Calcium bis[2-[(2-hydroxynaphthyl)azo]naphthalenesulphonate]

Endpoint summary

Description of key information

Studies on the irritating potential of the test item were not performed. Since all substances are metal laked salts with comparable structur and similar solubility, information on skin and eye irritation were also derived from experimental data of a structural analogue. Several studies in rabbits were performed to evaluate irritating or corrosive properties to skin or eyes (OECD guideline 403, 404 and AFDO regulation). Application of the test substance or the analogue did not provoke skin irritation. Treatment of rabbits eyes caused slight conjuctival irritation. All reaction resolved within 2 days or were below  the treshold of regualtion. Therefore, the substance is considered to be not-irritating.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

october 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well documented, GLP conform, according then in force OECD guideline (7 days post observation period only), acclimatization period not mentioned, in life data not given, rationale for vehicle (undiluted PEG 400) not given

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Chemisch pharmazeutische Fabrik Dr. K. Thomae, 88400 Biberach
- Age at study initiation: about 3 - 5 months
- Weight at study initiation: 2.3 - 2.7 kg
- Housing: singly
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: /

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 ·C
- Humidity (%): 55 ± 20 %
- Photoperiod (hrs dark / hrs light): 12 hours per day

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: PEG 400

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): pasted with 0.9 ml polyethylene glycol 400

VEHICLE (PEG 400, Riedel-de Häen Ag, Seelze)
- Amount(s) applied (volume or weight with unit): about 1 ml

Duration of treatment / exposure:

4h

Observation period:

30 - 60 minutes, and 24, 48 and 72 hours after removal of the patches

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: dorsal region
- % coverage: 25 cm2
- Type of wrap if used: surgical plaster and semi-occlusive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): after 4h, with luke warm water

SCORING SYSTEM: Draize

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: all time points

Score:

0.3

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Time point:

other: all time p oints

Score:

0

Max. score:

4

Irritant / corrosive response data:

Three days after the application 2 animals showed very slight up to well-defined erythema. The skin surfaces were slightly discolourered, and dry-rough and fine up to coarse scales were noted. Seven days after the application all signs of irritation were reversible.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

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:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

november 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well documented, GLP conform, according then in force OECD guideline (7 days post observation period only), acclimatization period not mentioned, in life data not given

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Chemisch pharmazeutische Fabrik Dr. K. Thomae, 88400 Biberach
- Age at study initiation: about 3 - 5 months
- Weight at study initiation: 2.3 - 3 kg
- Housing: singly
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: /

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%): 55 ± 20 %
- Photoperiod (hrs dark / hrs light): 12 hours per day

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

Observation period (in vivo):

1, 24, 48 and 72 hours after application

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): 24 hours after application and at all other designated examination times at which the tr ated eyes still showed discharge or at which a corneal examination with fluorescein-sodium solution took place, the treated eyes were washed out thoroughly with physiological saline at approx. 37 °C.

SCORING SYSTEM:

CORNEA

Degree of opacity (most dense area used)

No opacity................................................................ 0
SCattered or diffuse areas, details of iris clearly visible............... 1
Easily discernible translucent areas, details of iris slightly obscured... 2
Op&lescent areas, no details of iris visible, size of pupilbarely di scernib1e. . . . . . . .3
Opaque, iris invisible ...........4

IRIS

Normal ................0
Folds above normal, congestion, swelling, circumcorneal injection
(any of all of these or cOMbination of any thereof); iris still reacting to light (sluggish reaction is positive)......................... 1
No reaction to light, haemorrhage, gross destruction (any or all of these) ................ 2

CONJUNCTIVAE

Redness (refers to palpebral and bulbar coniunctivae)

Blood vessels nomal......... 0
Blood vessels definitely injected above normal............................ 1
More diffuse, deeper crimson red, individual blood vessels not easily discernible..........................2
Diffuse beefy red............................3

Chemosis (refers to palpebral and bylbar conjunctivae)

no swelling..............0
Any swelling bove normal (includes nictitating membran).................. 1
Obvious swelling with partial eversion of lids............................ 2
Swell ing with lids about half closed...................................... 3
Swelling with lids half closed to completely closed....................... 4

