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Description of key information

Acute Oral Toxicity: A group of Sprague-Dawley rats (5 males and 5 females, each) received a single oral dose of tert. amylperoxy-2- ethylhexylcarbonate at 5000 mg/kg body weight. No mortalities occurred and, with exception of occasional diarrhoea in the beginning of the study, no signs of systemic toxicity were observed during the 14-day observation period. Weekly group mean body weight gain was normal. There was no evident sex related effect. Macroscopic examination of all animals at the end of the study revealed no test substance related gross abnormalities. Since no mortalities occurred, the LD50 value for males and females combined was estimated to exceed 5.0 g/kg body weight.

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:
14 Days (Main Study)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: A GLP study done according to OECD guideline 401. Has supporting documentation
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
1. the relative humidity was on 4 occasions for periods between 8 and 16 hours below 30%. 2.Due to an infection with a virus at the animal breeder, the main study was performed with Sprague-Dawley rats instead of the protocolled Wistar rats.
Principles of method if other than guideline:
A prelimiary study was conducted using only one male and one female per dose level at 1800, 2400, 3200, 4200 and 5000 mg/kg body weight. No mortality was observed. therefore the main study was a limit dose study at 5000mg/kg.
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Ten young adult rats of the Sprague-Dawley strain (SPF-qual ity, randomly bred) were obtained from Iffa-Credo, Brussels, Belgium. The body weights
of the males on day 0 ranged from 264 to 285 9 and those of the females from 188 to 205 g. Date of arrival at the animal house: October 30, 1985.
The quarantine period was 7 days. Six days prior to dosing the animals were individually housed in Macrolon cages (acclimation period). The bedding material, purified sawdust (Woody Clean), was received from The Broekman Institute, Someren, The Netherlands. The animals had free access to tap-water and standard laboratory animal diet (RMH-B, pellet diameter 10 mm), which was obtained from Hope Farms, Woerden, The Netherlands. The animal room temperature was maintained at 20-25°C and the relative humidity at 25-70 percent. The artificial light sequence was 12 hours light, 12 hours dark. Feed was withheld overnight before dosing till approximately 4 hours after administration of the test substance.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test substance was removed from storage and was immediately dosed as such as a single dose using a stomach cannula. The dose volume was 5.405 ml/kg body weight.
Doses:
Range Finding: 1800, 2400, 3200, 4200 and 5000 mg/kg body weight
Main Study: 5000 mg/kg body weight
No. of animals per sex per dose:
Range Finding: 1 male; 1 female
Main Study: 5 male; 5 female
Control animals:
no
Details on study design:
4.2.1 Dose selection
Based on the absence of toxicity in the dose range finding investigation only one group of animals, comprising 5 males and 5 females, was dosed with a single oral dose of the test substance at 5000 mg/kg body weight.
4.2.2 CIinical observations.
No mortalities occurred and no signs of systemic toxicity were observed during the 14-day observation period with exception of four animals which occasionally showed diarrhoea on days 0 through 2. Weekly group mean body weight ga in was normal. There was no evident sex reIated effect.
4.2.3 Pathology report
Macroscopic examination of animals at the end of the study revealed no test substance related gross abnormalities. Enlarged cervical Iymph node,
observed in one animal, was considered incidental and not test substance related.
4.2.4 Calculation of the LD50 value
Since no mortalities occurred, the LD50 value for males and females combined was estimated to exceed 5.0 g/kg body weight.
Statistics:
none
Preliminary study:
Range Finding: 1800, 2400, 3200, 4200 and 5000 mg/kg body weight
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
none
Gross pathology:
none
Other findings:
No mortalities occurred and no evident
signs of systemic toxicity were observed during the 13-day observation period with exception of the male of the 3200 mg/kg group which showed
slight diarrhoea on days 0 and 1, and the male of the 4200 mg/kg group which was slightly apathetic on day 1. Macroscopic examination of all
animals at autopsy revealed no gross abnormalities with exception of the male of the 5000 mg/kg group which showed a slightly increased blood
circulation of the stomach wall.
Interpretation of results:
Category 1 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Since no mortal ities occurred, the LD50 value for males and females combined was estimated to exceed 5.0 g/kg body weight.
Executive summary:

One group of Sprague-Dawley rats, each comprising 5 males and 5 females, received a single oral dose of tert. amylperoxy-2- ethylhexylcarbonate at 5000 mg/kg body weight. No mortalities occurred and, with exception of occasional diarrhoea in the beginning of the study, no signs of systemic toxicity were observed during the 14-day observation period. Weekly group mean body weight gain was normal. There was no evident sex related effect. Macroscopic examination of all animals at the end of the study revealed no test substance related gross abnormalities. Since no mortalities occurred, the LD50 value for males and females combined was estimated to exceed 5.0 g/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw
Quality of whole database:
An apparently well-conducted study based on OECD 401 and rated reliable without restrictions.

Acute toxicity: via inhalation route

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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
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

Acute inhalation toxicity: Due to its low vapor pressure, exposure to the test substance through inhalation is not expected.

Acute dermal toxicity study is not available. Due to the physicochemical characteristics of the test material (e.g., low water solubility) and the non-irritanting nature (to the skin) of the test material, dermal exposure is not expected. In an apprently well conducted acute oral toxicity study, the the test substance did not show toxicity and the data resulted in non-classification of the test material.

Justification for selection of acute toxicity – oral endpoint

A well-conducted, recent GLP oral study based on OECD 423.

Justification for selection of acute toxicity – inhalation endpoint

Due to its low vapor pressure ( 10 Pa at 50 degrees C), exposure to the test material by inhalation is not expected.

Justification for selection of acute toxicity – dermal endpoint

Numerous organic peroxides have been tested in acute dermal toxicity tests (41 organic peroxides covering all chemical subgroups/families of organic peroxides, excluding hydroperoxides). Experimental data of all of these organic peroxides, (except hydroperoxides), show no toxic effects at dermal application up to the tested concentration limit of 2000 mg/kg bw and show for this reason an acute dermal toxicity of >2000 mg/kg bw.

Therefore, a weight of evidence approach is scientifically applicable for chemically comparable organic peroxides and allows one to conclude also a dermal LD50 > 2000 mg/kg bw for the untested organic peroxide.  Additional testing for such organic peroxides is therefore not required and would not be in line with animal welfare legislation

Justification for classification or non-classification

The acute oral toxicity study data are conclusive but not sufficient for classification.