[No public or meaningful name is available]

Endpoint summary

Description of key information

Based on an in vivo skin irritation study (Safepharm Laboratories Ltd., 1999a) conducted to OECD 404 and in compliance with GLP, the submission substance is irritating to the skin.

Based on an in vivo eye irritation study (Safepharm Laboratories Ltd., 1999b) conducted to OECD 405 and in compliance with GLP, the submission substance is not irritating to eyes.

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:

13/01/1999 to 02/02/1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

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: David Percival Ltd., Cheshire, UK.
- Age at study initiation: 12-16 weeks.
- Weight at study initiation: 2.77-3.17 kg.
- Housing: Individually housed in suspended metal cages.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-21
- Humidity (%): 44-70
- Air changes (per hr): Approximately 15.
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: No data

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

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

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

Three

Details on study design:

TEST SITE
- Area of exposure: Three suitable test sites selected on the backs of the rabbits. A 2.5 x 2.5 cm cotton gauze was used.
- % coverage: No data
- Type of wrap if used: Patch was secured with a strip of surgical adhesive tape and covered with an elasticated corset.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test substance was removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated spirits.
- Time after start of exposure: 4 hours.

SCORING SYSTEM: Draize, 1977

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible

Remarks:

erythema

Remarks on result:

other: Reduced fur growth at 14 days.

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible

Remarks:

erythema

Remarks on result:

other: Reduced fur growth and mild desquamation at 14 days.

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible

Remarks:

erythema

Remarks on result:

other: Reduced fur growth and mild desquamation at 14 days.

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible

Remarks:

edema

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

fully reversible

Remarks:

edema

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible

Remarks:

edema

Irritant / corrosive response data:

Loss of skin flexibility and/or loss of skin elasticity were noted at all of the treated skin sites at the 72-hour observation. Crust formation, which precluded the evaluation of erythema and oedema, was noted at all of the treated sites at the 7-day observation. Slight desquamation or reduced regrowth of fur were noted at all of the treated skin sites at the 14-day observation.

Other effects:

At 7 days following exposure the erythema and oedema could not be assessed due to 'crust formation'. At 14 days erythema and oedema had reversed but there was reduced fur growth in 3/3 animals and mild desquamation in 2/3 animals.

Table 1 Skin irritation results

   

Skin reaction	Reading (hours)	Individual scores
		Male 1	Male 2	Female
	24	2	2	2
Erythema/eschar formation	48	2	2	2
	72	2	2	2
Total		6	6	6
Mean score		2.0	2.0	2.0
	24	2	3	2
Oedema	48	2	2	2
	72	2	2	2
Total		6	7	6
Mean score		2.0	2.3	2.0

                                           

Interpretation of results:

Category 2 (irritant)

Conclusions:

Based on a skin irritation study conducted to OECD 404 and in compliance with GLP, the test substance was irritating to the skin of rabbits. Erythema were observed in all three animals tested, with mean 24-72 hour scores of 2 in all three animals tested. For oedema the mean 24-72 hour score was 2 in 2/3 animals and 2.3 in 1/3 animals tested. At 7 days following exposure the erythema and oedema could not be assessed due to 'crust formation'. At 14 days erythema and oedema had reversed but there was reduced fur growth in 3/3 animals and mild desquamation in 2/3 animals. Therefore due to the reduced fur growth and desquamation at the end of the observation period (14 days), the test substance is concluded to be irritating to skin.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (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:

27/01/1999 to 04/02/1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd. Cheshire, UK.
- Age at study initiation: 12-16 weeks.
- Weight at study initiation: 3.10-3.43 kg.
- Housing: Individually housed in suspended metal cages.
- Diet (e.g. ad libitum): Ad libitum.
- Water (e.g. ad libitum): Ad libitum.
- Acclimation period: Minimum of 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-22
- Humidity (%): 44-70
- Air changes (per hr): Approximately 15.
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: No data

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml

Duration of treatment / exposure:

N/A

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

Three

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not done.
- Time after start of exposure: N/A

SCORING SYSTEM: Draize, 1977

TOOL USED TO ASSESS SCORE: standard ophthalmoscope.

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

72 hours

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Table 1 Eye irritation results

Rabbit	Time after treatment (hr)	Corneal opacity	Iridial inflammation	Conjunctival redness	Conjunctival chemosis
Female 1	24	0	0	2	1
	48	0	0	1	0
	72	0	0	0	0
	Mean	0	0	1	0.3
Female 2	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	Mean	0	0	0	0
Male	24	0	0	2	1
	48	0	0	1	1
	72	0	0	0	0
	Mean	0	0	1	0.7

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance was not irritating to the eyes of rabbits in an eye irritation test conducted according to OECD 405 and in compliance with GLP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In an in vivo skin irritation study (Safepharm Laboratories Ltd., 1999a) conducted according to OECD Test Guideline 404 and in compliance with GLP, three New Zealand white rabbits were exposed to 0.5 ml undiluted test substance under a semi-occlusive dressing for four hours. The test site was then washed and signs of irritation recorded for 14 days. Erythema were observed in all three animals tested, with mean 24-72 hour scores of 2 (3/3 animals). For oedema the mean 24-72 hour score was 2 in 2/3 animals and 2.3 in 1/3 animals tested. At 7 days following exposure the erythema and oedema could not be assessed due to 'crust formation'. At 14 days erythema and oedema had reversed but there was reduced fur growth in 3/3 animals and mild desquamation in 2/3 animals. Therefore, due to the reduced fur growth and desquamation at the end of the observation period (14 days), the test substance is concluded to be irritating to skin.

In an in vivo eye irritation study (Safepharm Laboratories Ltd., 1999b) conducted according to OECD Test Guideline 405 and in compliance with GLP, three New Zealand white rabbits had 0.1 ml undiluted test substance instilled into one eye. Irritation was then scored for 72 hours. Apart from some minor, reversible effects on the conjunctiva there were no signs of irritation. Overall, therefore it was concluded that the test substance is not irritating to the eyes.

Justification for classification or non-classification

Based on a skin irritation study conducted to OECD 404 and in compliance with GLP, the submission substance is classified as Skin Irritant, Category 2 according to Regulation (EC) No 1272/2008 due to irreversible effects at the end of the 14-day observation period.

Based on the eye irritation study conducted to OECD 405 and in compliance with GLP, the submission substance does not require classification for eye irritation according to Regulation (EC) No 1272/2008.