Registration Dossier

Administrative data

Description of key information

Acute toxicity has been tested in an oral toxicity study according to OECD 423 and a dermal toxicity study comparable to OECD 402, at doses of 2000 mg/kg bw. 

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:
2012-04-02 to 2012-04-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: 8 - 11 weeks old
- Weight at study initiation: Step 1 / animals no. 1-3: 140-152 g; Step 2 / animals no. 4-6: 162-178 g;
- Fasting period before study: Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted).
- Housing: The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 110811)
- Diet (e.g. ad libitum): Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 0815)
- Water (e.g. ad libitum): Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: Adequate acclimatisation period (at least five days) under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): 10 x / hour
- Photoperiod (hrs dark / hrs light): Artificial light, sequence being 12 hours light, 12 hours dark

Route of administration:
oral: gavage
Vehicle:
corn oil
Remarks:
Sigma, lot no. MKBF8603V, expiry date: 05/2012; suggested by the sponsor
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 g/mL
- For all animals of both steps, 2 g of the test item were dissolved in the vehicle to gain a final volume of 10 mL and to achieve a dose of 2000 mg/kg body weight at a dose volume of 10 mL/kg body weight.
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: corn oil was suggested as vehicle by the sponsor.
- Lot/batch no. (if required): MKBF8603V
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual): The test item was weighed out into a tared plastic vial on a precision balance. The dose formulations were made shortly before each dosing occasion at room temperature and were stored on ice until administration.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The starting dose was selected to be 2000 mg/kg body weight. No compound-related mortality was recorded for any animal of step 1 or 2. Based on these results and according to the acute toxic class method regime no further testing was required.
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
3 female rats per step resulting; 2 steps -> 6 animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs were examined several times on day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights; all gross pathological changes were recorded and in case of findings the tissues were preserved for a possible histopathological evaluation.
Statistics:
no data
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None of the animals died.
Clinical signs:
Reduced spontaneous activity, kyphosis, piloerection and half eyelid-closure. The clinical signs were observed within 4 hours after the administration. Signs of toxicity were fully reversible within 24 hours.
Body weight:
Throughout the 14-day observation period, the weight gain of the animals was within the normal range of variation for this strain.
Gross pathology:
At necropsy, no macroscopic findings were observed in any animal of any step.
Other findings:
no other findings

The starting dose was selected to be 2000 mg/kg body weight. No compound-related mortality was recorded for any animal of step 1 or 2. Based on these results and according to the acute toxic class method regime no further testing was required.

Table 1: Clinical Signs - Individual Data

Animal No. / Sex

Time of Observation

Observations

Step 1 (2000 mg/kg Body Weight)

1 / female,

2 / female,

3 / female

 

30 min post-dose

kyphosis, slight piloerection

1 h post-dose

slightly reduced spontaneous activity, kyphosis, slight piloerection, half eyelid-closure

2 h post-dose

slightly reduced spontaneous activity, kyphosis, moderate piloerection, half eyelid-closure

3 h post-dose

moderately reduced spontaneous activity, kyphosis, moderate piloerection, half eyelid-closure

4 h post-dose

slightly reduced spontaneous activity, moderate piloerection, half eyelid-closure

d 2 until the end of the observation period

no signs of toxicity

d = day (day 1 = day of administration); h = hour(s); min = minute(s)

Table 2: Clinical Signs - Individual Data

Animal No. / Sex

Time of Observation

Observations

Step 2 (2000 mg/kg Body Weight)

4 / female,

5 / female,

6 / female

 

30 min post-dose

kyphosis

1 h post-dose

slightly reduced spontaneous activity, slight piloerection, half eyelid-closure

2 h post-dose

slightly reduced spontaneous activity, kyphosis, slight piloerection, half eyelid-closure

3 h post-dose

slightly reduced spontaneous activity, moderate piloerection, half eyelid-closure

4 h post-dose

slightly reduced spontaneous activity, moderate piloerection, half eyelid-closure

d 2 until the end of the observation period

no signs of toxicity

d = day (day 1 = day of administration); h = hour(s); min = minute(s)

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 of Peroxan EPC S in the rat was determined to be > 2000 mg/kg bw and =< 5000 mg/kg bw.
Executive summary:

In an acute oral toxicity study according to OECD guideline 423 (Acute Oral Toxicity - Acute Toxic Class Method) 2 groups of fasted, female Wistar rats Crl: WI(Han) (full barrier) (3 animals per step; 2 steps) were given a single oral dose of Peroxan EPC S (Bis(2-ethylhexyl)peroxydicarbonate) (98.1%) in corn oil at a dose of 2.000 mg/kg bw and observed for14 days. A limit test was conducted. No mortality was observed.

The median lethal dose of PEROXAN EPC S after a single oral administration to female rats, observed over a period of 14 days was determined to be: LD50 cut-off (rat): > 2.000 mg/kg <=5.000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
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:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
: no analytics; 2 animals/sex/dose
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1810 to 2450 g
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Type of wrap if used: gauze bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): tepid tap water
- Time after start of exposure: 24 h
Duration of exposure:
24 h
Doses:
200 mg/kg and 2000 mg/kg
No. of animals per sex per dose:
2
Control animals:
not specified
Details on study design:
The hair was removed from the back of each rabbit with an electric clipper. The skin of one male and one female rabbit in each group was abraded with a scalpel blade.
The test material was applied only once, following which the site of application was occluded and wrapped with a gauze bandage. 24 hours later the bandages were removed and the backs washed with tepid tap water.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at the beginning of the study, 7 days and 14 days after compound application
- Necropsy of survivors performed: no

Statistics:
none
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
None
Body weight:
Each of the rabbits showed gains in body weight during the 14 day period of observation
Gross pathology:
None
Other findings:
At 24 hours following application, erythema (moderate to marked) and edema (slight to moderate) was observed in all rabbits. Additionally blanching was observed. Desquamation was noted during the 14 day observation period. Each of the rabbits showed gains in body weight during the observation period.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 is > 2000 mg/kg. Thus, the test item is not considered a toxic substance by the dermal route of administration.
Executive summary:

In an acute dermal toxicity study groups of male and female New Zealand white rabbits (2 male and 2 females) were dermal exposed in a limit test to Lupersol 223(Bis-(2 -ethylhexyl)) peroxycarbonate for 24 hours at doses of  200 and 2000  mg/kg bw.  Animals then were observed for 14 days. At 24 hours following application, erythema (moderate to marked) and edema (slight to moderate) was observed in all rabbits. Additionally blanching was observed. Desquamation was noted during the 14 day observation period. Each of the rabbits showed gains in body weight during the observation period.

The dermal LD0 is 2000 mg/kg bw. Lupersol 223 (Bis-(2 -ethylhexyl)peroxycarbonate) is not toxic by the dermal route.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw

Additional information

No mortality has been reported in an acute oral toxicity study according to OECD 423 and a dermal toxicity study comparable to OECD 402.



Justification for selection of acute toxicity – oral endpoint
No mortality was observed in an acute oral toxicity GLP study according to OECD 423 at a limit dose of 2000 mg/kg bw.

Justification for selection of acute toxicity – dermal endpoint
No mortality was observed in an acute dermal toxicity study similar to OECD 402 at a limit dose of 2000 mg/kg bw.

Justification for classification or non-classification

No mortality has been reported in an acute oral toxicity study according to OECD 423 or a dermal toxicity study comparable to OECD 402.