Barium bis[2-[(2-hydroxy-1-naphthyl)azo]benzoate]

Endpoint summary

Description of key information

Skin
RA_PR 53.1_key_404_1988_Hoechst_88.1297: not irritating / not corrosive
QSAR PR 50.1 skin irritation OECD Toolbox: not classified
QSAR PR 53.1 skin irritation OECD Toolbox: not irritating
Eye
RA PR 53:1_key_405_1988_Hoechst_88.1376: not irritating
QSAR PR 50.1 eye irritation OECD Toolbox: not classified
QSAR PR 53.1 eye irritation OECD Toolbox: 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:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

according to OECD and GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

84/449/EEC

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Animal specifics: New Zealand White , conventional breed
- Source: Hoechst AG, breeding colony
- Age at study initiation: 3 - 5 months
- Weight at study initiation: 2.3 - 2.6 kg
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls
- Diet (e.g. ad libitum): standard laboratory diet (Altromin 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 (fully air-conditioned)
- Humidity (%): 50 ± 20 %
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: polyethylene glycol 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): polyethylene glycol 400, 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
approximately 24 h before treatment the test site was clipped free of hair (25 cm2).
- Area of exposure: approximately 2.5 cm x 2.5 cm
- Type of wrap if used: surgical gauze patch (Beiersdorf AG), fixed with a semiocclusive bandage.

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 removal of the test item

Irritation parameter:

erythema score

Basis:

animal: #1, #2, #3 each

Time point:

other: mean of the 24, 48 and 72 hours reading

Score:

0

Max. score:

4

Reversibility:

other: Animal 1: Erythema grade 1 observed at 30-60 min reading was fully reversible within 24 hours. Animal 2 & 3: Reversibility not relevant since no effects occured.

Irritation parameter:

edema score

Basis:

animal: #1, #2, #3 each

Time point:

other: mean of the 24, 48 and 72 hours reading

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

Other effects:

light-red staining produced by the color of the test item was present in all animals at all reading time points.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item has not to be classified for skin irritation/corrosion according to Regulation (EC) No 1272/2008

Executive summary:

The primary skin irritation potential of the test item was investigated according to OECD 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 slight, early-onset and transient erythema in one animal. This effect was reversible and no longer evident 24 hours after treatment. Light-red staining of the treated skin (caused by the color of the test item) was noted in all animals throughout the whole study. Mean scores of all animals for edema and erythema were 0. 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.

Therefore, the test item has not to be classified for skin irritation/corrosion according to Regulation (EC) No 1272/2008.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

According to OECD and GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

84/449/EEC

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Animal specifics: New Zealand White, conventional breed
- Source: Hoechst AG, breeding colony
- Age at study initiation: 3 to 5 months
- Weight at study initiation: 2.5 kg to 2.8 kg
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls
- Diet (e.g. ad libitum): standard laboratory diet (Altromin 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 (%): 50 ± 20%
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: the right untreated eye of each animal served as control respectively

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:

animal: #1, #2, #3 each

Time point:

other: mean of the 24, 48 and 72 hours reading

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since on effects occured

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3 each

Time point:

other: mean of the 24, 48 and 72 hours reading

Score:

0

Max. score:

2

Reversibility:

other: reversibility not relevant since no effects occured

Irritation parameter:

chemosis score

Basis:

animal: #1, #2, #3 each

Time point:

other: mean of the 24, 48 and 72 hours reading

Score:

0

Max. score:

4

Reversibility:

other: grade 2 (2 anmials) and 1 (1 animal) was observed 1 hour after administration and was fully reversible within 24 hours

Irritation parameter:

conjunctivae score

Basis:

animal: #1, #2 each

Time point:

other: mean of the 24, 48 and 72 hours reading

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: mean of the 24, 48 and 72 hours reading

Score:

0

Max. score:

3

Reversibility:

other: grade 1 was observed 1 hour after administration and was fully reversible within 24 hours

Irritant / corrosive response data:

1 hour after administration injected vessels up to diffuse crimson red colour and slight swelling of conjunctivae was observed in all animals. All signs of irritation were fully reversible after 48 h.

Other effects:

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

Animal	Evaluation interval (after application)	Opacity of cornea	Redness of conjunctiva	Chemosis of conjunctiva	Iris	Red eye discharge	Fluoresceinestaining
# 1	1 hour	0	2	2	0	x
# 2		0	2	2	0	x
# 3		0	1	1	0	x
# 1	24 hours	0	1	0	0		0
# 2		0	1	0	0		0
# 3		0	0	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:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a OECD guideline and GLP compliant primary eye irritation test in rabbits mean scores for cornea, iris and chemosis of conjunctiva were 0 for all animals. Mean scores for redness of conjunctiva were 0.3 for two and 0 for one animal. All signs of irritation were fully reversible after 48 h.

Therefore, the test item has not to be classified according to Regulation (EC) No 1272/2008.

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 injected blood vessels up to a diffuse crimson red colour. Additionally, a slight swelling and slight from substance coloured eye discharge were observed in the animals one hour after treatment. Mean scores for cornea, iris and chemosis of conjunctiva were 0 for all animals. Mean scores for redness of conjunctiva were 0.3 for two and 0 for one animal. 48 hours after treatment all signs of irritation were reversible.

