5-methoxy-2-methylsulphanilic acid

Endpoint summary

Description of key information

5-methoxy-2-methylsulphanilic acid  should be not irritating for skin based on data available for similar substances  but it is corrosive for the eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

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

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.

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

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

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

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.

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).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion

No data are available for skin irritation of 5-methoxy-2-methylsulphanilic acid. 

We can assume the absence of concern regarding skin irritation of 5-methoxy-2-methylsulphanilic acid based on read-across with two compounds of similar structure (more similar substance: 4-aminotoluene-3-sulfonic acid; less similar substance: sulphanilic acid).

For justification of read-across see attachment document in section 13.

As reported in SIDS Dossier of 4-aminotoluene-3-sulfonic acid approved at SIAM 16 (27 -30 May 2003) with reference to Mitsuboshi Chemical Co., Ltd.: unpublished report, 2003, 4-aminotoluene-3-sulfonic acid was not irritant on the skin of human arm in 6hr patch test after 14 days of observation.  Also from information published in ECHA website, compounds with similar structure to 5-methoxy-2-methylsulphanilic acid are of none concern for skin irritation: in ECHA website in vitro study study of 2010 (Episkin) regarding  4-aminotoluene-3-sulfonic acid and in vitro study of 2009 (RhE test) regarding sulphanilic acid are reported and both the substances result not skin irritant. Despite of experimental in vitro result published on ECHA website, Sulphanic acid is classified H315 (Skin irritation cat. 2) according to Annex VI of CLP Regulation (EC n. 1272/2008). However, reasonably there is no concern regarding skin irritation for 5-methoxy-2-methylsulphanilic acid based on the experimental in vitro data for more similar substance using for read-across (4-aminotoluene-3-sulfonic acid).

The public ECHA database contains data that are proprietary and cannot be used without the formal consent of the owner. In this summary, some of them have been used for precautionary purposes and for the benefit of the human health and the environment. Those data are not necessary for the registration of the target substance which is used exclusively as isolated and transported intermediate, but they can be very helpful for a better definition of the (eco) toxicological property of the substance. No other use and no commercial advantage will derive from the use of those data.

Eye irritation

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 substance5-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).

Regarding eye irritation for two substances used for read-across:

- no assessment is possible for 4-aminotoluene-3-sulfonic acid based on information published on ECHA website (Eye irritation evaluated by BCOP and IVIS obtained = 24 and according to OECD 437 no evaluation of eye irritation is possible if 3< IVIS ≤ 55;

- sulphanilic acid is classified H319 (eye irritant cat.2) according to Annex VIof CLP Regulation (EC n. 1272/2008). The Annex VI classification is confirmed by experimental data published on ECHA website. The study regarding sulphanilic acid confirms the concern regarding eye irritation on 5-methoxy-2-methylsulphanilic acid.

The public ECHA database contains data that are proprietary and cannot be used without the formal consent of the owner. In this summary, some of them have been used for precautionary purposes and for the benefit of the human health and the environment. Those data are not necessary for the registration of the target substance which is used exclusively as isolated and transported intermediate, but they can be very helpful for a better definition of the (eco) toxicological property of the substance. No other use and no commercial advantage will derive from the use of those data.

Justification for selection of skin irritation / corrosion endpoint:
Read across with similar substances.

Justification for selection of eye irritation endpoint:
Reliable study: study GLP compliant and conducted according to internationally accepted testing guidelines.

Effects on eye irritation: corrosive

Justification for classification or non-classification

According to the CLP Regulation (EC 1272/2008) skin Irritation means the production of reversible damage to the skin following the application of a test substance for up to 4 hours.

There are no data for skin irritation of 5-methoxy-2-methylsulphanilic acid but from information regarding substances with similar structure (4-aminotoluene-3-sulfonic acid and sulphanilic acid) no classification is warranted according to the CLP Regulation (EC n. 1272/2008).

 

According to the CLP Regulation (EC n. 1272/2008) eye corrosion means the production of changes in the eye following the application of test substance to the anterior surface of the eye, which are not fully reversible within 21 days of application.

Based on Clariant study of 1989 and applying precautionary principle, 5-methoxy-2-methylsulphanilic acid is classified as corrosive for the eye category 1 (H318) according to the CLP Regulation (EC n. 1272/2008).