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Administrative data

Description of key information

Based on the results of this study, the level of positive responses to challenge with Incozol LV was insufficient for classification for skin sensitisation according to Regulation (EC) 1272/2008. The substance is officially classified as skin sensitisingcaccording to table 3.2 of Annex VI CLP. Thus, Incozol LV has to be classified until further clarification.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 1998-02-12 to 1998-04-28
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
cited as: Directive 96/54/EC method B.6 of 30 Jul 1996
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted: 17 Jul 1992
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Test was performed before the LLNA guideline was available.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D Hall Ltd. Burton
- Age at study initiation: four to six weeks
- Weight at study initiation: 251 to 363g
- Housing: suspended polypropylene cages (six per battery) with open tops, solid floors and stainless steel mesh front panels (providing minimum internal dimensions of 61 x 81 x 25 cm)
- Diet: ad libitum; SQC FD1 (pelleted) diet from Special Diets Services Ltd.. Witham
- Water: tab water, ad libitum
- Acclimation period: 16 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 40 - 80 % RH.
- Air changes: 10 air changes per hour
- Photoperiod: 12 hours light, from 6:00 a.m. to 6:00 p.m.
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Concentration / amount:
First screening test (intradermal injection phase of induction):
from 0.1 % m/v in Alembicol D up to the maximum practical concentration of 20 % m/v in Alembicol D),
Second screening test (topical application phase of induction):
the test item at a range of concentrations from 40 % to 80 % m/m in Alembicol D. plus the undiluted test article
Third screening test (topical application at challenge):
test item ranging from 25 to 70 % m/m in Alembicol D.

Concentration of test material and vehicle used at induction: Test group : Anterior site: FCA; middle site: Incozol LV, 2.5 % m/v in Alembicol D; posterior site: Incozol LV, 2.5 % m/v in FCA
control group: Anterior site: FCA; middle site: Alembicol D; posterior site: 50 % v/v Alembicol D in FCA
Route:
other: Finn chamber (epicutaneous)
Vehicle:
arachis oil
Concentration / amount:
First screening test (intradermal injection phase of induction):
from 0.1 % m/v in Alembicol D up to the maximum practical concentration of 20 % m/v in Alembicol D),
Second screening test (topical application phase of induction):
the test item at a range of concentrations from 40 % to 80 % m/m in Alembicol D. plus the undiluted test article
Third screening test (topical application at challenge):
test item ranging from 25 to 70 % m/m in Alembicol D.

Concentration of test material and vehicle used at induction: Test group : Anterior site: FCA; middle site: Incozol LV, 2.5 % m/v in Alembicol D; posterior site: Incozol LV, 2.5 % m/v in FCA
control group: Anterior site: FCA; middle site: Alembicol D; posterior site: 50 % v/v Alembicol D in FCA
No. of animals per dose:
First screening test: two animals per dose
Second screening test: two animals per dose
Third screening test: two animals per does
Main study:
Number of animals in test group: 20
Number of animals in negative control group: 10
Details on study design:
RANGE FINDING TESTS:
First screening test (intradermal injection phase of induction)
The vehicle and six formulations were selected. The dorsa of two guinea pigs were clipped on the day prior to dosing. On Day 1, intradermal injections [0.1 mL per site], incorporating a range of test article concentrations, (from 0.1 % m/v in Alembicol D up to the maximum practical concentration of 20 % m/v in Alembicol D), were made into the scapular zone of the denuded dorsum. Dermal reactions were individually assessed and recorded approximately 24 and 72 hours later.
Second screening test (topical application phase of induction)
Three formulations, incorporating the test article at a range of concentrations from 40 % to 80 % m/m in Alembicol D. plus the undiluted test article as supplied, were selected. Two guinea pigs were prepared by receiving two 0.1 mL intradermal injections of FCA into the suprascapular dorsum at least five days prior to application of the test formulation. The dorsum and flanks were clipped and shaved on the day before application of the test formulations. The animals were subject to occluded, topical application of four 20 x 20 mm patches of Whatman No 4 filter paper each saturated with approximately 0.2 mL of one of the test formulations. Occlusion was effected by covering the Whatman patches with successive layers of "Blenderm" adhesive dressing from 3M Co. Loughborough and "Steroban" open-weave, elasticated bandage. The last layer completely enveloped the torso to ensure the patches remained secure. The dressings and bandages were removed approximately 48 hours after application and the treatment sites were washed with arachis oil. The location of each patch was marked with indelible ink. Treated areas of skin were reshaved approximately 21 hours after removal of the bandages. Dermal reactions were assessed approximately 24 and 96 hours after removal of the patches.

