature (15-25 ºC, below 70 RH%), protected from light and humidity

Species:

rat

Strain:

other: CRL:(WI) rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: young healthy adult rats
- Weight at study initiation: 214 - 252 g
- Fasting period before study: no
- Housing: individual caging in Type II polypropylene/polycarbonate cages
- Diet: Ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, Soest, Germany (Batch No.: 540 5117, expiry date: 31 July 2016), ad libitum
- Water: tap water from the municipal supply, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.9 – 24.9
- Humidity (%): 24 – 58
- Air changes (per hr): 15 - 20
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: 10
- Type of wrap if used: Sterile gauze pads were placed on the skin of rats to cover the test item. These gauze pads were kept in contact with the skin using a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap for 24 h.

REMOVAL OF TEST SUBSTANCE
- Washing: yes, with water of body temperature
- Time after start of exposure: 24 h

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 and weighing:
Clinical observations: on the day of treatment at 1 and 5 h after application of the test item and once each day for 14 days thereafter
Adverse skin reactions at the site of application: daily following the removal of the dressing
Body weights: on Day 0 (before test item administration) and on Days 7 and 14 just before necropsy
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality observed at the dose level of 2000 mg/kg bw.

Clinical signs:

other: There were no systemic clinical signs noted in any animal throughout the study. No local dermal signs were observed after treatment with the test item during the 14 days observation period.

Gross pathology:

There was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw.

Interpretation of results:

other: CLP/EU GHS criteria not met; no classification required according to Regulation (EC) No. 1272/2008

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable (RL1) study, and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Acute toxicity

Justification for read-across

There are data available regarding acute oral and dermal toxicity for Polyaldo 2-1-IS (CAS 73296-86-3). In addition, read-across from an appropriate substance is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. in order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VIII, 8.5. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

As data on acute oral toxicity is available for Polyaldo 2-1-IS (CAS 73296-86-3) in mice supportive information in rats are taken into account from the analogue substance Di(isooctadecanoic) acid, diester with oxydi(propanediol) (CAS 67938-21-0) to fulfill the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VIII, 8.5.

 

Acute oral toxicity

CAS 73296-86-3

An acute oral toxicity study (limit test) was performed with the test substance similar to OECD guideline 401 and GLP conditions (Mallory, 1990). Groups of 5 male and female fasted CD-1 mice received single oral gavage doses of 5000 mg/kg bw. The animals were observed for 14 days after administration. No mortalities occurred. On Day 1 (4 h /24 h) and Day 2 and 3 decreased activity was observed in one male animal. From Day 4 to Day 14, no clinical signs were observed in any of the animals. Necropsy revealed that one male mouse had a small left testis. The rest of the animals showed no abnormal gross findings in the examined organs and tissues. The acute oral LD50 was found to be greater than 5000 mg/kg bw.

CAS 67938-21-0

The read-across substance was tested for acute oral toxicity similarly to OECD guideline 401 (Mayer, 1980). Ten female Wistar rats received single oral gavage doses of the test substance in water at a dose level 5000 mg/kg bw. No mortalities occurred. 50 minutes after application of the test substance all rats showed crouching and hair-raising. No clinical signs of toxicity were detectable 24 h after application until the end of the observation period of 14 days. All animals showed normal body weight gain during the observation period and no abnormal gross findings in the examined organs. Thus, the acute oral LD50 for female rats was found to be greater than 5000 mg/kg bw.

 

Acute dermal toxicity

CAS 73296-86-3

An acute dermal toxicity study (limit test) was performed with the test substance according to OECD guideline 402 and GLP conditions (Weisz, 2016). 5 male and 5 female CRL:(WI) rats were exposed to 2000 mg test substance /kg bw for 24 h on the back skin under semiocclusive conditions. The observation period was 14 days. No mortality was observed. There were no systemic clinical signs noted in any animal throughout the study. Body weight gains and necropsy at study termination revealed no abnormalities. The application site did not display any signs of skin irritation. Thus, the acute dermal LD50 in rats was found to be greater than 2000 mg/kg bw.

Justification for classification or non-classification

The available data on acute oral toxicity with Reaction product of Isooctadecanoic acid, ester with oxybis[propanediol] (CAS 73296-86-3) and appropriate read-across substance Di(isooctadecanoic) acid, diester with oxydi(propanediol) (CAS 67938-21-0) do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification.

The available data on acute dermal toxicity with Reaction product of Isooctadecanoic acid, ester with oxybis[propanediol] (CAS 73296-86-3) do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification.

There is no data on acute inhalation toxicity.

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