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Toxicological information

Sensitisation data (human)

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Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1988/09/26 - 1988/11/11
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: In accordance with sound scientific principles and performed with good laboratory standards.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Type of sensitisation studied:
skin
Study type:
study with volunteers
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
human skin patch test
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Type of population:
general
Ethical approval:
confirmed, but no further information available
Subjects:
30 participants; 29 participants completed the study.
Clinical history:
A past/present medical history and a brief physical was performed for each individual. Candidates were excluded for any one of the following reasons: systemic illness which might have contra-indicated participation, skin disease, medication which might augment/suppress effects of test material, participation in another sensitization study within the past 10 weeks.
Controls:
Controls were performed
Route of administration:
dermal
Details on study design:
Phase I: Determination of MED (Minimum Erythemogenic Dose - UVB light produced Erythemogenic Effects)
-Design: 5 sites on the back and 5 sites on the arm were exposed to UVB light for either 10,20,30,40, or 50 seconds at 10cm from the exposure site. Sites were examined at 18 and 24 hours.

Phase II: Determination of Phototoxicity and Primary Irritancy
-Design: On each arm, 4 test sites were used with a 5th site serving as a control (no test material applied). Day 1: each testing site had 0.3g of a 50% w/w MRD-88-296 (in U.S.P. Petrolatum) solution applied to it and held in contact with the skin for 24 hours under a semi-occlusive dressing. Day 2: After 24 hours, participants returned and had 0.3 ml of a neat solution of MRD-88-296 (or water if control) applied to the same sites, which was removed after 10 minutes. The right arm was exposed to 15 min UVA and the left arm was not (primary irritant study), both arms were examined for irritation. Participants returned at 24, 48, and 72 hours for an examination for dermal irritation.

Phase III - Determination of Photocontact and Contact Allergenic Capabilities
-Design: On each side of the back, 9 test sites were used for experimental purposes with a 10th site serving as a control (no test material applied). The left side of the back was used to evaluate the irritant and contact allegenic propensities and the evaluation of photocontact allergenic propensities were performed on the right side. 0.3g of a 50% w/w MRD-88-296 solution was used at each experimental site for the evaluation of the propensities.

Results and discussion

Results of examinations:
Phase II: Determination of Phototoxicity and Primary Irritancy
-Results: MRD-88-296 did not elicit any effects which could be construed as a characteristic of a phototoxic propensity or of a primary irritant.
Skin patches exposed to MRD-88-296 displayed no signs of skin irritation. The dermal irritation scores were 0 for all subjects (26 people), on all days of exposure to MRD-88-296. A faint erythema (score of 1) was observed in skin patches exposed to MRD-88-296 and UV light for most subjects, however subjects exposed to only UV light displayed a similar erythema (score of 1).

Phase III - Determination of Photocontact and Contact Allergenic Capabilities
-Results: MRD-88-296 showed no evidence of being a photocontact allergen and no evidence of being either a primary irritant or a contact allergen. No erythema was observed during the rechallenge phase of exposure (score of 0 for all subjects).

Applicant's summary and conclusion

Conclusions:
Based on these data and results, MRD-88-296 would not be classified as a dermal irritant or as a dermal sensitizer.
Executive summary:

This study was conducted to determine the potential of MRD-88-296 to cause dermal irritation and sensitization in humans with or without UV irradiation. Twenty-eight humans were exposed to MRD-88-296. Dermal examinations occurred after exposures (day 1 and day 2) and then at 24h, 48h, and 72h post exposure. Dermal irritation and damage was assessed and scored according to a modified Draize scale. The most severe reaction noted in all experimental paradigms was noted as a "1" or slight erythema. MRD-88-296 did not elicit any effects which could be construed as a characteristic of a phototoxic propensity or of a primary irritant. MRD-88-296 showed no evidence of being a photocontact allergen and no evidence of being either a primary irritant or a contact allergen. Based on these data and results, MRD-88-296 would not be classified as a dermal irritant or as a dermal sensitizer.