6-diazo-5,6-dihydro-5-oxonaphthalene-2-sulphonyl chloride

Endpoint summary

Description of key information

Skin irritation in vivo: not irritanting to skin

Eye irritation in vitro: irritant Cat 2

A WoE Approach was applied to investigate the eye irritation/corrosion potential of the test item. Based on the results of the OECD 492 study the test item is considered to be GHS Cat. 1 or GHS Cat. 2. Since the OECD 492 study cannot differ between GHS Cat. 1 or GHS Cat. 2 an OECD 437 study was performed. Since the IVIS Score was 50.1 in the OECD 437 study, it can be excluded that the test item caused serious eye damage. In conclusion, the test item is considered to be irrating to eye (GHS Cat. 2).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November 05, 1996 - November 26, 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

07-1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

07-1992

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Remarks:

Chbb:NZW (SPF)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. Thomae, Biberach
- Age at study initiation: no data
- Weight at study initiation: 2.9 - 3.1 kg
- Housing: individually in suspended metal cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 50 +/- 20
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: sesame oil

Controls:

not required

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4 h

Observation period:

Up to 14 days

Number of animals:

3

Details on study design:

About 24 hours before the start of the study the hair in the dorsal region of the body of 3 rabbits was removed with an electric clipper over an area of about 25 cm2. Only animals with intact skin were used.
Administration of the test substance and exposure period was performed under protection from light.
Each animal was treated with 500 mg of the test item pasted with 0.6 mL sesame oil. The substance was applied over the whole surface of a 2.5*2.5 cm cellulose patch on a piece of surgical plaster. The plaster was fixed to the prepared skin area and then covered with a semi-occlusive bandage.
The exposure period was 4 hours. After the exposure period all remnants of the test substance were carefully removed from the skin with warm tap water.
Examinations of the skin took place after 30 - 60 minutes as well as 24, 48 and 72 hours after removal of the patches. Because of persistent irritations in one animal 72 hours after removal of the patches, additional readings were performed in this animal after 7 and 14 days.
Erythema, eschar formation and oedema were evaluated numerically according to the score of DRAIZE. All other changes of the skin were recorded.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.1

Max. score:

4

Reversibility:

fully reversible within: 2 days

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

30 - 60 minutes up to one day after removal of the patches the skin of the animals showed very slight to moderate erythema and a very slight oedema. Two days after removal of the patches the signs of irritation were reversible in two animals. The third animal still exhibited well-defined to moderate erythema up to 7 days after application. 14 days after application the signs of irritation were reversible in the animal. Additionally 30 - 60 minutes up to 3 days after removal of the patches the skin of the animals was discoloured light yellow.

Study design

The purpose of this GLP study performed according to OECD GL 404 was to assess the irritancy potential of the test item to the skin of the New Zealand White rabbits.

Results

30 - 60 minutes up to one day after removal of the patches the skin of the animals showed very slight to moderate erythema and a very slight oedema. Two days after removal of the patches the signs of irritation were reversible in two animals. The third animal still exhibited well-defined to moderate erythema up to 7 days after application. 14 days after application the signs of irritation were reversible in the animal. Additionally 30 - 60 minutes up to 3 days after removal of the patches the skin of the animals was discoloured light yellow.

Conclusion

The test material gave no indication for a skin irritation potential when tested in NZW rabbits.

Interpretation of results:

GHS criteria not met

Conclusions:

The test material gave no indication for a skin irritation potential when tested in NZW rabbits.

Executive summary:

This study was performed according to GLP and is fully compliant with OECD GL 404. Based on the results of this study it was concluded that the test item is not irritant to the rabbit skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

October 10, 2017 - January 30, 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)

Version / remarks:

2017

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)

Version / remarks:

Commission Regulation (EU) 2017/735 of 14 February 2017 amending, for the purpose of its adaption to technical progress, the Annex to Regulation (EC) No 440/2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

PREPARATION OF THE TEST MATERIAL
The test item was prepared as a 20% (w/v) suspension in a 0.9% sodium chloride solution. The stability in the vehicle was not investigated. The test item preparation was administered within <1 hour after preparation.

Vehicle:

physiological saline

Controls:

yes, concurrent vehicle

yes, concurrent positive control

Amount / concentration applied:

TEST MATERIAL: 750 µL (i.e. 150mg/750µL)

NEGATIVE / VEHICLE CONTROL: 750 µL

Designation: 0.9% sodium chloride solution
Supplier: B. Braun Melsungen AG, Germany
Batch: 16455011
Storage: 2 to 8°C
Released until: October 2019


POSITIVE CONTROL: 750 µL

Designation: Art. 814223
Synonym: Imidazole
Supplier: Merck KGaA, Germany
Batch: S6746923
Purity (GC) 99.8% (a/a)
Storage: At room temperature
Released until: August 31, 2018

Imidazole was dissolved with 0.9% sodium chloride solution to a concentration of 20% (w/v).