Discharge

No discharge............................................................... 0
Any a.ount different from normal (does not include small amounts normally observed in inner canthus) ..........1
Discharge with moistening of the lids and hairs just adjacent to the lids...................2
Discharge with moistening of the lids and hairs, and considerable area around the eye........................................... 3

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: all time points

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

other: all time points

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: all time points

Score:

0.1

Max. score:

3

Reversibility:

fully reversible within: 2d

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: all time points

Score:

0

Max. score:

4

Irritant / corrosive response data:

One hour up to 24 hours after application of the test substance the conjunctiva of the animals showed definitely injected blood vessels and slight swellings. Additionally clear from substance coloured discharge was observed up to one hour after application. Two days after application all signs of irritationes were reversible.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Read across justification

Studies on eye or skin irritating properties of the test item were not performed. The test material shares structural similarity to analogue substances. All of them are metal laked salts and include 1 -amino-2 -naphthol which is connected via azo bond with an aromatic sulfonic acid. The salts are solid pigmets and poor soluble in water and octanol. Therefore, it is acceptable to derive information on skin and eye irritation from experimental data of the analogue substance.

Procedure and observations The test item, 0.5g dissolved in 50% PEG, was applied onto shaved or abraded, dorsal rabbits skin (3/sex) and animals were exposed to the substance under occlusive conditions for 24h (Ciba 1975). Effects on application site were scored 24h and 72h after treatment. Very slight to slight oedema were seen in 5/6 intact and abraded sites 24 hours after application of the compound. All sites were normal by 72h post observation period.

In the course of a pre-GLP study, six rabbits (3/sex/dose) were each administered a single dose of 0.5 g given as 50% suspension of the analogue substance onto shaved skin of back and flanks (Ciba 1974). Occlusive application of the test material to intact rabbit skin for 24 hours did not cause any reaction on animals skin.

The second, GLP and OECD guideline study was conducted in 1993 (Hoechst 1993). The analogue (0.5g, 50% solution) was applied onto shaved, intact dorsal skin of 6 rabbits (3/sex/dose) for 4h under semi-occlusive conditions. After removal of the test substance effects and symptoms were scored at 0.5, 1, 24, 48 and 72h. Slight erythema formation was observed. All effects resolved fully within 7 days.

To evaluate the eye irritation potential of the test material, 100 mg of unchanged test material was installed into the conjuctival sac of six rabbits (3/sex). After 30 seconds the eyes of 3/6 rabbits were rinsed with luke warm water. Effects were scored 1, 6, 24, 48 and 72h after treatment. A slight to mild conjunctiual reaction was seen in 5/6 eyes one hour after application the compound. After 5 hours the reaction subsided, washed eyes returning to normal slightly more quickly. All were normal by day 3.

Six rabbits (3/sex/dose) were each administrated a single ocular dose of 100 mg of the analogue substance and observed for seven days after instillation (Ciba 1974). In half of the animals the eye was rinsed 30 sec after installation, the eyes of the remaining animals were not rinsed. The substance did not cause any effect. Neither swelling, not redness or chemosis were observed.

In a second key study (Hoechst 1993) 0.1 g test material were administrated into the conjunctival sac of one each rabbits eye. The eyes were not rinsed and effects were scored 1, 24, 48 and 72h after application. The single instillation of the test material into the eye of the rabbits elicited slight swelling and injected blood vessels which was not fully reversible within 2 days.

In addition, several supporting studies on eye irritation tests are available (Hoechst 1973, 1982 and 1988). In all of these assays the test substance induced slight sweling and redness. All symptoms resolved latest within 48h.

There are no data available about irritation to the respiratory system.

Discussion

Application of the test substance or the analogue onto skin caused very slight to slight edema which were reversible wihtin post observation period. Application into the conjunctival sac of the eye caused slight conjuctival irritation which was latest reversible within 3 days and which was below the treshold of regulation.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified as irritating for skin or eyes under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC.

 

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for irritation under Regulation (EC) No. 1272/2008,as amended for the second time in Directive (EC 286/2011).