Registration Dossier

Administrative data

Description of key information

In the key skin irritation study (Dow Corning Corporation, 1996)  repeated 24 hour occluded contact with HMDS caused slight to well defined erythema and moist exfoliation. Semi-occluded and open contacts did not cause test material-related irritation to the skin of albino rabbits.

In the key eye irritation study (Stauffer Chemical Company, 1973) HMDS was not irritating to the eyes of rabbits.

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:
1994/05/12 - 1996/04/11
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
according to
Guideline:
other: modified methods of CTFA Safety Testing Guidelines, published by the Cosmetic, Toiletry and Fragrancy Association on September 27, 1985, and Preclinical Safety Evaluation of Materials used in Medical Devices HIMA Report 85-1.
Deviations:
yes
Remarks:
The water contained Trihalomethane (162 μg/l) that was above the EPA recommended level of 100 μg/l.
GLP compliance:
yes
Species:
guinea pig
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS

- Source: not stated

- Age at study initiation: ca. 3 months

- Weight at study initiation: 2.31-2.59 kg

- Housing: individual housing, in conventional design stainless steel cages

- Diet: Purina 5325 Certified High Fiber Rabbit Chow, ad libitum

- Water: ad libitum

- Acclimation period: 7 day quarantine


ENVIRONMENTAL CONDITIONS

- Temperature (°F): 61-70

- Humidity (%): 40-60

- Air changes (per hr): 10-15

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


Type of coverage:
other: occluded, semi-occluded or open
Preparation of test site:
other: intact and abraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL

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

- Concentration (if solution): undiluted


Duration of treatment / exposure:
10 applications over 14 days
Observation period:
14 days
Number of animals:
3/group
Details on study design:
TEST SITE

- Area of exposure: the back

- Type of wrap if used: For occlusive application; a cotton gauze patch covered with a piece of SARAN plastic wrap, held in place by a cotton cloth bandage taped to their hair for 24 hours. Semi-occlusive wrap; a cotton gauze patch, held in place by a cotton cloth bandage taped to the hair for 24 hours. For unocculuded applicaiton, no wrap was used.


REMOVAL OF TEST SUBSTANCE

- Washing (if done): not reported


SCORING SYSTEM: The skin responses were cored on a 0-4 scale, 0 representing no reaction and 4 representing a severe reaction.
Irritation parameter:
other: Occluded application
Basis:
other: Repeated application
Time point:
other: Repeated 14 day exposure
Max. score:
2
Remarks on result:
other: Very slight to well defined erythema. See Table 1 for complete mean values.
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
Irritant / corrosive response data:
Occlusive group: very slight to well defined erythema and moist exfoliation was observed in all animals in this group by the fourth day of testing and continued throughout the study (abraded sites were healed by the fourth test day). A difference between intact and abraded sites showed a persistence of exfoliation at the abraded sites (exfoliation was present days 4 through 6 at intact sites and days 4 through 10 at abraded sites).

Semi-occlusive group: no test material - related irritation was observed in these animals during the study (abraded sites were healed by the fourth test day). No differences were observed between the intact and abraded sites.

Unoccluded group: No irritation was observed in animals during the course of the study (abraded sites were healed by the fourth day). No differences were seen between the intact and abraded sites.
Other effects:
There were no apparent test material-related effects on clinical signs, food consumption or body weight gains. The occluded wrapped animals gained less weight than the other groups. This equivocal result was possibly due to the occlusive wrappings.

Table 1: Mean Skin irritation scores at various intervals (30 minutes scoring)

Method

Skin Response

 

Score after application number*

1

2

3

4

5

6

7

8

9

10

Occlusive

ErythemaMax. score: 4

0/0

0/0

0/0

2/2

2/2

1.3/1.3

0/1

0.7/1.7

1/1.7

0/1

 

Edema     Max. score: 4

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

Semi-occlusive

ErythemaMax. score: 4

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

 

Edema     Max. score: 2

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

Unoccluded

ErythemaMax. score: 4

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

 

Edema     Max. score: 2

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

0/0

 *intact/abraded

Interpretation of results:
GHS criteria not met
Conclusions:
In a test that was conducted in accordance with a suitable test guideline and in compliance with GLP, L2 did not meet the criteria for classification as a skin irritant in the EU. The study involved repeated applications over 14 days and as such exceeds the requirements of the OECD 404 skin irritation study.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
It was not compliant with GLP.
Qualifier:
according to
Guideline:
other: CFR 191.12 Ch Title 21
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS

- Weight at study initiation: 1.6-2.1 kg


Vehicle:
unchanged (no vehicle)
Controls:
other: Untreated eye.
Amount / concentration applied:
TEST MATERIAL

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



Duration of treatment / exposure:
Single instillation, not rinsed.
Observation period (in vivo):
Eyes were observed at 24, 48 and 72 hours and scored for irritation.
Number of animals or in vitro replicates:
6
Details on study design:
SCORING SYSTEM: Eye irritation was determined according to the method outlined in the "Illustrated Guide for Grading Eye Irritation by Hazardous Substances" (Total possible score 110). If at the end of 72 hours ocular damage appears to be remissable (reversible), the animal is observed for additional 4-7 days before final scoring is possible.

Irritation parameter:
other: Ocular irritation.
Basis:
other: not specified
Time point:
other: 24/48/72h
Score:
0
Remarks on result:
other: Not irritating
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:
4
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:
No signs of eye irritation were observed.
Other effects:
None reported.

No apparent signs of eye irritation were observed. The test animals appeared normal when necropsied 14 days after treatment.

Interpretation of results:
GHS criteria not met
Conclusions:
The test material was found not irritating as determined in a reliable study conducted according to generally accepted scientific principles.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In the key skin irritation study (Dow Corning Corporation, 1996), intact and abraded skin of New Zealand white rabbits (3 animals/group) were exposed to HMDS under occlusive, semi-occlusive or open conditions for ten 24 hour periods over 14 days. There were no apparent test substance-related effects on clinical signs, food consumption or body weight gains. The occluded wrapped animals gained less weight than the other groups. This equivocal result was possibly due to the occlusive wrappings. Under the test conditions, repeated 24-hour occluded contacts with the test substance caused slight to well defined erythema and moist exfoliation. Semi-occluded and non-occluded contacts did not cause test substance-related irritation to the skin of albino rabbits. The observed minor irritation did not meet the criteria for classification.

In the key eye irritation study (Stauffer Chemical Company, 1973) the eyes of New Zealand white rabbits (6 animals) were exposed to a single dose of HMDS and irritation graded after 24, 48 and 72 hours. No apparent signs of eye irritation were observed. The eyes also appeared normal when necropsied 14 days after treatment. Therefore HMDS was concluded not to be irritating to eyes.

Supporting studies for skin and eye irritation are in agreement with the results of the key studies.


Justification for classification or non-classification

Based on the available in vivo skin and eye irritation data, HMDS does not meet the criteria for classification as irritant

according to Regulation (EC) 1272/2008.