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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2018-03-12 - 2018-04-20
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:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
Buehler test
Justification for non-LLNA method:
Test was sponsored by supplier in India. Since no other data is available no new animal study was performed.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
other: analytical grade water with 0.2% Tween 80
Concentration / amount:
63%
Day(s)/duration:
28
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: analytical grade water with 0.2% Tween 80
Concentration / amount:
63%
Day(s)/duration:
2
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20
Details on study design:
The induction and challenge was made by epidermal (topical) application of the test item, employing a patch under occlusive dressing, on the clipped skin of the flanks.
The sites and days of application were as follows.
Induction : Topical application on the clipped skin of the left flank,
On days 0, 7 and 14 of the study.
Challenge : Topical application on the clipped skin of the right flank.
On day 28 of the study.
INDUCTION PROCEDURES
Approximately 24 hours before treatment, the hair on the left flank was closely clipped with an electric clipper exposing an area of approximately 80 cm2 (8 x 10 cm). The gauze patch (occlusive dressing) admeasuring about 4 to 6 cm2 (at least 2 cm x 2 cm), fully loaded with formulated test item (treatment group) and vehicle control group (Analytical grade water with 0.2% Tween 80) was applied to the prepared area and was covered with an aluminum foil and secured in position with an adhesive tape wound around the torso for a period of 6 hours. After 6 hours contact period the test patch was removed and skin was wiped with analytical grade water and dried. The skin reaction was evaluated at 24 and 48 hours after removal of the skin patch by Magnusson and Kligman grading scale
CHALLENGE PROCEDURES
Treatment group and control group were challenged at 4 weeks after first induction application. The untreated flanks of animals were cleared of hair by close-clipping. The gauze patch fully loaded with 0.5 ml of test item was applied to the posterior part of the untreated (right) flanks of treatment and control group animals. The procedure of application and the exposure period was same as that during the induction.
Challenge controls:
vehicle control group
Positive control substance(s):
yes
Remarks:
α-Hexylcinnamaldehyde ≥ 95%

Results and discussion

Positive control results:
For induction 40% v/v concentration while for challenge 10% v/v concentration of α-Hexylcinnamaldehyde ≥ 95% was used. Acetone was used as vehicle for purpose of induction as well as challenge. In this test, a positive response was observed in 50% of the tested animals, thereby meeting the requirements specified by OECD Test Guideline No. 406, and classifying the positive control item as a moderate sensitiser.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
63%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
63%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Key result
Reading:
2nd reading
Hours after challenge:
24
Group:
positive control
Dose level:
40%
No. with + reactions:
5
Total no. in group:
10
Remarks on result:
other: α-Hexylcinnamaldehyde ≥ 95%

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The allergic contact sensitisation potential of trans-2,3-Dibromo-2-Butene-1,4-Diol was assessed in guinea pigs as per the method described by Buehler E. V., in compliance with the Organization for Economic Co-operation and Development (OECD) Guidelines for Testing of Chemicals, Section 4, No. 406 - Skin sensitisation, adopted by the council on 17 July 1992.
In this test, induction of sensitisation was attempted by exposing the guinea pigs to 63% w/v of trans-2,3-Dibromo-2-Butene-1,4-Diol in analytical grade water with 0.2% Tween 80 on days 0, 7 and 14 by epidermal route on the clipped left flank area, there was no evidence of erythema and / or swelling at the site of application. After an induction period of 14 days, the animals were similarly subjected to a ‘challenge application’ with 63% w/v of trans-2,3-Dibromo-2-Butene-1,4-Diol in analytical grade water with 0.2% Tween 80 on day 28 of the study, on their right flank.
In absence of a sensitisation response in any of the treated animals to challenge by the test item, trans-2,3-Dibromo-2-Butene-1,4-Diol is classified as non sensitiser to guinea pigs as per the criteria of classification for the Buehler test (Kimber et. al., 1990).
Executive summary:

The allergic contact sensitisation potential of trans-2,3-Dibromo-2-Butene-1,4-Diol was assessed in guinea pigs as per the method described by Buehler E. V., in compliance with the Organization for Economic Co-operation and Development (OECD) Guidelines for Testing of Chemicals, Section 4, No. 406 - Skin sensitisation, adopted by the council on 17 July 1992.

In this test, induction of sensitisation was attempted by exposing the guinea pigs to 63% w/v of trans-2,3-Dibromo-2-Butene-1,4-Diol in analytical grade water with 0.2% Tween 80 on days 0, 7 and 14 by epidermal route on the clipped left flank area, there was no evidence of erythema and / or swelling at the site of application. After an induction period of 14 days, the animals were similarly subjected to a ‘challenge application’ with 63% w/v of trans-2,3-Dibromo-2-Butene-1,4-Diol in analytical grade water with 0.2% Tween 80 on day 28 of the study, on their right flank.

In absence of a sensitisation response in any of the treated animals to challenge by the test item, trans-2,3-Dibromo-2-Butene-1,4-Diol is classified as non sensitiser to guinea pigs as per the criteria of classification for the Buehler test (Kimber et. al., 1990).