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Description of key information

In an acute oral toxicity study the LD50 in rats was determined to be > 5000 mg/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:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: valid with restrictions; meets generally accepted scientific standards, well documented and acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
- body weight was not determined; 10 animals were used per sex
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: from the Institutes colony
- Age at study initiation: young adults
- Weight at study initiation: males 243-300 g, females 135-192 g
- Fasting period before study: before dosing the animals were fasted overnight
- Housing: groups of five
- Diet (e.g. ad libitum): after dosing ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25°C
Route of administration:
oral: gavage
Vehicle:
other: Shellsol T
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50% (w/v)
- Amount of vehicle (if gavage): 10 ml per kg body weight which is equivalent to 5 g test material per kg body weight

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: preliminary observations; LD50 of Shellsol T was stated about 8 ml/kg; no higher dose of the suspension was considered to be tolerated
Doses:
10 ml per kg body weight of a 50% (w/v) suspension of bis(4-tert-butylcyclohexyl)peroxydicarbonate in Shellsol T
No. of animals per sex per dose:
10 males and 10 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, macroscopic examination
Statistics:
no statistics
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
One male and five females died between 6 hours and 3 days after dosing
Clinical signs:
Within a few hours after treatment all rats showed tremors. Convulsions were frequently observed.
Body weight:
No data
Gross pathology:
No treatment related gross alterations were examined
Other findings:
Three days after dosing the survivors recovered gradually
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
From the mortality figures (30% mortality) it can be concluded that the LD50 of bis(4-tert-butylcyclohexyl)peroxydicarbonate is higher than 5 g per kg body weight. Therefore the material can be classified as practically non-toxic.
Executive summary:

In an acute oral toxicity study similar the the OECD guideline 420 groups of 10 female and 10 male rats (Wistar) (young adults; females 135-192 g; males 243-300 g) were given a single oral dose of bis(4-tert-butylcyclohexyl)peroxydicarbonate) (50% (w/v) in Shellsol T) at doses of 10 ml/kg bw which corresponds to 5 g/kg bw bis(4-tert-butylcyclohexyl)peroxydicarbonate. Animals were then observed for 14 days. Within a few hours after treatment all rats showed tremors. Convulsions were frequently observed. One male and five females died between 6 hours and 3 days after dosing. Three days after dosing the survivors recovered gradually. A LD50 > 5 g per kg body weight was established. Bis(4-tert-butylcyclohexyl)peroxydicarbonate is therefore practically non-toxic. This acute oral study is classified as acceptable. It does satisfy the guideline requirement for an acute oral in the rat.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

An acute oral toxicity limit dose study in rats is available. Within a few hours after treatment all rats showed tremor. Convulsions were frequently observed. One male (1/10) and five females (5/10) died between 6 hours and 3 days after dosing. Three days after dosing the survivors recovered gradually. An LD50 > 5 g/kg bw was established. Di(4-tert-butylcyclohexyl)peroxydicarbonate is therefore practically non-toxic with respect to acute systemic effects.

Acute dermal toxicity was not assessed in an animal test. 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 on all of these organic peroxides (except hydroperoxides) show no toxic effects upon dermal administration up to the limit dose of 2000 mg/kg bw.

Therefore, a weight of evidence approach is scientifically justified for chemically comparable organic peroxides. It can be concluded that a dermal LD50 > 2000 mg/kg bw applies also to di(4-tert-butylcyclohexyl) peroxydicarbonate. Additional testing for such organic peroxides is therefore not required and would be in conflict with animal welfare principles.

Inhalation exposure is considered to be negligible as the vapour pressure of di(4-tert-butylcyclohexyl) peroxydicarbonate is very low (< 0.01 Pa at 20 °C, see IUCLID-section 4.6). The median particle size is 96 µm (10 % smaller than 32 µm), thus the amount of inhalable particulate mass is low and the thoracic and respirable fraction is negligible. Additional testing is therefore not required and would be in conflict with animal welfare considerations.


Justification for selection of acute toxicity – oral endpoint
Comparable to guideline study with acceptable restrictions (key study).

Justification for classification or non-classification

According to Regulation (EC) No 1272/2008 an LD50 of > 5000 mg/kg is not considered to indicate acute toxicity.