Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 December 2010 - 6 January 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Version / remarks:
3 October 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
December 2002
Deviations:
no
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: no data
- Expiration date of the lot/batch: no data
The identity, purity, strength and stability of the test article were the responsibility of the Sponsor.

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Solubility and stability of the test substance in the solvent/vehicle: no data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: the test article was dosed as received

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan
- Age at study initiation: 8-10 weeks at start of dosing
- Fasting : yes, animals were fasted overnight prior to dose administration. Food was returned to the animals ~ 30 minutes after dosing.
- Weight at study initiation: 185-199 grams
- Fasting period before study: yes
- Housing: Animals were group housed by sex upon receipt and individually housed upon assigment to study in compliance with the National Research Council "Guide for the Care and Use of Laboratory Animals". No other species were kept in the same room.
- Diet (e.g. ad libitum): Harlan Teklad Rodent Diet (certified)
- Water (e.g. ad libitum): Tap water was available ad libitum
- Acclimation period: Minimum of five (5) days prior to dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 23
- Humidity (%): 17 to 54%.
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The dose volumes were 0.54 and 1.98 mL/kg and were based on the relative density of 1.01 g/mL as per MSDS.

Method of study performance:
The first animal was dosed at an initial dose level of 550 mg/kg. Since this animal survived, the second animal received a higher dose (2000 mg/kg). Two additional animals were dosed at 2000 mg/kg. The dose for each successive animal was adjusted up or down, depending on the previous result. The test continued based on the fixed time interval outcomes of all the animals up to that point and until one of the stopping criteria was first met. There were three possible stopping criteria.
• 3 consecutive animals survive at the limit dose;
• 5 reversals occur in any 6 consecutive animals test;
• or at least 4 animals have followed the first reversal and the specific likelihood-ratios exceed the critical value.
Dose progression and stopping criteria were calculated using a dedicated software program [Acute Oral Toxicity (Guideline 425) Statistical Program, Version 1.0] provided by the EPA.
Doses:
550 and 2000 mg/kg
No. of animals per sex per dose:
4 females in total
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Morbidity: manually recorded once daily
Clinical observations: on the day of dosing (Day 1) animals were observed prior to dosing and approximately 30 minutes and 4 hours post-dose. Animals were observed once daily thereafter (Days 2-15).
Body weights - at study initiation (Day 1), Days 8 and 15
- Necropsy of survivors performed: yes
All surviving rats were sacrificed by CO2 inhalation and a gross necropsy was performed at termination of the study
The necropsy included examination of:
• the external body surface
• all orifices
• the cranial, thoracic and abdominal cavities and their contents.
Statistics:
The LD50 was calculated for the main test (when the data allow) using the AOT425StatPgm developed by Westat May, 2001 (available via EPA website).

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Mortality was not observed in any of the animals dosed at 550 or 2000 mg/kg
Clinical signs:
All animals appeared normal throughout the study at 550 and 2000 mg/kg
Body weight:
No biologically significant effect was seen on body weights of animals on Day 8 and 15.
Gross pathology:
Terminal necropsy revealed no visible lesions in any of the animals at 550 or 2000 mg/kg.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Based on the results of this study, the oral LD50 for the test substance in rats was estimated to be greater than 2000 mg/kg and hence a Risk Phrase Not Required by EEC and a category 5 according to GHS.