title: Dose-time relationships for elicitation of contact allergy to para-phenylenediamine.
abstract: Skin-sensitizing chemicals exhibit dose-response relationships for the elicitation of contact dermatitis. Previously, considerable work has been carried out in which the elicitation of allergic skin reaction has been examined as a function of the applied concentration. However, the relationship between exposure time, dose and response has not been explored in any depth. The present work has extended our initial assessment of the relationship between both exposure time and concentration for para-phenylenediamine (PPD) in a group of 19 PPD-allergic volunteers. The results clearly demonstrate that a relationship exists between both exposure time and concentration. Positive responses to PPD were directly proportional to exposure time: at 5 min 16% responded; at 15 min, 38%; at 30 min, 50%; and at 120 min, 69%. A similar direct relationship was found between concentration of PPD and response: after 120 min, 22% of patients had responded to 0.01%, and 69% to 1% PPD. All exposures for 1 and 2 min were negative. Subsequent evaluation using repeated 5 min open application testing demonstrated a cumulative effect, as after 8 days 39% of the panel reacted, more than double the number that reacted to a single occluded 5-min treatment. It was noted that there was marked subject variability in exposure time and dose required to elicit an allergic response. These results are of relevance for the general interpretation of patch test data, especially with regard to risk assessment.
authors.affiliation: St. John's Institute of Dermatology, St. Thomas' Hospital, London, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Hextall
authors.forename: N J
authors.initials: NJ
authors.lastname: Alagaratnam
authors.forename: A K
authors.initials: AK
authors.lastname: Glendinning
authors.forename: D B
authors.initials: DB
authors.lastname: Holloway
authors.forename: L
authors.initials: L
authors.lastname: Blaikie
authors.forename: D A
authors.initials: DA
authors.lastname: Basketter
authors.forename: J P
authors.initials: JP
authors.lastname: McFadden
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017449:Dermatitis, Allergic Contact / Q000175:diagnosis* / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010328:Patch Tests / Q000379:methods*; D010655:Phenylenediamines / Q000009:adverse effects* / Q000494:pharmacology*; D011446:Prospective Studies; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D010655:Phenylenediamines