Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Based on weight of evidence for a number of related substances the registered substance is not irritating to rabbit skin or eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
other: FDA (1965). Part 191, Section 11.
Deviations:
not applicable
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: No information available
- Age at study initiation: No information available
- Weight at study initiation: 2.3 - 2.8 kg
- Housing: Animals were individually housed in V2A steel cages with a ground area of 0.4 m2
- Diet: ALTROMIN 2023 ad libitum except during treatment
- Water: Tap water ad libitum except during treatment
- Acclimation period: No information available


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2°
- Humidity (%): 60 ± 3%
- Air changes (per hr): No information available
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: No information available
Type of coverage:
occlusive
Preparation of test site:
other: shaved, intact and abraded
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 ml
- Concentration (if solution): Neat

Duration of treatment / exposure:
24 h exposure
Observation period:
Observed at 48, 72, 96 and 120 h following application.
Number of animals:
6 (3 male, 3 female). 3 intact; 3 abraded.
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: No information available
- Type of wrap: Plastic foil fastened with a gum patch.


REMOVAL OF TEST SUBSTANCE
- Washing: No information available


SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Remarks:
intact and abraded skin
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable; no skin reactions observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
intact and abraded skin
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
intact and abraded skin
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
intact and abraded skin
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
intact and abraded skin
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
intact and abraded skin
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
intact and abraded skin
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
intact and abraded skin
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
intact and abraded skin
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
intact and abraded skin
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
intact and abraded skin
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
intact and abraded skin
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Other effects:
No skin reactions or clinical signs were observed in any animal. Re-growth of hair was unaffected by treatment.
Interpretation of results:
GHS criteria not met
Conclusions:
In a reliable study conducted in accordance with an appropriate national test guideline, similar to OECD 404, the substance was found to be non-irritant to rabbit skin. The test pre-dated GLP.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
From 6 Feb 1996 to 19 Feb 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
fully occlusive covering
GLP compliance:
yes
Species:
rabbit
Strain:
other: White Russian
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: ASTA Medica AG, GERMANY
- Age at study initiation: 18-53 months
- Weight at study initiation: 2.41-2.71 kg
- Housing: 1/cage
- Diet (e.g. ad libitum): standard diet, ad libitum
- Water (e.g. ad libitum): drinking water, ad libitum
- Acclimation period: at least 1 day


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.0-20.0
- Humidity (%): 48-78
- Photoperiod (hrs dark / hrs light): 12h/12 h

IN-LIFE DATES: From: 1996-02-06 To: 1996-02-19
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: control: adjacent area of skin
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): neat

Duration of treatment / exposure:
4 h
Observation period:
9 days (study period suggests 13 days)
Number of animals:
3 (males)
Details on study design:
TEST SITE
- Area of exposure: 6.25 cm2
- % coverage: not stated
- Type of wrap if used: occlusive: cellulose gauze/cellulose fibre coated with natural rubber/synthetic film glue

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle washing "as far as possible"
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize, 1944; OECD 404
Irritation parameter:
primary dermal irritation index (PDII)
Remarks:
erythema, eschar and oedema
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 1, 24, 48, 72 h
Score:
1.5
Max. score:
8
Reversibility:
fully reversible within: 9 days
Remarks on result:
other: EU criteria (24, 48, 72 h): no two animals with a mean score >=2.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 9 days
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within:
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 9 days
Remarks:
Initial edema reversed by 24 hours, edema observed days 4, 6 and 7
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within:
Remarks:
6 days
Remarks on result:
no indication of irritation
Other effects:
No systemic effects reported

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Erythema & Eschar

Edema

Max. score: 4

Max. score: 4

60 min

1,0,1

0,0,0

24 h

1,1,2

1,0,1

48 h

1,1,2

0,0,1

72 h

1,1,2

0,0,1

4 days

2,1,2

1,0,11

6 days

2,0,0,

1,0,0,

7 days

1

1

9 days

0

0

Average 24h, 48h, 72h

1.3

0.4

Reversibility*)

c

c

Longest time (unit) for reversion

9 days

9 days

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Interpretation of results:
GHS criteria not met
Conclusions:
An otherwise reliable study, conducted in accordance with OECD 404 and GLP but using an occlusive dressing, found the test material to be slightly irritating (PII 1.5) based on readings at 1, 24, 48 and 72 h. This result would be judged to be not irritating according to EU criteria. It is possible that the use of a semi-occlusive dressing might reduce irritation.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From 16 Nov 1999 to 19 Nov 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP. The test material was similar to the registered substance but contained a higher proportion of an S3 isomer. The original study and the read-across are considered to be reliability 2.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Source: Covance Research Products, USA