Third screening test (topical application at challenge)
Four formulations, ranging from 25 to 70 % m/m in Alembicol D. were chosen to identify the maximum non-irritant concentration of test article after occluded, topical application to skin. Two guinea pigs were prepared by receiving two 0.1 mL intradermal injections of FCA into the suprascapular dorsum between 14 and 28 days prior to application of the test formulations. The flanks were clipped on the day before application. The same areas were shaved at least two hours before treatment. Each animal was subject to occluded topical application of four 12 mm Finn chambers from Biodiagnostics Ltd. Upton-upon-Severn, each loaded with approximately 0.1 mL of one of the four selected test formulations. The Finn chambers were secured by successive applications of Blenderm and Steroban. The dressings and chambers were removed after approximately 24 hours and the treated areas of skin were washed with arachis oil. The location of each challenge site was marked on the skin using indelible ink. The treated areas of skin were reshaved approximately 18 hours after removal of the chambers. Dermal reactions were assessed approximately 24 and 48 hours after removal of the chambers.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures:
induction phase intradermal injection
- intradermal (test animals): three pairs of injections on day 0
a. Injection anterior: 0.1 mL of FCA emulsion
b. Injection middle: 0.1 mL of 2.5 % test item in Alembicol D
c. Injection Pair C: 0.1 mL of 2.5 % test itemin FCA emulsion
- intradermal (control animals): three pairs of injections on day 0
a. Injection anterior: 0.1 mL of FCA emulsion
b. Injection middle: 0.1 mL of Alembicol D
c. Injection Pair C: 0.1 mL of 50 % v/v Alembicol D in FCA
induction phase topical application
On Day 7 the areas of dorsum denuded for the first phase of induction were clipped. On Day 8 each dorsum was shaved. The area of skin including the intradermal injection sites was subject to application of a 25 x 45 mm patch of Whatman No 4 filter paper loaded with approximately 0.5 mL of 80 % m/m Incozol LV in Alembicol D (test animals) or Alembicol D alone (control group).
- Test groups: one test group
- Control group: one control group

B. CHALLENGE EXPOSURE
- No. of exposures: once, plus one re-challenge to test group
- Day(s) of challenge: day 22
- Exposure period: 24 hours
- Test groups: one test group
- Control group: one control group
- Concentrations: Finn chambers containing the formulations selected for challenge, 25 and 12.5 % m/m Incozol LV in Alembicol D were applied to the right flank.
- Evaluation: approximately 24 and 48 hours following chamber removal

C. RE-CHALLENGE EXPOSURE
- No. of exposures: once, plus one re-challenge to test group
- Day(s) of challenge: day 29
- Exposure period: 24 hours
- Test groups: one test group
- Control group: one control group
- Concentrations: Finn chambers containing the formulations selected for re-challenge. 10 and 5 % m/m Incozol LV in Alembicol D were applied to naive sites on the left flank.
- Evaluation: approximately 24 and 48 hours following chamber removal
Positive control substance(s):
yes
Remarks:
2-Mercaptobenzothiazole (MBTZ); positive control Magnusson and Kligman studies
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25 %
No. with + reactions:
16
Total no. in group:
20
Clinical observations:
Desquamation and Slight erythema to Well defined erythema
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
12.5 %
No. with + reactions:
17
Total no. in group:
20
Clinical observations:
Desquamation and Slight erythema to Well defined erythema
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0 %
No. with + reactions:
12
Total no. in group:
20
Clinical observations:
Desquamation and Slight erythema to Well defined erythema
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25 %
No. with + reactions:
17
Total no. in group:
20
Clinical observations:
Desquamation and Slight erythema to Well defined erythema
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
12.5 %
No. with + reactions:
18
Total no. in group:
20
Clinical observations:
Desquamation and Slight erythema to Well defined erythema
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0 %
No. with + reactions:
6
Total no. in group:
20
Clinical observations:
Desquamation and Slight erythema to Well defined erythema
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
0 %
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
Desquamation and Slight erythema to Well defined erythema
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
5 %
No. with + reactions:
13
Total no. in group:
20
Clinical observations:
Desquamation and Slight erythema to Well defined erythema
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
10 %
No. with + reactions:
17
Total no. in group:
20
Clinical observations:
Desquamation and Slight erythema to Well defined erythema
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
0 %
No. with + reactions:
4
Total no. in group:
20
Clinical observations:
Desquamation and Slight erythema to Well defined erythema
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
5 %
No. with + reactions:
19
Total no. in group:
20
Clinical observations:
Desquamation and Slight erythema to Well defined erythema
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
10 %
No. with + reactions:
19
Total no. in group:
20
Clinical observations:
Desquamation and Slight erythema to Well defined erythema
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25 %
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
Desquamation and Slight erythema to Well defined erythema
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
12.5 %
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
Desquamation and Slight erythema to Well defined erythema
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0 %
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
Desquamation and Slight erythema to Well defined erythema
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25 %
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
Desquamation and Slight erythema to Well defined erythema
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
12.5 %
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
Desquamation and Slight erythema to Well defined erythema
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0 %
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
Desquamation and Slight erythema to Well defined erythema
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
10 %
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
Desquamation and Slight erythema to Well defined erythema
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
5 %
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
Desquamation and Slight erythema to Well defined erythema
Reading:
1st reading
Group:
positive control
Dose level:
2.5 %
No. with + reactions:
6
Total no. in group:
9
Reading:
2nd reading
Group:
positive control
Dose level:
2.5 %
No. with + reactions:
6
Total no. in group:
10
Interpretation of results:
GHS criteria not met
Conclusions:
The results from the two challenge applications indicated that none of the animals gave a positive response indicative of delayed contact hypersensitivity, the response for five animals was considered to be inconclusive and the result for the remaining guinea pigs was negative. Based on the results of this study, the level of positive responses to challenge with Incozol LV was insufficient for classification for skin sensitisation according to Regulation (EC) 1272/2008.
Executive summary:

