Pesticides in Occupational Contact Dermatitis PAOLO
LISI, MD
P
esticides are a heterogenous group of toxic chemicals used to destroy or to prevent growth of living organisms and weeds that damage agriculture. Among the cutaneous disorders caused by chronic exposure to these chemicals, contact dermatitis and mainly irritant contact dermatitis are the most frequent. The lesions seem slightly more common in men in the fourth decade of life, and during spring and summer. Pesticide contact dermatitis can be caused by many active ingredients, but positive patch test reactions are almost always attributable to thiophthalimides (captan, difolatan, and folpet) and, perhaps, bisdithiocarbamates and benomyl, used as fungicides. Multiple sensitivity to these compounds is possible, whereas contact dermatitis to other pesticides (insecticides, herbicides, fumigants, etc) is not significant. Health hazards from pesticides depend not only on the greater or lesser toxicity of these chemicals, but also on environmental conditions, modalities of application, incorrect use of formulations, lack of use of adequate skin protection, and lack of personal and environmental hygiene. In this context, educational efforts to promote knowledge on potential damage should be intensified. Agricultural workers as well as horticulturists, floriculturists, foresters, and cattle breeders are exposed daily to a wide variety of chemical, biologic, and physical hazards during their different working activities. Because of this, the use of chemicals and especially of pesticides and fertilizers has greatly increased over the past 40 years, and they are now an accepted part of our environment. The increasingly wide utilization of pesticides in all countries of the world has undoubtedly helped to reduce losses in production but, at the same time, has induced a From the Department of Dermatology, University of Perugia, Perugia, Italy. Address correspondence to Paolo Lisi, Via XIV Settembre, 69, I 06122 Perugia, Italy.
0 1992 by Elsevier Science Publishing
Co., Inc.
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progressive increase in incidence of illnesses and injuries caused by these compounds among factory workers involved in producing them, farmers, nonagricultural consumers, and the general population. In a study of 10,000 U.S. households, Savage et al’ found that 9 of 10 subjects used some type of pesticides; more recently, Hogan2 reported that 15% of pesticides sold were used in homes and gardens.
Definition and Classification of Pesticides Pesticides are a heterogenous group of toxic chemicals used to destroy or to prevent growth of living organisms and weeds that damage agriculture. According to their prevalent action, they may be classified as fungicides, insecticides and insect repellents, rodenticides and animal repellents, acaricides, nematicides, mulluscides, and herbicides. There are different formulations of these compounds, such as liquids, wettable powders, and dusts. Fumigants are volatile substances that are dispersed in the air to kill insects, fungi, bacteria, and rodents present in soil and on trees and stored grain. More than 5000 pesticide products, which contain one or more of the approximately 300 active registered ingredients, are on the market in Italy today. Their complete chemical classification is not easy; on the other hand, we believe that it is more useful to list only the substances more commonly sold in our country (Table 1). Among the fungicides, inorganic compounds (sulfur, copper sulfate) and bisdithiocarbamates (zineb, mancozeb) are the most frequently sold, whereas among the insecticides and acaricides, organophosphate compounds and white liquid petrolatum are still widely employed. Also in Italy, the use of herbicides and, above all, thiocarbamates, atrazine, and dipyridinium compounds has increased in recent years, whereas the sale of fumigants is not remarkable. Organic mercurials (phenylmercuric acetate, phenylmercuric chloride, etc), chlorobenzols (pentachloronitrobenzene), and dichlorodiphenyl-trichloroeth-
