GOLDEN YELLOW SCJ 1006

Endpoint summary

Description of key information

Skin corrosion/irritation: non-irritant
Eye-damage/irritation: non-irritant

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:

1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline study performed under GLP without deviations

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:

92/69/EEC

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Species: Albino Rabbit, New Zealand White, (SPF-Quality), Source: Broekman Institute, Someren, The Netherlands.
Number of animals: 3 male rabbits
Age at start of treatment: Approx. 7 weeks
Body weight at start of treatment: 1401 - 1510 grams
Identification: Ear tag.
ANIMAL HUSBANDRY
Conditions: Air-conditioned room with approximately 15 air changes per hour and the environment controlled with optimal conditions considered as being a temperature of 21 °C and a relative humidity of 50%. Fluctuations from these optimal conditions were noted, but were considered not to have affected study integrity. Lighting was 12 hours artificial fluorescent light and 12 hours dark per day.
Accommodation: Individually in labelled cages with perforated floors (Scanbur Denmark) and equipped with an automatic drinking system (ITL, Bergen, The Netherlands). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Standard laboratory rabbit diet (LKK-20, pellet diameter 4mm, Hope Farms, Woerden, The Netherlands) approx. 100 gram per day. Certificates of analysis were examined and retained in the NOTOX archives. In addition, hay (BMI, Helmond, The Netherlands) was provided once a week.
Water: Free access to tap-water diluted with decalcified water. Certificates of analysis were examined and retained in the NOTOX archives.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: The powdery test substance was moistened with distilled water.

Controls:

no

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4 h

Observation period:

terminated after 7 days as all scores were 0.

Number of animals:

3

Details on study design:

Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm ²).
The animals were examined, and the skin to be treated in particular, prior to test substance administration and no abnormalities were detected. On test day 1, 0.5 grams of the test substance was moistened (The 0.5 grams was moistened with 2 ml of distilled water, to obtain a mixture that was suitable for application) and subsequently applied to the intact skin of the clipped area on one flank, using a Scotchpak-non-woven patch (Supplier, 3M, St. Paul, U.S.A.) of 2x3 cm. A similar patch (but without test substance and water) was applied to the contralateral flank, to act as a procedural control. Both patches were mounted on Micropore tape*, which was wrapped around the abdomen and secured with Coban elastic bandage.
Four hours after the application, the dressing was removed and the remaining test substance removed using a tissue moistened with tap-water and subsequently a dry tissue. Whenever considered necessary the skin areas concerned of the animals were re-clipped and/or washed with moistened tissues at least 3 hours before the observations, to facilitate the scoring.
Based on the results obtained in this study and after consultation with the sponsor, the study was repeated. In this repeat, the skin of the rabbits was cleaned by depilation after exposure to the test substance in order to facilitate scoring. This study (NOTOX project 171056) is reported in the Appendix.
OBSERVATIONS
Mortality/Viability: Twice daily
Toxicity: At least once daily.
Body Weight: Day of treatment (prior to application).
Irritation : The skin reactions were assessed at approximately 1, 24, 48 and 72 hours and 7 days after the removal of the dressings and test substance. The irritation scores and a description of all other (local) effects were recorded.
The skin reactions were graded according to the following numerical scoring system:
ERYTHEMA AND ESCHAR FORMATION
No erythema: 0
Very slight erythema (barely perceptible): 1
Well defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness): 4 (In case of signs of necrosis or corrosion (injuries in depth) preventing erythema reading, the maximum grade for erythema (= 4) is given)
OEDEMA FORMATION
No oedema: 0
Very slight oedema (barely perceptible): 1
Slight oedema (edges of area well defined by definite raising): 2
Moderate oedema (raised approximately 1 mm): 3
Severe oedema (raised more than 1 mm and extending beyond area of exposure): 4
INTERPRETATION OF RESULTS
The irritation scores and all other observations were transcribed for compilation and analysis.
The individual scores for erythema and oedema are summarised in tabular form.
A primary irritation index was calculated (the sum of the irritation scores for erythema and oedema obtained at 24 and 72 hours after exposure, divided by 2 times the number of animals used in the study). With the primary irritation index a degree of irritation was obtained, using the table described below (based on Draize et.al. (1944) J.Pharmacol .Exp. 82, 377):
Primary irritation index Degree of irritation
0: non-irritating
> 0 - 0.4: negligibly irritating
>0.4 - 2.0: mildly irritating
>2.0 - 5.0: moderately irritating
>5.0 - 8.0: severely irritating
Note: Where the scoring procedure and the clinical judgement were not in agreement, the assessment of irritancy was based on the latter.

