Chapter 9
Downloaded by UNIV OF CALIFORNIA SANTA BARBARA on May 28, 2018 | https://pubs.acs.org Publication Date: May 5, 1995 | doi: 10.1021/bk-1995-0606.ch009
The Incidence of Delayed-Type Contact Dermatitis in Modern Pesticides Philip S. Magee BIOSAR Research Project, 141 Sealion Place, Vallejo, C A 94591 and School of Medicine, University of California, San Francisco, C A 94143
A recently developed model for allergic contact dermatitis (ACD) is applied to 148 pesticides to assess both allergens and nonallergens. Those reported to be moderate to strong irritants, but scoring as probable non-allergens, are classified as immediate type primary irritants. Although there is no certainty in the absence of animal testing, the performance of the model with respect to non-irritating pesticides is exceptional and those classified as A C D are considered as highly probable allergens based on previous validation experience. To the credit of the modern pesticide industry, only 13 of the 148 pesticides were identified as probable A C D problems with 25 others showing some form of direct irritation. As the seriousness of dermal irritation in the handling of pesticides becomes more clearly recognized, it can be expected that early animal testing will allow few of these problems to reach the future market without appropriate handling precautions. Both acute and chronic hazards of pesticides have long been recognized by obligatory animal testing to cover every reasonable toxicology problem that plant personnel, shippers, farmers and the ingesting public might encounter. Thus, it is common to find the oral and dermal LD50 against common laboratory animals and often some mention of chronic feeding results in most pesticide compilations. Less commonly reported are the non-lethal effects of lung and skin irritation which can lead to serious job and personal problems. While an exposed worker can easily protect from lung irritation when the hazard is known, equivalent protection from skin irritation is much more difficult and virtually impossible for field workers in the heat of summer. The ultimate solution, of course, is the denial of registration for future pesticides exhibiting severe lung and dermal irritation. The purpose of this study is to assess the nature of dermal irritation of currently registered modern pesticides. To accomplish this goal, a large sample of pesticides was selected from The Agrochemicals Handbook(7), with the following distribution: 0097-6156/95/0606-0120$12.00/0 © 1995 American Chemical Society Hansch and Fujita; Classical and Three-Dimensional QSAR in Agrochemistry ACS Symposium Series; American Chemical Society: Washington, DC, 1995.
9. MAGEE
Delayed-Type Contact Dermatitis in Modern Pesticides
Downloaded by UNIV OF CALIFORNIA SANTA BARBARA on May 28, 2018 | https://pubs.acs.org Publication Date: May 5, 1995 | doi: 10.1021/bk-1995-0606.ch009
Class insecticides herbicides fungicides other TOTAL
121
Number 27 61 42 18 (miticides, ovicides, growth regulators, etc.) 148
In all of the selected cases, there was sufficient mention of dermal effects to allow a numerical rating of severity ranging from 1.0 to 0.0. Handbook comments are rated as follows: Comment strong skin irritant inflammation of skin allergen/sensitizer moderate skin irritation local skin irritation possible skin irritant no mention of irritation slight skin irritation no skin irritation
Rating 1.0 1.0 1.0 0.7 0.7 0.5 0.5 0.3 0.0
Note that the ambiguous statements are given an arbitrary nul or indeterminate rating of 0.5. Only 9 of the 148 pesticides were so rated and do not detract from the firmer ratings of 0.0-0.3 and 0.7-1.0 which provide the basis for this study. By comparing these experiential ratings with the results of the classification model, we hope to achieve a more incisive look into pesticide dermal problems. The model detects compounds likely to induce allergic contact dermatitis or delayed type hypersensitivity, a T-cell mediated immune response reacting in 24-72 hours after initial sensitization^). Immediate type hypersensitivity (contact urticaria or hives) is a different immune response based on rapid humoral reaction with immunoglobin-E in sensitive individuals. In addition, there are several other irritation responses that do not involve the immune system.. As examples of each type, bromoxynil is a strong immediate type irritant, especially of the mucous membranes (nasal, lung), while captan, a protein reactive, neutral sulfenylating agent, causes delayed contact dermatitis (ACD). Some chemicals, such as 2,4-dinitrochlorobenzene and phthalic anhydride, are capable of both immediate and delayed responses. Immune System Activation Activation of the immune system as explained in detail by von Blomberg, Bruynzeel and Scheper (2) can be summarized as follows. Penetration of the stratum corneum into the viable epidermis is required to reach the domain of the allergen presenting Langerhans cells. The causative, protein-reactive allergen may be directly reactive (hapten) or may require prior metabolic activation in the epidermal tissue (prohapten).
Hansch and Fujita; Classical and Three-Dimensional QSAR in Agrochemistry ACS Symposium Series; American Chemical Society: Washington, DC, 1995.
Downloaded by UNIV OF CALIFORNIA SANTA BARBARA on May 28, 2018 | https://pubs.acs.org Publication Date: May 5, 1995 | doi: 10.1021/bk-1995-0606.ch009
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CLASSICAL AND THREE-DIMENSIONAL QSAR IN AGROCHEMISTRY
In either case, the activating reaction occurs with surface molecules on the Langerhans cells. Reactions may occur with reactive residues such as cysteine, lysine, histidine and serine (nucleophilic), cystine and carboxamide linkages (electrophilic) or tyrosine (radical). The most common hapten reactants are electrophilic (anhydrides, activated halides, conjugated olefins, aldehydes, epoxides, quinones), while strong nucleophiles such as primary amines and thiols form a smaller class(5). The incidence of irritant contact dermatitis from the nicotine smoking withdrawal patch can be as high as 30% (
