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Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
20 February 2017 to 30 March 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
Type of study:
Buehler test
Justification for non-LLNA method:
The results of in vitro assays are indicative for no sensitization, but an LLNA test showed ambiguous results. Therefore in order to exclude false positive results in the LLNA test this additional in vivo test was performed.
The standard study plan related to this study was approved by the registered Ethics Committee No. 76.

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(2-ethylhexyl) azelate
EC Number:
203-091-7
EC Name:
Bis(2-ethylhexyl) azelate
Cas Number:
103-24-2
Molecular formula:
C25H48O4
IUPAC Name:
bis(2-ethylhexyl) azelate

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: ENVIGO (Kreuzelweg 53, 5961 NM HORST The Netherlands
- Age at study initiation: 3-4 weeks
- Weight at study initiation: 270-306 g
- Housing: groups of maximum 3 in polycarbonate cages.
- Diet: ENVIGO, 2040C ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days
- Indication of any skin lesions: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 ° C
- Humidity (%): 30-70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
other: liquid paraffin
Remarks:
50% gave colorless solution
Concentration / amount:
100%
Day(s)/duration:
6
Adequacy of induction:
highest technically applicable concentration used
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: liquid paraffin
Concentration / amount:
100%
Day(s)/duration:
6 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20 treatment and 10 controls
Details on study design:
RANGE FINDING TESTS:
Three guinea pigs were treated with the test item placed onto the selected treatment sites and covered with an occlusive dressing for a period of 6 hours at 4 different concentrations: 100%, and diluted at 75%, 50% and 25% in liquid paraffin.
Washing of the skin after removal of the dressing was done with liquid paraffin.
maximal non-irritant concentration was 100%

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours (on day 0, 6 and 13)
- Test groups: 20 females treated with 0.5 mL 100% undiluted substance
- Control group: 10 females treated with 0.5 mL liquid paraffin
- Site: scapular zone
- Frequency of applications: 3 times

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: on day 26
- Exposure period: 6 hours
- Test groups: 20 females treated with 0.5 mL 100% undiluted substance
- Control group: 10 females treated with 0.5 mL 100% undiluted substance
- Site: dorso-lumbar zone of the left flank
- Evaluation (hr after challenge): at 24, 48 and 72 hour

Challenge controls:
0.5 mL of liquid paraffin was applied on the right flank.
Positive control substance(s):
yes
Remarks:
α-Hexylcinnamaldehyde in 3 separate tests

Results and discussion

Positive control results:
positive in 3 applications

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0 (100% in challenge)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100% (100% in challenge)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0 (challenge 100%)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100% (100% in challenge)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
0 (100% challenge)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
100% (100% in challenge)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation

Any other information on results incl. tables

On the challenge control sites (challenged at the other flank with liquid paraffin) one animal was observed with discrete to intense erythema at the 24 and 48 hours reading. This effect was fully reversible at the 72 hours reading.

groups

Time (h)

Concentrations

Incidence

 

% of

positive

responses

% of

sensitized

 

 

 

 

0

1

2

3

 

 

Control

Group 1

 

24

100%

10

0

0

0

0%

 

48

100%

10

0

0

0

0%

 

72

100%

10

0

0

0

0%

 

24

0%

10

0

0

0

0%

 

48

0%

10

0

0

0

0%

 

72

0%

10

0

0

0

0%

 

Treated Group 2

24

100%

20

0

0

0

0%

0%

48

100%

20

0

0

0

0%

0%

72

100%

20

0

0

0

0%

0%

24

0%

19

0

0

1

5%

0%

48

0%

19

1

0

0

5%

0%

72

0%

20

0

0

0

0%

0%

 

Grading scale

0....... No visible change

1....... Discrete or patchy erythema

2....... Moderate and confluent erythema

3....... Intense erythema and swelling

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In a Buehler test the substance was not sensitizing to the skin.
Executive summary:

In a test according to OECD 406 (Buehler) 20 female guinea pigs were exposed to the undiluted substance on day 0, 6 and 13 during 6 hours epicutaneously under occlusion. A group of 10 female guinea pigs received a similar treatment with liquid paraffin on day 0, 6 and 13. Both groups were challenged with undiluted substance on day 26 during 6 hours epicutaneously under occlusion and were checked 24, 48 and 72 hours thereafter for signs of skin reaction.

In the treated group (treatment and challenge dose of 100%), no macroscopic cutaneous reactions attributable to allergy were observed during the examination following the removal of the occlusive dressing.

In the control group (associated with the challenge dose of 100%), no cutaneous intolerance reactions were observed during the examination following the removal of the occlusive dressing.

No cutaneous reaction was recorded in animals from the control group after the challenge phase, on the treated area with liquid paraffin.

In conclusion, the substance does not have to be classified in category 1 as a skin sensitiser, in accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures.