Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
05 January 2016 -- 10 February 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Compliant to GLP and testing guidelines; adequate consistence between data, comments and conclusions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Butyl 4,4-bis(tert-butyldioxy)valerate
EC Number:
213-626-6
EC Name:
Butyl 4,4-bis(tert-butyldioxy)valerate
Cas Number:
995-33-5
Molecular formula:
C17H34O6
IUPAC Name:
butyl 4,4-bis(tert-butylperoxy)pentanoate
Test material form:
other: Colorless to yellow liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: breeder: Janvier, Le Genest-Saint-Isle, France.
- Age/Weight: on the day of treatment, the females were approximately 8 weeks old and had a mean body weight of 216 g (range: 196 g to 226 g).
- Fasting period before study: yes, during the night before treatment
- Housing: polycarbonate cages
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: 19 January 2016 to 10 February 2016

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL

- Maximum dose-volume applied: 10 mL/kg

DOSAGE PREPARATION (if unusual): fresh dose formulations were prepared by the CiToxLAB France Pharmacy on the day of each administration and kept at room temperature prior to administration.

CLASS METHOD (if applicable):
- Rationale for the selection of the starting dose: 2000 mg/kg based on available toxicity data before initiation of the study.
Doses:
2000 mg/kg
No. of animals per sex per dose:
six nulliparous and non-pregnant female rats per treatment step
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight: just before treatment on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD0
Effect level:
> 2 000 other: mg/kg
Based on:
test mat.
Mortality:
No unscheduled deaths occurred during the study.
Clinical signs:
At 2000 mg/kg, hunched posture together with dyspnea were observed on Day 1, 1 to 3 hours and 4 hours after treatment in 1/6 females. Hunched posture persisted from Day 2 to Day 6. No clinical signs were noted in the other 5/6 females treated at the same dose-level.

Body weight:
No relevant differences from CiToxLAB France historical control data were noted in the body weight and body weight change of test item-treated animals over the study period.
Gross pathology:
There were no macroscopic findings related to treatment with LUPEROX® 230 in the study.

One unilateral renal cyst was noted in one female treated at 2000 mg/kg (group 2).
It was considered to be incidental and not related to treatment, as it is a common background finding for the species.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
Under the experimental conditions of this study, the oral LD0 of the test item was higher than 2000 mg/kg in rats.
Executive summary:

The potential acute toxicity of Luperox 230 was evaluated following a single oral administration (gavage) to rats. This study was conducted in compliance with the OECD guideline No. 423 and the principles of Good Laboratory Practice. The test item was administered once by oral route (gavage) to two groups of three fasted female Sprague-Dawley rats under a dosage-volume of 10 mL/kg. The test item was prepared in corn oil.

Based on available test item toxicity data, the starting dose-level of 2000 mg/kg was chosen. After the first assay, as no toxicity was observed, the results were confirmed in other females. Each animal was observed at least once a day for mortality and clinical signs for 15 days. Body weight was recorded on Day 1 and then on Days 8 and 15. On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination. Macroscopic lesions preserved in 10% buffered formalin were destroyed at the finalization of the study report.

No unscheduled deaths occurred during the study. At 2000 mg/kg, hunched posture together with dyspnea were observed on Day 1, 1 to 3 hours and 4 hours after treatment in 1/6 females. Hunched posture persisted from Day 2 to Day 6 in this animal. No clinical signs were noted in the other 5/6 females treated at the same dose-level. No relevant differences from CiToxLAB France historical control data were noted in the body weight and body weight change of test item-treated animals over the study period. There were no macroscopic findings related to treatment withLUPEROX 230 in the study.

Under the experimental conditions of this study, the oral LD0 of Luperox 230 was higher than 2000 mg/kg in rats.