Reaction mass of (4RS,4aRS,8RS,8aRS)-4-ethyl-8-methyloctahydronaphthalen-1(2H)-one and (4RS,4aSR,8SR,8aRS)-4-ethyl-8-methyloctahydronaphthalen-1(2H)-one and (4RS,4aSR,8SR,8aSR)-4-ethyl-8-methyloctahydronaphthalen-1(2H)-one

Endpoint summary

Description of key information

Skin irritation, in vivo: irritating, OECD TG 404, 2014

Eye irritation, in vivo: not eye irritating, OECD TG 405, 2014

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. Information as to the availability of the in vivo study is provided in 'attached justification'.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23-09-2013 To: 31-12-2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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

Remarks:

To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations ; this may inadvertently enhance scoring observations due to potential abrasion of the skin. The OECD TG 404 guideline specifies pre-exposure clipping only. Additionally, there was some indications that the test item was not fully removed after 4 hours exposure. This would lead to increased potential for classification due to enhancement of response observations.

Justification for type of information:

Information as to the availability of the in vivo study is provided in 'attached justification'.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Deviation: to facilitate scoring, treated skin areas were re-clipped before the observations. Additionally, some indications that the test item was not fully removed post 4-hour exposure. This would lead to increased potential for classification.

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

see above

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

yes

Remarks:

see above

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000

Deviations:

yes

Remarks:

see above

GLP compliance:

yes (incl. QA statement)

Remarks:

inspected: March 2013 ; signature: May 2013

Species:

rabbit

Strain:

New Zealand White

Remarks:

Hsdlf: NZW

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Recognised Supplier
- Age at study initiation: 12 to 24 weeks
- Weight at study initiation: 2574 to 2753 g
- Housing: Individually housed in cages with perforated floors, with shelters and cage enrichment including wooden sticks
- Diet (ad libitum): Global Diet 2030 (Recognised Supplier); provided ad libitum (approximately 100 g per day)
- Water (ad libitum): mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0
- Humidity (%): 40 to 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 h light / 12 h dark

IN-LIFE DATES: From: 23-09-2013 To: 31-12-2013

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL.
- Concentration (if solution): Not applicable.

VEHICLE
- Amount applied: Not applicable.

Duration of treatment / exposure:

4 hours

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 (2 cm x 3 cm metalline patch secured with adhesive tape)
- % coverage: Not reported
- Type of wrap if used: metalline patch secured with adhesive tape and elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: Four hours after the application, the dressing was removed and the skin cleaned of residual test item using tap water and watery ethanol (50%v/v). Note: that a sticky residue was reported at the 1 hour observation, indicating incomplete removal.

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): 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:
- Method of calculation:
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
*. Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, 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 millimeter) ........................................................... 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure) 4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

n = 3

Time point:

24/48/72 h

Score:

2.47

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

n = 3

Time point:

24/48/72 h

Score:

3.43

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3.3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritant / corrosive response data:

Moderate to severe erythema and moderate or severe oedema in the treated skin areas of the three rabbits, which remained present until termination (after 14 days). Reduced flexibility of the skin was noted for one animal at 72 hours and 7 Days after exposure. Scaliness and/or bald skin were noted for all animals 7 days after exposure, and persisted until termination.

Other effects:

All males showed expected gain in body weight during the study.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the test item is considered to be irritating to the skin.

Executive summary:

The study was performed to OECD TG 404, EU Method B.4, US EPA OPPTS 870.2500 and Japan (JMAFF) 12 Nousan, Notification No 8147 guidelines 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. Three rabbits were exposed for 4-hour by semi-occluded application of the test item to the intact clipped skin with 0.5 mL test item introduced under a 2 cm x 3 cm semi-occlusive patch. The patch was secured in position with adhesive tape and elasticated bandage. After exposure to the test item the patches were removed and individual dose sites were scored at approximately 1, 24, 48, and 72 hours. Treated sites were reclipped at least 3 hours before observations.Sticky remnants of the test item were present on the skin on Day 1.Moderate to severe erythema and moderate or severe oedema in the treated skin areaswhich remained present until termination (after 14 days). Reduced flexibility of the skin was noted for one animal at 72 hours and 7 Days after exposure. Scaliness and/or bald skin were noted for all males 7 days after exposure, and persisted until termination. Under the conditions of the study, the test item is considered to be a skin irritant.