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Table 1. Chemical Classification Pesticide
of
Pesticides and Repellents More Commonly Sold in Italy
Chemical Group
Fungicides
Inorganic
compounds*
Dithiocarbamates (DTCs)
Organostannics Thiophthalimides
Organonitrogens
Insecticides acaricides
and
Dinitrophenols Organophosphate compounds*
Chemical Name Sulfur Copper (sulfate, oxychloride, etc) Iron sulfate Barium polysultide Zinc ethylene-bis-DTC Zinc and manganese ethylene-bis-DTC Zinc dimethyl-DTC Bis(dimethylthiocarbamoy1) disulfite Manganese ethylene-bis-DCT Triphenyl-tin(l+) hydroxide Triphenyl-tin(l+) acetate N-[(Trichloromethyl)thio]-4-cyclohexene-2-~carbo~mide N-(Trichloromethylthio)phthaliide N-(1,1,2,2-Tetrachloroethylthio)-3a,4,7,7otetrahydrophthalimide Methyl-1-(butylcarbamoyl)-2-benzimidazole Monoacetate dodecylguanidine 2-(1-Methylheptyl)-4,6dinitrophenyl ester O,O-Diethyl-S-(ethylthio)methylphosphorodithioate O,O-Diethyl-0-p-nitrophenyl
Common Name
Zineb Mancozeb Ziram Thiram Maneb Fentin hydroxide Fentin acetate Captan Folpet or phaltan Captafol or difolatan carbamate
thiophosphate
0,0-Diethyl-0-(2-isopropyl-6-methyl-4pyrimidinyl)phosphorothioate O,O-Dimethyl-S-[4-oxo-1,2,3-benzotriazin-3(4H)-ylmethyl]phosphorodithioate 0,0-Dimethyl-0-4nitrophenylphosphorothioate 0,0-Dimethyl-S-(N-methyl carbamoylmethyl)phosphorodithioate O,O-Dimethyl-S-(l,2-dicarbethoxyethyl)phosphorodithioate 2-Carbomethoxy-1-methylvinyldimethyl phosphate 0,0-Dimethyl-2,2dichlorovinyl phosphate O,O-Dimethyl-0-1,2-dibromo-2,2dichloroethyl phosphate Mineral oils* MethylcarbamateP Organochlorates
Natural
compounds
Pyrethroids Herbicides
Thiocarbamates* Organonitrogens Triazines Anilides Phenylureas
Nitroanilines Others
1-Naphthyl-N-methylcarbamate 1,2,3,4,5,6-Hexachlorocyclohexane 6,7,8,9,10,10-Hexachloro-1,5,5a,6,9,9~-hexahy~o-6,9methano-2,4,3-benzodiaxathiepin-3-oxide Pyretrins cu-Cyano-3-phenoxybenzyl-2-(4chlorophenyl)3methylbutyrate S-Ethyl-hexahydro-lH-azepine-1-carbothioate 2-Chloro-4-ethylamino-6-isopropylamino-s-triazine 2-Chloro-4,6-bis(ethylamino)-s-triazine N-(3,4-Dichlorophenyl) propionamide 2-Chloro-2’,6-diethyl-N-(methoxymethyl)acetanilide 3-(3,4-Dichlorophenyl)-1-methoxy-l-methylurea 3-(3-Chloro-4-methoxyphenyl)-l,l-dimethylurea 3-(3,4-Dichlorophenyl)-1,1-dimethylurea N,N-Di-n-propyl-2,6-dinitro-4-(trifluoromethyl)aniline 5-Amino-4-chloro-2-phenylpyridazin-3-one 2,6-Dichlorobenzonitrile 2,4-Dichlorophenyl-p-nitrophenyl ether
Benomyl Dodine Dinocap Phorate Parathion-ethyl diazinon Diazinon Azinphos-methyl Parathion-methyl dimethoate Dimethoate Malathion Mevinphos Dichlorvos or DDVP Naled or dibrom White liquid petrolatum Carbaryl Lindane or HCH Endosulfan Pyretrins Nicotine Fenvalerate Molinate Atrazine* Simazine Propanil Alachlor Linuron Metoxuron Diuron Trifluralin Chloridazon Dichlobenil Nitrofen Continued
or pyrazon
on next page
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Table 2. Chemical Classification of Pesticidesand Repellents More Commonly Sold in Italy (continued) Pesticide
Chemical Group Dipyridinium compounds*
l,l’-Dimethyl-4,4’-dipyridinium
Aliphatic chloroacids Phenoxycarboxylic
Fumigants
Molluscides Rodenticides l
Chemical Name
Dinitrophenols Halogenated hydrocarbons
acids
dichloride
