Reaction mass of (Z)-3-(9-octadecenyloxy)propane-1,2-diol and alpha-(Z)-octadec-9-en-1-yl-omega-hydroxy-di[oxy[(hydroxymethyl)-1,2-ethanediyl]] and alpha-(Z)-octadec-9-en-1-yl-omega-hydroxy-tri[oxy[(hydroxymethyl)-1,2-ethanediyl]]

Endpoint summary

Description of key information

Acute oral  and dermal toxicity studies (limit test) with CHIMEXANE NB were conducted in Sprague-Dawley rats following OECD guidelines 401 and 402. Under the conditions used in these studies, oral and dermal LD50 of the test substance were higher than 2000 mg/kg bw for males and females.

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:

10-24 July 1997

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP study following OECD guideline 401 with minor deviations: environmental conditions not reported

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

environmental conditions not reported

Principles of method if other than guideline:

Not applicable

GLP compliance:

no

Remarks:

COFRAC accredidation on technical ability

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: IFFA-CREDO (L'Arbresle, France)
- Age at study initiation: About 6 weeks
- Weight at study initiation: Male: 184-209 g; female: 174-187 g
- Fasting period before study: Overnight
- Housing: Housed in groups of five by sex in polypropylene cages
- Diet (e.g. ad libitum): Complete pelleted rat maintenance diet UAR A04-10 (Epinay Sur Orge, France)
- Acclimation period: At least 5 days

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 400 mg/mL
- Amount of vehicle (if gavage): 5 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs: Animals were observed frequently during the 5 h following administration of the test item; subsequently once daily up to 14 days.
Body weight was recorded on Days 1 (just before administration), 4, 8 and 15.
- Necropsy of survivors performed: Yes, all surviving animals were sacrificed by barbituric anaesthesia on Day 15 and then autopsied.

Statistics:

None

Preliminary study:

Not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

No clinical signs were observed.

Body weight:

All animals showed expected gain in bodyweight over the study period.

Gross pathology:

No macroscopic abnormalities were observed at necropsy.

Other findings:

None

None

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 for CHIMEXANE NB - Batch M 824 is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Annex VI of the Directive 67/548/EEC and the CLP Regulation (EC) N° (1272-2008).

Executive summary:

In an acute oral toxicity (limit test) study performed in accordance with OECD guideline 401, groups (5/sex) of Sprague-Dawley OFA rats were given a single oral dose of CHIMEXANE NB - Batch M 824 in distilled water at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all macroscopically necropsied after sacrifice.

 

No deaths were observed and animals appeared normal throughout the study period. All animals showed expected gain in bodyweight over the study period. No abnormalities were noted at necropsy. The combined oral LD50 was considered to be greater than 2000 mg/kg bw.

 

The oral LD50 for CHIMEXANE NB - Batch M 824 is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Annex VI of the Directive 67/548/EEC and the CLP Regulation (EC) N° (1272-2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

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:

experimental study

Adequacy of study:

key study

Study period:

09 March - 11 May 2006

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in compliance with OECD guideline 402 with deviations: temperature and relative humidity recorded in the animal room were sometimes outside of the target ranges

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

temperature and relative humidity recorded in the animal room were sometimes outside of the target ranges

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: Approximately 8 weeks old
- Weight at study initiation: Males: 326 ± 6 g; females: 212 ± 4 g
- Housing: Housed individually in polycarbonate cages
- Diet: SsniffR/M-H pelleted diet (SSNIFF Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: Drinking water filtered by a FG Millipore membrane (0.22 µm), ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 30-70 %
- Air changes: Approximately 12 cycles/h of filtered, non-recycled air
- Photoperiod: 12 h dark / 12 h light

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal area, approximately 5 cm x 7 cm for males and 5 cm x 6 cm for females
- % coverage: Approximately 10 % of the total body surface area
- Undiluted test item was placed on a hydrophilic gauze pad and then applied on the clipped skin. The test item and the gauze pad were held in contact with the skin for 24 h by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- No residual test item was observed on removal of the dressing.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.06 mL/kg
- Constant volume or concentration used: Yes

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

- Sighting test: 1/sex
- Main test: 4/sex

Control animals:

other: historical control data

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs and mortality: Animals were observed frequently during the hours following administration of the test item, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day until Day 15. From Day 2, any local cutaneous reaction was recorded.
Bodyweight was recorded on Days 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: Yes; all animals were killed by carbon dioxide asphyxiation on Day 15 and all animals were subjected to a macroscopic examination.

Statistics:

None

Preliminary study:

Not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

No clinical signs were observed.

