Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 days
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The report satisfies the GLP regulations and specific test guidelines in general, except that the concentration/purity of the test substance could not be directly verified from the Certificate of Analysis.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
EU B.1 ofAnnex V was also followed
Deviations:
yes
Remarks:
1. Test substance characterization and stability data, while available, were not developed in accordance with GLP. Report stated that stability was not expected to impact the study results.
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Trigonox 44B
- Physical state: Clear colorless liquid
- Analytical purity: no information
- Impurities (identity and concentrations): no info
- Composition of test material, percentage of components: The test material, Trigonox 44B, was identified by the Batch No. 0419207045262, CAS Nos 37187-22-7, 123-42-2, and 111-46-6 and the EINECS Nos. 2533849, 2046267, and 2038722. It was stated to be 33% Acetylacetone Peroxide in solvent (Diethylene glycol, water and diacetone alcohol. The Certificate of Analysis contains only the batch number of the test substance. The identity, strength and purity of the test material, and the stability under sstorage conditions were said to be the responsibility of the Sponsor. No expiration date could be found in the Certificate of Analysis.
- Lot/batch No.: Batch No. 0419207045262
- Storage condition of test material: Refrigetrator (approximately 4 degrees Celcius) in the original container
- Other: received from the sponsor, Akzo (Chemical Division); No analyses were undertaken to access the stability, homogeneity or achieved concentration of the test material in the vehicle.

Test animals

Species:
rat
Strain:
other: CD strain (remote Sprague-Dawley origin) from Charles River (UK) Limited, Kent, England.
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Margate, Kent, England
- Age at study initiation: Five weeks old
- Weight at study initiation: males, 122 - 133 g; females, 114 - 138 g on the day prior to initiation.
- Fasting period before study: 17 hours before dosing
- Housing: Five animals of the same sex per stainless steel grid cage
- Diet (e.g. ad libitum): commercially-available, pelleted rodent diet was available ad libitum.
- Water (e.g. ad libitum): Free access to tap water
- Acclimation period: Atleast five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21°C
- Humidity (%): 38 -57%
- Air changes (per hr): 15
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From 14 October, 1992 to 5 Nov, 1992

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Test formulation was prepared at the appropriate concentration in purified water shortly before administration. Oral gavage was carried out with a flexible rubber catheter allowing instillation of the dose into the lumen of the stomach into overnight fasted rats. Food was made available three hours after dosing. On the basis of the preliminary results, the main study was done.
Doses:
One dose, 2000 mg/kg [the maximum practical dose]
No. of animals per sex per dose:
Preliminary Study: one male and one female rat given a single oral dose of 800 mg/kg at a constant dose-volume of 20mL/kg.

Main study: five rats of each sex per dose at a constant dose-volume of 20mL/kg.
Control animals:
no
Details on study design:
Animals were observed daily (five inspections on Day 1; twice per day from Day 2 onwards). Body weights were recorded on the day before dosing and on Days 1,8 and 15. All animals were necropsied on Day 15.
Statistics:
None

Results and discussion

Preliminary study:
No death noticed.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One male rat died three hours after dosing on Day 1 in the main study.
Clinical signs:
Ante mortem signs of the animal that died comprised lethargy, staggering gait, prone position, bradypnoea, hyperpnoea, piloerection, and salivation.

Signs of reaction to treatment in the surviving animals comprised of underactivity, staggering gait, piloerection, salivation, and hunched posture. The surviving animals were overly normal on the third day after treatment.
Body weight:
The surviving animals achieved expected bodyweight gain.
Gross pathology:
Necropsy of the decedent animal (male) revealed pale muzzule staining. Necropsy of the surviving animals, on Day 15, revealed no significant macroscopic lesion.

Applicant's summary and conclusion

Interpretation of results:
sligthly toxic
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Under the conditions of this study, the oral median lethal dosage (LD50) of the test material was greater than 2000 mg/kg.
Executive summary:

Acute oral toxicity of Trigonox 44B was investigated in a fourteen-day study in five male and female CD rats after a single oral gavage dose of 2000 mg/kg. One male rat showed treatment-related clinical signs and died three hours after dosing, but the rest of the animals survived till the end of the study. Surviving animals were overtly normal on the third day after treatment, but none of the surviving animals showed an effect of Trigonox 44B on body weight gain or macroscopic lesions at necropsy. Under the conditions of this study, the oral median lethal dosage (LD50) of the test material was greater than 2000 mg/kg.