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Toxicological information

Sensitisation data (human)

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Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008-04-09 - 2008-05-23
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well document and acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Type of sensitisation studied:
skin
Study type:
study with volunteers
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Repeated occlusive patch test on human volunteers
GLP compliance:
yes
Remarks:
GCP

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: aqueous formulation
Details on test material:
- Name of test material (as cited in study report): BIO-TERGE AS-40 and BIO-TERGE AS-40-2
- Physical state: Transparent liquid
- Analytical purity: concentration tested: 04-09-08 to 04-14-081: 2%, 04-15-08 to 05-23-08: 1%

Method

Type of population:
general
Ethical approval:
confirmed, but no further information available
Subjects:
- Number of subjects exposed: 52
- Sex: 5 male, 47 female
- Age: Mean age 49 years
- Race: 38 caucasian, 9 asian, 5 hispanic
Controls:
The test will include a positive (1% Sodium lauryl sulfate, SLS) and a negative (blank) control patch. SLS will be provided by Stephens.
Route of administration:
dermal
Details on study design:
TYPE OF TEST(S) USED: repeat insult human patch test (epicutaneous test)

ADMINISTRATION
- Type of application: 9x occlusive
- Vehicle / solvent: water
- Concentrations: 1% solution
- Volume applied: 50 µL

EXAMINATIONS
- Grading/Scoring system:
Induction grading scale:

Erythema and Elevated Responses
0 No evidence of irritation
1 Minimal erythema, barely perceptible
2 Definite erythema, readily visible; or minimal edema; or minimal papular response
3 Erythema and papules
4 Definite edema
5 Erythema, edema, and papules
6 Vesicular eruption
7 Strong reaction spreading beyond test site

Effects on Superficial Layers of the skin
A 0 Slight glazed appearance
B 1 Marked glazing
C 2 Glazing with peeling and cracking
D 3 Glazing with fissures
E 3 Film of dried serous exudate covering all or portion of the patch site
F 3 Small petechial erosions and/or scabs

W Weeping - evidence of release of fluid from a vesicular or bullons reaction
T Marked reaction to adhesive (patch relocated)
X Succeeding patch not applied and succeeding grade is for residual reaction
R Subject did not remove the patch at the assigned time
L-1 Subject report of lost patch (came off) during first 12 hours of exposure
L-2 Subject report of lost patch (came off) between 12 and 48 hours of exposure
(-) Subject absent

Challenge grading scale:
Erythema Scale: This scale was used only for grading degree of erythema (redness).
0 No visible erythema
1 Mild erythema (faint pink to definite pink)
2 Moderate erythema (definite redness)
3 Severe erythema (very intense redness)
Designation for Elevated Responses: Edema, papules, vesicles, and bullae, it present, were graded as independent responses.
E Edema - definite swelling
P Papules - small, red, solid elevations; surface of reaction has granular feeling
V Vesicies - small, circumscribed elevations having translucent surfaces so that fluid is visible (blister-like); vesicles are no larger than 0.5 cm in diameter
B Bullse - vesicles with a diameter >0.5 cm; vesicles may coalesce to form one or a few large blisters that till the patch site

Other Response Characteristics
S Spreading - evidenice of the reaction beyond the chamber area (does not include obvious signs of leakage of test material away from chamber)
W Weeping - evidence of release of fluid from a vesicular or bullous reaction

Other Recording Designations
T Marked reaction to adhesive
R Subject did not remove the patch at the assigned time
L-1 Subject report of lost patch (came off) during first 12 hours of exposure
L-2 Subject report of lost patch (came off) between 12 and 48 hours of exposure
(-) Subject absent

- Statistical analysis:
Mean cumulative irritation scores were compared among the sites using ANOVA with pairwise comparisons (Fishers LSD). All differences are considered significant at the p<=0.05 level

Results and discussion

Results of examinations:
SYMPTOMS
- Frequency, level, duration of symptoms observed:
Induction 1: 6/52 pos
Induction 2: 11/52 pos
Induction 3: 18/52 pos
Induction 4: 25/52 pos
Induction 5: 21/52 pos
Induction 6: 15/52 pos
Induction 7: 19/52 pos
Induction 8: 11/52 pos
Induction 9: 11/52 pos
48h after challenge at induction site: 24/52 pos
96h after challenge at induction site: 21/52 pos
48h after challenge at alternative site: 27/52 pos
96h after challenge at alternative site: 27/52 pos

NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
- Number of subjects with positive reactions: 27/52
- Number of subjects with negative reactions: 25/52
- Number of subjects with irritating reactions: 27/52

Under the conditions of this test the test material did not induce delayed contact sensitisation (allergic contact dermatitis) in any of the subjects, but has a clear irritation potential to human skin.

Any other information on results incl. tables

Table 1: Irritation scores at the study stages

Study stage

Subjects with positive reactions/all subjects

Induction 1

6/52

Induction 2

11/52

Induction 3

18/52

Induction 4

25/52

Induction 5

21/52

Induction 6

15/52

Induction 7

19/52

Induction 8

11/52

Induction 9

11/52

48h after challenge at induction site

24/52

96h after challenge at induction site

21/52

48h after challenge at alternative site

27/52

96h after challenge at alternative site

27/52

Under the exposure conditions of this test the test material did not induce delayed contact sensitisation (allergic contact dermatitis) in any of the subjects.

BioTerge-AS40 was not sensitising for humans but has a clear irritation potential to human skin.

Applicant's summary and conclusion