Pregna-1,4-diene-3,20-dione, 9-bromo-6-fluoro-11-hydroxy-16-methyl-21-[(1-oxopentyl)oxy]-, (6.alpha.,11.beta.,16.alpha.)-

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

read-across: supporting information

Cross-reference 2

Reason / purpose for cross-reference:

other: expert statement

Reference

Endpoint:

sensitisation data (humans)

Type of information:

other: expert opinion

Adequacy of study:

other information

Executive summary:

Overall there is proven broad exposure related to the therapeutic topical use of fluocortolone and related substances and there is a very low incidence of positive patch test reactions compared to the very substantial therapeutic use in patients with skin diseases. Therefore based on the available reliable and relevant human data the assessment of the skin sensitization potential (hazard identification) is possible. Based on all available data fluocortolone and structurally related substances are unlikely to be significant skin sensitizers and the criteria for classification are not met.

Cross-reference 3

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

other information

Study period:

1992 to 1993

Justification for type of information:

JUSTIFICATION FOR READ-ACROSS FROM SUPPORTING SUBSTANCE (STRUCTURAL ANALOGUE OR SURROGATE)
For bromhydrin-valerate (CAS No. 54605-02-6) no skin sensitisation data in animals or humans are available. Therefore, human skin sensitisation data of diflucortolone-21-valerate (CAS No. 59198-70-8) were used since these data are regarded as representative. In diflucortolone-21-valerate the bromine atom in position 9 of the target molecule (bromhydrin-valerate) is replaced by a fluorine atom. No other changes in the molecule occured. No relevant toxicological effects are expected by the change of a halogen atom (Br) versus another (F). A search for structure-analogue substances using the QSAR OECD Toolbox 3.4 recommended diflucortolone-21-valerate as one out of 8 category substances for a read-across approach (for additional information see QSAR OECD Toolbox Report on Bromhydrin-valerat in "Attached justification").

Type of sensitisation studied:

skin

Study type:

other: study with patients

Principles of method if other than guideline:

Tests were performed using Finn chambers on Scanpor tape left on the skin of the back for 2 days. The patch tests were read at 2 and 4 days, and reactions were scored in accordance with the International Contact Dermatitis Research Group guidelines (Wilkinson DS et al. (1970): Terminology of contact dermatitis. Acta Dermato-venereologica 50, 287-292).

Results of examinations:

For diflucortolone valerate the relative number of allergic reactions was 1.15 %, compared to hydrocortisone (30.76 %), hydrocortisone-17-butyrate (16.34 %), budesonide (15.06 %) or betamethasone valerate (3.52 %).

Executive summary:

The authors demonstrated that the number of glucocorticoids allergic reactions is dependent on usage and the intrinsic ability of the glucocorticoid to degrade and bind to arginine. For diflucortolone valerate the relative number of allergic reactions was 1.15 %, compared to hydrocortisone (30.76 %), hydrocortisone-17-butyrate (16.34 %), budesonide (15.06 %) or betamethasone valerate (3.52 %).

Cross-reference 4

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

other information

Justification for type of information:

JUSTIFICATION FOR READ-ACROSS FROM SUPPORTING SUBSTANCE (STRUCTURAL ANALOGUE OR SURROGATE)
For bromhydrin-valerate (CAS No. 54605-02-6) no skin sensitisation data in animals or humans are available. Therefore, human skin sensitisation data of diflucortolone-21-valerate (CAS No. 59198-70-8) were used since these data are regarded as representative. In diflucortolone-21-valerate the bromine atom in position 9 of the target molecule (bromhydrin-valerate) is replaced by a fluorine atom. No other changes in the molecule occured. No relevant toxicological effects are expected by the change of a halogen atom (Br) versus another (F). A search for structure-analogue substances using the QSAR OECD Toolbox 3.4 recommended diflucortolone-21-valerate as one out of 8 category substances for a read-across approach (for additional information see QSAR OECD Toolbox Report on Bromhydrin-valerat in "Attached justification").

