Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 March 2003 - 04 April 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study is performed according to OECD guidelines and GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Identity: 1,1,3,3-Tetramethylbutyl peroxy-2-ethylhexanoate
CAS Number: 22288-43-3

Test animals

Species:
rat
Strain:
other: Crl:CD®(SD)IGS BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, a USDA-approved supplier located in Raleigh, North Carolina.
- Age at study initiation: young
- Weight at study initiation: 200 to 300 g
- Fasting period before study: The animals were fasted overnight (17 to 20 hours before test material administration) and for approximately 4 hours after dosing and overnight prior to sacrifice on Day 16.
- Housing: The animals were pair or individually housed at receipt. After randomization, the animals were individually housed in sanitary, stainless-steel, hanging, wire cages.
- Diet (e.g. ad libitum): ad libitum, Certified Rodent Diet #5002 (PMI® Feeds, Inc)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26
- Humidity (%): 50 ± 20
- Air changes (per hr): 10 or > 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 11 March 2003 - 04 April 2003

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
The vehicle for test article administration was com oil (Welch, Holme, & Clarke; Lot No. 12-406; CAS No. 8001-30-7). The vehicle was stored under refrigerated conditions (>0 to 10C).

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual): The dose formulation was prepared surrounded with wet ice to minimize decomposition and to assure temperatures below 25°C. The test article was added to corn oil and mixed until in suspension. The dose formulation was stirred in a wet ice bath while dosing to control the temperature. The temperature while dosing was approximately 13 to 15°C. Dose calculations were adjusted for a purity of 90.54%. Individual doses were calculated based on each animal's fasted body weight taken just before test article administration and a dose volume of 10 mL/kg.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no data
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for general health and mortality at least once daily during acclimation and twice daily (at least 4 hours apart) for the duration ofthe study. Observations were performed for clinical signs oftoxicity and mortality predose on the day of dosing (Day I) and at approximately I, 2.5 and 4 hours postdose. Daily observations were performed thereafter for until the day prior to sacrifice. The animals were weighed predose on the day of dosing (Day I; fasted), on Days 8 and 15, and at termination (fasted; Day 16).
- Necropsy of survivors performed: yes
Statistics:
Other than the calculation ofthe LD50 and the descriptive statistics ofthe body weights (when applicable), no statistical analyses were required.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortalities
Mortality:
All males and females survived until the scheduled sacrifice.
Clinical signs:
Clinical signs included yellow staining in the anal/genital area in all females and one male on Day 2 and in one female on Day 3.
Body weight:
All surviving animals gained weight from initiation of dosing to study termination.
Gross pathology:
were no abnormal findings noted in any ofthe animals at necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50>2000 mg/kg bw, no mortalities.
Executive summary:

The toxicity ofthe test article, 1,1,3,3-Tetramethylbutyl peroxy-2-ethylhexanoate, was evaluated following a single oral dose to the rat based on the OECD Guidelines for Testing of Chemicals, No. 423 ("Acute Oral Toxicity - Acute Toxic Class Method;" adopted 17 December 2001).

The test article was suspended in com oil and administered by oral gavage at dose level of 2000 mg/kg body weight to a total of six healthy, male and female rats (three animals/sex).

The animals were observed for general health and mortality at least once daily during acclimation and twice daily (at least 4 hours apart) for the duration of the study. Observations were performed for clinical signs of toxicity and mortality predose on the day of dosing (Day 1) and at approximately 1 hour, 2.5 hours and 4 hours postdose. Daily observations were performed thereafter for 16 days. The animals were weighed

predose on the day of dosing (Day 1; fasted), on Days 8 and 15. After 15 days of observation, all surviving animals were food fasted overnight, weighed (Day 16), and anesthetized with an appropriate barbiturate. All animals were subjected to an abbreviated gross necropsy examination of the external features of the carcass, external body orifices, the abdominal, thoracic, and cranial cavities, and organs/tissues. Clinical signs for the animals were limited to yellow staining in the anal genital area in three females and one male. All animals gained weight from initiation of dosing to study termination.

At necropsy, there were no abnormal findings noted in any ofthe animals.

Under the conditions of this study, the oral LD50 ofthe test article appears to be greater than 2000 mg/kg.