Epidemiological studies have described an increasing prevalence of fragrance allergy and indicated an association with hand eczema. 59 domestic and occupational products intended for hand exposure were subjected to gas chromatography-mass spectrometric (GC-MS) analyses to test the hypothesis that fragrance chemicals known to have the potential to cause contact allergy but not included in fragrance mix (FM) may be common ingredients in these products. A quantitative analysis of 19 selected fragrances was performed by GC-MS. Further analysis of GC-MS data revealed the presence of 43 other fragrance chemicals/groups of fragrance chemicals in the products investigated. Among the 19 target substances the most commonly detected were limonene in 78%, linalool in 61% and citronellol in 47% of the products investigated. The FM ingredients were present in these products with the following frequencies: oak moss (evernic acid methylester) 2%, cinnamic alcohol 2%, cinnamic aldehyde (cinnamal) 3%, isoeugenol 5%, alpha-amylcinnamic aldehyde (amyl cinnamal) 8%, hydroxycitronellal 12%, eugenol 27%, and geraniol 41%. Thus, the chemical analyses of domestic and occupational products indicates that investigation of potential contact allergy related to these products types should consider fragrance allergens additional to those in the FM, since these may occur with high frequency.

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Cutaneous irritation presents a major health problem with serious social and occupational impact. The interaction between an irritant and the human skin depends on multiple factors: the intrinsic properties and the nature of the irritant itself, and specific individual- and environment-related variables. The main pathological mechanisms of irritancy include skin barrier disruption, induction of a cytokine cascade and involvement of the oxidative stress network; all of them resulting in a visible or subclinical inflammatory reaction. In vivo, different non-invasive parameters for the evaluation of skin irritation and irritant potential of compounds and their specific formulations have been introduced, such as epidermal barrier function, skin hydration, surface pH, lipid composition, skin colour and skin blood flow. The diverse physiological changes caused by irritating agents require implementation of a multiparametric approach in the evaluation of cutaneous irritancy.

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.

In an evaluation of the safety of new chemicals, of products containing them, or of novel formulations of existing chemicals which may come into contact with the skin, it is important to incorporate an assessment of specially susceptible sub-populations. Such a group is represented by those who are more likely to experience sensory effects such as stinging. Since these individuals are easily and rapidly identifiable, we investigated whether they represented a group who were also more susceptible to the effects of an irritant. The primary purpose was to discover whether 'stingers' might represent an easily and rapidly identifiable sub-population with a more generally increased tendency to give skin responses. The response to a 0.3% sodium dodecyl sulphate patch test was assessed in a group of 25 'stingers' and compared to the response in 25 'non-stingers'. There was no difference in either the pattern or strength of the irritant response assessed by subjective erythema and dryness scores. Thus the data suggest that there is no correlation between the susceptibility of an individual to a skin stinging response and an irritation reaction.

The murine local lymph node assay (LLNA) is a method for the identification of skin sensitizing chemicals in which activity is measured as a function of proliferative responses induced in draining lymph nodes following topical exposure of mice to the test material. More recently, the LLNA has also been used for the determination of relative skin sensitizing potency based upon the mathematical derivation of an EC3 value, this being the estimated concentration of test chemical necessary to provoke a 3-fold increase in lymph-node cell-proliferative activity compared with concurrent vehicle-treated controls. Here we describe the use of the LLNA to determine the influence of vehicle on the skin-sensitizing potency of methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), the active ingredient of preservatives such as Kathon CG. To this end, LLNA responses to MCI/ MI were measured using the vehicles 4:1 acetone:olive oil (AOO), methyl ethyl ketone, dimethylsulfoxide, dimethylformamide, propylene glycol (PG) and acetone. It was found that the vehicle in which MCI/MI was applied had a substantial impact on activity, with derived EC3 values varying from 0.0049% with AOO to 0.048% with PG. With the other vehicles, EC3 values ranged from 0.0068 to 0.0076%. The skin sensitizing potency of MCI/MI as judged from LLNA responses is consistent with what is known of the requirements for sensitization in humans. It is proposed that the LLNA not only provides a method for determination of relative skin sensitizing potency, but is also appropriate for assessing the influence of vehicle matrix on sensitizing activity.