Type of sensitisation studied:

skin

Study type:

other: study with patients

Principles of method if other than guideline:

Patch tests were performed using Finn chambers® on Scanpor® tape, left on the skin of the back for 48 h. The patch tests were read at 2 and 4 days. Patients were asked to return for a further reading if they developed a reaction after 4 days. Reactions were scored as recommended by the International Contact Dermatitis Research Group, and were considered positive when a palpable erythematous (+) reaction or greater was present.

A patch test with diflucortolone valerate in patients allergic to hydrocortisone revealed only a few cases with positive skin reactions (1.2 %).

Executive summary:

The allergic potential of diflucortolone valerate has been investigated extensively in a risk group of 96 patients with allergic contact dermatitis induced by hydrocortisone. While , as expected, there were frequent positive patch test reactions to hydrocortisone-17-butyrate (43.8 %) and budesonide (28.1 %), a cross-reaction with diflucortolone valerate was rare (1.2 %).

Cross-reference 5

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

other information

Justification for type of information:

JUSTIFICATION FOR READ-ACROSS FROM SUPPORTING SUBSTANCE (STRUCTURAL ANALOGUE OR SURROGATE)
For bromhydrin-valerate (CAS No. 54605-02-6) no skin sensitisation data in animals or humans are available. Therefore, human skin sensitisation data of diflucortolone-21-valerate (CAS No. 59198-70-8) were used since these data are regarded as representative. In diflucortolone-21-valerate the bromine atom in position 9 of the target molecule (bromhydrin-valerate) is replaced by a fluorine atom. No other changes in the molecule occured. No relevant toxicological effects are expected by the change of a halogen atom (Br) versus another (F). A search for structure-analogue substances using the QSAR OECD Toolbox 3.4 recommended diflucortolone-21-valerate as one out of 8 category substances for a read-across approach (for additional information see QSAR OECD Toolbox Report on Bromhydrin-valerat in "Attached justification").

Type of sensitisation studied:

skin

Study type:

case report

Principles of method if other than guideline:

not specified

Results of examinations:

A patch test with diflucortolone valerate (TemetexR ointment) in a female patient with a budesonide allergy showed no reactions at D2, D3 and D4.

Executive summary:

A 54-year old female patient with a budesonide allergy was patch tested to diflucortolone valerate (Temetex^R ointment). No reactions were observed at D2, D3 and D4.

Cross-reference 6

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

other information

Study period:

May 1992 to Dec 1993

Justification for type of information:

JUSTIFICATION FOR READ-ACROSS FROM SUPPORTING SUBSTANCE (STRUCTURAL ANALOGUE OR SURROGATE)
For bromhydrin-valerate (CAS No. 54605-02-6) no skin sensitisation data in animals or humans are available. Therefore, human skin sensitisation data of diflucortolone-21-valerate (CAS No. 59198-70-8) were used since these data are regarded as representative. In diflucortolone-21-valerate the bromine atom in position 9 of the target molecule (bromhydrin-valerate) is replaced by a fluorine atom. No other changes in the molecule occured. No relevant toxicological effects are expected by the change of a halogen atom (Br) versus another (F). A search for structure-analogue substances using the QSAR OECD Toolbox 3.4 recommended diflucortolone-21-valerate as one out of 8 category substances for a read-across approach (for additional information see QSAR OECD Toolbox Report on Bromhydrin-valerat in "Attached justification").

Type of sensitisation studied:

skin

Study type:

other: study with patients

Principles of method if other than guideline:

Tests were performed using Finn chambers on Scanpor tape left on the skin of the back for 2 days. The patch tests were read at 2 and 4 days, and reactions were scored in accordance with the International Contact Dermatitis Research Group guidelines (Wilkinson DS et al. (1970): Terminology of contact dermatitis. Acta Dermato-venereologica 50, 287-292).

Results of examinations:

Of 106 patients tested with diflucortolone valerate, only 3 patients (2.83 %) were positive.

Executive summary:

2123 patients attending a contact dermatitis clinic were patch tested with a series of six glucocorticoids, in parallel with a standard series, and other relevant investigations. 127 patients were allergic to one or more glucocorticoids, mainly to tixocortol pivalate (96), hydrocortisone butyrate (51), budesonide (47) or betamethasone valerate (11). Of 106 patients tested with diflucortolone valerate, only 3 patients (2.83 %) were positive.