Indeno[4,5-d]-1,3-dioxin, 4,4a,5,6,7,8,9,9b-octahydro-7,7,8,9,9-pentamethyl-

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

11th June - 18th July 2003

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reliability 2 is assigned because the method is according to standard HRIPT guidelines and the results are reliable but without GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Materials and methods

Type of sensitisation studied:

skin

Study type:

study with volunteers

Principles of method if other than guideline:

In a human Repeated Insult Patch test according to a modified Shelanski - Shelanski human patch test method, 102 human subjects (male/female) were treated on the (cleaned) upper back to 4% (w/w) of the test article in EtOH: DEP (1:3) with an occlusive patch for 24 hours (0.2 ml on 3.63 cm2 patch) and 100 subjects finalised the study. This results in an exposure of 2360 ug/cm2 (0.2 g x 1.07 (RD x 1000 x 0.04 (%)/ 3.63). This was repeated 9 times on Monday, Wednesday and Friday during the induction period. Sites were graded for dermal irritation 24 hours after removal of the patches on Tuesday and Thursday and 48 hours after removal on Saturday. After a 2-week rest period challenge patches were applied on untreated test sites for 24 hours. Dermal irritation was evaluated 0, 24 and 48 hours after removal of the patches. An extra assessment was done after 96 hours in case of reactions.

GLP compliance:

yes

Remarks:

In compliance with good clinical practice

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

446-220-4

EC Name:

-

Cas Number:

365411-50-3

Molecular formula:

C16 H26 O2

IUPAC Name:

7,7,8,9,9-pentamethyl-2H,4H,4aH,5H,6H,7H,8H,9H,9bH-indeno[4,5-d][1,3]dioxine

Test material form:

other: test substance supplied in preparation

Method

Type of population:

general

Ethical approval:

confirmed and informed consent free of coercion received

Subjects:

102 individuals were used and 100 finished the study

Clinical history:

No subjects were impanelled if they exibited or had a history of any acute or chronic dermal, medical or physiological condition that could interfere with scoring.

Route of administration:

dermal

Details on study design:

TYPE OF TEST(S) USED: the 9 repeated insult (occlusive) patch test (9 RIPT)
ADMINISTRATION: INDUCTION PHASE
- Type of application: occlusive patch
- Description of patch: Parke-Davis Readi-Bandage
- Vehicle / solvent: test substance 4.0% in DEP, volatilized at least 30 minutes on the patch prior to application.
- Concentrations: 4.0%
- Volume applied: 0.2 ml
- Aria: 3.63 cm2
- Testing/scoring schedule: rest period after removal: on Tuesday and Thursday: 24h, on Saturday: 48h, on Monday and Wednesday: 24h, on Friday: 48h.
Test site was scored by a trained examiner just prior to the next patch application. This procedure was repeated until nine application of the test article had been made.
- Removal of test substance: 24 hours after application
- Other: if a subject developed a positive reaction of a 2-level erythema or greater during the induction phase or if the skin response warranted a change in site, the patch would be applied to a previously unpatched, adjacent site for the next application. If a 2-level reaction (or greater) occurred at the new site, no further applications would be made.
ADMINISTRATION: CHALLENGE PHASE
- Rest period after induction: 10 to 21 days
- Type of application: previously unpatched test site (occlusive)
- Testing/scoring schedule: test site was scored 24 and 48h after application
EXAMINATIONS
- Grading/Scoring system: according to a 6-point scale:
0 = no evidence of any effect
1 = barely perceptible
2 = moderate
3 = marked
4 = severe
accompanying oedema was recorded with an "e"
- Statistical analysis: no data

Results and discussion

Results of examinations:

There were 100 subjects who completed the study. All 9 scores during induction and challenge (24, 48 and 72 hours) were tabulated and were zero.

Applicant's summary and conclusion

Conclusions:

During inducation and during challenge all 100 subjects scored zero during induction and challenge exposure of 4% test concentration. This means that the substance did not show skin sensitising properties in human volunteers up to 4% (2360 ug/cm2).

Executive summary:

In a human Repeated Insult Patch test according to a modified Shelanski - Shelanski human patch test method, 102 human subjects (male/female) were treated on the (cleaned) upper back to 4% (w/w) of the test article in EtOH: DEP (1:3) with an occlusive patch for 24 hours (0.2 ml on 3.63 cm2 patch). This application results in an exposure of 2360 ug/cm2 (0.2 g x 1.07 (RD) x 0.04 (fraction test substance) x 1000 (conversion to ug) / 3.63 cm2). This application was repeated 9 times on Monday, Wednesday and Friday during the induction period. Sites were graded for dermal irritation 24 hours after removal of the patches on Tuesday and Thursday and 48 hours after removal on Saturday. After a 2-week rest period challenge patches were applied on untreated test sites for 24 hours. Dermal irritation was evaluated 0, 24 and 48 hours after removal of the patches. Hundred subjects completed the study. Challenge reactions were scored at 24, 48 and 72 hours. During inducation and during challenge all scores were zero. This means that the substance did not show skin sensitising properties in human volunteers up to 4% (2360 ug/cm2).