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Diss Factsheets

Administrative data

Description of key information

Maximisation study in guinea pigs (OECD406, GLP), using an intradermal induction of the test substance at 10% w/v in corn oil, followeed by a topical application with the undiluted test substance:


- challenge at 75%: response in 15% of the animals of the treated group (0 in negative control group)


- challenge with undiluted substance: net response of 15% (35% response in the treated group, and 20% in the negative control group)

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:
29 January 2003 to 12 June 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(1992)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
(1996)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Version / remarks:
(1998)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was conducted prior to the regulation requiring the use of the LLNA method
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: young adults
- Weight at study initiation: 270-340 grams
- Housing: five per cage in cage suitable for animals of this strain and weight range expected during the course of the study.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +/- 3 °C
- Humidity (%): 30-70%
- Air changes (per hr): a minimum of 15 changes per hour
- Photoperiod (hrs dark / hrs light): artificial, 12 hours light, 12 hours dark.

IN-LIFE DATES: From: 4-FEB-2003 To: 6-APR-2003.
Positive controls: From 20-MAR-2003 to: 14-APR-2003
Route:
intradermal
Vehicle:
corn oil
Concentration / amount:
Concentration for the intradermal injections: 10% w/v test substance
Intradermal injections:
i) 1:1 preparation of corn oil and Freund's Complete Adjuvant (FCA),
ii) 10% w/v test substance in corn oil,
iii) 10% w/v test substance in a 1:1 preparation of corn oil and FCA)
Day(s)/duration:
single intradermal injection
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
Undiluted substance
6 days after the intradermal injection 0.5 ml of 10% w/v Sodium Lauryl Sulphate mixed in paraffin wax was applied prior to topical application.
Day(s)/duration:
2 days
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Topical application: Undiluted substance on the left flank.
Day(s)/duration:
24 hours
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:

Topical application: 75% w/v substance in corn oil on the right flank
Day(s)/duration:
24 hours
No. of animals per dose:
20 test animals
10 control animals
Details on study design:
RANGE FINDING TESTS:
The dose-levels selected for the induction and the challenge stages of this study were determined by a sighting phase in the guinea pig.

A. INDUCTION EXPOSURE
An area approximately 5x5 cm on the scapular region of each animal was clipped free of hair with a pair of veterinary clippers and a row of three injections (0.05 - 0.1 ml each) was made on each site of the mid-line. The injections were: i) Top: Freund's Complete Adjuvant plus corn oil in the ratio 1.1; ii) Middle: a 10% w/v preparation of the test substance in corn oil; iii) Bottom: a 10% w/v preparation of the test substance in a 1:1 preparation of Freund's Complete Adjuvant plus corn oil. Control animals were treated the same as the test animals, except that they were treated with corn oil in place of the test substance. The injections were checked for any adverse effects approximately 1 day after dosing. Six days after intradermal induction, the application site was clipped and 0.5 ml of a 10% w/v of sodiyum lauryl sulphate (SLS) in paraffin wax was applied in order to provoke a mild infiammatory response. One day after dosing with SLS (one week after intradermal injection) , the scapular area was treated with a topical application of the undiluted test substance. This preparation (0.2-0.3 ml) was applied on filter paper (approximately size 4cm x 2cm) which was held in place by a piece of surgical tape. The tape was covered by a strip of adhesive bandage (approximately size 20-30cm x 5 cm) and secured by a piece of self-adhesive PVC tape. This occlusive dressing was kept in place for at least 48 hours. For the control animals, an untreated filter paper was used. The application sites were checked on removal of the dressing, apprximately 1 day later, and further twice prior to challenge.

