2,20-dichloro-13,31-diethyl-4,22-dioxa-13,18,31,36-tetraazanonacyclo[19.15.0.03,19.05,17.06,14.07,12.023,25.024,32.025,30]hexatriaconta-1(36),2,5,7,9,11,14,16,18,20,23,25,27,29,32,34-hexadecaene

Endpoint summary

Description of key information

Skin irritation:
In a OECD guideline and GLP compliant primary skin irritation test in rabbits, the test item

(Pigment Violet 23) caused grade 0-2 erythema after 30-60 minutes, while neither erythema nor edema were observed 24, 48 and 72 hours after application of the test substance. Therefore, the test item (Pigment Violet 23) can be regarded as not skin irritating.
Eye irritation:
In a OECD guideline and GLP compliant primary eye irritation test in rabbits, the test item (Pigment Violet 23) caused grade 1 chemosis after one hour and conjunctival reddening grade 2 after 1 hours and grade 1 after 24 hours. No effects were observed for these and other parameters at the other reading times up to 72 hours. Therefore, the test item (Pigment Violet 23) can be regarded as not eye irritating.
Respiratory tract:
Study was waived; substance is not classified for this endpoint. The substance is considered not to exert any special local irritative or systemic adverse effects; the substance is considered likely to behave like an inert dust.
Non-human information: This information is not available.
Human information: No human information is available

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study meets the requirements of OECD Guideline 404 and EU Method B.4 (84/449/EEC)

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

84/449/EEC

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Animal specifics: Hoechst AG, conventional breed
- Source: Hoechst AG, Kastengrund
- Age at study initiation: 2 months to 5 months
- Weight at study initiation: 2,2 kg to 4,1 kg
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls
- Diet (e.g. ad libitum): standard laboratory diet (Albtromin 2123) ad libitum, appr. 15 g hay daily
- Water (e.g. ad libitum): deionized chlorinated water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20° ± 3°C (air-condition)
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: Polyethyleneglycol 400

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit):1.0 ml to moisten the test item
- Lot/batch no. (if required): Ch-B 2322 , Riedel de Haen AG

Duration of treatment / exposure:

4 hours

Observation period:

3 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: approximately 2.5 cm x 2.5 cm
- Type of wrap if used: surgical gauze patch (Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): flushed with lukewarm tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM:
as in EU Method B.4, assessed approximately 30 - 60 min, 24, 48, and 72 h after the romoval of the test item

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: erythema grade 0, 1 and 2 observed in the three animals at 30-60 min reading were fully reversible within 24 hours

Irritation parameter:

edema score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effects occured

Irritant / corrosive response data:

Scores (oedema or erythema) were 0 at 24, 48 and 72 h after removal of dressing in all animals (see table below for individual data).

Other effects:

Staining produced by the test item was present at all reading time points.

Animal number	Evaluation interval (after removal of dressing)	Erythema score	Oedema score	Violet staining
#1	30 - 60 min	2	0	x
#2		1	0	x
#3		0	0	x
#1	24 hours	0	0	x
#2		0	0	x
#3		0	0	x
#1	48 hours	0	0	x
#2		0	0	x
#3		0	0	x
#1	72 hours	0	0	x
#2		0	0	x
#3		0	0	x

Interpretation of results:

GHS criteria not met

Conclusions:

67/548/EEC: Skin irritation: no classification warranted
1272/2008/EC: Skin irritation: no classification warranted

In a OECD guideline and GLP compliant primary skin irritation test in rabbits, Hostaperm-Violett RL spez. (Pigment Violet 23) caused grade 0-2 erythema after 30-60 minutes, while neither erythema nor edema were observed 24, 48 and 72 hours after application of the test substance. Therefore, Hostaperm-Violett RL spez. (Pigment Violet 23) can be regarded as not skin irritating.

Executive summary:

The primary skin irritation potential of the test item was investigated according to OECD test guideline no. 404. The test item was applied by topical semi-occlusive application of 0.5 g to the intact flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 30 - 60 min, 24, 48 and 72 hours after removal of the dressing. The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. The application of the test item to the skin resulted in mild, early-onset and transient signs of irritation such as erythema. These effects were reversible and were no longer evident 24 hours after treatment for all animals. Staining of the treated skin was noted in all animals throughout the whole study. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the skin. Based upon the referred classification criteria (Commission Directive 84/449/EC of April 1984), the test item is considered to be "not irritating" to rabbit skin.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study meets the requirements of OECD Guideline 405 and EU Method B.5 (84/449/EEC)

