Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Peroxan EPC S;
- Substance type: organic peroxide
- Physical state: liquid
- Analytical purity: 98.1% (Jodometrie Hauseigene Methode 04Mo111 B)
- Lot/batch No.: 1081430
- Expiration date of the lot/batch: 20 April 2012
- Storage condition of test material: -20° to -30° C, protected from light
- Other:

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels
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

Any other information on results incl. tables

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)

 

Applicant's summary and conclusion

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.