Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 20 July 2011 and 03 August 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 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (MAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147, amended 26 June 2001
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Health and Welfare, 1992
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

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:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Five male and five 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: At the start of the study the animals weighed at least 200g. The weight variation did not exceed ±20% of the mean weight for each sex.- Fasting period before study: None.- Housing: The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24 Hour exposure period and in groups of five, by sex, for the remainder of the study. - Diet (e.g. ad libitum): Free access to 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- Acclimation period: At least five days.ENVIRONMENTAL CONDITIONS- Temperature (°C): 19 to 25°C - Humidity (%): 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

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITEOn the day before treatment the back and flanks of each animal were clipped free of hair.Using available information on the toxicity of the test item, a group of five male and five female rats was treated with the test item at a dose level of 2000 mg/kg. The appropriate amount of test item, moistened with distilled water, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area). A piece of surgical gauze was placed over the treatment area and semi occluded with a piece of self adhesive bandage. The animals were caged individually for the 24 Hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place.One female animal escaped from its dressing four hours after dosing. The dressing was re-applied for the remainder of the exposure period.REMOVAL OF TEST SUBSTANCEAfter the 24 Hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test item. The animals were returned to group housing for the remainder of the study period.
Duration of exposure:
24 hour contact period.
Doses:
Using available information on the toxicity of the test item, a group of five male and five female rats was treated with the test item at a dose level of 2000 mg/kg.
No. of animals per sex per dose:
Five males and five 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 fourteen days.After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the Draize scale (see evaluation of skin reactions).Any other skin reactions, if present were also recorded.Individual bodyweights were recorded prior to application of the test item on Day 0 and on Days 7 and 14. - Necropsy of survivors performed: yesAt the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Preliminary study:
No preliminary study.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
There were no signs of systemic toxicity.
Body weight:
Individual bodyweights and weekly bodyweight changes are given in the table below (any other information on results incl. tables section).Animals showed expected gains in bodyweight over the study period, except for three females which showed bodyweight loss during the first week but expected gain in bodyweight during the second week.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
There were no signs of dermal irritation.

Any other information on results incl. tables

Individual Bodyweights and Weekly Bodyweight Changes

Dose Level mg/kg

Animal Number and Sex

Bodyweight (g) at Day

Bodyweight Change (g) During Week

0

7

14

1

2

2000

1-0 Male

232

256

280

24

24

1-1 Male

244

269

283

25

14

1-2 Male

248

271

281

23

10

1-3 Male

255

274

293

19

19

1-4 Male

253

283

302

30

19

2-0 Female

211

207

212

-4

5

2-1 Female

205

204

206

-1

2

2-2 Female

216

223

230

7

7

2-3 Female

209

208

221

-1

13

2-4 Female

218

230

231

12

1

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.The test item did not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation (CLP) or the Globally Harmonised Classification System).
Executive summary:

Introduction. 

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

-      OECD Guidelines for the Testing of Chemicals No. 402 “Acute Dermal Toxicity” (adopted 24 February 1987)

-      Method B3 Acute Toxicity (Dermal) of CommissionRegulation (EC) No. 440/2008

- United States Environmental Protection Agency Health Effects Tesat Guidelines OPPTS 870.1200 Acute Dermal Toxicity August 1998

- Japanese Ministry of Agriculture, Forestry and Fisheries (MAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147, amended 26 June 2001

- Japanese Ministry of Health and Welfare, 1992

Method. 

A group of ten animals (five males and five females) was given a single, 24 hour, semi‑occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg bodyweight. 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.

Dermal Irritation. 

There were no signs of dermal irritation.

Bodyweight. 

Animals showed expected gains in bodyweight over the study period, except for three females which showed bodyweight loss during the first week but expected gain in bodyweight during the second week.

Necropsy. 

No abnormalities were noted at necropsy.

Conclusion. 

The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

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