Registration Dossier
Registration Dossier
Diss Factsheets
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EC number: 915-748-1 | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data

Endpoint summary
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
- 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
- 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
- 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.
Referenceopen allclose all
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
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
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Link to relevant study records
- 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.
- 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
- 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
- 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.
Referenceopen allclose all
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
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.
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
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.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
