4,4'-[2,2,2-trifluoro-1-(trifluoromethyl)ethylidene]diphenol; bisphenol AF

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

25 June - 08 August 2001

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Remarks:

Test conducted in accordance with International guidance and in accordance with GCP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Type of sensitisation studied:

skin

Study type:

study with volunteers

GLP compliance:

no

Remarks:

Conducted in accordance with GCP since this was a clinical study.

Test material

Specific details on test material used for the study:

- Principle of test:

Skin tolerance of the test item had previously been investigated in animals models. Because of its intended use, where it is widely used in the production of plastics, skin irritation potential in human adults also had to be investigated. Patch testing are widely used to predict irritating and allergenic properties of compounds and products intended for public use.

The study was conducted accordance with the following recommendations and guidelines;

Recommended Basis for the Conduct of Clinical Trials of Medicinal Products in the European Community; EEC/CPMP Working Party on Efficacy of Drugs, July 03, 1987.

Durchführung von klinischen Arzneimittelprüfungen in der Bundesrepublik Deutschland, Merkblatt des BPI. Pharmazeut. Ind. 50, 1223-1240 (1988)

Declaration of Helsinki. Recommendation guiding physicians in biomedical research involving human subjects. Adopted by the 18th World Medical Assembly, Helsinki, Finland, June 1964, amended by the 29th World Assembly, Tokyo, Japan, October 1975, and revised by the World Medical Assembly, Venice, Italy, October 1983, and Hong Kong, September 1989, Somerset West, South Africa, October 1996 and Edinburgh, Scotland, October 2000.

- Short description of test conditions:

30 mg of test item was applied to 30 healthy caucasian volunteers for 24 h under occlusion. After 24 h the test site was cleaned and observations made (0h, 24, 48 h and 72 h after patch removal).

Volunteers were selected on the basis of questionnaire and by clinical inspection.

Inclusion criteria were;

Male or female
18-70 years old
Clean skin in testing area

Exclusion criteria were;

Outwith specified age range
Known allergy to plasters
Intake of antiallergic or antiinflammatory drugs in last 2 weeks
Inflammatory, eczematous or any other clinical sign of skin alterations in the test area
Moderate or severe ilness with last 2 weeks before exposure
Hyperpigmentation and multiple liver spots (lentigines) on possible test site
Extreme tanning of the skin of the test area

- Parameters analysed / observed:

Reading of skin reactions was conducted by the Principal Investigator or experienced staff member. Reactions were recorded on the CRF and graded on a 5 point scale;

0: negative (no reaction)
+: doubtful reaction
1: weak reaction (well-defined erythema)
2: moderate reaction (erthema with slight-moderate oedema)
3: strong reaction (vesicles and papules)
4: extreme reaction (bullous, spreading or other severe reaction)

Mean values were calculated (with standard deviation). An Overall Irrittion Score (OIS: sum of all reactions scores divided by the sum of readings) was calculated.

Method

Type of population:

general

Ethical approval:

no

Remarks:

Approval by Ethics Committes was considered as unnecessary because of the nature of the material and type of testing

Subjects:

33 volunteers, 25 females and 8 males

Clinical history:

Vlunteers were age 18 - 70 years of age, with clean skin in the testing area.
No known allergic reaction to plasters
All volunteers had no history of;
Inflammatory, eczematous or any other clinical signs of skin alterations in the test area
Moderate or severe illiness within the last two weeks before exposure
Hyperpigmentation or multiple liver spots (lentigines) on possible test site

Controls:

Liquid paraffin was given as control

Route of administration:

dermal

Details on study design:

TEST SITE

- Area of exposure: Scapular

- % coverage: Not reported

- Type of wrap if used: Occlusive- Haye's Test Chamber used

REMOVAL OF TEST SUBSTANCE

- Washing (if done): Not reported

- Time after start of exposure: 24 h

OBSERVATION TIME POINTS

(indicate if minutes, hours or days) 0, 24, 48 and 72 h after patch removal

SCORING SYSTEM:

- Method of calculation:

Reading of skin reactions was conducted by the Principal Investigator or experienced staff member. Reactions were recorded on the CRF and graded on a 5 point scale;

0: negative (no reaction)

+: doubtful reaction

1: weak reaction (well-defined erythema)

2: moderate reaction (erthema with slight-moderate oedema)

3: strong reaction (vesicles and papules)

4: extreme reaction (bullous, spreading or other severe reaction)

Mean values were calculated (with standard deviation). An Overall Irrittion Score (OIS: sum of all reactions scores divided by the sum of readings) was calculated.

Results and discussion

Any other information on results incl. tables

Table 1:       Overall Irritation Score (OIS)

st Item	Reading	Sum of Scores	Sum of Readings	OIS
Bisphenol AF	0 h	4	33
	24 h	4	33
	48 h	5	33
	Total	13	99	0.13
Negative Control (Paraffin Liquid)	0 h	0	33
	24 h	0	33
	48 h	0	33
	Total	0	99	0.00

Applicant's summary and conclusion

Conclusions:

The test item has irritating properties, at least under the exaggerated conditions of complete occlusive application.

Executive summary:

In a clinical dermal irritation study, 33 healthy caucasian individuals (8 males, 25 female) were dermally exposed to 30 mg of Bisphenol AF 24 hours under occluded conditions.  Individuals then were observed for 3 days.  Irritation, including erythema and oedema formation, was scored numerically on a scale of 0 - 4 based on severity.

A weak reaction (well-defined erythema, max. score 1) was observed in 4 of the individuals at the 0 and 24 h observation period and 5 individuals at the 48 h observation period. With a combined score of 13 (4 / 4 / 5) out of 99 (33 / 33 / 33) readings, an Overall Irritation Score of 0.13 was calculated.

In this study, Bisphenol AF was found to have irritating properties at least under the exaggerated conditions of complete occlusive application.