l,l’-Ethylene-2,2’-dipyridinium dibromide Natrium trichloroacetate 2,4-Dichlorophenoxyacetic acid 2(2,4-Dichlorophenoxyl)propionic acid 4-chloro-2-methylphenoxyacetic acid 4,6-Dinitro-o-cresol 1,3-Dichloropropene + 1,2dichloropropane
Dithiocarbamates Thioazo compounds
Methyl bromide Carbon tetrachloride Dichloroethane Sodium N-methyldithiocarbamate Tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione
Coumarin
3-(a-Acetonylbenzyl)-4-hydroxycoumarin
compounds
Common Name Paraquat Diquat TCA sodium 2,4-D 2,4-DP MCPA DNOC DD
Metham sodium Dazomet Metaldehyde Warfarin’
The most widely used compounds
ane (DDT) have been banned, as have several chlorocyclodienes (aldrin, dieldrin), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), and 2-(2,4,5+ichlorophenoxy)propionic acid (2,4,5-TP).
Incidence of Skin Diseases Caused by Pesticides The skin, with its extensive surface directly exposed to the environment, is particularly susceptible to damage induced by pesticides, which may be introduced into the body by ingestion, inhalation, and skin contact. Among these ways of penetration, skin contact is by far the most important and, according to Wolfe,3 over 97% of pesticides is deposited on the cutaneous surface, especially when liquid formulations are used. Present laws that fix the highest limits of exposure to agricultural chemicals have significantly helped to reduce the incidence of acute intoxication among manufacturers, formulators, and farmers; however, the widespread use of these compounds has caused a progressive increase in chronic systemic effects and cutaneous disorders, but the real incidence of the latter (eg, contact dermatitis, chloracne, porphyria cutanea tarda, dyschromia, keratosis, non-Hodgkin’s lymphoma) still remains unknown.4*5 Until more than two decades ago, contact dermatitis has been regarded as rare, 6 but several large studies on patients who were diagnosed and treated as having pesticide poisoning by physicians in California (749 cases)’ and Japan (815 cases)a show a high incidence of contact dermatitis (55 and 26.5%, respectively).
Clinical Features of Contact Dermatitis Irritant contact dermatitis is more frequent than allergic contact dermatitis. The clinical spectrum may range from a mild reaction with erythema, scales, or chapping to a more florid dermatitis with edema, papules, vesicles, bullae, and, sometimes, eschars. Lichenification and fissures are very frequent in the chronic phase. The circumscribed or diffuse but mostly ill-defined patches develop on the skin areas more commonly subjected to occupational exposure, usually on the hands, forearms, face, and neck. Also, allergic contact dermatitis is generally located on these sites, but its clinical features are more often characterized by papulovesicles, exudation, and intense itching. Allergic dyshidrosiform contact dermatitis,9 morbilliform or urticarial eruptions,‘O erysipeloid-like lesions,” erythema multiforme,12 pellagroid dermatitis,13 as well as depigmentation following the resolution of dermatitis and/or on patch-tested areas, have been reported.“-l6 The very rare cases of contact leukoderma are produced by some herbicides, such as barban,14 alachlor,15 and, probably, paraquat dichloride,16 and by DD, which is a soil fumigant.” Nail damage associated or not with periungual irritant contact dermatitis is possible in workers whose fingernails are exposed to the weed killer paraquat,18-21 but it has been observed also in some subjects following contact with the acaricide dinobuton (2-(l-methyl-2-propyl)4,6dinitrophenyl isopropylcarbonate) and the insecticide 4,6-dinitro-o-cresol (DNOC).20 The most common lesions are softening and/or gross deformity of the nail
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plate, yellow or whitish and loss of the nails.
