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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 23 June 2011 and 08 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 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147, amended 10 December 2002
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Health and Welfare, 1992
Deviations:
no
GLP compliance:
yes (incl. certificate)

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:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Three New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd., Leicestershire, UK. - Age at study initiation: twelve to twenty weeks old- Weight at study initiation: At the start of the study the animals weighed 2.18 to 2.78 kg- Housing: The animals were individually housed in suspended cages. - Diet (e.g. ad libitum): Free access to food (2930 Teklad Global Rabbit 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): 17 to 23°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.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped free of fur
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIALFor the purpose of the study the test item was ground to a powder before use.The absorption of the test item was not determined.At each test site a quantity of 0.5 g of the test item, moistened sufficiently with 0.5 ml of distilled water, was introduced
Duration of treatment / exposure:
3 minutes (initial animal), 1 hour (initial animal) and 4 hours (all animals)
Observation period:
72 hours plus an additional observation was made at one treated skin site on Day 7.
Number of animals:
3
Details on study design:
MEASUREMENT OF PH:The pH of the test item was determined prior to commencement of the study and found to be as follows:10% w/w aqueous preparation of the test item: pH 8.1 (immediately) : pH 8.5 (after 10 minutes)PROCEDURE:On the day before the test each rabbit was clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.One rabbit was initially treated. Three suitable sites were selected on the back of the rabbit. At each test site a quantity of 0.5 g of the test item, moistened sufficiently with 0.5 ml of distilled water, was introduced under a 2.5 cm x 2.5 cm cotton gauze patch. Each patch was secured in position with a strip of surgical adhesive tape. To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset for the duration of the exposure period.One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application. Any residual test item was removed by gentle swabbing with cotton wool soaked in distilled water.After consideration of the skin reactions produced in the first animal, an additional two animals were treated with 0.5 g of test item, moistened sufficiently with 0.5 ml of distilled water. One patch was applied to the back of each rabbit and was allowed to remain in contact with the skin for a period of four hours.SCORING SYSTEM:Immediately following removal of the patches and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the Draize scale (see evaluation of skin reactions below).Any other skin reactions and clinical signs of toxicity, if present, were also recorded.An additional observation was made at one treated skin site on Day 7 to assess the reversibility of skin reactions. Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
(Animal 1 - 70542)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Results of 4 hour exposure. Light brown discolouration of the epidermis noted at 48 and 72 hours. Loss of skin elasticity noted at 72 hours.
Irritation parameter:
edema score
Basis:
mean
Remarks:
(Animal 1 - 70542)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Results of 4 hour exposure
Irritation parameter:
erythema score
Basis:
mean
Remarks:
(Animal 2 - 70657)
Time point:
other: Mean scores of 24, 48 and 72 hours
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Results from 4 hour exposure
Irritation parameter:
edema score
Basis:
mean
Remarks:
(Animal 2 - 70657)
Time point:
other: Mean scores of 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: Results from 4 hour exposure
Irritation parameter:
erythema score
Basis:
mean
Remarks:
(Animal 3 - 70658)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: Results from 4 hour exposure
Irritation parameter:
edema score
Basis:
mean
Remarks:
(Animal 3 - 70658)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: Results from 4 hour exposure
Irritant / corrosive response data:
Skin Reactions3-Minute Exposure Period:The individual scores for erythema/eschar and oedema are given in Table 1.No evidence of skin irritation was noted during the study.1-Hour Exposure Period:The individual scores for erythema/eschar and oedema are given in Table 1.Very slight erythema was noted at the treated skin site immediately and one hour after patch removal and at the 24, 48 and 72-Hour observations.The treated skin site appeared normal at the 7-Day observation.4-Hour Exposure PeriodThe individual scores for erythema/eschar and oedema are given in Table 2.Very slight erythema was noted at one treated skin site immediately after patch removal and at two treated skin sites one and 24 hours after patch removal. Well-defined erythema, very slight oedema and light brown discolouration of the epidermis were noted at one treated skin site at the 48 and 72-Hour observations with loss of skin elasticity also noted at this treated skin site at the 72-Hour observation.No evidence of skin irritation was noted at one treated skin site during the study. One treated skin site appeared normal at the 48-Hour observation and the remaining treated skin site appeared normal at the 7-Day observation.The individual mean scores for erythema and oedema required for classification according to the Globally Harmonised System of Classification and Labelling ofChemicals were as follows:Animal 1 (70542):Mean score erythema/eschar formation: 1.7Mean score for oedema formation: 0.7Animal 2 (70657):Mean score erythema/eschar formation: 0.3Mean score for oedema formation: 0Animal 3 (70658):Mean score erythema/eschar formation: 0.0Mean score for oedema formation: 0.0
Other effects:
Bodyweight:Individual bodyweights and bodyweight changes are given in Table 3.No bodyweight gain was noted in one animal. Two animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Table 1              Individual Skin Reactions Following 3-Minute and 1-Hour Exposures

