Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 28 June 2011 and 26 July 2011.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 2000
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Sponsor's identification:Sodium SulphamateDescription:white solidBatch Number: LE12568Purity: 99.67%Date received:06 May 2011Expiry date:06 May 2013Storage conditions:room temperature in the dark over silica gel

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Female Wistar (RccHan:WIST) strain rats were supplied by Harlan Laboratories UK Ltd., Oxon, UK.- Age at study initiation: Eight to twelve weeks of age- Weight at study initiation: 157 - 184 g (bodyweights fell within an interval of ±20% of the mean initial bodyweight of the first treated group).- Fasting period before study: Overnight fast immediately before dosing and for approximately three to four hours after dosing- Housing: The animals were housed in groups of three in suspended solid floor polypropylene cages furnished with woodflakes.- Diet (e.g. ad libitum): Food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study.- Water (e.g. ad libitum): Free access to mains drinking water 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.- Acclimation period: At least five days.ENVIRONMENTAL CONDITIONS- Temperature (°C): Set to achieve limits of 19 to 25°C - Humidity (%): Set to achieve limits of 30 to 70%Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. - Air changes (per hr): At least fifteen changes per hour - Photoperiod (hrs dark / hrs light): lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE- Concentration in vehicle: 30 mg/ml or 200 mg/mlMAXIMUM DOSE VOLUME APPLIED: 10 ml/kgDOSAGE PREPARATION: The test item was freshly prepared, as required, as a solution at the appropriate concentration in distilled water. The test item was formulated within two hours of being applied to the test system. It is assumed that the formulation was stable for this duration. CLASS METHOD (if applicable)- Rationale for the selection of the starting dose: In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the starting dose.
Doses:
300 mg/kg and 2000 mg/kg
No. of animals per sex per dose:
3 females at 300 mg/kg. 6 females at 2000 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days - Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for up to fourteen days. Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment.- Necropsy of survivors performed: yes; At the end of the observation period the surviving 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
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths at 300 mg/kg bw or 2000 mg/kg bw
Clinical signs:
There were no signs of systemic toxicity at 300 mg/kg bw or 2000 mg/kg bw
Body weight:
Individual bodyweights and weekly bodyweight changes are given in the tables below (any other information on results incl. tables section).The surviving animals showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy at 300 mg/kg bw or 2000 mg/kg bw

Any other information on results incl. tables

Individual Bodyweights and Weekly Bodyweight Changes - 300 mg/kg

Dose Level

mg/kg

Animal Number
and Sex

Bodyweight (g) at Day

Bodyweight Gain (g) During Week

0

7

14

1

2

300

1-0 Female

184

200

205

16

5

1-1 Female

183

190

199

7

9

1-2 Female

174

194

204

20

10

Individual Bodyweights and Weekly Bodyweight Changes - 2000 mg/kg

Dose Level

mg/kg

Animal Number
and Sex

Bodyweight (g) at Day

Bodyweight Gain (g) During Week

0

7

14

1

2

2000

2-0 Female

180

186

196

6

10

2-1 Female

171

191

201

20

10

2-2 Female

175

183

197

8

14

3-0 Female

167

177

187

10

10

3-1 Female

174

180

196

6

16

3-2 Female

157

166

178

9

12

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2500 mg/kg bodyweight
Executive summary:

Introduction.

The study was performed to assess the acute oral toxicity of the test item following a single oral administration in the Wistar strain rat. The method was designed to be compatible with the following:

- OECD Guidelines for the Testing of Chemicals No. 423 “Acute Oral Toxicity – Acute Toxic Class Method” (adopted 17 December 2001)

- Method B1 tris Acute Toxicity (Oral) of Commission Regulation (EC) No. 440/2008

- United States Environmental Protection Agency Health Effects Test Guidelines OPPTS 870.1100 Acute Oral Toxicity, 2002

- Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 2000

Method. 

A group of three fasted females was treated with the test item at a dose level of 300 mg/kg bodyweight. Based on the results from this dose level further groups of fasted females were treated at a dose level of 2000 mg/kg bodyweight. Dosing was performed sequentially.

The test item was administered orally as asolution in distilled water. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. 

There were no deaths.

Clinical Observations. 

There were no signs of systemic toxicity.

Bodyweight. 

All animals showed expected gains in bodyweight over the study period.

Necropsy. 

No abnormalities were noted at necropsy.

Conclusion. 

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

The test item did not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation (CLP).