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: scoring was hardly possible due to red staining but deduced from the preliminary test in the skin sensitisation study in which the skin was depilated prior to treatment

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: scoring was hardly possible due to red staining but deduced from the preliminary test in the skin sensitisation study in which the skin was depilated prior to treatment

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: scoring was hardly possible due to red staining but deduced from the preliminary test in the skin sensitisation study in which the skin was depilated prior to treatment

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: mean of 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: scoring was hardly possible due to red staining but deduced from the preliminary test in the skin sensitisation study in which the skin was depilated prior to treatment

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: 7 days following treatment

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: mean of 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

Due to the absence of available scores for erythema during the first 72 hours of the study, no primary irritation index could be calculated. A repeat of the study, in which the skin was cleaned after exposure to the test substance by depilation, also allowed no conclusion to be drawn, since comparable reactions were observed in the test substance treated skin area and the control site. These reactions were considered to be caused by the depilation procedures. For the sensitisation study with the same substance (NOTOX project 162258), a preliminary irritation test was carried out in guinea pigs. In this test, to remove the staining caused by the test substance and to facilitate scoring, the treated skin was depilated. The results obtained indicate that no irritation was caused by similar concentrations of FAT40543/A after an exposure period of 24 hours. Based on the results obtained in this study and in the preliminary irritation test of the sensitisation study with the same test substance, it is concluded that no irritation is caused by FAT40543/A after 4 hours of exposure. However, red staining of the skin occurred, which persisted for at least 7 days after exposure.

Other effects:

Red staining of the treated skin was observed throughout the 7 day observation period. No oedema were observed. No erythema were observed on day 7.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

FAT40543/A was shown to be non-irritant to rabbit skin. However, red staining of the skin was noted for 7 days.

Executive summary:

The study was carried out in accordance with the OECD guideline No. 404, 'Acute Dermal Irritation/Corrosion' and the EEC Directive 92/69/EEC, B.4, 'Acute Toxicity - Skin irritation.

Three rabbits were exposed to 0.5 grams of FAT40543/A, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours and 7 days after exposure. Exposure to FAT40543/A resulted in red staining of the treated skin, and hence scoring for erythema was made impossible for the first 72 hours after application. No erythema was observed at the observation 7 days after exposure. No oedema was observed during the study. No signs of systemic intoxication were observed during the study period. Due to the absence of available scores for erythema during the first 72 hours of the study, no primary irritation index could be calculated. A repeat of the study, in which the skin was cleaned after exposure to the test substance by depilation, also allowed no conclusion to be drawn, since comparable reactions were observed in the test substance treated skin area and the control site. These reactions were considered to be caused by the depilation procedures. For the sensitisation study with the same substance (NOTOX project 162258), a preliminary irritation test was carried out in guinea pigs. In this test, to remove the staining caused by the test substance and to facilitate scoring, the treated skin was depilated. The results obtained indicate that no irritation was caused by similar concentrations of FAT40543/A after an exposure period of 24 hours. Based on the results obtained in this study and in the preliminary irritation test of the sensitisation study with the same test substance, it is concluded that no irritation is caused by FAT40543/A after 4 hours of exposure. However, red staining of the skin occurred, which persisted for at least 7 days after exposure.

CORROSION: There was no evidence of a corrosive effect on the skin

COLOURATION: Red staining of the treated skin by the test substance was observed.

TOXICITY SYMPTOMS / MORTALITY: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

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:

1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline study under GLP without deviations

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

92/69/EEC

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Species: Albino rabbit, New Zealand White (SPF-Quality), Source: Broekman Institute, Someren, The Netherlands.
Number of animals: 3 male rabbits
Age at start of treatment: Approx. 8 weeks
Body weight at start of treatment: 1412 - 1511 grams
Identification: Ear tag.
ANIMAL HUSBANDRY
Conditions: Air-conditioned room with approximately 15 air changes per hour and the environment controlled with optimal conditions considered as being a temperature of 21 °C and a relative humidity of 50%. Fluctuations from these optimal conditions were noted, but were considered not to have affected study integrity. Lighting was 12 hours artificial fluorescent light and 12 hours dark per day.
Accommodation: Individually in labelled cages with perforated floors (Scanbur, Denmark) and equipped with an automatic drinking system (ITL, Bergen, The Netherlands). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Standard laboratory rabbit diet (LKK-20, pellet diameter 4 mm, Hope Farms, Woerden, The Netherlands) approx. 100 g per day. Certificates of analysis were examined and retained in the NOTOX archives. In addition, hay (BMI, Helmond, the Netherlands) was provided once a week.
Water: Free access to tap-water diluted with decalcified water. Certificates of analysis were examined and retained in the NOTOX archives.

Vehicle:

unchanged (no vehicle)

Remarks:

The powdery test substance was instilled as delivered by the sponsor.

Controls:

other: opposite eye served as control

Amount / concentration applied:

20.6 ±0.3 mg (0.1 mL)

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3

Details on study design:

The animals were examined, and the eyes in particular, prior to test substance administration and no abnormalities were detected. On test day 1, 20.6 ±0.3 mg (0.1 ml) of the test substance was instilled in the conjunctival sac of one eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control. Immediately after the 24 hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.
OBSERVATIONS
Mortality/Viability: Twice daily
Toxicity: At least once daily.
Body Weight: Day of treatment (prior to instillation).
Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7 days after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded.

