5-methoxy-2-methylsulphanilic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From November 14th to November 21st, 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study GLP compliant and conducted according to internationally accepted testing guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Kresidinsulfosäure

IUPAC Name:

Kresidinsulfosäure

Constituent 2

Reference substance name:

5-methoxy-2-methylsulphanilic acid

EC Number:

229-319-5

EC Name:

5-methoxy-2-methylsulphanilic acid

Cas Number:

6471-78-9

Molecular formula:

C8H11NO4S

IUPAC Name:

5-methoxy-2-methylsulphanilic acid

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: HOECHST AG
- Age at study initiation: 3-5 months
- Weight at study initiation: 3.6 kg
- Housing: in air-conditions room in individual cages
- Diet: ad libitum with maintenance diet for rabbit and hay (about 15 g daily)
- Water: deionized and chlorinated water from automatic soak ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): The animals were housed in an air-conditioned room at a temperature of 20 ± 3°C
- Humidity (%): 50 ± 20 %.
- Photoperiod (hrs dark / hrs light): The light/dark cycle was 12 hours per day

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied : 100 mg in left eye

Observation period (in vivo):

7 days. The effects were recorded after 1h, 24h, 48h and till 7 days after treatment.

Number of animals or in vitro replicates:

One rabbit

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done):24 hours after testing the treated eye was washed with saline solution.

TOOL USED TO ASSESS SCORE: For the assessment of damages a drop of sodium fluorescein solution (0.01%) were put in the eye and the eye was examined by UV-light.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24h, 48h, 72h

Score:

ca. 4

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Eye rinsed. The data for 72h was extrapolated by data for 48h

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24h, 48h, 72 h

Score:

ca. 1

Max. score:

2

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Eye rinsed. The data for 72h was extrapolated by data for 48h

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24h , 48h, 72 h

Score:

ca. 2

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Eye rinsed. The data for 72h was extrapolated by data for 48h

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24h, 48h, 72h

Score:

ca. 4

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Eye rinsed. The data for 72h was extrapolated by data for 48h

Other effects:

One hour after the application hyperemia and a clear swelling of the conjunctiva appeared.
From day 1 to day 7 a diffuse redness and swelling with half or more than half closed eyelids were observed as well as cornea discharge, nictitating membrane and the conjunctiva .
On day 7 diffuse vascularization was present as result of treatment.

Applicant's summary and conclusion

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on precautionary principle the substance 5-methoxy-2-methylsulphanilic acid is classified H318 (Causes serious eye damage) according to CLP Regulation (EC n. 1272/2008).

Executive summary:

Based on precautionary principle the substance 5-methoxy-2-methylsulphanilic acid is classified H318 (Causes serious eye damage) according to CLP Regulation (EC n. 1272/2008).

In fact, the test of eye irritation was conducted only on one rabbit but as reported in OECD 405 if the resultant of the initial test on the first animal indicate the substance to be corrosive or a severe irritant to the eye using the further testing for ocular irritancy should not be perform. In fact, after application of 5-methoxy-2-methylsulphanilic acid on the first rabbit high level of cornea opacity (mean value:4 /max score: 4), extent redness of conjunctivae (mean value:2 /max score: 3) and big swelling or chemosis (mean value:4 /max value:4) in the treated eye were observed and all these effect are not fully reversible within 7 days. The treated eye was washed after 24h from application.

According to CLP Regulation(EC n. 1272/2008) the criteria to classified a substance as eye corrosive (cat.1) are:

— at least in one animal effects on the cornea, iris or conjunctiva that are not expected to reverse or have not fully reversed within an observation period of normally 21 days; and/ or

— at least in 2 of 3 tested animals, a positive response of:

    — corneal opacity ≥ 3 and/or

    — iritis > 1,5

calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material.

From this study for the substance 5-methoxy-2-methylsulphanilic acid the criteria to classified the substance as eye corrosive (cat.1) are not completely fullfilled (the effects are not fully reversible within 7 days but no information are available till 21 days and the mean of cornea opacity is greater than 3 but data are available only for one animal).

Based on severe effect observed on one rabbit and based on precautionary principle the substance 5-methoxy-2-methylsulphanilic acid is classified H318 (Causes serious eye damage) according to CLP Regulation (EC n. 1272/2008).

The applicant agrees with the author of the study that in 1989 classified the substance as R41 according to Directive 83/467/CEE (Note: Directive 83/467/CEE is an update of Directive 67/548/EEC). As reported in annex VII of CLP Regulation (EC n. 1272/2008) classification R41 according to Directive 67/548/EEC is equivalent to H318 according to CLP Regulation (EC n. 1272/2008).