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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 25th May 2010 and 10th June 2010. The final report was issued 28th October 2010.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
3-((3,4-Dicyanophenyl)sulfonyl)-N-(2-hydroxypropyl)propane-1-sulfonamide
Cas Number:
569316-81-0
Molecular formula:
C14H17N3O5S2
IUPAC Name:
3-((3,4-Dicyanophenyl)sulfonyl)-N-(2-hydroxypropyl)propane-1-sulfonamide
Test material form:
solid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
Female Wistar (HsdRccHan®™:WIST®™) strain rats were supplied by Harlan laboratories U.K. Ltd, Oxon, UK. On receipt the animals were randomly allocated to cages. The animals were nulliparous and non-pregnant. After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals were eight to twelve weeks of age. The bodyweights fell within an interval of ± 20% of the mean initial bodyweight of the first treated group.

The animals were housed in groups of three in suspended solid-floor polypropylene cages furnished with woodflakes . With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (2014 Teklad Global Rodent diet supplied by Harlan Laboratories U.K. Ltd, Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
2000mg/kg was chosen as the starting dose. Dose volume 10 ml/kg.
Doses:
one dose
No. of animals per sex per dose:
3 animals per group.
Control animals:
no
Details on study design:
The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.

Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment.

At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
Hunched position was noticed on day of administration.
Body weight:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2500 mg/kg bodyweight (Globally Harmonised Classification System - Unclassified).

The test material does not meet the criteria for classification according to EU labelling regulations Commission Directive 2001/59/EC for classification and labelling of dangerous substances.
Executive summary:

Introduction

The study was performed to assess the acute oral toxicity of the test material following a single oral administration in the Wistar strain rat. The method was designed to meet the requirements of the following: OECD Guidelines for the Testing of Chemicals No. 423 "Acute Oral Toxicity - Acute Toxic Class Method" (adopted 17 December 2001) and Method 81 tris Acute Toxicity (Oral) of Commission Regulation (EC) No. 440/2008

Method

A group of three fasted females was treated with the test material at a dose level of 2000 mg/kg bodyweight. This was followed by a further group of three fasted females at the same dose level. All animals were subjected to gross necropsy.

Results

There were no deaths. Hunched posture was noted during the day of dosing, but all animals appeared normal one day after dosing and showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy.

Conclusion

The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2500 mg/kg bodyweight (Globally Harmonised Classification System - Unclassified).