Skin Reaction

Observation Time
(following patch removal)

Individual Scores - Rabbit Number and Sex

70542Male

3-Minute Exposure

1-Hour Exposure

Erythema/Eschar Formation

Immediately

0

1

1 Hour

0

1

24 Hours

0

1

48 Hours

0

1

72 Hours

0

1

7 Days

0

0

Oedema Formation

Immediately

0

0

1 Hour

0

0

24 Hours

0

0

48 Hours

0

0

72 Hours

0

0

7 Days

0

0

Table 2              Individual Skin ReactionsFollowing 4-Hour Exposure

Skin Reaction

Observation Time
(following patch removal)

Individual Scores – Rabbit Number and Sex

Total

70542Male

70657Male

70658Male

Erythema/Eschar Formation

Immediately

1

0

0

(1 )

1 Hour

1

1

0

( 2 )

24 Hours

1

1

0

2

48 Hours

2Br

0

0

( 2 )

72 Hours

2BrLe

0

0

2

7 Days

0

-

-

( 0 )

Oedema Formation

Immediately

0

0

0

( 0 )

1 Hour

0

0

0

( 0 )

24 Hours

0

0

0

0

48 Hours

1

0

0

( 1 )

72 Hours

1

0

0

1

7 Days

0

-

-

( 0 )

Sum of 24 and 72-hour Readings (S)       :          5

Primary Irritation Index (S/6)                   :          5/6 = 0.8

Classification                                        :          MILD IRRITANT


(   ) =  Total values not used for calculation of primary irritation index

Br=     Light brown discolouration of the epidermis

Le=     Loss of skin elasticity

- =       Not applicable

Table 3              Individual Bodyweights and Bodyweight Changes

Rabbit Number
and Sex

Individual Bodyweight (kg)

Bodyweight Change (kg)

70542Male

Day 0

Day 7

0.15

2.41

2.56

70657Male

Day 0

Day 3

0.04

2.78

2.82

70658Male

Day 0

Day 3

0.00

2.18

2.18

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item produced a primary irritation index of 0.8 and was classified as a MILD IRRITANT to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.The test item produced a maximum individual mean score of 1.7 and therefore did not meet the criteria for classification according to the Globally Harmonised System of Classification and Labelling of Chemicals.
Executive summary:

Introduction. 

The study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit. The method was designed to be compatible with the following:

- OECD Guidelines for the Testing of Chemicals No. 404 “Acute Dermal Irritation/Corrosion” (adopted 24 April 2002)

- Method B4 Acute Toxicity (Skin Irritation) of Commission Regulation (EC) No. 440/2008

- United States Environmental Protection Agency Health Effects Tesat Guidelines OPPTS 870.2500 Acute Dermal Irritation August 1998

- Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147, amended 10 December 2002

- Japanese Ministry of Health and Welfare, 1992

Results. 

3-minute and 1-hour semi-occluded applications of the test item to the intact skin of one rabbit produced no corrosive effects.

A single 4-hour, semi-occluded application of the test item to the intact skin of three rabbits produced very slight to well-defined erythema at two treated skin sites. Very slight oedema, light brown discolouration of the epidermis and loss of skin elasticity were

also noted at one treated skin site. No evidence of skin irritation was noted at one treated skin site during the study. One treated skin site appeared normal at the 48-Hour observation and the remaining treated skin site appeared normal at the 7-Day

observation.

Conclusion. 

The test item produced a primary irritation index of 0.8 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme.

The test item produced a maximum individual mean score of 1.7 and therefore did not meet the criteria for classification according to the Globally Harmonised System of Classification and Labelling of Chemicals.