B. CHALLENGE EXPOSURE
Two weeks after the topical indiction, an area, approximately 15cm x 5cm, on both flanks of all the test and control animals, was clipped free of hair with a pair of veterinary clippers. An occlusive dressing was prepared which consisted of two pieces of filter paper (approximate size 1cm x 2cm) stitched to a piece of rubber sheeting (approximate size 12cm x 5cm). The undiluted test substance (0.05-0.1 ml) was applied to one of the pieces of filter paper and a 75 % w/v preparation in corn oil (0.05-0.1 ml) was applied to the second piece of filter paper. The dressing was placed on the shorn flake of the guinea pig so that the undiluted test substance was on the left and the 75% w/v preparation was on the right. It was then covered with a strip of adhesive bandage (approximate size 25-40cm x 7.5cm) which was secured by a self adhesive PVC tape. After 24 hours, the dressing were carefully cut, using blunt-tipped scissors, removed and discarded. The position of the pieces of filter paper on the skin were identified using a black waterproof marker-pen. Skin sites were examinated approximately 1 and 2 days after removal of the dressings.
Challenge controls:
not required
Positive control substance(s):
yes
Remarks:
Hexylcinnamaldehyde
Positive control results:
The reliability of the test system is assessed at approximately 6-monthly intervals using Hexylcinnamaldehyde (known sensitizer).
The sensitising potential of Hexylcinnamaldehyde was assessed using a method essentially as the one described above.
The net percentage response was calculated to be 60 %.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
UNDILUTED Top Left
No. with + reactions:
7
Total no. in group:
20
Remarks on result:
other: grade 1: scattered mild redness
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
UNDILUTED Top Left
No. with + reactions:
0
Total no. in group:
20
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
75% w/v Top Right
No. with + reactions:
3
Total no. in group:
20
Remarks on result:
other: grade 1: scattered mild redness
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
75% w/v Top Right
No. with + reactions:
0
Total no. in group:
20
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
UNDILUTED Top Left
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
other: grade 1: scattered mild redness
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
UNDILUTED Top Left
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
other: grade 1: scattered mild redness
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
75% w/v Top Right
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
75% w/v Top Right
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
undiluted
No. with + reactions:
6
Total no. in group:
15
Remarks on result:
other: grade 1: scattered mild redness
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
undiluted
No. with + reactions:
4
Total no. in group:
15
Remarks on result:
other: grade 1: scattered mild redness
Interpretation of results:
other: mild sensitiser
Conclusions:
Based on the results of this study, 1,2,3,4-tetrachloro-hexafluorobutane is considered to be a mild sensitiser in the guinea pig.
Executive summary:

The purpose of this study was to assess the skin sensitisation potential of 1,2,3,4-tetrachloro-hexafluorobutane to guinea pigs.

The sensitisation potential was assessed used a method based on the maximisation test described by Magnusson and Kligman (1970). The study involved the treatment of guinea pigs using two procedures: the potential induction of an immune response and a challenge of that response.

The sensitisation response of the animals was determined 1 and 2 days after challenge by assessing the degree of erithema.

There were no signs of skin irritation during the induction phase of the study.

Following challenge of previously-induced guinea pigs with the undiluted test substance, scattered mild redness was seen in seven of the twenty test animals and in two of the ten control animals. The net response was 15%.

Following challenge of previously-induced guinea pigs with a 75% w/v preparation of the test substance in corn oil, scattered mild redness was seen in three of the twenty test animals. There was no erythematous response in any of the control animal. The net response was 15%

Based on the results of this study, 1,2,3,4-tetrachloro-hexafluorobutane is considered to be a mild sensitiser in the guinea pig.

A positive control study using hexylcinnamaldehyde demostrated the sensitivity of the test system.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

A traditional study on guinea pigs was performed in order to assess the skin sensitisation potential of 1,2,3,4-tetrachloro-hexafluorobutane, according to OECD guideline No. 406. The reported study is based on the maximisation test described by Magnusson and Kligman (1970), which involves the use of adjuvant by intradermal injection during the induction phase.

Following the challenge phase the net response of treated animals was 15 %.

Based on the results of the study, 1,2,3,4-tetrachloro-hexafluorobutane is considered to be a mild sensitizer in the guinea pig.


Migrated from Short description of key information:
A study based on the maximisation test described by Magnusson and Kligman (1970) is reported.
A net response of 15 % of treated animals resulted.
According to Regulation EC No. 1272/2008, the substance does not meet the classification criteria for human health for skin sensitisation.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Skin sensitisation

According to Regulation EC No. 1272/2008, when an adjuvant type guinea pig test method for skin sensitisation is used, a response of at least 30 % of the animals is required to consider the substance as skin sensitizer.

Under the test conditions, following the challenge phase the net response of treated animals was 15 %

Consequently 1,2,3,4-tetrachloro-hexafluorobutane does not meet the classification criteria for human health for skin sensitisation.