Methyl 4(or 1)-isopropyl-1(or 4)-methylbicyclo[2.2.2]oct-5-ene-2-carboxylate

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

25 March 2013 - 3 May 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

A skin sensitiser is an agent that will lead to an allergic response in susceptible individuals following skin contact. Human experimental studies are not recommended to fulfil REACH Annex VII information requirements. However, all existing available information should be evaluated, including any available human data.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Type of sensitisation studied:

skin

Study type:

other: Human Repeat Insult Patch Test in volunteers

Test guideline

Qualifier:

according to guideline

Guideline:

other: ICH Guideline E6

Principles of method if other than guideline:

Study was conducted according to CPTC procedure CP-01.01S

GLP compliance:

no

Remarks:

Good Clinical Practice (GCP)

Method

Type of population:

general

Ethical approval:

not specified

Subjects:

111 qualified subjects, male and female, ranging in age from 16 to 78 years, were selected for evaluation and 107 completed the study. The remaining subjects discontinued their participation for various reasons, none of which were related to the application of the test material

Clinical history:

INCLUSION CRITERIA:
- male and female subjects aged 16 and over
- absence of visible skin disease
- prohibition of use of topical systemic steroids and/or antihistamines for 7 days prior to study initiation (acclimatisation)
- complete medical history and informed consent
- considered reliable and capable of following directions

EXCLUSION CRITERIA:
- ill health
- receiving medical attention which could influence the outcome of the study
- females who are pregnant or nursing
- a history of adverse reactions to topical ointments

Controls:

Subjects acted as their own control i.e. challenge control was the untreated skin

Route of administration:

dermal

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 9 applications
- Site: upper back between the scapulae
- Frequency of applications: 0.2ml of test material was applied three times per week for a total of nine applications
- Exposure period: 24 hours (9 x 24 hour exposure)
- Rest periods: 24-48 hours
- Duration: 3 weeks
- Concentrations: 4% test substance in EtOH/DEP solution

B. CHALLENGE EXPOSURE (two weeks after the final induction patch application)
- No. of exposures: one
- Exposure period: 24 hours
- Site: virgin test site adjacent to induction exposure sites on the upper back between the scapulae
- Concentrations: 4% test substance in EtOH/DEP solution
- Evaluation (hr after challenge): 24 and 72 hours post-application

Results and discussion

Results of examinations:

The observations for each participant remained negative throughout the test interval

Applicant's summary and conclusion

Conclusions:

The human repeated insult patch test (HRIPT) is a confirmatory test in the safety evaluation of skin sensitisers, that can substantiate no-effect levels and ensure that matrix effects are not making an unexpected contribution to sensitising potency. HRIPT demonstrated that the test item does not have the potential to irritate or sensitise the dermis in 107 human participants. No adverse events were observed.

Executive summary:

Human Repeat Insult Patch Test (HRIPT) aims to determine sensitisation potential via repeat epidermal contact induction phases and latent challenge. Small quantities (0.2ml) of test material were applied to occlusive patches of 3/4" absorbent pads in adhesive dressing between the scapulae on the upper back and sealed with a hypoallergenic adhesive tape. Signs of irritation were recorded by a dermatologist at 48 and 72 hours, following 9 applications with 24-48 hour rest periods.

 

No adverse events effects were observed in 107 participants following a 24-hour challenge test, subsequent to an induction phase of nine 24 hour applications (0.2ml of 4% test material in DEP/EtOH). No adverse events were observed and the test item did not demonstrate potential to irritate or sensitise the dermis in human participants.