Resin acids and Rosin acids, cobalt salts

Endpoint summary

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:

2006-04-11 to 2006-05-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Minor deviations with no effects on the study: - According to the guideline, for the initial test in one animal, the test site is also examined immediately after the patch has been removed. In this study report there was no statement indicating if this was done. - According to the guideline a rationale for in vivo testing should be stated in the study report. This is missing in this study report. - According to the guideline, the individual animal weights at the start and at the conclusion of the test should be stated. In this study report only a mean body weight with standard deviation was stated, which only indicated the mean body weight at the beginning of the study. - According to the guideline, in the test report the volume of vehicle used should be stated. This was missing in this study report.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002-04-24

Deviations:

yes

Remarks:

Minor deviations with no effect on the study (see rationale for reliability)

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: Grimaud frères selection S.A.S., La Corbière, Roussay, France
- Age at study initiation: On the day of treatment, the animals were 2 to 4 months old
- Weight at study initiation: On the day of treatment, the animals had a mean body weight +/- standard deviation of 2.8 +/- 0.1 kg
- Housing: The animals were housed individually in Pajon cages (50 cm X 57 cm X 75 cm). Each cage was equipped with a food container and a water bottle.
- Diet: During the study, the animals had free access to 110C pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France).
- Water (ad libitum): Drinking water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 +/- 3 °C
- Relative humidity: 30 to 70 %
- Ventilation: approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: corn oil

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg of the test item
VEHICLE:
Due to the properties of the test item (degradation on contact with water), corn oil, batch No. 015K0115 (Sigma, Saint-Quentin-Falavier, France was used in order to moisten a gauze pad and ensure a good contact with the skin.
No further information on amount/concentration applied was stated.

Duration of treatment / exposure:

One animal : 3 minutes, 1 hour and 4 hours
Other animals: 4 hours

Observation period:

Observation period was approximately 1 hour, 24, 48 and 72 hours after removal of the dressing. Since there were persistent irritation reactions at 72 hours, the observation period was extended (15 days).

Number of animals:

3 male rabbits

Details on study design:

TEST SITE
The day before treatment, both flanks of each animal were clipped using electric clippers. Clipping was repeated thereafter on days 12 and 13 for one animal and on days 2 and 5 for one animal. Doses of 500 mg of the test item in its original form were placed on a gauze pad moistened with corn oil, which was then applied to an area of approximately 6 cm^2 of the anterior left flank (application for 3 minutes), the anterior right flank (application for 1 hour) or the posterior right flank (application for 4 hours) of the animals. For the 4 hour exposure, a gauze pad moistened with corn oil was applied to the opposite flank, which acted as control. The gauze pad was held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
After removal of the dressing, any residual test item was wiped off by means of a dry cotton pad ofr of a moistened cotton pad with corn oil.

SCORING SYSTEM:
Draize scoring system
No further information on details on study design was stated.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal # 1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 15 days

Remarks on result:

other: On day 15 very slight erythema was still seen.

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days.

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal # 2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal # 3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal # 3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

After a 3 minute exposure (one animal):
A very slight or well-defined erythema (grade 1 or 2) was noted from day 2 until day 8. A slight brown colouration of the skin, associated with a dryness of the skin on day 7, was observed from day 1 until day 9.
After 1 hour exposure (one animal):
A very slight or well-defined erythema (grade 1 or 2) was noted from day 1 until day 15 (end of the observation period).
A slight brwon colouration of the skin was observed from day 1 until day 15 (end of the observation period). A dryness of the skin was recorded from day 6 until day 15 (end of the observation period).
After a 4 -hour exposure (three animals):
On the psoterior right flank (test item application)
A very slight or well-defined erythema (grade 1 or 2) was noted in all the animals from day 1 until day 7 (one animal), 12 (one animal) or 15 (end of the observation period) (one animal). A brown colouration of the skin was observed in all the animals from day 1 until day 4 (one animal), 7 (one animal) or 15 (end of the observation period) (one animal).
A dryness of the skin was recorded in all the animals between day 5 and day 15 (end of the observation preiod). A residual of test item was recorded in 2/3 animals from day 1 until day 4 (one animal() or 15 (end of the observation period) (one animal).
On the posterior left flank (corn oil application)
A very slight erythema (grade 1) was noted in 1/3 animals from day 1 until day 5.

Only the raw data up to 72 hours are stated:

Raw data for 3 -minute exposure:

Rabbit No.	Dermal irritation	1 hour	24 hours	48 hours	72 hours	Mean irritation score (24 h, 48 h, 72h)
1	Erythema	0	2	2	2	2.0
	Oedema	0	0	0	0	0.0

Raw data for 1 hour-exposure:

Rabbit No.	Dermal irritation	1 hour	24 hours	48 hours	72 hours	Mean irritation score (24 h, 48 h, 72h)
1	Erythema	2	2	2	2	2.0
	Oedema	0	0	0	0	0.0

Raw data for 4 hour-exposure:

Rabbit No.	Dermal irritation	1 hour Day 1	24 hours Day 2	48 hours Day 3	72 hours Day 4	Mean irritation score (24 h, 48 h, 72h)
1	Erythema	2	2	2	2	2.0
	Oedema	0	0	0	0	0.0
2	Erythema	2	2	2	2	2.0
	Oedema	0	0	0	0	0.0
3	Erythema	2	2	2	2	2.0
	Oedema	0	0	0	0	0.0

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions, the test item Produit Y was irritant when applied topically to rabbits.
According to (EC) No.: 1272/2008, and subsequent regulations, the test item is not classified as skin irritant.