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

84/449/EEC

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Animal specifics: Hoechst AG, conventional breed
- Source: Hoechst AG, Kastengrund
- Age at study initiation: 3 months to 5 months
- Weight at study initiation: 2.2 kg to 3.9 kg
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls
- Diet (e.g. ad libitum): standard laboratory diet (Albtromin 2123) ad libitum, appr. 15 g hay daily
- Water (e.g. ad libitum): deionized chlorinated water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20° ± 3°C (air-condition)
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

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

Duration of treatment / exposure:

One administration 24 hours

Observation period (in vivo):

3 days

Number of animals or in vitro replicates:

3

Details on study design:

Application of the substance to the conjunctival sac of the left eye of each animal, the right eyes served as control respectively

REMOVAL OF TEST SUBSTANCE
- Washing: Washing with physiological saline at approx. 37 °C 24 h after administration and at all other designated examination times at which the treated eyes still showed discharge or at which a corneal examination with fluorescein sodium solution (24, 48 and 72 h after administration) took place
- Time after start of exposure: see above

TOOL USED TO ASSESS SCORE: 0.01 % solution of fluorescein sodium, under UV light

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since on effects occured

Irritation parameter:

iris score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: reversibility not relevant since no effects occured

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: grade 1 chemosis was observed in all animals at 1 hour and was fully reversible within 24 hours

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

The score refers to redness of conjunctiva, which was evident in all animals 1 h after treatment (score 2 in all 3 animals). The value of 0.3 is the mean (of the three assessments at 24, 48 and 72 h) for all animals combined as well as for each individual animal. At 48 and 72 h, this score was 0 in all animals. Other parameters examined (opacity of cornea, iris, chemosis of conjunctiva) showed scores of 0 at all time points.

Other effects:

Blue staining of eye discharge was observed at 1 hour after application.

Results table:

Animal	Evaluation interval(after application)	Opacity ofcornea	Redness ofconjunctiva	Chemosis ofconjunctiva	Iris	Violet eyedischarge	Fluoresceinestaining
# 1	1 hour	0	2	1	0	x
# 2		0	2	1	0	x
# 3		0	2	1	0	x
# 1	24 hours	0	1	0	0		0
# 2		0	1	0	0		0
# 3		0	1	0	0		0
# 1	48 hours	0	0	0	0
# 2		0	0	0	0
# 3		0	0	0	0
# 1	72 hours	0	0	0	0		0
# 2		0	0	0	0		0
# 3		0	0	0	0		0

Interpretation of results:

GHS criteria not met

Conclusions:

67/548/EEC: Eye irritation: no classification warranted
1272/2008/EC: Eye irritation: no classification warranted

In a OECD guideline and GLP compliant primary eye irritation test in rabbits, Hostaperm-Violett RL spez. (Pigment Violet 23) caused grade 1 chemosis after one hour and conjunctival reddening grade 2 after 1 hours and grade 1 after 24 hours. No effects were observed for these and other parameters at the other reading times up to 72 hours. Therefore, Hostaperm-Violett RL spez. (Pigment Violet 23) can be regarded as not eye irritating.

Executive summary:

A study with the test item according to OECD Guideline 405 and EU Method B.5 was performed to investigate the irritation potential to the rabbit eye.

One and 24 hours after treatment the conjunctivae of the animals showed definitely injected blood vessels up to a diffuse crimson red colour. Additionally, a very slight swelling and slight from substance coloured eye discharge were observed in the animals one hour after treatment. 48 hours after treatment all signs of irritation were reversible.

Testing of Pigment Violet for primary eye irritation in the rabbit showed that the substance is not irritating to the eye.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Pigment Violet 23 has been tested in vivo for irritative properties in a skin irritation test in rabbits. In this GLP and OECD guideline compliant study, the substance caused only slight, transient coloration to the skin at the 30-60 minute reading. The individual and group mean of scores read 1, 2 and 3 days after treatment were all 0 and thus well below the classification criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC). Therefore, Pigment Violet 23 does not have to be classified as skin irritating.

 

Pigment Violet 23 has been tested in vivo for irritative properties in an eye irritation test in rabbits. The substance caused only very slight, transient irritation to the conjunctivae. The individual and group mean of scores read 1, 2 and 3 days after treatment were well below the classification criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC). Therefore, Pigment Violet 23 does not have to be classified as eye irritating.

 

It can reasonably be deduced that Pigment Violet 23 does not cause respiratory tract irritation and thus does not have to be classified according to the criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC), because Pigment Violet 23 did cause only very slight, fully reversible irritative effects in the eyes and on the skin and does not have to be classified as either skin or eye irritating. Moreover, Pigment Violet 23, in the unlikely event of being inhaled as a dust, is considered not to cause more severe effects than an inert dust, because its chemical inertness and extremely low solubility in water and n-octanol largely prevent interaction with living cells and tissues.