Sodium sulphamidate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 11 July 2011 and 21 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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

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

Test guideline 5

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Health and Welfare, 1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Sodium sulphamidate

EC Number:

237-572-8

EC Name:

Sodium sulphamidate

Cas Number:

13845-18-6

Molecular formula:

H3NO3S.Na

IUPAC Name:

sodium sulfamate

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 / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues 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 2.50 to 3.40 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

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIALA volume of 0.1 ml of the test item, which was found to weigh approximately 73 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye.

Duration of treatment / exposure:

SIngle application for 72 hour exposure.

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

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:Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used.Initially, a single rabbit was treated. A volume of 0.1 ml of the test item, which was found to weigh approximately 73 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test item, an assessment of the initial pain reaction was made according to the six point scale shown in Appendix 1 (see attached background material).After consideration of the ocular responses produced in the first treated animal, two additional animals were treated. SCORING SYSTEM:Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical Draize Scale for Scoring Ocular Irritation (see Appendix 2 - attached background material).Any other ocular effects were also noted.TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.Other:Any clinical signs of toxicity, if present, were also recorded.Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(Animal 1 - 70680)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 2

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(Animal 2 - 70735)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 3

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(Animal 3 - 70735)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 4

Irritation parameter:

iris score

Basis:

mean

Remarks:

(Animal 1 - 70680)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

2

Results 5

Irritation parameter:

iris score

Basis:

mean

Remarks:

(Animal 2 - 70734)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

2

Results 6

Irritation parameter:

iris score

Basis:

mean

Remarks:

(Animal 3 - 70735)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

2

Results 7

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

(Animal 1 - 70680)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 8

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

(Animal 2 - 70734)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 9

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

(Animal 3 - 70735)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 10

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal 1 - 70680)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 11

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal 2 - 70734)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 12

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(Animal 3 - 70735)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

Ocular Reactions:Individual and group mean scores for ocular irritation are given in Table 1 and Table 2.No corneal or iridial effects were noted during the study.Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24 and 48-Hour observations.All treated eyes appeared normal at the 72-Hour observation.

Other effects:

Individual bodyweights and bodyweight changes are given in Table 3.Bodyweight loss 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 Scores and Individual Total Scoresfor Ocular Irritation

Rabbit Number and Sex	70680 Male				70734Male				70735Male
	IPR= 2				IPR = 2				IPR = 2
Time After Treatment	1 Hour	24 Hours	48 Hours	72 Hours	1 Hour	24 Hours	48 Hours	72 Hours	1 Hour	24 Hours	48 Hours	72 Hours
CORNEA
E = Degree of Opacity	0	0	0	0	0	0	0	0	0	0	0	0
F = Area of Cornea Involved	0	0	0	0	0	0	0	0	0	0	0	0
Score (E x F) x 5	0	0	0	0	0	0	0	0	0	0	0	0
IRIS
D	0	0	0	0	0	0	0	0	0	0	0	0
Score (D x 5)	0	0	0	0	0	0	0	0	0	0	0	0
CONJUNCTIVAE
A = Redness	2	1	1	0	2	1	1	0	2	1	1	0
B = Chemosis	2	1	1	0	2	1	1	0	2	1	1	0
C = Discharge	1	0	0	0	1	0	0	0	1	0	0	0
Score (A + B + C) x 2	10	4	4	0	10	4	4	0	10	4	4	0
Total Score	10	4	4	0	10	4	4	0	10	4	4	0

 

IPR=  Initial pain reaction

Table 2              Individual Total Scores and Group Mean Scores for Ocular Irritation

Rabbit Number and Sex	Individual Total Scores At:
	1 Hour	24 Hours	48 Hours	72 Hours
70680 Male	10	4	4	0
70734Male	10	4	4	0
70735Male	10	4	4	0
Group Total	30	12	12	0
Group Mean Score	10.0	4.0	4.0	0.0

Table 3              Individual Bodyweights and Bodyweight Changes

Rabbit Number and Sex	Individual Bodyweight (kg)		Bodyweight Change (kg)
	Day 0	Day 3
70680 Male	3.40	3.28	-0.12
70734Male	2.69	2.80	0.11
70735Male	2.50	2.66	0.16

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

A single application of the test item to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. All treated eyes appeared normal at the 72 Hour observation.The test item does not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation or the Globally Harmonised Classification System.

Executive summary:

Introduction. 

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit. The method was designed tobe compatible with thefollowing:

- OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted 24 April 2002)

- Method B5 Acute Toxicity (Eye Irritation) of CommissionRegulation (EC) No. 440/2008

- United States Environmental Protection Agency Health Effects Tesat Guidelines OPPTS 870.2400 Acute Eye 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

Result. 

A single application of the test item to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. All treated eyes appeared normal at the 72‑Hour observation.

Conclusion. 

The test item produced a maximum group mean score of 10.0 and was classified as a mild irritant (Class 4on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

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