Registration Dossier

Administrative data

Endpoint:
skin sensitisation, other
Remarks:
Human Repeated Patch Test
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22 July 1991 - 1 November 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Modified Draize Patch Test
Principles of method if other than guideline:
- Principle of test: To evaluate the test materials for the induction of contact sensitization by repetitive applications to the skin of human volunteers and to report any irritation observed with the test material.
- Short description of test conditions: Patches were applied for 24-hour contact to the lateral surface of the right and left upper arm. Nine induction applications were made to the same site unless reactions
became so strong that a first or second adjacent site had to be employed to complete induction. A 10 to 15 day rest period following the last induction application. A naive alternate site and the original
induction site were used for the challenge applications. The test material was applied under semi-occlusive conditions, using the Professional Medical Products, Inc. patches. Challenge application consisted
of a single 24-hour contact period. Rechallenge application was a single 24-hour contact period applied to the lower back.
GLP compliance:
not specified
Type of study:
patch test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
The study investigated the skin sensitization potential of four test samples: MRD 90-726, MRD 91-009, MRD 91- 972, and MRD 90-903.

In vivo test system

Test animals

Species:
other: Human
Sex:
male/female
Details on test animals and environmental conditions:
One hundred thirty-nine volunteers entered the study. One hundred eighteen subjects completed the study. Subjects consisted of 74 females and 44 males.

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, semiocclusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.1 ml
Day(s)/duration:
24 hours, three times per week for three weeks
Challengeopen allclose all
No.:
#1
Route:
epicutaneous, semiocclusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.1ml of MRD 90-726, MRD 91-009, MRD 91- 972, and MRD 90-903.
Day(s)/duration:
24 hours
No.:
#2
Route:
epicutaneous, semiocclusive
Vehicle:
other: Mineral Oil
Concentration / amount:
10% dilution of Samples MRD 9D-009 and 93-903 was prepared in Mineral Oil and 0.05 ml was applied to the patches.
Day(s)/duration:
24 hours
No. of animals per dose:
74 females and 44 male
Details on study design:
Nine induction applications were made to the same site. Patches were applied for 24-hour contact to the lateral surface of the right and left upper arm. Nine induction applications were made to the same site unless reactions became so strong that a first or second adjacent site had to be employed to complete induction. A 10 to 15 day rest period following the last induction application. A naive alternate site and the original induction site were used for the challenge applications. The test material was applied under semi-occlusive conditions, using the Professional Medical Products, Inc. patches. Challenge application consisted of a single 24-hour contact period. Rechallenge application was a single 24-hour contact period applied to the lower back.
Challenge controls:
0.05 ml Mineral Oil was used as the negative control in the mineral oil rechallange.
Positive control substance(s):
not specified

Results and discussion

Positive control results:
Not Specified

In vivo (non-LLNA)

Results
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
0.1 ml
No. with + reactions:
51
Total no. in group:
118
Clinical observations:
51 subjects showed cutaneous reactions consistent with erythema, papules and edema. 31 of these responses had no observable or mild erythema by the 96 hr. reading.

Any other information on results incl. tables

Sixty-one subjects exhibited strong erythema, edema, papules and vesicular responses to Sample MRD 91-972 at the first induction evaluation. Subsequent applications of the sample were discontinued on July 26, 1991.

Sixty-two subjects exhibited reactions consisting of strong erythema and/or edema accompanied by erythema to Sample MRD 90-903 beginning with the first induction evaluation. Fifty-nine subjects exhibited cutaneous reactions consisting of erythema, papules and edema at the 48 hour challenge evaluation. Thirty-one of these responses had subsided to no observable or mild erythema at the 96 hour challenge evaluation.

Fourteen subjects exhibited reactions consisting of mild erythema to Sample MRD 91-009 beginning with the second induction evaluation. Seven subjects exhibited cutaneous reactions consisting of strong erythema or edema at the 48 challenge evaluation. One subject exhibited mild erythema on the original and naive sites and one subject exhibited a papular response on the original

at the 96 hour evaluation. One subject exhibited the same response at the 96 hr evaluation and the responses of the remaining subjects subsided to no observable or mild erythema.

Two subjects were asked to participate in a subsequent confirmatory rechallenge to sample MRD-91 -009 and twenty-nine subjects to samples MRD-90 -903. There was no evidence of cutaneous reactions observed at the 48 and 96 hour evaluation for the twenty-four subjects conpleting the re-challenge. The overall response patterns (induction, challenge, and rechallenge) to Samples MRD 91-009 and MRD 90-903 are consistent with clinically irritation.

Under the test conditions, no identifiable cutaneous reactions were observed for Sample MRD 90-726.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, no identifiable cutaneous reactions were observed for Sample MRD 90-726. The responses to Sample MRD 91-972 is consistent with a severe clinical irritant and the responses to Samples MRD 91-009 and 90-903 are consistent with clinical irritation.
Executive summary:

One hundred thirty - nine subjects entered the study. One hundred eighteen subjects completed the study. Twenty-one subjects withdrew for reasons unrelated to the study. All exposures were by 24-hour contact semi-occlusive patches applied to sites on the upper arms.

 

Sixty-one subjects exhibited strong erythema, edema, papules and vesicular responses to Sample MRD 91-972 at the first induction evaluation.

 

Sixty-two subjects exhibited reactions consisting of strong erythema and/or edema accompanied by erythema to Sample MRD 90- 903 beginning with the first induction evaluation. Fifty-nine subjects exhibited cutaneous reactions consisting of erythema, papules and edema at the 48 hour challenge evaluation. Thirty-one of these responses had subsided to no observable or mild erythema at the 96 hour challenge evaluation.

 

Fourteen subjects exhibited reactions consisting of mild erythema to Sample MRD 91-009 beginning with the second induction evaluation. Seven subjects exhibited cutaneous reactions consisting of strong erythema or edema at the 48 challenge evaluation. One subject exhibited a papular response and one subject exhibited mild erythema at the 96 hour evaluation with the remaining reactions exhibiting mild or no observable erythema.

 

After discussion with the sponsor, thirty-one subjects were asked to participate in a subsequent confirmatory rechallenge. No observable cutaneous reactions were observed during rechallenge. The overall response patterns (induction, challenge, and rechallenge) to Samples MRD 91-009 and MRD 90- 903 are consistent with clinically identifiable irritation.

 

Under the test conditions, no identifiable cutaneous reactions were observed for Sample MRD 90-726