Dermal reaction discussion

One study, which showed no sensitization reactions in guinea pigs following dermal application of tetryl (Gale 1944), is discussed below. No other health effects were studied in animals. 

Sensitizer. A chemical that causes vulnerable, exposed individuals to develop a respiratory allergic reaction following repeated exposure. Methylene bisphenyl isocyanate, toluene diisocyanate, and trimellitic anhydride are examples of respiratory sensitizers. It should be noted that sensitizing chemicals that are inhaled have the propensity to also induce dermal sensitization and that skin exposure to sensitizers (e.g., ammonium thioglycolate) can induce respiratory sensitization. Such cross-sensitization is discussed below and in Chapter 29. 

Although the focus of this chapter is modeling dermal absorption, it is worth digressing to discuss the types of toxicological reactions that can occur in skin if a penetrating compound has activity against epidermal or dermal constituents. The field of dermatotoxicology has been extensively reviewed elsewhere [22,23] and will only be discussed here in relation to factors that affect computational issues. 

It must be stressed that the primary mechanism of many topical irritants (e.g., organic solvents, corrosives) is the impairment to the stratum corneum barrier properties discussed earlier. If the stratum corneum barrier is perturbed, a feedback response may be initiated whereby regeneration of the barrier occurs. This reaction is mediated by cytokines (especially TNF-a) originating locally within the epidermis. However, additional responses to these inflammatory mediators may in themselves launch an irritation response mediated by the keratinocytes. Thus, regardless of the initiating mechanism, the sequelae to many irritants is the same, making the definition of unique dermal computational toxicology models difficult. 

No studies were located regarding dermal effects following oral exposure to organic manganese. Reports of contact dermatitis in people exposed to maneb or mancozeb are discussed in Section 2.2.3.2 because the route of exposure is assumed to be dermal. None of these studies indicate that ingestion of either pesticide occurred or would contribute to the allergic skin reactions. 

Dermal exposure to toxicants can produce a variety of effects, such as primary irritation, sensitization reactions, phototoxic skin reactions, photoallergy, urticarial reactions, hair loss, chloracne, and cutaneous cancer. These toxic effects and the nature of the reactions are discussed in this section. 

Ctvalues of 14,040 and 17,700 mg min/m3 caused a more severe initial dermal response, which required 3 hours to disappear. After 12 to 24 hours, a delayed reaction, consisting of first- and second-degree burns, appeared. Blistering occurred in four of the eight subjects (Figure 12-1). With treatment (discussed below), these lesions resolved in 10 to 14 days by 6 weeks later, a small amount of post-inflammatory pigmentation remained.11... 

A major review discussed cutaneous adverse effects associated with penicillamine [67 ]. It has been associated with toxicity in patients with histocompatibility antigens DRl, DR3, DR4, Al, C4QO, BW35 and B8. Autoimmune and immediate hypersensitivity reactions are associated with patients with altered immunity such as rheumatoid arthritis of scleroderma. Cutaneous adverse effects occur in 25-50% of patients, causing withdrawal in 10% of patients. This review provides a comprehensive analysis of dermal toxicities associated with penicillamine. A second review discussed eosinophilic fasciitis [68 ]. 

---