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nail discoloration,
onycholysis,
Epidemiologic Features of Contact Dermatitis There are a reasonable number of case reports on contact dermatitis from pesticides, but little is known about the epidemiology of this disorder. Contact dermatitis seems slightly more common in men than in women, in the fourth decade of life, and during spring and summer.s The lesion onset is closely related to the percutaneous absorption of pesticides which is influenced by some characteristics of formulation active ingredients, such as chemical structure, lipid solubility, dispersion in organic solvents (eg, xylene, alcohols, and ketones), concentration, and adhesive properties; however, other environmental and occupational factors are important. The relapses of clinical manifestations in farmers and agricultural workers, in fact, are more frequent after the application of pesticides, primarily when these are sprayed in the air or scattered in the atmosphere in the form of gas by helicopters and airplanes. The other possible sources of contact, such as the transport of products, their preparation and transfer into spray equipment, cleaning and repair of this equipment, should not be underevaluated. On the contrary, crushing, pulverizing, and mixing of pesticides are especially dangerous for workers employed in the manufacture of these products.
Etiology of Contact Dermatitis Pesticide contact dermatitis can be caused by many active ingredients present in commercial products, but also by carrier liquids and dusts, emulsifiers, adjuvants, surfactants, propellents, and, sometimes, contaminants. Nevertheless, the real etiologic relevance of these substances is not easy to determine because epidemiologic studies on this subject are not large and often poorly documented. On the other hand, data collection is impeded by territorial dispersion of agricultural workers, by the difficulty in organizing collective preventive medicine programs, and by the fact that clinical manifestations are often mild, localized, and of short duration and seasonal course. Despite these difficulties in assessing the incidence of etiologic agents of occupational contact dermatitis in the agricultural sector, in 1960 Kleinman and co-workers’ reported that the most common causes of skin lesions attributed to pesticides in California were herbicides and defoliants (15%), halogenated hydrocarbons (lo%), and organophosphate compounds (8%). Hearnz3 analyzed 250 cases of poisoning from pesticides occurring between
1952 and 1971 in England and Wales and found that the dermatitis was ascribed to organomercurial compounds, paraquat, and thiram. More recently, Matsushita et al* pointed out that the principal chemicals responsible for the outbreak of contact dermatitis in the rural regions of Japan were captafol(28.7%), sulfurs (18.5%), highly and moderately toxic organic phosphates (18.1%), and chlorinated hydrocarbons (9.7%). In conclusion, these data show that health hazards from pesticides depend not only on the toxicity of these substances, but also on the extent of their sales.
Irritant
Contact Dermatitis
A large number of pesticides are known to cause irritant contact dermatitis, especially when the products are used too concentrated and/or without suitable protective precautions. Among fungicides, copper sulfate, barium polysulfide, thiophanat-methyl,24 chlorothalonil,25 and captafol (difolatan)24~26-2* are regarded as irritant compounds. In particular, it has been reported that at least one third of exposed subjects in the timber industry develop captafol dermatitis, 29but this risk can be minimized by appropriate worker training and industrial hygiene. Also, chlorothalonil is a potent skin irritant and, sometimes, a contact allergen in vegetable growers30 and floriculturists.3~ Irritant contact dermatitis from organophosphate insecticides, when adequate precautions are taken, is not common32 despite their massive sales throughout the world following the banning of DDT. It is quite probable that the usage concentration of these compounds and their persistence in the environment are too low to provoke skin lesions and sensitization; however, some cases of both irritant and allergic contact dermatitis caused by dichlorvos,33-37 naled,38 mevinphos,39 parathion,40,41 plondrel (ditalimfos),42 promecarb,24 tetrachloroacetophenone (TCAP),43 and thiometon24 have been published. The scanty data in the literature on irritant properties of herbicides and fumigants do not allow conclusions to be drawn. In 1981, Peachp4 stated that no cases of contact dermatitis from the herbicides paraquat or diquat have so far been reported, but a study by Howard45 revealed an acute irritant bullous dermatitis in several of the 36 workers employed in a paraquat factory. Also, glyphosate,46 propachlor,47 acaricides omite,48 dinobuton,** and fumigant DD49 may be irritating to the skin. The last is a highly toxic mixture of chlorinated hydrocarbons (1,3-dichloropropene and 1,2-dichloropropane) that causes an irritant dermatitis, but also can occasionally sensitize.*7,50
