Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2013 March 07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD guideline and according to GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Specific details on test material used for the study:
Identifier: EXP1200078
Appearance: Very dark brown (almost black) viscous liquid
Batch: E00275-350
Sample Expiration Date: end-2013
Purity:100%

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
female
Details on test animals and environmental conditions:
- Source: Charles River Laboratories, Inc., Raleigh, NC, USA.
- Age at study initiation: Young adult animals (approx. 11 weeks old).
- Weight at study initiation: Body weight values ranged from 214 g to 253 g.
- Fasting period before study: Yes, 18-20 hours prior to dosing, food was returned approximately four hours after dosing.
- Housing: Individually in clean, stainless steel, wire-mesh cages.
- Diet: Free access to pelleted rodent diet (PMI Nutrition International, LLC, Certified Rodent LabDiet® 5002).
- Water: Free access to tap water.
- Acclimation period: At least 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.4 - 21.6
- Humidity (%): 43.9 - 53.7
- Air changes (per hr): minimum 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 23 October 2012 to 09 November 2012

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: mineral oil
Details on oral exposure:
GAVAGE METHOD:
- Not specified.

Frequency:
- Single dosage, on Day 1.

VEHICLE:
- Mineral oil (manufactured by Spectrum Chemical Manufacturing Corp., Gardena, CA; Lot no. 2AB0895; expiration date 16 May 2013).

MAXIMUM DOSE VOLUME APPLIED:
- 2000 mg/kg based on a dose concentration of 400 mg/mL and dose volume of 5 mL/kg.

DOSAGE PREPARATION:
- On the day of dosing, an appropriate amount of the test substance was weighed and added to a sufficient volume of mineral oil in a storage container. The test substance formulation was stirred throughout use with a magnetic stirrer.
Doses:
2000 mg/kg body weight.

No. of animals per sex per dose:
6 (2 groups of three females in a stepwise manner).
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Rats were observed at approximately 15 minutes and 1, 2 and 4 hours post-dosing on study day 0 and twice daily, once in the morning and once in the afternoon, thereafter for 14 days.
Body weights: Body weights were obtained and recorded on study days 0 (initiation), 7, and 14 (termination).
Clinical signs: Rats were observed at approximately 15 minutes and 1, 2, and 4 hours post-dosing on study day 0 and once daily thereafter for 14 days.
- Necropsy of survivors performed: On study day 14, all rats were euthanized by carbon dioxide inhalation. The major organ systems of the cranial, thoracic, and abdominal cavities were examined for all animals.
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
No significant clinical signs were noted up to 14 days after dosage.
Body weight:
There were no remarkable body weight changes noted during the study.
Gross pathology:
There were no macroscopic findings at the scheduled necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute oral toxicity study with rats, performed according to OECD test guideline 423, for EXP1200078 an LD50 of >2000 mg/kg bw was determined.
Executive summary:

An acute oral toxicity study with rats was performed according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method) and GLP guidelines. Three female rats were dosed with 2000 mg/kg bw of the test substance, followed by three additional female rats.

No deaths occurred. No clinical signs were noted and no remarkable body weight changes occurred. Gross pathology did not reveal any abnormalities in the examined organs and tissues.

Based on the results of this study, the estimated oral LD50 of EXP1200078 is greater than 2000 mg/kg. EXP1200078

is not classified for acute oral toxicity according to EC regulation No 1272/2008.