[No public or meaningful name is available]

Endpoint summary

Description of key information

Skin irritation, in vivo: non-irritating, OECD TG 404, 2004

Eye irritation, in vivo: non-irritating, OECD TG 405, 2004

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin corrosion: in vitro / ex vivo

Data waiving:

other justification

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
In accordance with REACH Regulation (EC) No. 1907/2006 Annex VII, column 2 section 8.1.1 (as amended by Commission Regulation (EU) 2016/863) the in vitro skin corrosion (OECD TG 431) study does not need to be conducted based on the available information allowing a definitive conclusion on the classification of the substance. An available in vivo (OECD TG 404) skin irritation study is available and data in other endpoints (such as skin sensitisation and/or acute dermal toxicity) indicates that the substance is not skin corrosive and a definitive conclusion on the classification can be made. Furthermore, in accordance with section 1.2 of REACH Regulation (EC) No. 1907/2006 Annex XI the weight of evidence indicates that the substance is not skin corrosive and therefore in vitro testing may be omitted. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.2, July 2017) the study does not need to be conducted.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25-11-2003 to 02-12-2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study performed under GLP. All relevant validity criteria were met.

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

GLP compliance:

yes (incl. QA statement)

Remarks:

inspected: December 2002 ; signature: February 2003

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Recognised Supplier
- Age at study initiation: 12 to 20 weeks
- Weight at study initiation: 2.0 to 3.5 kg
- Housing: Individually housed in suspended cages.
- Diet (ad libitum): Certified Rabbit diet (Recognised Supplier); provided ad libitum
- Water (ad libitum): mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23
- Humidity (%): 30 to 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 h light / 12 h dark

IN-LIFE DATES: From: 12-11-2003 To: 02-12-2003

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 ml
- Concentration (if solution): Used as supplied (liquid)

VEHICLE
- Amount applied: Not applicable.

Duration of treatment / exposure:

4 hours - 3 males

Observation period:

72 hours (initial observation); additional observations are made daily up to Days 7 and 14 to assess the reversibility of skin reactions (as appropriate).

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: dorsal
- Type of wrap if used: semi-occlusive (2.5 cm x 2.5 cm cotton gauze patch secured with surgical adhesive tape)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, any residual test item removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 4 hours. Earlier if appropriate based on observations.

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): 3 males: Immediately, 1 hour, 4 hours, 24 hours, 48 hours and 72 hours. Additional observations daily up to 7 or 14 days, as appropriate

SCORING SYSTEM: Draize Scale:
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) to slight eschar formation (injuries in depth) _______ 4

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 millimetre) _______________________________ 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) ___4
Any other skin reactions and clinical signs of toxicity, if present, were also recorded.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

n = 3

Time point:

24/48/72 h

Score:

0.9

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

mean

Remarks:

n = 3

Time point:

24/48/72 h

Score:

0.2

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

Very slight erythema (score = 1) was noted at all treated sites one hour after patch removal and at the 24 and 48-hour observations and persisted at two treated skin sites at the 72-hour observation. Very slight oedema (score = 1) was noted at two treated sites at the 24-hour observation. All sites were normal at the 7 day observation period.

Table 1. Individual Scores and Mean Scores following 4-hour exposure

Skin Reaction	Reading (hours)	1# Male	#2 Male	3# Male
Erythema/Escar Formation	24	1	1	1
	48	1	1	1
	72	1 Le	1	0
	Total	3.0	3.0	2.0
	Mean	1.0	1.0	0.7
Oedema Formation	24	1	0	1
	48	0	0	0
	72	0	0	0
	Total	1.0	0.0	1.0
	Mean	0.3	0.0	0.3

 * Le : loss of elasticity

Note: All effects reversed by day 7 (score = 0.0)

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the test item is not considered to be irritating.