Applicant assessment indicates: to facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations ; this may inadvertently enhance scoring observations due to potential abrasion of the skin. The OECD TG 404 guideline specifies pre-exposure clipping only. Additionally, there was some indications that the test item was not fully removed after 4 hours exposure. Whilst this may not of invalidated the study conclusions, this would lead to highly conservative conclusion due to increased potential for classification due to enhancement of response observations.

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:

09-09-2013 to 19-09-2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

Information as to the availability of the in vivo study is provided in 'attached justification'.

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

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

inspected: March 2013 ; signature: May 2013

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 24 weeks
- Weight at study initiation: 2688 to 3164 g
- Housing: Individually housed in cages with perforated floors, with shelters and cage enrichment
- Diet (ad libitum): Global Diet 2030 (Recognised Supplier); provided ad libitum (approximately 100 g per day)
- Water (ad libitum): mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0
- Humidity (%): 40 to 70 (Deviations from the minimum and maximum level of daily mean relative humidity occurred. Laboratory historical data do not indicate an effects resulting).
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 h light / 12 h dark

IN-LIFE DATES: From: 09-09-2013 To: 19-09-2013

Vehicle:

unchanged (no vehicle)

Controls:

other: one eye remained untreated

Amount / concentration applied:

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

VEHICLE
- Amount(s) applied (volume or weight with unit): Not applicable.

Duration of treatment / exposure:

A volume of 0.1 mL of the test item, was placed into the conjunctival sac of the 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 item, and then released. The other 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 or was not reported 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:
- 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. This procedure was repeated to assess recovery.
- 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

Max. score:

4

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:

0.33

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

n = 3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

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:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No corneal effects were noted, all scores were zero.
No iridial effects were noted, all scores were zero.
Some conjunctival irritation (score = 2 or 1) was noted in all treated eyes 1 h and reduced (score =1) through 24h or 48 h after treatment. Chemosis was minimal (score = 1) at 1 hour to none (score = 0) at the 24 h through 72 h observation.
In all treated eyes and all effects had reversed (score = 0) at the 72 h observation.

Other effects:

All animals showed expected gain in bodyweight during the study.

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
Mean		0.0		0.0	0.0 #	0.0 #
#2 Male	24 Hours	0		0	1	0
	48 Hours	0	0		1	0
	72 Hours	0	0		0	0
Total		0		0	2	0
Mean		0.0		0.0	0.7 #	0.0 #
#3 Male	24 Hours	0		0	1	0
	48 Hours	0	0		0	0
	72 Hours	0	0		0	0
Total		0		0	1	0
Mean		0.0	0.0		0.3 #	0.0 #

# All effects reversed by day 3

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 irritating to the eye.

Executive summary:

The study was performed to OECD TG 405, EU Method B.5, US EPA OPPTS 870.2400 and Japan (JMAFF) 12 Nousan, Notification No 8147 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 rabbits. 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. 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 no corneal opacity, no iridial inflammation and conjunctival irritation (redness, score = 1) and no chemosis (score = 0) at 24 hours through 72 hours. All treated eyes appeared normal at the 72 hour 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 adverse effect observed (not irritating)

Additional information

Skin Irritation:

Key study : In vivo, OECD TG 404, 2014 : The study was performed to OECD TG 404, EU Method B.4, US EPA OPPTS 870.2500 and Japan (JMAFF) 12 Nousan, Notification No 8147 guidelines 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. Three rabbits were exposed for 4-hour by semi-occluded application of the test item to the intact clipped skin with 0.5 mL test item introduced under a 2 cm x 3 cm semi-occlusive patch. The patch was secured in position with adhesive tape and elasticated bandage. After exposure to the test item the patches were removed and individual dose sites were scored at approximately 1, 24, 48, and 72 hours. Treated sites were reclipped at least 3 hours before observations.Sticky remnants of the test item were present on the skin on Day 1.Moderate to severe erythema and moderate or severe oedema in the treated skin areaswhich remained present until termination (after 14 days). Reduced flexibility of the skin was noted for one animal at 72 hours and 7 Days after exposure. Scaliness and/or bald skin were noted for all males 7 days after exposure, and persisted until termination. Under the conditions of the study, the test item is considered to be a skin irritant.

