reaction mass of isomers of: C7-9-alkyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate

Endpoint summary

Description of key information

The substance caused no mortality in rats upon single oral or dermal exposure to 2000 mg/kg bw (GLP, OECD 401 and 402).

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:

From June 22, 1989 to July 17, 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed according to OECD guideline and GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

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: bred and raisedon the premises of CIBA-GEIGY Ltd (CIBA-GEIGY Ltd, Animal Production, 4332 Stein, Switzerland)
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 177-213 g
- Fasting period before study: over night
- Housing: 5 animals per cage (segregated by sex) in Macrolon cages type 4, with standardized soft wood bedding (Société Parisienne des Sciures, Pantin, France)
- Diet (e.g. ad libitum): Rat chow (NAFAG 890 Tox, NAFAG, Gossau/SG, Switerzland) ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at 5 days before administration

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12h / 12h

Route of administration:

oral: gavage

Vehicle:

other: 0.5 % (w/v) carboxymethylcellulose in 0.1 % (w/v) aqueous polysorbate 80

Doses:

2000 mg/kg bw (application volume was 10 mL/kg bw)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Mortality: daily; a.m. and p.m. on working days, a.m. on weekend days.
Signs and symptoms: daily.
Body weight: immediately before administration and on days 7 and 14.
Necropsies: The animals were sacrificed and submitted to a gross necropsy at the end of the observation period.

Statistics:

From the body weights, the group means and their standard deviations were calculated.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortalities occurred. Common clinical symptoms including piloerection, hunched posture, and dyspnea were seen; the animals recovered within 6 days. Body weight was inconspicuous, Necropsy revealed no abnormalities.

Mortality:

None.

Clinical signs:

other: Piloerection, hunched posture, and dyspnea were seen (common symptoms in acute tests). The animals recovered within 6 days.

Gross pathology:

At necropsy, no deviations from normal morphology were found.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: EU 67/548/EEC and EC/1271/2008

Conclusions:

Upon an acute oral administration and a 14 day post-treatment observation period, the following LD50 (with 95% confidence limits calculated,
where possible) was determined in rats of both sexes: greater than 2000 mg/kg body weight

Executive summary:

Sprague-Dawley rats of both sexes were treated by single gavage with 2000 mg/kg bw according to the OECD TG 401 (1987); treatment was followed by a 14 day post-treatment observation; at the end of this period the animals were sacrificed for the purpose of necropsy. No mortalities occurred. Common clinical symptoms including piloerection, hunched posture, and dyspnea were seen; the animals recovered within 6 days. Body weight was inconspicuous, Necropsy revealed no abnormalities. The LD50 for both sexes was > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

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:

From June 6, 1989 to August 1, 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed according to OECD guideline and GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

(1987)

Deviations:

no

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: bred and raised on the premises (CIBA-GEIGY Ltd, Animal Production, 4332 Stein, Switzerland)
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 215 to 249 g
- Housing: individually housed in Macrolon cages type 3 with standardized soft wood bedding (Société Parisienne des Sciures, Pantin, France)
- Diet: Rat chow (NAFAG 890 Tox, NAFAG, Gossau/SG, Switzerland) ad libitum
- Water: water ad libitum
- Acclimation period: at least 5 days before exposure

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/ -2°C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12h / 12h

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Approximately 24 hours before treatment an area on the back of the rat of at least 10% of the body surface was shaved with an electric clipper.
The required amount of the test substance was evenly dispersed on the skin (single application at 2000 mg/kg bw). It was covered with a gauze-lined semiocclusive dressing fastened around the trunk with an adhesive elastic bandage.
After an exposure period of 24 hours the dressing was removed and the skin was cleaned with lukewarm water. Thereafter the skin reaction was appraised repeatedly.

Duration of exposure:

Single exposure, 24 hours.

Doses:

2000 mg/kg bw.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Mortality: daily; a.m. and p.m. on working days, a.m. on weekend days
Signs and symptoms: daily
Body weight: immediately before application and on days 7 and 14
Necropsies: The animals were sacrificed and submitted to a gross necropsy at the end of the observation period.

Statistics:

From the body weights, the group means and their standard deviations were calculated.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortalities occurred. Common clinical symptoms including piloerection, hunched posture, and dyspnea were seen; the animals recovered within 5 to 7 days. Body weight was inconspicuous, Necropsy revealed no abnormalities

Mortality:

None.

Clinical signs:

other: Piloerection, abnormal body positions, and dyspnea were seen (common symptoms in acute tests). The animals recovered within 5 to 7 days.

Gross pathology:

At autopsy, no deviations from normal morphology were found.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: EU 67/548/EEC and EC/1271/2008

Conclusions:

Upon an acute dermal administration and a 14 day post-treatment observation period, the following LD50 (with 95% confidence limits calculated, where possible) was determined for both sexes: greater than 2000 mg/kg body weight.

Executive summary:

Sprague-Dawley rats of both sexes were treated by single dermal application of 2000 mg/kg bw under semiocclusive conditions according to the OECD TG 402 (1987); treatment was followed by a 14 day post-treatment observation; at the end of this period the animals were sacrificed for the purpose of necropsy. No mortalities occurred. Common clinical symptoms including piloerection, hunched posture, and dyspnea were seen; the animals recovered within 5 to 7 days. Body weight was inconspicuous, Necropsy revealed no abnormalities. The LD50 for both sexes was > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute oral toxicity

Acute oral toxicity was tested by gavage application of 2000 mg/kg bw to rats (Ciba-Geigy, 1989). No mortalities occurred. Common clinical symptoms including piloerection, hunched posture, and dyspnea were seen; the animals recovered within 6 days. Body weight was inconspicuous, Necropsy revealed no abnormalities. The study was performed under GLP and according to OECD testing guideline 401.

Acute dermal toxicity

Acute dermal toxicity was tested by semi-occlusive application of 2000 mg/kg bw to rats (Ciba-Geigy, 1989). No mortalities occurred. Common clinical symptoms including piloerection, hunched posture, and dyspnea were seen; the animals recovered within 5 to 7 days. Body weight was inconspicuous, Necropsy revealed no abnormalities. The study was performed under GLP and according to OECD testing guideline 402.

The substance is a viscous, non volalite liquid. Therefore, inhalation testing was not performed.

Justification for selection of acute toxicity – oral endpoint
Study performed according to OECD guideline and GLP

Justification for selection of acute toxicity – dermal endpoint
Study performed according to OECD guideline and GLP

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for acute oral or dermal toxicity under Directive 67/548/EEC.

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute oral or dermal toxicity under Regulation (EC) No. 1272/2008.