Executive summary:

The study was performed to OECD TG 404 and to assess the primary skin irritancy potential of the test item in accordance with GLP in New Zealand White rabbits. The test item was applied sequentially. Initially, one male for 3-minute, 1-hour and 4-hour by semi-occluded application to the intact rabbit skin with 0.5 mL test item introduced under a 2.5 cm x 2.5 cm cotton gauze patch on the clipped skin. The patch was secured in position with a strip of surgical adhesive tape. After exposure to the test item, the patches were removed and individual dose sites were scored at approximately 1, 24, 48, and 72 hours. Very slight erythema (score = 1) was noted at all treated sites one hour after patch removal and at the 24 and 48-hour observations and persisted at two treated skin sites at the 72-hour observation. Very slight oedema (score = 1) was noted at two treated sites at the 24-hour observation. Loss of skin elasticity was noted at one site. One treated site was normal at 72 hours. All sites were normal at the 7 day observation period. No corrosive effects were noted. Mean scores following grading at 24, 48 and 72h were score 1.0/1.0/0.7 in erythema and eschar and score 0.3/0.0/0.3 in oedema scoring criteria, respectively. Under the conditions of the study, the test item is not considered to be a skin irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

other justification

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
In accordance with REACH Regulation (EC) No. 1907/2006 Annex VII, column 2 section 8.1.2 (as amended by Commission Regulation (EU) 2016/863) the serious eye damage / eye irritation (OECD TG 437 or OECD TG 438) study does not need to be conducted based on the available information allowing a definitive conclusion on the classification of the substance. An available in vivo (OECD TG 405) eye irritation study is available that indicates that the substance is not eye irritating and a definitive conclusion on the classification can be made. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.2, July 2017) the study does not need to be conducted.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04-12-2003 to 22-12-2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study performed under GLP. All relevant validity criteria were met.

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

GLP compliance:

yes (incl. QA statement)

Remarks:

inspected: December 2002 ; signature: February 2003

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Recognised Supplier
- Age at study initiation: 12 to 20 weeks
- Weight at study initiation: 2.0 to 3.5 kg
- Housing: Individually housed in suspended cages.
- Diet (ad libitum): Certified Rabbit diet (Recognised Supplier); provided ad libitum
- Water (ad libitum): mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23
- Humidity (%): 30 to 70
- Air changes (per hr): at least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour light / 12 hour dark

IN-LIFE DATES: From: 04-12-2003 To: 22-12-2003

Vehicle:

unchanged (no vehicle)

Controls:

other: left eye remained untreated

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): undiluted

Duration of treatment / exposure:

A volume of 0.1 mL of the test material, was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test material, and then released. The left eye remained untreated and was used for control purposes. Irrigation of the eye with distilled water or saline, after 1 hour was deemed not necessary during the study.

Observation period (in vivo):

Ocular assessment was conducted at approximately 1, 24, 48 and 72 hours after instillation of the test item, according to numerical evaluation.

Number of animals or in vitro replicates:

3 (male). Testing was conducted sequentially following testing with a sentinel.

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none

SCORING SYSTEM:
The irritation was assessed according to Draize (1977) numerical scoring system. At each observation period, the highest scores given were recorded. Any other ocular effects were also noted.

TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

n = 3

Time point:

24/48/72 h

Score:

0.23

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

mean

Remarks:

n = 3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

n = 3

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

n = 3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible

Irritant / corrosive response data:

No corneal effects were noted in two treated eyes, all scores were zero. Scattered or diffuse corneal opacity was noted in one treated eye at the 48 and 72-hour observations.
No iridial effects were noted, all scores were zero.
Moderate conjunctival irritation (score = 2) was noted in one treated eye 1 h to 72 h after treatment. No conjunctival irritation (score = 0) was noted in two treated eyes 1 h to 14 days after treatment. Chemosis and Redness was minimal (score = 1) to zero at the 72 hour observation in all treated eyes and all effects had reversed (score = 0) at 14 days.

Table 1.0: Individual and Mean Scores for Cornea, Iris and Conjunctivae

Number and Sex	Time After Treatment	Corneal Opacity		Iridial Inflammation	Conjunctival Redness	Conjunctival Chemosis
1# Male	24 Hours	0		0	0	0
	48 Hours	0	0		0	0
	72 Hours	0	0		0	0
Total		0.0		0.0	0.0	0.0
Mean		0.0		0.0	0.0	0.0
#2 Male	24 Hours	0		0	0	0
	48 Hours	0	0		0	0
	72 Hours	0	0		0	0
Total		0.0		0.0	0.0	0.0
Mean		0.0		0.0	0.0	0.0
#3 Male	24 Hours	0		0	2	1
	48 Hours	1	0		2	1
	72 Hours	1	0		2	1
Total		2.0		0.0	6.0	3.0
Mean		0.7	0.0		2.0	1.0

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the test item is not irritating to the eye.

