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Description of key information

In the key skin irritation study, conducted according to OECD Test Guideline 404 and in compliance with GLP, a single semi-occlusive application of the registered substance, N-[3-(dimethoxymethylsilyl)propyl]ethylenediamine (CAS No. 3069-29-2, EC No. 221-336-6), to intact rabbit skin for four hours elicited well-defined to moderate to severe dermal irritation in all three animals (Huntingdon Life Sciences, 1999). The test material is concluded to be a skin irritant, based on the erythema reading of 3 in two of the tested animals from the gradings at 24, 48 and 72 hours after patch removal.

The key eye irritation study, conducted according to OECD Test Guideline 405 and in compliance with GLP, found the registered substance, N-[3-(dimethoxymethylsilyl)propyl]ethylenediamine, to be a severe irritant to the eye based on a test in one rabbit in which a pain response, corneal opacity, iridial inflammation and severe conjunctival irritation were evident (SafePharm, 1987).

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:
6 and 19 July 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan UK, England
- Age at study initiation: minimum of 11 weeks
- Weight at study initiation: 2.3-2.7kg
- Housing: individually housed in stainless steel cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 19 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 13-27.5
- Humidity (%): 38-68
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5ml
Duration of treatment / exposure:
4 hours
Observation period:
Examination of the treated skin was made at 1, 24, 48, 72 hours after exposure. Additional observations were made for all animals on days 5 through 10 and two animals on days 11 through 14.
Number of animals:
1 male, 2 females
Details on study design:
TEST SITE
- Area of exposure: dorso-lumbar region
- Type of wrap if used: gauze pad, and elastic adhesive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with warm water
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritant / corrosive response data:
Well-defined to moderate to severe erythema with slight oedema was observed in all three animals. In addition, desquamation of the corneum stratum (characterised by dryness and sloughing) was seen in three animals, thickening of the skin in two animals and cracking of the skin in one animal. Reactions gradually ameliorated and had resolved completely in one animal by day 10, however, very slight to well-defined erythema was still present in the remaining two animals at study termination on day 14.
Other effects:
There were no signs of toxicity or ill health in any rabbit during the observation period.
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
In a reliable study conducted according to OECD Test Guideline 404 and in compliance with GLP, the test material is concluded to be a Category 2 skin irritant, based on the erythema reading of 3 in two of the tested animals from the gradings at 24, 48 and 72 hours after patch removal.
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:
9 Nov 1987
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:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Sandbach, UK
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 3.05 kg
- Housing: 1/suspended metal cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-18
- Humidity (%): 50%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 1987-11-09 To: 1987-11-09
Vehicle:
unchanged (no vehicle)
Controls:
other: not required - untreated eye is the control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 ml
- Concentration: neat
Duration of treatment / exposure:
30 mins. (Test animal sacrificed for humane reasons after 30 mins.)
Observation period (in vivo):
30 mins
Number of animals or in vitro replicates:
1
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: not irrigated

SCORING SYSTEM: Draize (max 110)

TOOL USED TO ASSESS SCORE: light from standard ophthalmoscope
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
other: 30 mins
Score:
85
Max. score:
110
Reversibility:
other: not possible to assess reversibility; unlikely to be reversible
Remarks on result:
other: one animal; observation 30 mins
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: The test substance was tested on one animal only and demonstrated irreversible eye damage.
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: The test substance was tested on one animal only and demonstrated irreversible eye damage.
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: The test substance was tested on one animal only and demonstrated irreversible eye damage.
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: The test substance was tested on one animal only and demonstrated irreversible eye damage.
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: The test substance was tested on one animal only and demonstrated irreversible eye damage.
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: The test substance was tested on one animal only and demonstrated irreversible eye damage.
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: The test substance was tested on one animal only and demonstrated irreversible eye damage.
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: The test substance was tested on one animal only and demonstrated irreversible eye damage.
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: The test substance was tested on one animal only and demonstrated irreversible eye damage.
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: The test substance was tested on one animal only and demonstrated irreversible eye damage.
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: The test substance was tested on one animal only and demonstrated irreversible eye damage.
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: The test substance was tested on one animal only and demonstrated irreversible eye damage.
Irritant / corrosive response data:
Total score (one rabbit @ 30 mins): 85/110. Opalescent corneal opacity, iridial inflammation, severe conjunctival irritation. See table 1.
Other effects:
Conjunctival blood stained discharge and haemorrhage. Haemorrhage from nictitating membranes.

