Strontium 3-hydroxy-4-[(1-sulfonato-2-naphthyl)azo]-2- naphthoate 5/2 hydrate

Endpoint summary

Description of key information

Based on the Eye irritation study and Skin irritation study, R507-2 does not have to be classified and has no obligatory labelling requirement for oral toxicity according to the GHS of Classification and labelling of Chemicals of the United nations (2004) and EC criteria for classification and labelling (1272/2008)

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:

07 December 2007- 21 December 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan, Horst, The Netherlands.
- Age at study initiation: 6 weeks old
- Weight at study initiation: at least 1.0 kg.
- Housing: Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56 x 44 x 37.5 cm).
- Diet (e.g. ad libitum): Pelleted diet for rabbits (K-H from SSNIFF® Spezialdiaten GmbH, Soest, Germany) approximately 100 grams per day. Hay (Tecnilab-BMI BV, Someren, The Netherlands) was provided at least three times a week.
- Water (e.g. ad libitum):Free access to tap water.
- Acclimation period: Acclimatization period was at least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0 °C (actual range: 20.7 - 21.7 °C), a relative humidity of 30-70 % (actual range: 26 - 59 %) and 12 hours artificial fluorescent light and 12 hours darkness per day.


IN-LIFE DATES: From:07 December 2007 To:-21 December 2007

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: Since the test substance did not mix with water, the powdery test substance was moistened with watery ethanol (50% v/v) (water, Elix, Millipore SAS., Molsheim, France; ethanol, Merck, Darmstadt, Germany)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):Each animal was treated by dermal application of 0.5 grams of the test substance.
- Concentration (if solution):The test substance was moistened with 1 ml of the vehicle.

Duration of treatment / exposure:

4 hours

Observation period:

The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance.

Number of animals:

3 animals

Details on study design:

TEST SITE
the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10 x 15 cm). To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations. Each animal was treated by dermal application of 0.5 grams of the test substance. The test substance was moistened with 1 mL of the vehicle and applied to the skin of one flank, using a metalline patch of 2 x 3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water, watery ethanol (50 % v/v) (water, Elix, Millipore SAS., Molsheim, France; ethanol, Merck, Darmstadt, Germany) and watery acetone (50 % v/v) (water, Elix, Millipore SAS., Molsheim, France; acetone, VWR Prolabo, Leuven, Belgium). On Day 3, the skin of one animal was cleaned of residual test substance using watery ethanol and watery acetone.

OBSERVATION TIME POINTS
The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance.

SCORING SYSTEM:
- Method of calculation: Scoring system for Erythema and eschar formation and Oedema formation.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

Mean value based on three animals.

Time point:

72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

Mean value based on three animals

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Interpretation of results:

GHS criteria not met

Conclusions:

Since no oedema was observed throughout the observation period and no erythema was observed after 72 hours, it was considered that no severe erythema was present during the first 48 hours after exposure. Therefore, the results were considered sufficient for classification and labelling purposes.

Based on these results, R507-2 does not have to be classified and has no obligatory labelling requirement for skin irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2004) and EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC).

Executive summary:

Primary skin irritation/corrosion study with R507-2 in the rabbit (4-hour semi-occlusive application).

 Three rabbits were exposed to 0.5 grams of R507 -2, moistened with 50 % watery ethanol by application onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were assessed 1, 24, 48 and 72 hours after exposure.

 

 

No oedema in the treated skin of the rabbits was caused by 4 hours exposure to 0.5 g of

R507-2. No erythema was noted at 72 hours after exposure.Red staining of the treated skin by the test substance prevented scoring for erythema at 1, 24 and 48 hours after exposure.

 

Following exposure and throughout the observation period, red staining of the treated skin by the test substance was observed.

 

 

Since no oedema was observed throughout the observation period and no erythema was observed after 72 hours, it was considered that no severe erythema was present during the first 48 hours after exposure. Therefore,the results were considered sufficient for classification and labeling purposes.

 

Based on these results, R507-2 does not have to be classified and has no obligatory labeling requirement for skin irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2004) and EC criteria for classification and labeling requirements for dangerous substances and preparations (Council Directive 67/548/EEC.

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:

11 December 2007 - 30 December 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan, Horst, The Netherlands.
- Age at study initiation: 6 weeks old.
- Weight at study initiation: 1 kg
- Housing: Housed individually in labelled cages with perforated floors.
- Diet (e.g. ad libitum): Pelleted diet for rabbits approx 100 grams per day. Hay (Tecnilab-BMI BV, Someren, The Netherlands) was provided at least three times a week.
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.6-21.7 °C
- Humidity (%): 42 %-60 %
- Air changes (per hr): 15 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours dark and 12 hours artificial light.

IN-LIFE DATES: From: 11 December 2007 To: 30 December 2007

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 30.3 - 30.4 mg (a volume of approximately 0.1 mL)

Duration of treatment / exposure:

72 Hours.

Observation period (in vivo):

1, 24, 48, and 72 hours.

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not specified
- Time after start of exposure:

SCORING SYSTEM: Not specified

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein- Not specified.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Reversibility:

fully reversible within: 48hours

Irritant / corrosive response data:

There was no evidence of occular corrosion.

No symptoms of systemic toxicity were observed in the animals during the test period, and no mortality occurred.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on these results, R507-2 does not have to be classified and has no obligatory labelling requirement for Eye irritation according to the GHS of Classification and labelling of Chemicals of the United nations (2004) and EC criteria for classification and labelling (1272/2008).

Executive summary:

Single samples of approximately 30mg of R507 -2 ( a volume of approx 0.1mL) were instilled into each eye of each of the three rabbits. Observations were made at 1, 24, 48, and 72 hours after instillation.

Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 48 hours.

Remnants of the test substance were present in the eye during Day 1 and on the outside of the eyelids during the observation period. Red staining of the fur on the head and the paws, caused by the test substance, was noted throughout the observation period.

Based on these results, R507-2 does not have to be classified and has no obligatory labelling requirement for Eye irritation according to the GHS of Classification and labelling of Chemicals of the United nations (2004) and EC criteria for classification and labelling (1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Justification for classification or non-classification

Both the skin and Eye irritation showed no adverse effects and no irritation to the animals.

Based on the Eye irritation study and Skin irritation study, R507-2 does not have to be classified and has no obligatory labelling requirement for oral toxicity according to the GHS of Classification and labelling of Chemicals of the United nations (2004) and EC criteria for classification and labelling (1272/2008)