This study was conducted to assess the potential of Incozol LV to elicit skin sensitisation (delayed contact hypersensitivity) in the guinea pig. The study was conducted according to by Directive 96/54/EEC, method B6 and OECD TG 406. Twenty test and ten control animals were used in this study. Based on the results of the preliminary studies, the following dose levels were chosen: Intradermal injection: 2.5 % m/v in Alembicol D and/or adjuvant Topical induction: 80 % m/m in Alembicol D Challenge application: 25 and 12.5 % m/m in Alembicol D. The animals were re-challenged, one week after the first challenge application, using dose concentrations of 10 and 5 % m/m Incozol LV in Alembicol D to clarify the initial challenge response in which three of the twenty test group animals gave an equivocal response. Following the second challenge application, the incidence and severity of reactions seen in the test group did not notably exceed the reactions seen in the control group. Taking into account changes at the vehicle and control group sites the overall response to two challenge applications of Incozol LV was not considered to be indicative of skin sensitisation (delayed contact hypersensitivity) in the guinea pig. The results from the two challenge applications indicated that none of the animals gave a positive response indicative of delayed contact hypersensitivity, the response for five animals was considered to be inconclusive and the result for the remaining guinea pigs was negative.

Based on the results of this study, the level of positive responses to challenge with Incozol LV was insufficient for classification for skin sensitisation according to Regulation (EC) 1272/2008. The substance is offically classified as skin sensitisingaccording to table 3.2 of Annex VI CLP. Thus, Incozol LV has to be calssified until further clarification.

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

This study was conducted to assess the potential of Incozol LV to elicit skin sensitisation (delayed contact hypersensitivity) in the guinea pig. The study was conducted according to Directive 96/54/EEC, method B6 and OECD TG 406. Twenty test and ten control animals were used in this study. Based on the results of the preliminary studies, the following dose levels were chosen: Intradermal injection: 2.5 % m/v in Alembicol D and/or adjuvant Topical induction: 80 % m/m in Alembicol D Challenge application: 25 and 12.5 % m/m in Alembicol D. The animals were re-challenged, one week after the first challenge application, using dose concentrations of 10 and 5 % m/m Incozol LV in Alembicol D to clarify the initial challenge response in which three of the twenty test group animals gave an equivocal response. Following the second challenge application, the incidence and severity of reactions seen in the test group did not notably exceed the reactions seen in the control group. Taking into account changes at the vehicle and control group sites the overall response to two challenge applications of Incozol LV was not considered to be indicative of skin sensitisation (delayed contact hypersensitivity) in the guinea pig. The results from the two challenge applications indicated that none of the animals gave a positive response indicative of delayed contact hypersensitivity, the response for five animals was considered to be inconclusive and the result for the remaining guinea pigs was negative.


Based on the results of this study, the level of positive responses to challenge with Incozol LV was insufficient for classification for skin sensitisation according to Regulation (EC) 1272/2008. The substance is officially classified as skin sensitising according to table 3.2 of Annex VI CLP. Thus, Incozol LV has to be classified until further clarification.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the Annex VI of Regulation (EC) No 1272/2008 Incozol LV is classified as skin sensitizer cat 1 H317 ( May cause an allergic skin reaction) according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EC) 2017/776.