Executive summary:

The study was performed to OECD TG 405 and EU Method B.5 guidelines under GLP to assess the irritancy potential of the test item to the eye following a single application in the New Zealand White rabbit. A volume of 0.1 ml of the test item was placed into the conjunctival sac of one eye of three animals. The other eye remained untreated and was used for control purposes. The test was conducted in a stepwise manner conducted singularly and then on a further two rabbits in accordance with the guideline. Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment. A single application of the test item to the non-irrigated eye of three rabbits produced scattered or diffuse corneal opacity (score =1) and minimal to moderate conjunctival irritation (score = 1 or 2). Two eyes appeared normal at the 24-hour observation and the remaining treated eye appeared normal at the 14 day observation (score = 0). Under the conditions of this study, the test item is not considered to be irritating to the eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation:

Key Study : in vivo, OECD TG 404, 2004 : The study was performed to OECD TG 404 and to assess the primary skin irritancy potential of the test item in accordance with GLP in New Zealand White rabbits. The test item was applied sequentially. Initially, one male for 3-minute, 1-hour and 4-hour by semi-occluded application to the intact rabbit skin with 0.5 mL test item introduced under a 2.5 cm x 2.5 cm cotton gauze patch on the clipped skin. The patch was secured in position with a strip of surgical adhesive tape. After exposure to the test item, the patches were removed and individual dose sites were scored at approximately 1, 24, 48, and 72 hours. Very slight erythema (score = 1) was noted at all treated sites one hour after patch removal and at the 24 and 48-hour observations and persisted at two treated skin sites at the 72-hour observation. Very slight oedema (score = 1) was noted at two treated sites at the 24-hour observation. Loss of skin elasticity was noted at one site. One treated site was normal at 72 hours. All sites were normal at the 7 day observation period. No corrosive effects were noted. Mean scores following grading at 24, 48 and 72h were score 1.0/1.0/0.7 in erythema and eschar and score 0.3/0.0/0.3 in oedema scoring criteria, respectively. Under the conditions of the study, the test item is not considered to be a skin irritant.

 

Eye Irritation:

Key Study : in vivo, OECD TG 405, 2004 : The study was performed to OECD TG 405 and EU Method B.5 guidelines under GLP to assess the irritancy potential of the test item to the eye following a single application in the New Zealand White rabbit. A volume of 0.1 ml of the test item was placed into the conjunctival sac of one eye of three animals. The other eye remained untreated and was used for control purposes. The test was conducted in a stepwise manner conducted singularly and then on a further two rabbits in accordance with the guideline. Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment. A single application of the test item to the non-irrigated eye of three rabbits produced scattered or diffuse corneal opacity (score =1) and minimal to moderate conjunctival irritation (score = 1 or 2). Two eyes appeared normal at the 24-hour observation and the remaining treated eye appeared normal at the 14 day observation (score = 0). Under the conditions of this study, the test item is not considered to be irritating to the eye.

Justification for classification or non-classification

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for dermal irritation.

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for eye irritation.

 

For skin irritation, further in vitro skin corrosion testing does not need to be conducted based on the available information allowing a definitive conclusion on the classification of the substance. The substance does not demonstrate significant skin irritation potential necessary for classification and labelling within an available skin irritation in vivo assay (OECD TG 404).

 

For eye irritation, the weight of evidence indicates that the substance has the potential to cause transient mild irritating effects to the eye but which are insufficient for classification based on the mean scoring and evaluation of the results in three organisms demonstrating that the EU criteria had not been met. Effects in vivo on corneal opacity and iritis are low to non-existent and conjunctival effects are moderate to low which fully reversed within 14 days ; the overall evidence is indicative of transient and reversible effects on the eye.

References:

1. Guidance on Application of the CLP Criteria, ECHA, version 5.0, July 2017