- Age at study initiation: young adult

- Weight at study initiation: 2646-2689 g

- Housing: 1/cage

- Diet (e.g. ad libitum): standard diet, ad libitum

- Water (e.g. ad libitum): drinking water, ad libitum

- Acclimation period: at least 7days


ENVIRONMENTAL CONDITIONS

- Temperature (°C): 68.4-68.7 deg F

- Humidity (%): 37.5-40.6

- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 1999-11-16 To: 1999-11-19
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: control: adjacent area of skin
Amount / concentration applied:
TEST MATERIAL

- Amount(s) applied: 0.5 ml

- Concentration: neat (100%)

Duration of treatment / exposure:
4 h
Observation period:
3 days
Number of animals:
3 (1 male, 2 female)
Details on study design:
TEST SITE

- Area of exposure: 2.5 x 2.5 cm = 6.25 cm2

- % coverage: not stated

- Type of wrap if used: semi occlusive: 2-ply gauze held with Micropore tape, overwrapped with gauze binder held with Dermiform tape


REMOVAL OF TEST SUBSTANCE

- Washing (if done): wiped with moist paper towels

- Time after start of exposure: 4 h

SCORING SYSTEM: Draize, 1965
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 30-60 mins
Score:
0.1
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 0.5-1, 24, 48, 72 h
Score:
< 0.1
Max. score:
8
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: EU criteria (24, 48, 72 h): erythema and oedema = 0
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Erythema

Edema

Max. score: 4

Max. score: 4

60 min

1,0,0

0,0,0

24 h

0,0,0

0,0,0

48 h

0,0,0

0,0,0

72 h

0,0,0

0,0,0

Average 24h, 48h, 72h

0/4

0/4

Reversibility*)

c

n/a

Average time (unit) for reversion

24 h

 n/a

 *) Reversibility: c. = completely reversible;

n.c. = not completely reversible; n. = not reversible

 

Interpretation of results:
GHS criteria not met
Conclusions:
A reliable study has been conducted in accordance with the OECD 404 and in compliance with GLP. The test material was similar to the registered substance but contained a higher proportion of an S3 isomer. The test material was found to be not irritating to the skin of rabbits.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
December 1976 - no further details
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
other: FDA 1965
Deviations:
not applicable
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.3-2.8 kg
- Housing: 1/cage
- Diet (e.g. ad libitum): standard diet ad libitum
- Water (e.g. ad libitum): drinking water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/-2
- Humidity (%): 60 +/- 3
- Photoperiod (hrs dark / hrs light): 12 h/12 h


IN-LIFE DATES: From: To: not stated in report
Vehicle:
unchanged (no vehicle)
Controls:
other: Control is the other eye, treated with physiological saline
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): neat
Duration of treatment / exposure:
Single application. Exposure until end of study - apparently 72 h.
Observation period (in vivo):
24, 48 and 72 h after application.
Number of animals or in vitro replicates:
3/sex
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Apparently no washing.

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: hand-slit lamp and fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
There was no indication of irritation in any of the 6 animals at 24, 48 or 72 h following treatment. Examinations at each time point were made using a hand slit lamp and fluorescein.

Table 1: Irritant/corrosive response data at each observation time up to removal of each animal from the test

Score at time point / Reversibility*

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

24 h

0

0

0

0

48 h

0

0

0

0

72 h

0

0

0

0

Average 24h, 48h, 72h

0

0

0

0

Area effected

0

0

0

0

Maximum average score (including area affected, max 110)

0

0

0

0

Reversibility

n/a

n/a

n/a

n/a

Average time (unit) for reversion

n/a

n/a

n/a

n/a

* Scores are average of 6 rabbits

Interpretation of results:
GHS criteria not met
Conclusions:
A reliable study conducted in accordance with a standard guideline very similar to OECD 405, but without GLP status, found the test material to be not irritating to the eyes of rabbits.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
From19 Feb 1996 to 1 Mar 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
other: White Russian
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: ASTA Medica AG, GERMANY

- Age at study initiation: 24, 60 months (males); 20 months (female)

- Weight at study initiation: 2.41-2.55 kg (male); 2.76 kg (female)

