Registration Dossier

Administrative data

Description of key information

No signs of irritation were observed in a skin irritation study in rabbits.
Irreversible eye damages were observed in rabbits.
Moreover Mexoryl SAB is a powder and contains from 13.23% to 26.71% of inhalable particles (i.e. diameter < 100 µm). Therefore a potential exposure of the worker cannot be excluded. However, due to the low acute toxicity by dermal and oral routes, it is considered that the only potential effects by inhalation may be local effects. Therefore, it is classified by default as R37 "Irritating to respiratory system" according to Directive 67/548/EC and H335 "May cause respiratory irritation" according to CLP Regulation.

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:
11 october 1989 to 14 october 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study following OECD and EU guidelines, with minor deviations: no certificate of analysis and housing temperature
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
No certificate of analysis, deviation in housing temperature
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Moston, U.K.
- Age at study initiation: approximately 12 weeks to 16 weeks old
- Weight at study initiation: 2.12 - 2.30 kg
- Housing: individually housed in suspended metal cages
- Diet (e.g. ad libitum): rabbit diet (Preston Farmers limited, New Leake, U.K.), ad libitum
- Water (e.g. ad libitum): normal drinking water, ad libitum
- Acclimation period: after a minimum acclimatisation period of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-20
- Humidity (%): 62-65
- Air changes (per hr): approximately 15 changes/h
- Photoperiod (hrs dark / hrs light): 12 h light and 12 h dark

IN-LIFE DATES: From: 11 October 1989 To 14 October 1989
Type of coverage:
other: elasticated corset
Preparation of test site:
other: clipped dorsal and flank area
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g moistened with 0.5 mL of distilled water

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:
4 h
Observation period:
72 h
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: 2.5 cm x 2.5 cm gauze patch secured with a strip of surgical adhesive tape. The trunk was wrapped in an elasticated corset (Tubigrip)

REMOVAL OF TEST SUBSTANCE
- Gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize J. H. scale (1959)
Irritation parameter:
overall irritation score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
overall irritation score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
overall irritation score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
No irritation
Other effects:
No data

No data

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material was regarded as not irritating according to the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation (EC) N° (1272-2008).
Executive summary:

In a primary dermal irritation GLP study performed according to OECD guideline 404, three young adult male White New-Zealand rabbits were dermally exposed to 0.5 g of ER 195 in 0.5 mL of distilled water for 4 hours to 6.25 cm² of clipped skin. Animals then were observed for 3 days. Irritation was scored by the method of Draize (1959).

There was no irritant effect at any observation time point. In this study, ER 195 is not a dermal irritant on male rabbits.

Under the test conditions, ER 195 is not classified as irritating to the skin according to the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation (EC) N° (1272-2008).

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:
23 October 1989 - 8 November 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study following OECD guideline 405 with minor deviations: no certificate of analysis and low housing temperature conditions
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
No certificate of analysis and low housing temperature
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David percival Ltd, Moston, U.K.
- Age at study initiation: between 12 and 16 weeks
- Weight at study initiation: 2.31 - 2.92 kg
- Housing: individually housed in metal cages
- Diet (e.g. ad libitum): rabbit diet (Preston Farmers limited, New Leake, U.K.), ad libitum
- Water (e.g. ad libitum): normal drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-19
- Humidity (%): 50-65
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

IN-LIFE DATES: From: 23 October 1989 To: 8 November 1989
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): approximately 65 mg
Duration of treatment / exposure:
Eye was not washed after exposure
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: no removal of substance

SCORING SYSTEM: by Kay J.H. and Calandra J.C., 1962

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48,72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
2.7
Max. score:
4
Reversibility:
other: the animal was killed after 72 h observation
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
2
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
2
Reversibility:
not specified
Remarks:
animal killed after 72 h observation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
2.7
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
2.3
Max. score:
3
Reversibility:
not specified
Remarks:
animal killed after 72 h observation
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
2.7
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48, 72 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks:
animal killed after 72 h observation
Irritant / corrosive response data:
Diffuse corneal opacity, iridial inflammation and moderate or severe conjunctival irritation were noted in all treated eyes one hour after treatment and
in two treated eyes at subsequent 24, 48 and 72-hour observations.
In one animal, the corneal opacity in the treated eye increased and areas of opalescent corneal opacity with iridial inflammation and moderate to severe conjunctival irritation were noted in this treated eye at the 48 and 72-hour observation. Other adverse effects noted on the nictitating and/or conjunctival membranes of this treated eye were pale appearance, small green-coloured or white areas and areas of haemorrhage. A blood stained discharge was also noted. For humane reasons this animal was killed after the 72-hour observation.
In another animal, diffuse corneal opacity, iridial inflammation and minimal conjunctival irritation persisted in the treated eye on day seven. No corneal opacity, iridial inflammation or conjunctival irritation was noted on day fourteen. Circumcorneal vascularisation and convoluted eyelids were also apparent during this period. The nictitating membrane was also pale in appearance.
The corneal opacity in the eye of the third treated animal increased and opalescent corneal opacity with pannus formation, indicative of irreversible ocular damage, had developed on day fourteen. The iridial inflammation could not be assessed at this time; minimal conjunctival irritation with convoluted eyelids were also noted. For humane reasons this animal was killed on day fourteen.
Other effects:
No data