Duration of treatment / exposure:

240 minutes

Number of animals or in vitro replicates:

in vitro: triplicate design

Irritation parameter:

in vitro irritation score

Run / experiment:

Run 1 / Experiment 1

Value:

50.1

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

not determinable

Remarks:

According to OECD 437 no prediction can be made regarding the eye hazard potential of the test item.

Other effects / acceptance of results:

OTHER EFFECTS:
- After treatment with test item a slightly yellowish staining of the corneas was observed.

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: After treatment with the negative control (0.9% sodium chloride solution) the calculated IVIS was -0.6 and, thus, within three standard deviations of the current historical mean of the negative control (IVIS: -1.4 – 3.2).
- Acceptance criteria met for positive control: After treatment with the positive control (20% Imidazole) the calculated IVIS was 116.5 and, thus, also within two standard deviations of the current historical mean of the positive control (IVIS: 81.2 – 132.9).

Therefore, the study fulfilled the acceptance criteria.

		Opacity	Permeability	IVIS
				per cornea	per group (mean value)	SD
Negative control	0.9% NaCl Solution	-0.8	-0.003	-0.845	-0.6	0.3
		-0.2	-0.002	-0.230
		-0.7	-0.003	-0.745
Positive control	20% Imidazole solution	73.2	2.967	117.705	116.5	15.5
		87.0	2.957	131.355
		77.0	1.558	100.370
Test item	Test item	55.3	0.046	55.990	50.1	6.5
		42.8	0.026	43.190
		50.5	0.034	51.010

Interpretation of results:

other: Under the conditions of the present study, the eye hazard potential of the test item cannot be predicted.

Conclusions:

Under the conditions of the present study, the eye hazard potential of the test item cannot be predicted.

Executive summary:

This study was performed according to GLP and the methods applied are fully compliant with OECD TG 437. Under the conditions of the present study, the eye hazard potential of the test item cannot be predicted.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

December 12, 2017 - February 26, 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 492 (Reconstructed Human Cornea-like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage)

Version / remarks:

October 9, 2017

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: DB-ALM Protocol No. 164: Ocular Irritation Assay for Chemicals using EpiOcular™ EIT,

Version / remarks:

September 14, 2015

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: EpiOcular Eye Irritation Test (OCL-200-EIT) for the prediction of acute ocular irritation of chemicals; For use with MatTek Corporation`s Reconstructed Human EpiOcular Model; MatTek Corporation

Version / remarks:

June 29, 2015

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: No pre-treatment, the test item was applied neat to the tissues.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

TEST MATERIAL: 50 mg per tissue

NEGATIVE / VEHICLE CONTROL: 50 µL per tissue

Sterile deionized water was used as negative control.


POSITIVE CONTROL: 50 µL per tissue

Designation: Methyl acetate
Supplier: MatTek In Vitro Life Science Laboratories
Lot-No.: 032817ISA
Catalog #: TC-MA
Purity (GC): 99.7%
Appearance: Colorless liquid
Expiration date: March 28, 2018
Storage: 15 to 30°C

Duration of treatment / exposure:

6 hours

Duration of post- treatment incubation (in vitro):

18 hours

Number of animals or in vitro replicates:

in vitro: duplicate design

Irritation parameter:

other: Viability %

Run / experiment:

Run 1 / Experiment 1

Value:

5.4

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

positive indication of irritation

Remarks:

According to OECD 492 the test item is labeled irritant (UN GHS Category 1 or Category 2).

Other effects / acceptance of results:

OTHER EFFECTS:
- Visible damage on test system: No observations

ACCEPTANCE OF RESULTS:
1. The negative control OD is >0.8 and <2.5 (1.293 and 1.501).
2. The mean relative viability of the positive control is below 50% of the negative control viability (45.9%).
3. The difference of viability between the two relating tissues of a single chemical is <20% (values between 0.1% to 14.8%) in the same run (for positive and negative control tissues and tissues of single chemicals).

The study met all acceptance criteria

	Mean OD	Mean Viability
Negative Control	1.397	100.0%
Positive Control	0.641	45.9%
Test Item	0.075	5.4%

Interpretation of results:

other: The test item is labeled irritant (UN GHS Category 1 or Category 2).

Conclusions:

Under the conditions of the present study, the test item did show an eye hazard potential. The test item is labeled irritant (UN GHS Category 1 or Category 2).

Executive summary:

This study was performed according to GLP and the methods applied are fully compliant with OECD TG 492. Under the conditions of the present study, the test item did show an eye hazard potential. The test item is labeled irritant (UN GHS Category 1 or Category 2).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the provided information there is no need for classification for skin irritation according to the EU Regulation (EC) No 1272/2008 on Classification,Lab elling and Packaging of Substances and Mixtures, as amended for the 10th time in Regulation (EU) No 2017/776.

Based on the provided information there is need for classification for eye irritation category 2 according to the EU Regulation (EC) No 1272/2008 on Classification,Lab elling and Packaging of Substances and Mixtures, as amended for the 10th time in Regulation (EU) No 2017/776.