Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 1a GLP guideline study (OECD)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name of test material (as cited in study report): TRICHLOROETHANE-1.1.1 NOT STABILIZED
Physical state: Colourless liquid
Purity test date: 24/06/08Analytical
purity: Purity 99.99 %
Lot/batch No.: Batch number R4801 du 24/06/08
Arkema filing number:GRL 0041/08
Expiry date: 30 September 2008
Storage conditions: room temperature protected from light and humidity
Supplied by Arkema France-

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS-
Source: - Charles River Laboratories France, L’Arbresle, France
Age at study initiation: - 1 – 2 months old
Weight at study initiation: - males: 345 – 383 g, females: 353 – 397 g
Housing: individually in polycarbonates cages (48x27x20cm)
Diet: ad libitum "106 pelleted diet" (SAFE, Augy, France)
Water: ad libitum drinking water filtered with a 0.22µm membrane
Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS-
Temperature (°C): 22+/-2°C
Humidity (%): 30-70%
Photoperiod (12 hrs dark /12 hrs light)

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
intradermal induction: 10 % (w/w)
cutaneous induction: undiluted test item
cutaneous challenge: 50 % (w/w) test item
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
intradermal induction: 10 % (w/w)
cutaneous induction: undiluted test item
cutaneous challenge: 50 % (w/w) test item
No. of animals per dose:
Control group: 5males and 5 females
Treated group: 10males and 10females
Details on study design:
RANGE FINDING TESTS: Intradermal test: (5, 10 and 25 % (w/w) Cutaneous test: 50 % (w/w) and 100 %
MAIN STUDY
A. INDUCTION EXPOSURE
* Intradermal induction: - On day 1, 3 injections are realized on each side of the scapular area:- 0.1mL of Freund's complete adjuvant at 50% in 0.9%NaCl- 0.1mL of the test item at 10 % (w/w) (for treated group) or 0.1mL of vehicle (corn oil) (for control group)- 0.1mL of a mixture 50/50 (v/v) of Freund's complete adjuvant in 0.9% NaCl and the test item at 10 % (w/w) (for treated group) or the vehicle (corn oil) (for control group).
* Cutaneous induction: - As the test item was shown to be irritant during the preliminary test, no topical application of sodium lauryl sulfate was required on day 7. On day 8, occlusive application on the scapular area of a pad of filter paper (approximately 8 cm 2) which was fully-loaded with the undiluted test item (for treated group) or vehicle (acetone)(for control group) for 48hours
B. CHALLENGE EXPOSURE
D22On day 22, 24 hours occlusive application on the scapular area of a filter paper of a chamber (Finn Chamber ®) fully-loaded with50 % (w/w) test item on the right flank and of the vehicle (acetone) on the left flank.
Reactions are evaluated 24 and 48 hours after removal of the dressing
Challenge controls:
Veihcle (acetone) only
Positive control substance(s):
yes
Remarks:
Mercaptobenzothiazole

Results and discussion

Positive control results:
October 2007-CIT Study n°: 33771 RDG
Mercaptobenzothiazole: Positive result in recent study on 10 females. Induction: test substance injected intradermally 1.0 % (d1) and applied cutaneously 20% (d8). Challenge (d22): 20% r flank control l flank. In the test a positive skin sensitisation reaction was recorded in 50 % (5/10) guinea pigs.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50 % (w/w)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50 % (w/w). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50 % (w/w)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50 % (w/w). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50 % (w/w)
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50 % (w/w). No with. + reactions: 2.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50 % (w/w)
No. with + reactions:
3
Total no. in group:
20
Clinical observations:
3 aniamls with dryness of skin
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50 % (w/w). No with. + reactions: 3.0. Total no. in groups: 20.0. Clinical observations: 3 aniamls with dryness of skin.

Any other information on results incl. tables

Table 1: Erythmea scores following topical challenge with 50 % (w/w) 1,1,1-trichloroethane

Group

Sex

Animal

24h

48h

Erythema

Erythema

LF

RF

LF

RF

Control

M

61 

 0

 0

 0

 0

 62

 0

 0

 0

 0

 63

 0

 0

 0

 0

 64

 0

 0

 0

 0

 65

 0

 0

 0

 0

Control

F

 76

 0

 0

 77

 0

 0

 0

 78

 0

 0

 0

 79

 0

 0

 0

 80

 0

 0

Treated

M

66 

 0

 67

 0

 0

 0

 68

 0

 0

 0

 69

 0

 0

 0

 70

 0

 0

 1/S

 71

 0

 0

 0

 72

 0

 0

 0

 73

 0

 0

 0

 74

 0

 0

 0

 75

 0

 0

 0

Treated

F

 81

 0

 0

 0

 82

 0

 0

 0

 83

 0

 0

 2/S

 84

 0

 0

 0

 85

 0

 0

 0

 86

 0

 0

 0

 87

 0

 0

 0

 88

 0

 0

 0

 89

 0

 0

 0

 90

 0

 0

 1/S

LF=left flank

RF=right flank

A=crusts

S=dryness of the skin

0 - no visible change

1 - discrete or patchy erythema

2 - moderate and confluent erythema

3 - intense erythema

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under these experimental conditions and according to the Magnusson and Kligman method, the test item TRICHLOROETHANE-1.1.1 NOT STABILIZED at the concentration of 50 % (w/w) induced positive skin sensitization reactions in 3/20 guinea pigs and is not considered as skin sensitizer.
Executive summary:

The delayed contact hypersensivity of TRICHLOROETHANE-1.1.1 NOT STABILIZED was evaluated in Guinea pigs according to OECD N°406 guideline (Magnusson and Kligman test).

The induction phase has been realized both by intradermal route on day 1 (10% in corn oil) and by cutaneous route on day 8 (undiluted) in 2 groups of guinea pigs: 5 males and 5 females for control group and 10 males and 10 females for treated group. The challenge phase was realized on day 22 by cutaneous application of 50 % (w/w)on the right (acetone on the left); the cutaneous reactions were scored 24 and 48 hours after the challenge phase.

In conclusion, the test item was considered as not sensitizing in guinea pigs.