Registration Dossier

Administrative data

Description of key information

The key study is a well conducted human patch test conducted in compliance with GLP (TKL research, 1992). In this study HMDS was not sensitising to the skin of human volunteers.

In a guinea pig maximisation study conducted using a study protocol comparable with OECD 406 and to GLP (Dow Corning Corporation, 1992) HMDS was not sensitising to the skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02.12.1991 to 10.01.1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
The study was not conducted in compliance with GLP, but with Good Clinical Practice.
Principles of method if other than guideline:
Human Patch test to determine whether the test material was capable of sensitising the skin of humans under controlled patch test conditions.
GLP compliance:
no
Remarks:
Conducted with Good Clinical Practice (GCP)
Type of study:
patch test
Justification for non-LLNA method:
The study was well documented and meets generally accepted scientific principles. The study was not conducted in compliance with GLP, but with GCP.
Species:
human
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Not applicable
- Age at study initiation: 18 to 78 years
- Weight at study initiation: Not applicable
- Housing: Not applicable
- Diet (e.g. ad libitum): Not applicable
- Water (e.g. ad libitum): Not applicable
- Acclimation period: Not applicable


ENVIRONMENTAL CONDITIONS: Not applicable


IN-LIFE DATES: From: 02.12.1991 to 10.01.1992
Route:
epicutaneous, semiocclusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Undiluted
Route:
epicutaneous, semiocclusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Undiluted
No. of animals per dose:
100
Details on study design:
1st application: Induction undiluted semiocclusive (0.2 ml)
2nd application: Challenge undiluted semiocclusive (0.2 ml)

One hundred subjects were enrolled in this study.  Semi-occlusive, 2 cm x 2 cm Webril pad patches were applied to the infrascapular area of the back, either to the right or left of the midline. The induction phase consisted of application of the test material every 48 hours for a total of nine applications  (applications made on Friday were not evaluated until Monday, prior to the re-application of test material) with the occlusive patch being removed after 24 hours.  The test sites were evaluated prior to each application. Following the ninth evaluation, the subjects were dismissed for a 14-day rest period. After the rest period, identical patches were applied to sites previously unexposed to test material. These patches were removed 24 hours after application and were evaluated 48 hours and 72 hours after application. Each person was considered a complete case and used for evaluation of the material if they had six or more applications and subsequent readings during the first phase and at least one reading during the final phase.
Test Subjects 
* 11 males and 97 females (enrolled).
Following the second application of the test material, a significant number of subjects developed superficial epidermal erosion. It was decided to change the occlusive patch condition to semi-occlusive, applying the material to the same site beginning with the third application.
Challenge controls:
None
Positive control substance(s):
no
Positive control results:
No positive control.
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
0.2 ml undiluted
No. with + reactions:
0
Total no. in group:
100
Clinical observations:
Under the conditions employed in this study, there was no evidence of skin sensitization to the test material.
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
0.2 ml undiluted
No. with + reactions:
0
Total no. in group:
100
Interpretation of results:
GHS criteria not met
Conclusions:
In a well conducted human patch test conducted to GCP (reliability score 2) L2 was not sensitising to the skin of human volunteers.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In a well conducted human patch test conducted to GLP (TKL Research, 1992) 100 subjects were exposed to an induction and challenge dose of undiluted HMDS under semi-occlusive conditions. There was no evidence of skin sensitisation under the conditions of this study.

In a guinea pig maximisation study conducted using a study protocol comparable with OECD 406 and to GLP (Dow Corning Corporation, 1992) guinea pigs were initially exposed to 25, 50, 75 or 100% HMDS (ethanol vehicle) to determine the irritating potential of HMDS. Since no irritation was observed in the preliminary test, undiluted HMDS was used in the main test. There was no evidence of skin irritation or skin sensitisation following the challenge phase. Intradermal injection sites showed necrosis and scabbing typical of Freund's Complete Complete Adjuvant response. There were no significant effects on body weight gain or food consumption.

Three additonal studies for which a study report was not available for review support the finding of 'non-sensitising' in the key study.


Justification for classification or non-classification

Based on the available studies hexamethyldisiloxane is not classified for skin sensitisation

according toRegulation (EC) 1272/2008.