Therefore, the test item has not to be classified according to Regulation (EC) No 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Discussion

No experimatal data are available for skin/eye irritation/corrosion of Pigment Red 50:1. Thus data were provided by application of read across using existing data from Pigment Red 53.1 to predict skin/eye irritation/corrosion of Pigment Red 50:1. The prediction for Pigment Red 50:1 reads as follows:

Skin: no irritating / not corrosive

Eye: not irritating

This read across derivation is strongly supported by QSAR analyses using the OECD Toolbox which predicts the following skin/eye irritation/corrosion:

Skin

Pigment Red 50:1: not classified

Pigment Red 53.1: not irritating

Eye

Pigment Red 50:1: not classified

Pigment Red 53:1: not irritating

The data sources used provide consistent data allowing the final conclusion that Pigment Red 50:1 is not irritating/corrosive to skin or eye.

Read Across Justification

The purpose of this assessment is to provide justification for read across in order to estimate acute oral toxicity of Pigment Red 50:1 (target substance) and to predict its possible irritant or corrosive properties after contact with skin or eyes based on existing date coming from Pigment Red 53:1 (source substance).

The pigments used in this approach are structurally similar and differ only by diverging substituents in the common core molecule. Target and source substance are solids which decompose at high temperatures (>= 306°C). Solubility in water or n-octanol is low or very low for the source substance (in water: 3.0 mg/L, in n-Octanol: 0.7 mg/L) and even lower for the target substance (in water: 0.3 mg/L, in n-Octanol: 0.6 mg/L). These values suggest poor absorption and low bioavailability for both pigments.

The log n-octanol-water partition coefficients were -0.62 and 0.41 for the source and for the target substance respectively. These values are far below the limit of concern considered to be critical for bio-accumulative properties.

The pH value of both pigments is not extreme and therefore gives no reason to assume corrosive properties.

Pigment Red 50:1 showed very limited biodegradability (not readily biodegradable in the 10-day-window and within 28 days), which is assumed to be due to its unavailability for microorganisms.

Poor bioavailability is probably also the reason for the absence of any relevant acute mammalian toxicity. The target pigment was not skin sensitising in the LLNA. Both pigments were not mutagenic in the Bacterial Reverse Mutation Assay neither with nor without S9-mix indicating that metabolic activation is not an issue.

Due to its low solubility and its inertness it can reasonably be assumed that considerable amounts of both pigments are virtually not present in a dissolved form on the skin or mucous membranes after single dermal or oral exposure, i.e. they cannot be absorbed in relevant amounts after single oral application and do not cause local effects after contact with skin or eyes. This reasoning is supported by the outcome of QSAR analyses predicting very low acute oral toxicity (LD50 values above 4000 mg/kg bw.) and the absence of skin and eye irritating properties for both the target and the source substance.

This assessment is based on experimental and QSAR data on the source pigment as compared to available data of the target pigment covering the following endpoints: Specific physicochemical properties, acute oral toxicity, skin and eye irritation/corrosion, skin sensitisation, genotoxicity in vitro, and biodegradability (for details see data matrix below).

In conclusion, the similar structure and the uniformity of physicochemical, environmental fate and toxicological properties justifies the application of read across to predict the outcome of acute oral toxicity and skin/eye irritation/corrosion studies of the target pigment based on existing date coming from the source pigment. Supporting evidence is provided by QSAR analysis predicting consistently a very low acute oral toxicity and the absence of irritating/corrosive properties to skin and eyes.

Data Matrix

CHEMICAL NAME	C.I. Pigment Red 50:1	C.I. Pigment Red 53:1
Role	Target Substance	Source Substance
CAS No.	6372-81-2	5160-02-1
Physical and Chemical Properties
Physical state of the substance at 20° C and 1013 hPa	red solid	red solid
Melting/freezing point	Decomp. Temp.: >=306°C	Decomp. Temp.: > 320°C
Water solubility	0.25 mg/L	2.986 mg/L
n-Octanol solubility	0.64 mg/L	0.716
log Partition coefficient n-octanol/water (logPow)	0.41	-0.62
pH	6.9 (10% suspension)	5 - 8
Environmental Fate and Pathways
Biodegradation in water: screening test	not readily biodegradable in the 10-d-window and after 28 days	no experimental data
Toxicological Information
Skin irritation (in vivo)	RA-conclusion: not irritating	not irritating
Skin irritation (QSAR)	OECD Toolbox: not irritating	OECD Toolbox: not irritating
Eye irritation (in vivo)	RA-conclusion: not irritating	not irritating
Eye irritation (QSAR)	OECD Toolbox: not irritating	OECD Toolbox: not irritating
Skin sensitisation	not skin sensitising (LLNA)	no experimental data
In vitro gene mutation study in bacteria	not mutagenic (AMES)	not mutagenic (AMES)
Acute toxicity, oral route, (experimental LD50 mg/kg b.w., rats)	RA-conclusion: > 2000	> 2000
Acute toxicity, oral route (QSAR, LD50 mg/kg b.w.)	OECD Toolbox: 4840	OECD Toolbox: 6670

Justification for selection of skin irritation / corrosion endpoint:
Eperimental data for read across come from the most similar substance available.

Justification for selection of eye irritation endpoint:
Eperimental data for read across come from the most similar substance available.

Justification for classification or non-classification

Based on available data Pigment Red 50:1 was predicted be read across and QSAR analyses to have no skin/eye irritant/corrosive properties. Therefore the test item has not to be classified for skin/eye irritation/corrosion according to Regulation (EC) No 1272/2008.