- Housing: 1/cage

- Diet (e.g. ad libitum): standard diet, ad libitum

- Water (e.g. ad libitum): drinking water, ad libitum

- Acclimation period: at least 1 day


ENVIRONMENTAL CONDITIONS

- Temperature (°C): 19.0-20.0

- Humidity (%): 50-84

- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: Not stated
Vehicle:
unchanged (no vehicle)
Controls:
other: none required - other eye used as control
Amount / concentration applied:
TEST MATERIAL

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

- Concentration (if solution): neat
Duration of treatment / exposure:
No washout (examinations: 1, 24, 48, 72 h)
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
3 (2 males, 1 female)
Details on study design:
REMOVAL OF TEST SUBSTANCE

- Washing (if done): no washing reported

SCORING SYSTEM: Draize 1944, 1994; OECD 404

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein: 'pencil light'
Irritation parameter:
overall irritation score
Remarks:
irritation index
Basis:
mean
Time point:
other: 1, 24, 48, 72 h
Score:
2
Max. score:
110
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: Irritation index 2/110 was deemed in this study to indicate no irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation

The test material did not cause significant ocular lesions, in two or more animals, as indicated by any of the following:

corneal opacity =>2...<3

iris lesion =>1...=<1.5

conjunctival redness =>2.5

conjunctival oedema (chemosis) =>2

Based, in each case, on mean values for each animal derived from readings at 24, 48 and 72 h.

(EU criteria).

There were no iridial or corneal effects.

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Cornea

Iris

Conjunctivae redness

Conjunctival chemosis

Conjunctivae discharge

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

Max score 3

60 min

0,0,0

0,0,0

1,1,1

1,1,0

2,2,2

24 h

0,0,0

0,0,0

0,1,1

0,0,0

0,0,0

48 h

0,0,0

0,0,0

0,0,0

0,0,0

0,0,0

72 h

0,0,0

0,0,0

0,0,0

0,0,0

0,0,0

Average 24h, 48h, 72h

0

0

0.2

0

0

Area effected

0

-

-

-

-

Maximum average score (including area affected, max 110; 24, 48, 72 h)

0/80

[corneal opacity x area x 5]

0/10

[iris score x 5]

0.4/20

[(redness + chemosis + discharge) x 2]

 

Reversibility*)

n/a

n/a

c

c

c

Average time (unit) for reversion

- 

 -

48 h

24 h

24 h

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Gilman, M. R., Jackson E. M., Cervernm, D. R., Moreno, M. T. (1983). Relationship between the primary dermal irritation index and ocular irritation. J. Toxicol-Cut & Ocular Toxicol; 2: 107-117.

Interpretation of results:
GHS criteria not met
Conclusions:
A reliable study conducted in accordance with the standard guideline and GLP found the test material to be not irritating to the eyes of rabbits.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
From 22 Nov 1999 to 2 Dec 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP. The test material was similar to the registered substance but contained a higher proportion of an S3 isomer. The original study and the read-across are considered to be reliability 2.
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:
TEST ANIMALS

- Source: Covance Research Products, USA

- Age at study initiation: young adults

- Weight at study initiation: 2919-2976 (males), 2801 (female)

- Housing: 1/cage

- Diet (e.g. ad libitum): standard diet, ad libitum

- Water (e.g. ad libitum): drinking water, ad libitum

- Acclimation period: at least 7 days



ENVIRONMENTAL CONDITIONS

- Temperature (°C): 68.3-68.8 deg F

- Humidity (%): 34.3-46.1

- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 1999-11-22 To: 1999-12-02
Vehicle:
unchanged (no vehicle)
Controls:
other: none required - other eye used as control
Amount / concentration applied:
TEST MATERIAL

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

- Concentration: neat (100%)
Duration of treatment / exposure:
Unwashed (examinations 1, 24, 48, 72 h)
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
3 (2 males, 1 female)
Details on study design:
REMOVAL OF TEST SUBSTANCE

- Washing (if done): unwashed

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein: fluorescein at 72 h
Irritation parameter:
maximum mean total score (MMTS)
Remarks:
described as (MAS) maximum average score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 1 hr
Score:
3.3
Max. score:
110
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: (redness 1 + chemosis 0.66 + discharge 0) x2 = 3.3
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation

The test material did not cause significant ocular lesions, in two or more animals, as indicated by any of the following:

corneal opacity =>2...<3

iris lesion =>1...=<1.5

conjunctival redness =>2.5

conjunctival oedema (chemosis) =>2

based, in each case, on mean values for each animal derived from readings at 24, 48 and 72 h.