Applicant assessment indicates: to facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations ; this may inadvertently enhance scoring observations due to potential abrasion of the skin. The OECD TG 404 guideline specifies pre-exposure clipping only. Additionally, there was some indications that the test item was not fully removed after 4 hours exposure. Whilst this may not of invalidated the study conclusions, this would lead to highly conservative conclusion due to increased potential for classification due to enhancement of response observations.

Eye Irritation:

Key study : In vivo, OECD TG 405, 2014 : The study was performed to OECD TG 405, EU Method B.5, US EPA OPPTS 870.2400 and Japan (JMAFF) 12 Nousan, Notification No 8147 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 rabbits. 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. 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 no corneal opacity, no iridial inflammation and conjunctival irritation (redness, score = 1) and no chemosis (score = 0) at 24 hours through 72 hours. All treated eyes appeared normal at the 72 hour observation (score = 0). Under the conditions of this study, the test item is not considered to be irritating to the eye.

 

Respiratory Irritation:

Key study : INHALATION: OECD TG 436, 2014 : The study was performed according to OECD TG 436 guideline in accordance with GLP to assess the acute inhalation toxicity of the test item. A single groups of six Wistar: Crl:WI(Han) strain rats (three males and three females) were exposed to an aerosol atmosphere of the test item. The groups were exposed for four hours using a nose only exposure system, followed by a fifteen day observation period. The time-weighted mean achieved atmosphere concentrations were as follows: 5.10 ± 0.11 mg/L based on a nominal concentration of 8.0 mg/L and/or 1.03 ± 0.03 mg/L based on a nominal concentration of 1.89 mg/L. The atmosphere generation efficiencies were 63% and 53%, respectively. The characteristics of the achieved atmosphere L were at 5 mg/: Mean Mass Median Diameter (particle size): > 3.7 μm and < 4.0 μm with geometric Standard Deviation 2.0 and 1 mg/L: Mean Mass Median Diameter (particle size): > 3.9 μm and < 4.3 μm with geometric Standard Deviation 1.9. At 5 mg/L, one male was humanely terminated on day 3 ; two females were humanely terminated on day 3. Slow breathing, was observed during exposure. After exposurelethargy, hunched posture, flat posture, uncoordinated movements, laboured respiration, ptosis, rales and/or hypothermia was observed. Surviving males/females had recovered by days 5 and 6. At 1 mg/L, there was no mortality and no significant clinical signs during or after exposure. Reduced body weight gain and body weight loss was noted among survivors during the first week post exposure. At all exposure levels. all animals regained weight during the second week and/or gained weight over the course of the study. At 5 mg/L, macroscopic post mortem examination of the two females humanely terminated revealed gelatinous contents in the stomach and/or duodenum. Macroscopic examination of the other females did not reveal any abnormalities. Pelvic dilation of the right kidney, as seen in one female exposed to 5 mg/L, is occasionally seen among rats of this age and strain and was therefore considered unrelated to treatment. At 1 mg/L, no macroscopic abnormalities were noted. Under the conditions of this study, the inhalation 4h-LC50 (male/female) was > 1 and ≤ 5 mg/L and the LC50 cut-off was considered to be 5 mg/L within the Wistar: Crl:WI(Han) rat. Under the conditions of this study, there were no indications of respiratory irritation.

 

References:

1. OECD TG 436 (2009)

2. OECD 39 (2009)

Justification for classification or non-classification

The substance meets classification criteria under Regulation (EC) No 1272/2008 for dermal irritation category 2: H315

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 sufficient skin corrosion potential necessary for classification and labelling. The substance was classified within an available skin irritation in vivo assay (OECD TG 404) for skin irritation.

 

For eye irritation, the weight of evidence indicates that the substance has the potential to cause transient irritating effects to the eye which are insufficient for classification based on the mean scoring and evaluation of the results in three organisms demonstrating that the EU criteria had been met. Effects in vivo on corneal opacity and iritis are low to non-existent and conjunctival effects are low to non-existent all of which fully reversed within 72 hours; the overall evidence is indicative of mild transient and reversible effects on the eye.

References:

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