Castor oil, ester with glycerol

Endpoint summary

Description of key information

Oral (OECD 401), mouse: LD50 > 2000 mg/kg bw

In the absence of data on acute dermal toxicity of Castor oil, ester with glycerol an analogue read-across approach was conducted on CAS 555 -43 -1:

Dermal (OECD 402), rat: LD50 > 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

Remarks:

no information on purity of test substance given; 10 animals per group; no males tested

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

24 Feb 1987

Deviations:

yes

Remarks:

10 animals per group; no males tested

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

mouse

Strain:

other: Tyler' s Original Strain

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Bantin and Kingman Ltd., Bull, Yorks, England
- Females nulliparous and non-pregnant: not specified
- Weight at study initiation: 20 ± 4 g
- Fasting period before study: overnight prior to dosing
- Housing: in solid-floor polycarbonate cages
- Diet: Standard Laboratory Diet (41B from E. Dixon and Sons (Ware) Ltd., Berts, England), ad libitum
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 25 mL/kg bw

Doses:

12.5, 20.0 and 25.0 mL/kg bw (corresponding to 12 326, 19 722 and 24 653 mg/kg bw, respectively, based on a relative density of 0.9861 g/cm³)

No. of animals per sex per dose:

10 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed immediately after dosing and thereafter daily for 14 days. Body weight was monitored throughout the period of study.
- Necropsy of survivors performed: no

Preliminary study:

A preliminary range-finding study was conducted in order to determine the order of acute oral toxicity with respect to lethal effect.
The test substance was administered undiluted by gavage at dose levels of 5, 10, 20 and 25 mL/kg bw to groups of 2 animals each. Animals were observed immediately after dosing and then for a period of 7 days. Any signs of toxicity were recorded. No mortality occured at any dose level, therefore a final maximum dose of 25.0 mL/kg bw and two additional dose levels of 12.5 and 20 mL/kg bw were selected for the main study.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 25 mL/kg bw

Based on:

test mat.

Remarks on result:

other: (corresponding to 24 653 mg/kg bw based on a relative density of 0.9861 g/cm³)

Mortality:

One death was observed within 24 hours of dosing in the 20 mL/kg dose level group. 2 further deaths occurred between Days 3 and 7, both in the 25.0 mL/kg dose level group.

Clinical signs:

Piloerection was observed within 30 min after dosing, and a general loss of activity was apparent for 2 h, persistent for up to 24 h. All survivors appeared asymptomatic after Day 7.

Body weight:

Animals showed a loss in weight prior to death. Other mice also exhibited weight loss particularly at Day 7.

Interpretation of results:

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

Conclusions:

In this acute oral toxicity study in mice a LD50 value of > 25.0 mL/kg bw (corresponding to 24 653 mg/kg bw based on a relative density of 0.9861 g/cm³) was found.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study, and is thus 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:

28 Jul - 26 Sep 2003

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

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

GLP compliance:

yes (incl. QA statement)

Remarks:

The Swiss GLP Monitoring Authorities, Bern, Switzerland

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: HanBrl: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, Füllinsdorf, Switzerland
- Age at study initiation: 8 weeks (males), 12 weeks (females)
- Weight at study initiation: 230.6 - 263.1 (males) and 195.7 - 204.4 (females)
- Housing: During acclimatisation animals were housed in groups of five per sex in Makrolon IV cages with standard softwood bedding. Animals were housed individually in Makrolon III cages with standard softwood bedding (Lignocel, Schill AG, Muttenz, Switzerland) during treatment and observation.
- Diet: pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 4/03 (Provimi Kliba AG, Kaiseraugust, Switzerland), ad libitum
- Water: community tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
- Other: music during the light period

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: clipped skin on the back of the animals
- % coverage: 10
- Type of wrap if used: The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: The skin was flushed with lukewarm tap water and dried with disposable paper towels.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 mL/kg bw

VEHICLE
- Lot/batch no.: 37255780

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: Animals were observed daily during acclimatisation and twice daily during Days 1-15.
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical signs were observed daily during acclimatisation and at approximately 1, 2, 3 and 5 h after administration on test Day 1. Afterwards, animals were observed once daily during Days 2-15. Body weights were examined on test Day 1 (prior to administration) and on Days 8 and 15.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

No clinical signs of toxicity were observed up to the end of the 14-day observation period.