Individual and mean scores for cornea, iris and conjunctivae

Rabbit number & sex

Time after treatment

Corneal opacity

Iridial inflammation

Conjunctival redness

Conjunctival chemosis

178 male

24 h

1

1

2

3

 

48 h

1

1

3

3

 

72 h

1

1

3

2

Total

 

3

3

8

8

Mean

 

1.0

1.0+

2.7+

2.7+

156 male

24 h

1

1

2

2

 

48 h

1

1

3

3

 

72 h

1

1

3

3

Total

 

3

3

8

8

Mean

 

1.0

1.0+

2.7+

2.7+

162 female

24 h

2

1

2

3

 

48 h

3

1

2

3

 

72 h

3

1

3

3

 Total    8  3  7  9
 Mean    2.7+  1.0+  2.3  3.0+
Interpretation of results:
highly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material ER 195, was found to be at least severe irritant to the rabbit eye and should be classified R41 according to the criteria of Annex VI to the Directive 67/548/EEC and category 1 according to CLP Regulation (EC) N° (1272-2008).
Executive summary:

In an eye irritation study conducted according to the OECD Guideline 405 and in compliance with GLP, 3 healthy (two males and one female) adult rabbits of the New Zealand White strain were exposed to 65 mg of undiluted ER 195 in their right eye while the other eye corresponded to the control. The eyes were examined unwashed and the changes were observed at 24, 48 and 72 h after dosing and graded according to Kay J. H. and Calandra J. C. (1962).

Diffuse corneal opacity, iridial inflammation and moderate or severe conjunctival irritation were noted in all treated eyes one hour after treatment and in two treated eyes at subsequent 24, 48 and 72-hour observations.

In one animal, the corneal opacity in the treated eye increased and areas of opalescent corneal opacity with iridial inflammation and moderate to severe conjunctival irritation were noted in this treated eye at the 48 and 72-hour observation. Other adverse effects noted on the nictitating and/or conjunctival membranes of this treated eye were pale appearance, small green-coloured or white areas and areas of haemorrhage. A blood stained discharge was also noted. For humane reasons this animal was killed after the 72-hour observation.

In another animal, diffuse corneal opacity, iridial inflammation and minimal conjunctival irritation persisted in the treated eye on day seven. No corneal opacity, iridial inflammation or conjunctival irritation was noted on day fourteen. Circumcorneal vascularisation and convoluted eyelids were also apparent during this period. The nictitating membrane was also pale in appearance.

The corneal opacity in the eye of the third treated animal increased and opalescent corneal opacity with pannus formation, indicative of irreversible ocular damage, had developed on day fourteen. The iridial inflammation could not be assessed at this time; minimal conjunctival irritation with convoluted eyelids were also noted. For humane reasons this animal was killed on day fourteen.

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 1, 1, 2.7 for cornea score, 1, 1, 1 for iris score, 2.7, 2.7, 2.3 for conjunctivae score and 2.7, 2.7, 3 for chemosis score.

Under these test conditions, ER 195, was found to be at least severe irritant to the rabbit eye and should be classified R41 according to the criteria of Annex VI to the Directive 67/548/EEC and category 1 according to CLP Regulation (EC) N° (1272-2008).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a primary dermal irritation GLP study performed according to OECD guideline 404, there was no irritant effect at any observation time point.

In an eye irritation study conducted according to the OECD Guideline 405 and in compliance with GLP, irreversible ocular damages were observed. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 1, 1, 2.7 for cornea score, 1, 1, 1 for iris score, 2.7, 2.7, 2.3 for conjunctivae score and 2.7, 2.7, 3 for chemosis score.


Effects on eye irritation: highly irritating

Effects on respiratory irritation: irritating

Justification for classification or non-classification

As no irritant effect was observed during a dermal irritation study performed in rabbits according to OECD guideline 404 and GLP conditions, Mexoryl SAB is not classified for skin irritation according to the Regulation (EC) No. 1272/2008 (CLP) and the Directive 67/548/EEC.

As irreversible eye damages were observed in an eye irritation study conducted in rabbits according to the OECD Guideline 405 and in compliance with GLP, Mexoryl SAB is classified R41 "Risk of serious damage to eyes" according to the Directive 67/548/EC and category 1 with risk phrase H318 "Causes serious eye damage" according to CLP Regulation (EC) N° (1272-2008).

Meroxyl SAB is a powder containing about 13% of particles < 100 µm therefore a potential exposure by inhalation cannot be excluded. Due to the potential exposure by inhalation and the irritating properties of Mexoryl SAB to the eyes, it is classified by default as R37 "Irritating to respiratory system" according to Directive 67/548/EC and H335 "May cause respiratory irritation" according to CLP Regulation.