Table 1: Irritant/corrosive response data for a single animal (study terminated at 30 mins)

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Discharge

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

Max. score: 3

30 min

3

1

3

4

3

Area effected

 4

-

-

-

-

Total score 85/110

60/80

5/10

20/20 

Reversibility

Not possible to assess; unlikely to be reversible

 

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
A reliable study, conducted according to OECD Test Guideline 405 and in compliance with GLP, reported corneal opacity, iridial inflammation and severe conjunctival irritation and a Draize score of 85 out of 110, in a single rabbit. The score was judged in the report to indicate that the test material was a very severe to extremely severe irritant to the eyes of rabbits, and would be considered to cause irreversible eye effects according to EU criteria.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In the key skin irritation study, a 4-hour semi-occlusive application of the test substance, N-[3-(dimethoxymethylsilyl)propyl]ethylenediamine, to rabbit skin elicited well-defined to moderate to severe dermal irritation in all three animals (Huntingdon Life Sciences, 1999). In addition, desquamation of the corneum stratum (characterised by dryness and sloughing) was seen in three animals, thickening of the skin in two animals and cracking of the skin in one animal. Reactions gradually ameliorated and had resolved completely in one animal by day 10, however, very slight to well-defined erythema was still present in the remaining two animals at study termination on day 14. Erythema readings of 3 in two of the tested animals from the gradings at 24, 48 and 72 hours after patch removal, are reported. The study was conducted according to OECD Test Guideline 404 and in compliance with GLP.

A reliable supporting study for skin irritation, conducted according to OECD Test Guideline 404 and in compliance with GLP, found the test material to be moderately irritating to the skin of rabbits (SafePharm, 1987). Erythema (very slight or well defined) was present in 6 of 6 animals at the 1, 24, 48 and 72 h observations, but absent on day 7. Oedema (very slight or slight) was noted in 6/6 at 1 and 24 h, and in 4/6 at 48 and 72 h, but was absent at 7 days. The Draize primary irritation index (PII; combined 24 h and 72 h averages for oedema and erythema) was 2.4 - indicating moderate irritation.

The second supporting study for skin irritation, lacking in detail and not conducted in compliance with GLP, reports no irritation in rabbits in response to application of 0.5 ml of test material onto skin (BRRC, 1982).

The key eye irritation study, conducted according to OECD Test Guideline 405 and in compliance with GLP, found the test material, N-[3-(dimethoxymethylsilyl)propyl]ethylenediamine, to be a severe irritant to the eye based on a test in one rabbit in which a pain response, corneal opacity, iridial inflammation and severe conjunctival irritation were evident (SafePharm, 1987). Other recorded effects include conjunctival blood-stained discharge and haemorrhage and haemorrhage from nictitating membranes. The study was terminated without treatment of additional animals, in accordance with the test guideline. In conclusion, the effects were judged to indicate that the test material was a very severe to extremely severe irritant to the eyes of rabbits.

A supporting study for eye irritation was also available which was carried out according to a protocol equivalent to guideline, reports the test substance mildly irritating to the eye of rabbits (BRRC, 1982). Moderate injury to the cornea, iris and conjunctivae were present in all animals after application of 0.1 ml of the test substance into the eye. Five of the eyes were substantially improved by 7 days, but injury to one eye persisted through 14 days. While the documentation of results is not sufficient for drawing a definitive conclusion regarding classification, the result indicates that the test substance has irritant effects in the eye.

Supporting skin and eye irritation tests for the analogue substance N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS No. 1760-24-3, EC No. 217-164-6) are included only to support the read-across justification for the genetic toxicity endpoint currently using this analogue substance.

Justification for classification or non-classification

Based on the available data, N-[3-(dimethoxymethylsilyl)propyl]ethylenediamine is classified for skin irritation Category 2, H315: "Causes skin irritation" and eye damage Category 1, H318: "Causes serious eye damage" according to Regulation (EC) No. 1272/2008.

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