Registration Dossier

Administrative data

Description of key information

In the key skin irritation study conducted to OECD Test Guideline 404 but not in compliance with GLP (ASTA Pharma AG, 1987a) trimethoxy(octyl)silane was irritating to the skin of rabbits under occluded conditions. There were no systemic effects.

In the key eye irritation study conducted to OECD Test Guideline 405 but not in compliance with GLP (ASTA Pharma AG, 1987b) trimethoxy(octyl)silane was not irritating to the eyes of rabbits. There were no systemic effects.

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:
13.07.1987 to 27.07.1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
other: white Russian
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: ASTA Pharma AG, D-4800 Bielefeld 14
- Age at study initiation: 9-11 months
- Weight at study initiation: 2.2-2.45 kg
- Housing: Stainless steel cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least one day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±2
- Humidity (%): 55 ±15
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 13.07.1987 to 27.07.1987
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
Four hours
Observation period:
14 days (observation times: 1, 24, 48 and 72 hours, then once daily
Number of animals:
Three
Details on study design:
TEST SITE
- Area of exposure: Dorsal skin
- % coverage: No data
- Type of wrap if used: Occlusive (linen cloth which adhered to a synthetic film glue, bandage wrapped several times around the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not mentioned, so assumed no washing

SCORING SYSTEM: Draize
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hours
Score:
4.9
Max. score:
8
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
Erythema occurred in all three animals immediately after removal of the patches. The erythema was moderate to severe, but had disappeared by day 10 of observation. Edema also occurred immediately after the end of exposure; slight in one animal and moderate in two animals. The findings had disappeared by day 9. From the middle of the first observation week all animals showed eschar formation, which had not competely peeled off in two animals until the end of the observation period.
Other effects:
The general condition of the animals was not affected by the treatment.

Table 1 summary of skin irritation results

Skin reaction  Hours after end of exposure         Draize score
     Animal 1  Animal 2  Animal 3
 Erythema and eschar formation  1  1  2
   24  3  2  3
   48  3  2  3
   72  3  3 3
 Edema Formation  1  2  2  2
   24  3  2  3
   48  3  2  3
   72  3  2  3

Mean value fotr erythema/eschar: 2.42

Mean value for edema: 2.5

Irritation index: 4.9

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
In a skin irritation study conducted to OECD 404 but not to GLP (reliability score 2) trimethoxyoctylsilane was irritating to the skin of rabbits. There were no systemic effects.
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:
14.07.1987 to 17.07.1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
other: white Russian (albino)
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: ASTA Pharma AG, D-4800 Bielefeld 14
- Age at study initiation: 5-6 months
- Weight at study initiation: 2.4 to 2.6 kg
- Housing: Individually in stainless steel cages
- Diet (e.g. ad libitum): Not stated, but assumed to be ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least one day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±2
- Humidity (%): 55 ±15
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 14.07.1987 to 17.07.1987
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Duration of treatment / exposure:
No rinsing
Observation period (in vivo):
Three days (1. 24. 48, 72 hours)
Number of animals or in vitro replicates:
Three (one male, two females)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: Cliptrix pencil light
Irritation parameter:
other: Irritation index
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hours
Score:
4
Max. score:
80
Reversibility:
fully reversible
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:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
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
Irritant / corrosive response data:
Cornea and iris did not show any findings. The conjunctiva reacted with hyperemia (grade 1) in one animal and in two animals diffuse crimson or beefy discolouration (grade 2 or 3) was observed. In addition, slight swelling (grade 1) or swelling with partial eversion of lids (grade 2) occurred. Swelling had completely disappeared at 24 hours and redness 48 or 96 hours after substance treatment. Discharge with moistening of considerable parts around the eye, was recorded in two animals only at observation time of one hour.
Other effects:
There were no systemic effects, and the general condition of the animals was undisturbed.

Effect  Hours after exposure      Animal irritation scores
  1 2 3
  Corneal opacity
  24 
  48 
  72
  Iritis
  24 
  48 
  72 0 0 0
 Conjunctival redness 1  1  2  3
  24  1  1  2
  48  0  0 2
  72  0  0  0
 Conjunctival chemosis  1  1  2  2
   24  0  0  0
   48  0  0  0
   72  0  0  0
 Conjunctival discharge  1  0  3  3
   24  0  0  0
   48  0  0  0
   72  0  0  0
Interpretation of results:
GHS criteria not met
Conclusions:
In an eye irritation study conducted to OECD 405 but not to GLP (reliability score 2) trimethoxyoctylsilane was not irritating to the eyes of rabbits. There were no systemic effects.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a skin irritation study conducted to OECD 404 but not to GLP (reliability score 2) trimethoxy(octyl)silane was irritating to the skin of rabbits.

Erythema occurred in all three animals immediately after removal of the patches. The erythema was moderate to severe, but had disappeared by day 10 of observation. Edema also occurred immediately after the end of exposure; slight in one animal and moderate in two animals. The findings had disappeared by day 9. From the middle of the first observation week all animals showed eschar formation, which had not completely peeled off in two animals until the end of the observation period. The general condition of the animals was not affected by the treatment (ASTA Pharma AG, 1987a).

In an eye irritation study conducted to OECD 405 but not to GLP (reliability score 2) trimethoxy(octyl)silane was not irritating to the eyes of rabbits. Cornea and iris did not show any findings. The conjunctiva reacted with hyperemia (grade 1) in one animal and in two animals diffuse crimson or beefy discolouration (grade 2 or 3) was observed. In addition, slight swelling (grade 1) or swelling with partial eversion of lids (grade 2) occurred. Swelling had completely disappeared at 24 hours and redness 48 or 96 hours after substance treatment. Discharge with moistening of considerable parts around the eye, was recorded in two animals only at observation time of one hour. There were no systemic effects, and the general condition of the animals was undisturbed (ASTA Pharma AG, 1987b).


Justification for classification or non-classification

Based on the available data, trimethoxy(octyl)silane is not classified for eye irritation according to Regulation (EC) No 1272/2008. Regarding skin irritation, the substance is classified as 'Cat 2: irritant', with the hazard statement 'H315: Causes skin irritation' according to Regulation (EC) No 1272/2008.