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:

2006-04-27 to 2006-05-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Minor deviations without an effect on the study: -According to the guideline, after recording the observations at 24 hours, the eyes may be further examined with the aid of fluorescein. In the study evaluation with the aid of fluorescein was performed at 24 hours and no after the recording of the observations at 24 hours. - According to the guideline a rationale for in vivo testing should be stated in the study report. This is missing in this study report. - According to the guideline, the individual body weight at start and conclusion of the the test should be stated. In this study, the individual body weight of the animals at the start and at the conclusion of the study were not stated. - In the Draize scoring system referes conjunctival redness to palpebral and bulbar conjunctivae and excludes cornea and iris. In this study cornea and iris are included in the scoring system.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2002-04-24

Deviations:

yes

Remarks:

Minor deviations with no effect on the study (see rationale for reliability)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Grimaud frères selection S.A.S., La Corbière, Roussay, France
- Age at study initiation: On the day of treatment, the animals were 2 to 4 months old
- Weight at study initiation: On the day of treatment, the animals had a mean body weight +/- standard deviation of 3.0 +/- 0.1 kg.
- Housing: The animals were housed individually in Pajon cages (50 cm X 57 cm X 75 cm) equipped with a food container and a water bottle.
- Diet: During the study, the animal had free access to 110C pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France).
- Water (ad libitum): Drinking water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 +/- 3 °C
- Relative humidity: 30 to 70 %
- Ventilation: approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg of the test item in its original form
No further information on amount/concentration applied was stated.

Duration of treatment / exposure:

not stated

Observation period (in vivo):

The eyes were examined approximately 1 hour, 24, 48 and 72 hours after administration of the test item.

Number of animals or in vitro replicates:

3 rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
The eyes were not rinsed after administration of the test item.
SCORING SYSTEM: Draize scoring system
TOOL USED TO ASSESS SCORE: Conjucntival reactions, iritis and corneal opacification were evaluated daily for each animal. For evaluation of corneal opacification (presence or absence, affected area), the eyes were examined under a UV lamp after instillation of one or two drops of 0.5 % sodium fluorescein solution (a clear fluorscence is visible in the area of opacification). This evaluation was performed on day 2 and repeated thereafter whenever necessary.
No further information in details on study design was stated.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal # 2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal # 2

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

Slight or moderate chemosis (grade 1 or 2), slight or moderate redness of the conjunctiva n(grade 1 or 2) and clear discharge were observed in all the animals on day 1; some of these reactions persisted until day 2 (one animal) or 3 (two animals).
A slight corneal opacity (grade 1 ) was recorded in 2/3 animals on day 2.
No other ocular reactions were noted during the study.

Raw data of individual ocular examinations and mean values of the scores recorded for each animal (24, 48 and 72 hours)

Rabbit No.	Region of eye	Eye irritation	1 hour Day 1	24 hours Day 2	48 hours Day 3	72 hours Day 4	Mean irritation score (24, 48 and 72 hours)
1	Conjunctivae	Chemosis	2	1	1	0	0.7
		Redness	2	1	1	0	0.7
		Discharge	1	0	0	0	0.0
	Iris		0	0	0	0	0.0
	Corneal opacity	Intensity	0	1	0	0	0.3
		Area	0	1	0	0	0.3
	Other		Residual test item
	Fluorescein		Fluorescein not used	Fluorescein used	Fluorescein used	Fluorescein used
2	Conjunctivae	Chemosis	2	1	0	0	0.3
		Redness	2	1	1	0	0.7
		Discharge	1	0	0	0	0.0
	Iris		0	0	0	0	0.0
	Corneal opacity	Intensity	0	0	0	0	0.0
		Area	0	0	0	0	0.0
	Other		Residual test item
	Fluorescein		Fluorescein not used	Fluorescein used	Fluorescein not used	Fluorescein not used
3	Conjunctivae	Chemosis	1	1	0	0	0.3
		Redness	2	1	0	0	0.3
		Discharge	1	0	0	0	0.0
	Iris		0	0	0	0	0.0
	Corneal opacity	Intensity	0	1	0	0	0.3
		Area	0	1	0	0	0.3
	Other		Residual test item
	Fluorescein		Fluorescein not used	Fluorescein used	Fluorescein used	Fluorescein not used

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions, the test item Produit Y was slightly irritant when administered by ocualr route to rabbits.
Also, the test item should not be classified as skin irritant according to Regulation (EC) No.: 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Justification for selection of skin irritation / corrosion endpoint:
Key study.

Justification for selection of eye irritation endpoint:
Key study.

Justification for classification or non-classification

Skin irritation

The reference Pelcot (2007) is considered as the key study for skin irritation and will be used for classification.

Under the experimental conditions, the test item cobalt resinate was irritant when applied topically to rabbits.

According to Directive 67/548/EEC (and subsequent adaptations) the test item is classified as irritating and assigned the symbol Xi, the indication of danger "Irritant" and the risk phrase R38: "Irritating to skin" to the skin.

According to (EC) No.: 1272/2008, and subsequent regulations, the test item is not classified as skin irritant.

Eye irritation

The reference Pelcot (2007) is considered as the key study for severe eye irritation and will be used for classification. The overall irritation results 24, 48 and 72 hours after application per animal are as follows:

-         Corneal opacity=0.3, 0.0, 0.3

-         Iris light reflex=0.0 for all three animals

-         Conjunctival redness=0.7, 0.7, 0.3

-         Conjunctival oedema (chemosis)=0.7, 0.3, 0.3

The classification criteria acc. to regulation (EC) 1272/2008 as irritating to eyes are not met, since the overall irritation results were below the thresholds as well as the effects were fully reversible within 48 hours or 72 hours. No classification required.