Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
406-040-9
EC Name:
-
Cas Number:
125643-61-0
Molecular formula:
C24-26 H40-44 O3
IUPAC Name:
2-ethylheptyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propanoate bis(2-ethylhexyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propanoate) 2-ethylpentyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propanoate 3-methylhexyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propanoate 4-methyloctyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propanoate 6-methylheptyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propanoate
Details on test material:
Physical properties: yellow liquid, insoluble in water
Storage conditions: room temperature
Validity: May 1992
Test material received: May 18, 1989

Test animals

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

Administration / exposure

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.

Results and discussion

Effect levels
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:
Piloerection, hunched posture, and dyspnea were seen (common symptoms in acute tests). The animals recovered within 6 days.
Body weight:
No effects.
Gross pathology:
At necropsy, no deviations from normal morphology were found.

Applicant's summary and conclusion

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.