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Allergic Contact Dermatitis Occupational allergic contact dermatitis does not seem to have a high incidence despite the massive sales of pesticides and the strong potential of some of these for allergic sensitization (see later). The most common causes of lesions are fungicides and, above all, bisdithiocarbamates (eg, maneb51-55 and/or zineb,9*56,57mancozeb,13,5*-60 and benomy135*6*-63). Recently, Larsen and colleague@’ suggested that the earlier reported allergy to benomyl may represent cross-reactions and/or that the development of contact allergy to this compound requires previous exposure to other chemically related pesticides. In fact, the authors did not observe contact dermatitis in a group of 62 present and former pickers in a large mushroom company, where benomyl has been used regularly for more than 10 years. Sensitivity to other less widely used fungicides such as captan, 65 dithianon 66 and thiram52*67,68 and to herbicides (eg, alachlor,69 ami;role,70 barban,14*7* chloridazon,” nitralin I 73nitrofen,74 phenmedipham” has been noted, but it appears to be uncommon. Sensitization to insecticides derived from plants (pyrethrum, nicotine, rotenone) and to lindane5* is rare and that to DDT has never been convincingly proved.* On the contrary, metham sodium, a broad-spectrum soil fumigant, may cause contact dermatitis in humans.77,78 Finally, it is worth emphasizing that several cases of dermatitis can be induced by pesticide contaminants such as diethyl fumarate79*80 and &heptachlorocyclohex-
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ane *i,s* present in technical-grade da& respectively.
malathion
Opinions on irritant and/or sensitization contact potential of pesticides are varied, mainly because some experimental results often are in contrast with clinical relevance. Experimentally, the organophosphorus compounds malathion79*80 and parathions3 have been shown to be strong sensitizers in humans, but Milby and Epsteinm found that only about 3% of individuals with occupational exposure to malathion had a positive patch test reaction to this chemical (1% in petrolatum) and no worker had to change jobs because of malathion allergy. Successively, Matsushita and colleagues,84 using the guinea pig maximization test, demonstrated the strong potential of maneb, mancozeb, and zineb for allergic sensitization, whereas they did not observe allergenicity of ethylene thiourea and dimethylditiocarbamic acid sodium salt. Also, the herbicide glyphosate, extensively investigated by Maibach, 85 has been found to be a nonsensitizer. These data were not confirmed by predictive testing in subjects with or without contact dermatitis by the members of the International Contact Dermatitis Research Group (ICDRG)52 and, more recently, by us and some other members of the Italian Group for the Study of Contact and Environmental Dermatitis (GIRDCA)*6JJ7 (Table 2). Italian results,86,87 moreover, demonstrate that
Concentration (%)
Zineb Mancozeb Ziram Thiram Maneb
ICDRG 1
1
Captan
Folpet
1 0.1
Difolatan
Parathion-ethyl Parathion-methyl Malathion
0.5
and lin-
Sensitizing Potential of Pesticides
Table 2. Positive Reactionsto PesticidePredictive TestsObservedby ICDRG and GIRDCA Members
Allergen
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GIRDCA 1 1 0.5 1 1 1 0.5 1 0.5 0.25 0.1 0.1 0.1 0.05 0.025 1 1 0.5
Positive reactions ICDRG 3/655
35/655 16/509
50/509 3/107
l/455
GIRDCA 2/389 o/149 o/149 l/348 7/442 3/389 3/386 17/442 17/389 6/279 2/279 6/442 5/389 3/279 O/282 O/280 l/294 o/351
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positive reactions to pesticides are not common and almost always attributable to fungicides, in particular, thiophthalimides (captan, difolatan, and folpet) which may also be irritant, as mentioned earlier.