Body weight:

Body weight gains were within the normal ranges in males and females during the whole study period.

Gross pathology:

No macroscopic findings were observed at necropsy.

Interpretation of results:

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate, reliable (Klimisch score 2) and consistent study from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to endpoint discussion for further details). The selected study is sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Justification for read-across

There is one study on the acute oral toxicity of Castor oil, ester with glycerol available. The assessment of acute oral and dermal toxicity was additionally based on studies conducted with source substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. 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).

 

Acute Toxicity

Oral

CAS 68459-67-6 (target substance)

The acute oral toxicity of Castor oil, ester with glycerol was assessed in a study similar to OECD Guideline 401 (Key, 1977). Based on a preliminary study total doses of 12.5, 20.0 and 25.0 mL/kg bw (corresponding to 12326, 19722 and 24653 mg/kg bw, respectively, based on a density of 0.9861 g/cm³) were administered to 10 female mice, respectively. Animals were observed for mortality and general clinical conditions immediately after administration and once daily thereafter for 14 days. Body weights were recorded throughout the study period. One animal at 20 mL/kg bw died within 24 h after dosing and two further animals at 25.0 mL/kg bw died between Days 3 and 7, after a loss in weight was observed. Piloerection occurred within 30 min after dosing and a general loss of activity was observed 2 h after dosing persisting up to 24 h. Based on the results of this study, the oral LD50 value was determined to be > 25.0 mL/kg bw (corresponding to 24653 mg/kg bw based on a density of 0.9861 g/cm³) in female mice.

CAS 111-03-5 (source substance)

The acute oral toxicity of 2,3-dihydroxypropyl oleate was studied in female Sprague-Dawley rats at a limit dose of 2000 mg/kg bw according to the acute toxic class method (OECD guideline 423) and under the requirements of GLP (2005). In two sequential steps, 3 animals each received formulations of test substance in corn oil via gavage. During the study period, no animal died and no clinical signs were observed. The body weights and gain were not affected by treatment and necropsy revealed no substance-related findings at study termination. Therefore, the oral LD50 value for female Sprague-Dawley rats is > 2000 mg/kg bw.

 

Dermal

CAS 736150-63-3 (source substance)

The acute dermal toxicity of Glycerides, castor-oil-mono, hydrogenated, acetates was tested in accordance with OECD guideline 402 and in compliance with GLP (Key, 2003). In this study, 5 male and 5 female rats were exposed to a limit dose of 2000 mg/kg bw for 24 h under semiocclusive conditions. The test substance was dissolved in corn oil and applied to the clipped skin at a dose volume of 4 mL/kg bw. No mortality and no clinical signs of toxicity were observed up to the end of the 14-day observation period. Body weight gain was not affected by treatment with the test substance in male and female animals. No macroscopic findings were observed at necropsy. Thus, a dermal LD50 greater than 2000 mg/kg bw was derived for male and female rats.

CAS 555-43-1 (source substance)

The acute dermal toxicity of glycerol tristearate was investigated in a limit test performed according to OECD guideline 402 and under GLP conditions (1998). 2000 mg/kg bw test substance dissolved in corn oil was applied to the shaved skin of 5 Wistar rats/sex for 24 h under semiocclusive conditions. After exposure, residual test substance was removed and animals were observed for a period of 14 days. No mortality occurred and no clinical signs were reported. Four female rats showed minimal body weight gain after the first week. One female had a body weight loss (-3.2%) after the first week. At the end of the study, minimal body weight gain was recorded in two female animals and one animal showed no body weight gain. Two female rats achieved satisfactory body weight gains throughout the study. The observed variation in body weight was limited to less than 10% and not considered to be treatment-related. The body weight gain during the study period of the male animals was within the normal range for this species and strain. No local skin effects were observed at the test site. At necropsy, no substance-related findings were noted. Therefore, the LD50 in male and female rats is > 2000 mg/kg bw.

 

Overall conclusion for acute toxicity

The reliable data available for the target and source substances indicate a very low level of acute toxicity following the oral and dermal route, as LD50 values were greater than the currently applied limit values. Therefore, as the available data did not identify any hazard for acute toxicity, Castor oil, ester with glycerol is not expected to be hazardous following acute exposure.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that "substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Castor oil, ester with glycerol, data will be generated from data available for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

The available data on acute toxicity via oral and dermal route do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.