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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010-01-26 to 2010-02-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Meets the requirements of GLP. There are no deviations from the recommended guideline.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of 2-tert-butyl-4,6-dimethylphenol and 4-tert-butyl-2,5-dimethylphenol
EC Number:
911-254-5
Molecular formula:
Not applicable - Multiconstituent substance
IUPAC Name:
Reaction mass of 2-tert-butyl-4,6-dimethylphenol and 4-tert-butyl-2,5-dimethylphenol
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Sprague Dawley rats (SPF Caw) originated from Elevage JANVIER (53940 Le Genest St Isle - France)
- Age at study initiation: 8 or 9 weeks old
- Weight at study initiation: 184 g and 232 g
- Fasting period before study: food was removed at D-1 and then redistributed 4 hours after the test item administration
- Housing: housed by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contains sawdust bedding which was changed at least 2 times a week.
- Diet: foodstuff (M20-SDS) was supplied freely. Food was removed at D-l and then redistributed 4 hours after the test item administration.
- Water (e.g. ad libitum): tap-water from public distribution system was supplied freely. Microbiological and chemical analyses of the water were carried out once every six months by the IPL, Santé, Environnement Durables - Atlantique.
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%):30 to 70%
- Air changes (per hr): approximately fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (07.00 to 19.00) and twelve hours darkness

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
Group treated with 300 mg/kg (step 1 and 2):

VEHICLE
- Concentration in vehicle: 300 mg/kg
- Amount of vehicle (if gavage): 1.79 mL

MAXIMUM DOSE VOLUME APPLIED: 2.1 mL/kg body weight

Group treated with 2000 mg/kg (step 3):

NO VEHICLE
- Concentration: 2000 mg/kg

MAXIMUM DOSE VOLUME APPLIED: 2.1 mL/kg body weight
Doses:
300 mg/kg bw and 2000 mg/kg bw
No. of animals per sex per dose:
300 mg/kg bw: 6 females
2000 mg/kg bw: 3 females
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Systematic examinations (list of symptoms, recorded as "present" or "absent" ) were carried out to identify any behavioural or toxic effects on the major physiological functions every day for 14 days or until the death of the animal.
The animals were weighed on day DO (just before administering the test item) then on D2, D7, and D14. Weight changes were calculated and recorded.
- Necropsy of survivors performed: yes, macroscopic observations were entered on individual autopsy sheets

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study at 300 mg/kg body weight.
It was noted the death of the three animals treated at 2000 mg/kg body weight, one at 29 hours 45 minutes post-dose and the two others at about 48 hours post-dose.
Clinical signs:
other: No clinical signs related to the administration of the test item were observed at the 300 mg/kg bw group. The mortalities at the 2000 mg/kg bw group were preceded by a decrease in spontaneous activity (313) and in rightiug reflex (113) and by a bradypnea
Gross pathology:
The macroscopical examination of the animals at the end of the study revealed a white thickness of the forestomach in three animals (3/6).
The macroscopical examination of the dead animals revealed a red thinning (2/3) or a red coloration (1/3) of the forestomach, associated or not with black spots on the forestomach (1/3) and a thinning of the corpus (2/3), associated or not with black spots on the corpus (1/3).

Applicant's summary and conclusion

Interpretation of results:
other: Category 4 (CLP Regulation EC no. 1272/2008)
Conclusions:
The LD50 of the test item is higher than 300 mg/kg body weight and lower than 2000 mg/kg body weight by oral route in the rat.



Executive summary:

The test item was administered to a group of 6 female Sprague Dawley rats at the single dose of 300 mg/kg body weight and to a group of 3 female Sprague Dawley rats at the single dose of 2000 mg/kg body weight. The experimental protocol was established according to the official method as defined in the O.E.C.D. guideline N° 423 and the test method B.lter of the Council regulation N°440/2008. No mortality occurred during the study at 300 mg/kg body weight. No clinical signs related to the administration of the test item were observed. The body weight evolution of the animals remained normal throughout the study. The macroscopical examination of the animals at the end of the study revealed a white thickness of the forestomach in three animals (3/6). It was noted the death of the three animals treated at 2000 mg/kg body weight, one at 29 hours 45 minutes post-dose and the two others at about 48 hours post-dose. The mortalities were preceded by a decrease in spontaneous activity (3/3) and in righting reflex (1/3) and by a bradypnea (3/3), a partial ptosis (3/3), and a staggering gait (3/3) on the first day of the study. At 24 hours post-dose, it was noted a decrease in spontaneous activity (3/3), in body temperature (1/3) and in muscle tone (3/3), an absence of Preyer's reflex (3/3) and of righting reflex (2/3), a bradypnea (3/3), a partial ptosis (2/3), mydriasis (2/3),anincreased lachrymation (3/3) and a piloerection (3/3). The macroscopical examination of the dead animals revealed a red thinning (2/3) or a red coloration (1/3) of the forestomach, associated or not with black spots on the forestomach (1/3) and a thinning of the corpus (2/3), associated or not with black spots on the corpus (1/3). In conclusion, the LD50 of the test item is higher than 300 mg/kg body weight and lower than 2000 mg/kg body weight by oral route in the rat. In accordance with the OECD guideline n°423, the LD50 cut-off of the test item may be considered as 500 mg/kg body weight by oral route in the rat.