(EU criteria).

There were no corneal or irridial effects.

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Cornea

Iris

Conjunctivae - redness

Conjunctivae chemosis

Conjunctivae - discharge

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

Max score: 3

60 min

0,0,0

0,0,0

1,1,1

1,1,0

0,0,0

24 h

0,0,0

0,0,0

0,0,1

0,0,0

0,0,0

48 h

0,0,0

0,0,0

0,0,0

0,0,0

0,0,0

72 h

0,0,0

0,0,0

0,0,0

0,0,0

0,0,0

Average 24h, 48h, 72h

0

0

0

0

0

Area effected

0

-

-

 

Maximum average score (including area affected, max 110; 24, 48, 72 h)

0/80 [corneal opacityxareax5]

0/10 [iris scorex5]

0/20

 [(redness + chemosis + discharge) x2]

Reversibility*)

n/a

n/a

c

c

n/a

Greatest time (unit) for reversion

 n/a

n/a

48 h

24 h

n/a

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Interpretation of results:
GHS criteria not met
Conclusions:
A reliable study conducted in accordance with the standard guideline and GLP found the test material to be not irritating to the eyes of rabbits. The test substance was similar to the registered substance but contained a higher proportion of an S3 isomer.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The registered substance is a reaction mixture comprising approximately 60% w/w of 4,4,13,13 -tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane (S2 constituent) and 40% w/w of 3,15-Dioxa-8,9,10-trithia-4,14-disilaheptadecane,4,4,14,14-tetraethoxy- (S3 constituent).

No in vitro or in vivo skin or eye irritation/corrosion data are available for the registered substance, therefore these endpoints are addressed using weight of evidence from reliable in vivo data for a number of related substances. The composition of these related substances includes different concentrations of both isomers present in the registration substance, and the available data indicate that there are no differences in skin and eye irritation properties for constituents with different numbers of sulfur atoms in a (poly)sulfide chain. Since the three test substances cover the composition range of the registered substance, and only minimal and transient were seen in the studies, additional testing with the registration substance itself is not warranted.

Skin irritation/corrosion

Information on the skin irritation potential of the S2 constituent comes from an in vivo skin irritation test using a pure grade of S2 (CAS 56706-10-6) (ASTA Medica AG, 1996) which found the test material to be slightly irritating to rabbit skin. The test was conducted in accordance with OECD 404 with minor deviations, specifically use of an occlusive dressing. Mild to moderate erythema and mild oedema were observed, persisting up to the day 7 observation. All skin reactions were fully resolved by Day 9 and were not sufficient to trigger classification for skin irritation according to EU criteria.

In a study conducted in accordance with OECD 404 (WIL, 2000c), a similar test substance (low purity S2) which contained a higher proportion of the S3 constituent than S2 but a lower proportion than the registered substance was found to be non-irritant. Mild erythema was observed in one animal one-hour examination only.

A third study is available for a closely related substance polysulfides, bis[3-(triethoxysilyl)propyl] (CAS 211519-85-6), which is a reaction mass containing principally the S2 (15-60%), S3 (25-40%) and S4 (5-30%) constituents. This study (LPT, 1976) was conducted according to FDA test guidelines, and no skin reactions were observed with either intact or abraded skin.

Eye irritation/corrosion

Information on the eye irritation potential of the S2 constituent is available from an in vivo eye irritation test using a pure grade of S2 (CAS 56706 -10 -6) (ASTA Medica, 1996), conducted in accordance with the standard guideline. This study found the test material to be not irritating to the eyes of rabbits. Mild conjunctival redness and chemosis and moderate discharge were observed at the one- hour examination only. There were no corneal or iridial effects.

In a study conducted in accordance with the OECD 405 (WIL, 2000d), a similar test substance (low purity S2) which contained a higher proportion of an S3 constituent was found to be non-irritant. Mild conjunctival redness and chemosis were observed at the one-hour examination only. There were no corneal or iridial effects.

A third study is available for a closely related substance polysulfides, bis[3-(triethoxysilyl)propyl] (CAS 211519-85-6), which is a reaction mass containing principally the S2 (15-60%), S3 (25-40%) and S4 (5-30%) constituents. This study (LPT, 1977) was conducted according to FDA test guidelines, and no effects were observed at any timepoint.

Justification for classification or non-classification

The available in vivo data do not support classification for skin or eye irritation or corrosion according to Regulation (EC) No 1272/2008.