Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 August 2013 to 20 January 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Compliant with OECD test guideline and GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
To minimise the number of animals used, Group 2 animals were administered at 2000 mg/kg instead of 300 mg/kg. There were no adverse signs so a third group of rats were treated at the same dose level (2000 mg/kg) to complete the study.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: extremely viscous amber liquid
- Analytical purity:
- Lot/batch No.: E00031-68-1
- Expiration date of the lot/batch: 16 October 2010
- Storage condition of test material:room temperature in the dark, under nitrogen

Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- lot/batch No.of test material: E00031-633
- Retest date of the lot/batch: 04 Febuary 2013
- Purity test date: >/= 99%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient temperature, in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS:
- Source: Charles River, Maragate, UK
- Age at study initiation: 8 to 11 weeks old
- Weight at study initiation: 196.2 to 227.7 g
- Fasting peroid before study: overnight before dosing
- Housing: Housed in groups of 3
- Diet: ad libitum (except fasting period before study)
- Water: ad libitum
- Acclimatisation: At least 9 days before dosing

ENVIRONMENTAL CONDITIONS:
- Temperature: Approximately 20 °C
- Humidity: Approximately 52% to 67%
- Photoperiod: 12 hours light/dark cycle (light hours 0700 to 1900 h)
- Air Changes: 10 air changes per hour

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
TEST ITEM
- Purity: 99%

MAXIMUM DOSE VOLUME APPLIED: 2.1 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: 300 mg/kg is recommended by the OECD 423 guidelines.
Doses:
300 mg/kg followed by 2000 mg/kg
No. of animals per sex per dose:
Three groups of three females
Control animals:
no
Details on study design:
- Housing: The rats were housed in groups of three, 9 days before dosing. Food and water were available ad libitum, except food was withdrawn overnight before dosing. Environmental conditions were monitored and recorded every 15 minutes.
- Observations and weighing: The rats were examined five times on the day of dosing, followed by daily observations up to Day 15. The body weight of the rats were recorded on Day 1 (before dosing), Day 8 and Day 15.
- Necropsy: All animals were euthanised on Day 15
Statistics:
None

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no unscheduled deaths at both 300 mg/kg and 2000 mg/kg dose levels.
Clinical signs:
There were no clinical signs of reaction to treatment in any animal thoughout the study period.
Body weight:
The body weight gains observed were considered acceptable for rats of that age and strain.
Gross pathology:
Dark discolouring to lung lobes were found in two animals dosed at 2000 mg/kg. As this finding is occationally noted in rats of this strain at these laboratories, it is regarded as a background finding and not a result of treatment. No other abnormalities were recorded.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the study, the median lethal dose level (LD50) of EXP0700332 in Sprague-Dawley rats was considered to exceed 2000 mg/kg.
This study is considered to be relevant, reliable and adequate for risk assessment and for classification purposes.
Executive summary:

The objective of this OECD 423 study was to assess the adverse effects of EXP0700332 after a single oral gavage administration to Sprague-Dawley rats. The test item was administered to three groups of rats, comprising of three females, with one group being tested at 300 mg/kg and the two remaining groups being tested at 2000 mg/kg. The dose volume was based on the density and purity of the test item, and the individual doses were based on the individual body weight of the animals on the day of dosing. The animals were observed daily for 14 days after dosing and their body weights recorded before dosing and on Days 8 and 15. The following parameters and endpoints were evaluated in this study: clinical signs, body weights, body weight changes and gross necropsy findings.

All animals survived the treatment with no adverse clinical signs or macroscopic findings recorded for any animal. Body weight gains were considered to be acceptable for rats of this age and strain. The median lethal dose level (LD50) of EXP0700332 in Sprague-Dawely rats was considered to be in excess of 2000 mg/kg.