Body weight:

- When compared to historical control animals, a slightly reduced body weight gain was seen in 3/5 males and 4/5 females between Days 8 and 15.
- Overall body weight gain of the other animals was similar to that of historical control animals.

Gross pathology:

- No macroscopic abnormalities were observed at necropsy.

Other findings:

Skin reactions:
- An erythema was noted in all animals from Day 2. It persisted up to Day 6 in 1/5 males, up to Day 7 in 1/5 females, up to Day 8 in 3/5 males, up to Day 10 in 1/5 males and up to Day 12 in 4/5 females.
- An edema was observed in all animals from Day 2. It persisted up to Day 5 in 4/5 males and 4/5 females and up to Day 7 in 1/5 males and 1/5 females.
- A dryness of the skin was noted on Day 6 in 4/5 males and 4/5 females and on Day 8 in 1/5 males and 1/5 females. It persisted up to Day 12 in 2/5 males and 1/5 females and up to Day 14 in 3/5 males and 4/5 females.
- Crusts were noted on Day 6 in 4/5 males and 4/5 females and on Day 8 in 1/5 males and 1/5 females. They persisted up to Day 8 in 2/5 males, Day 10 in 1/5 males, Day 12 in 1/5 males and 2/5 females and Day 15 (end of the observation period) in 1/5 males and 2/5 females.

None

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, CHIMEXANE NB should not be classified according to the criteria of the Annex VI of the Directive 67/548/EEC and the CLP Regulation (EC) N° (1272-2008).

Executive summary:

CHIMEXANE NB was tested for acute dermal toxicity in Sprague-Dawley [Rj: SD (IOPS Han)] rats in a limit dose assay according to OECD guideline 402 and in compliance with GLP. Groups of rats (5/sex) were administered a single dermal dose of undiluted test material at 2000 mg/kg bw on clipped skin (approximately 10 % of the total body surface area) using a semi-occlusive patch held in place for 24 h. Examinations for mortality, clinical signs, body weight gain and dermal reactions were performed during a 14-day observation period. All surviving animals were necropsied at the end of the observation period.

No deaths and clinical signs occurred during the observation period. When compared to historical control animals, a slightly reduced body weight gain was seen in 3/5 males and 4/5 females between Days 8 and 15. Overall body weight gain of the other animals was similar to that of historical control animals. At necropsy, macroscopic examination of main organs showed no abnormalities. The acute dermal combined LD50 was greater than 2000 mg/kg bw.

An erythema was noted in all animals from Day 2. It persisted up to Day 6 in 1/5 males, up to Day 7 in 1/5 females, up to Day 8 in 3/5 males, up to Day 10 in 1/5 males and up to Day 12 in 4/5 females. An edema was observed in all animals from Day 2. It persisted up to Day 5 in 4/5 males and 4/5 females and up to Day 7 in 1/5 males and 1/5 females. A dryness of the skin was noted on Day 6 in 4/5 males and 4/5 females and on Day 8 in 1/5 males and 1/5 females. It persisted up to Day 12 in 2/5 males and 1/5 females and up to Day 14 in 3/5 males and 4/5 females. Crusts were noted on Day 6 in 4/5 males and 4/5 females and on Day 8 in 1/5 males and 1/5 females. They persisted up to Day 8 in 2/5 males, Day 10 in 1/5 males, Day 12 in 1/5 males and 2/5 females and Day 15 (end of the observation period) in 1/5 males and 2/5 females.

Under the test conditions, CHIMEXANE NB should not be classified according to the criteria of the Annex VI of the Directive 67/548/EEC and the CLP Regulation (EC) N° (1272-2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute oral toxicity study (limit test) with CHIMEXANE NB was conducted in rats according to OECD guideline 401. No mortality and no clinical signs related to treatment were observed, therefore LD50 was higher than 2000 mg/kg bw.

Acute dermal toxicity study with CHIMEXANE NB as a limit test was conducted in rats according to OECD guideline 402. The test substance was applied to the skin by topical application for 24 h, under semi-occlusive conditions, at 2000 mg/kg bw, with a volume of 2.06 mL/kg bw. No systemic toxic effects were observed. Dermal LD50 > 2000 mg/kg for males and females.

Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for selection of acute toxicity – inhalation endpoint
Acute toxicity already assessed via two different routes of exposure. Two acute toxicity studies were provided by oral and dermal routes showing no acute effects.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

Under the test conditions used in the above studies, and according to the criteria of Annex VI of the directive 67/548/EEC and CLP regulation (EC) n° 1272/2008, CHIMEXANE NB should not be classified for oral and dermal acute toxicity.