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritant / corrosive response data:

Instillation of approximately 20 mg (0.1 ml) of FAT40543/A into one eye of each of the rabbits resulted in effects on the conjunctivae. The irritation of the conjunctivae, consisting of redness and Chemosis of the conjunctival tissues and a small amount of discharge, had resolved within 7 days after instillation. Treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage in any of the animals.
CORROSION: There was no evidence of ocular corrosion.

Other effects:

COLOURATION: Remnants of the test substance were noted in the treated eyes of all animals on day 1 and on the outside of the eyelids of one animal on day 2. Red staining of the fur on the head and paws, caused by the test substance, was noted during the observation period.
TOXICITY SYMPTOMS / MORTALITY: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

FAT40543/A, when exposed to rabbit eyes, caused slight conjunctival effects that reversed within 7 days. However, the effects were weak and consequently th substance is not considered an eye irritant following criteria in Regulation EC No 1272/2008 (CLP).

Executive summary:

The study was carried out in accordance with the OECD guideline No. 405, 'Acute Eye Irritation/Corrosion' and the EEC Directive 92/69/EEC, B.5, 'Acute Toxicity - Eye irritation.

Single samples of approximately 20 mg of FAT40543/A (a volume of approximately 0.1 ml) were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours and 7 days after instillation. Instillation of FAT40543/A resulted in irritation of the conjunctivae, which had resolved within 7 days in all animals. Remnants of the test substance were noted in the treated eyes of all animals on day 1 and on the outside of the eyelids of one animal on day 2. Red staining of the fur on the head and paws, caused by the test substance, was noted during the observation period. No signs of systemic intoxication were observed during the study period. FAT40543/A was considered mildly irritating (M2) to the rabbit eye (Kay and Calandra interpretation of the calculated maximum Draize score: 8 ) and consequently not subject to classification following CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Corrosion/Irritation

A study in accordance with the OECD guideline No. 404, 'Acute Dermal Irritation/Corrosion' and the EEC Directive 92/69/EEC, B.4, 'Acute Toxicity - Skin irritation is available in which three rabbits were exposed to 0.5 grams of FAT 40543/A, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours and 7 days after exposure. Exposure to FAT 40543/A resulted in red staining of the treated skin, and hence scoring for erythema was made impossible for the first 72 hours after application. No erythema was observed at the observation 7 days after exposure. No oedema was observed during the study. No signs of systemic intoxication were observed during the study period. Due to the absence of available scores for erythema during the first 72 hours of the study, no primary irritation index could be calculated. A repeat of the study, in which the skin was cleaned after exposure to the test substance by depilation, also allowed no conclusion to be drawn, since comparable reactions were observed in the test substance treated skin area and the control site. These reactions were considered to be caused by the depilation procedures. For the sensitisation study with the same substance (NOTOX project 162258), a preliminary irritation test was carried out in guinea pigs. In this test, to remove the staining caused by the test substance and to facilitate scoring, the treated skin was depilated. The results obtained indicate that no irritation was caused by similar concentrations of FAT 40543/A after an exposure period of 24 hours. Based on the results obtained in this study and in the preliminary irritation test of the sensitisation study with the same test substance, it is concluded that no irritation is caused by FAT 40543/A after 4 hours of exposure. However, red staining of the skin occurred, which persisted for at least 7 days after exposure.

CORROSION: There was no evidence of a corrosive effect on the skin

COLOURATION: Red staining of the treated skin by the test substance was observed.

TOXICITY SYMPTOMS / MORTALITY: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Eye Damage/Irritation

In a study in accordance with the OECD guideline No. 405, 'Acute Eye Irritation/Corrosion' and the EEC Directive 92/69/EEC, B.5, 'Acute Toxicity - Eye irritation a single sample of approximately 20 mg of FAT 40543/A (a volume of approximately 0.1 ml) was instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours and 7 days after instillation. Instillation of FAT 40543/A resulted in irritation of the conjunctivae, which had resolved within 7 days in all animals. Remnants of the test substance were noted in the treated eyes of all animals on day 1 and on the outside of the eyelids of one animal on day 2. Red staining of the fur on the head and paws, caused by the test substance, was noted during the observation period. No signs of systemic intoxication were observed during the study period. FAT 40543/A was considered mildly irritating (M2) to the rabbit eye (Kay and Calandra interpretation of the calculated maximum Draize score: 8 ) and consequently not subject to classification following CLP criteria.

Justification for classification or non-classification

Based on test data the substance FAT 40543/A is not subject to classification for skin corrosion/irritation or eye-damage/irritation according to CLP (Regulation EC No 1272/2008) or DSD (Directive 67/548/EEC).