Multiple Sensitivity Simultaneous sensitivity to pesticides has never been examined extensively but our data on irritation and sensitization potential of pesticides*’ showed multiple positive reactions to bisdithiocarbamates and/or thiophthalimides in 10 of 652 subjects patch tested with a standard series of 36 pesticides. Six of these were sensitized to two fungicides (zineb and folpet in one, captan and difolatan in three, captan and folpet in two) and four subjects were sensitized to three fungicides (zineb, maneb, and difolatan in one; maneb, thiram, and captan in one; captan, folpet, and difolatan in one; captan, folpet, and phorate in one). Nevertheless, multiple sensitivity to bisdithiocarbamate and thiuram compounds has already been described in some case reports 13,52,53,57,60,88 and considered as cross-sensitivity. Positive reactions to several thiophthalimides have not been documented, but could be the result of impurities or small amounts of cross-sensitizing materials.
Diagnosis The diagnosis of occupational contact dermatitis from pesticides is not always easy because its clinical picture is mostly of short duration and therefore not present at the
moment of physical examination, as many agricultural workers are transient and almost all centers for occupational skin diseases are located only in regional hospitals. Despite these difficulties, a careful detailed history, the observation of the dermatitis course before and after 2 weeks off work, and patch testing usually make it possible to decide whether or not a case is pesticide related. The results of patch tests must, however, be interpreted in the light of the history, and the relevance of a positive reaction must be accurately determined, especially when patch testing has not been carried out with pure active ingredients. Many pesticide formulations on the market, in fact, are dissolved in solvents that are irritating to the skin or may contain impurities that cause more problems than the active chemical. The nonirritating concentrations of analytic-grade pesticides in appropriate vehicles have been investigated by a number of authors2,52,86*87,89-91who suggested different standard test series. Tables 3 and 4 show our updated series.
Prevention and Rehabilitation As happens in other productive sectors, the incidence of pesticide contact dermatitis might at least be partly reduced by programming suitable interventions of primary and secondary prevention. Their development encounters a great amount of difficulty of different nature, which is more prevalent in agricultural workers than in pesticide factory workers. The territorial distribution of the farmers and their often seasonal exposure to different
Table 3. Patch Testing for Fungicides and Insectides* Fungicides Benomyl Captafol (difolatan) Captan Chlorothalonil Copper Sulfate Dinocap Dithianon
0.1 0.1 0.5 0.01 1 1 1
Azynphos-methyl Carbaryl Diazinon Dichlorvos (DDVP) Dimethoate Endosulfan Lindane (HCH) Malathion Mevinphos Naled (dibrom)
1 1 1 0.05 1 1 1 0.5 0.25 .I
Fentin hydroxide Folpet (phaltan) Mancozeb Maneb Thiram Zineb Ziram
0.5 0.1 1 1 1 1 1
Nicotine sulfate Parathion-ethyl Parathion-methyl Phorate Pyrethrum Rotenone Tetrachloroacetophenone White liquid petrolatum
5 1 1 1 2 5 0.01 1
Insecticides
*All in talc.
in petrolatum,
except dichlorvos,
mevinphos,
and nicotine
sulfate in water, parathion-ethyl
in alcohol, and rotenone
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Table 4. Patch Testing for Herbicides, Fumigants, Acaricides, Molluscides, and Rodenticides Herbicides Alachlor Amitrole Atrazine Barban Chloridazon Diquat DNOC
Glyphosate Molinate Nitrofen Paraquat Phenmedipham Propanil
1
(pyrazon)
1 0.1 0.1 0.1 0.5
10 1 0.5 0.1 2 1
Fumigants Dazomet
0.25
Metham
sodium
0.03
Acaricides Dinobuton
10
Omite
0.05
Warfarin
0.05
Molluscides Metaldehyde Rodenticides Antu All in petdatum, in oil.
except barban in acetone; DNOC, ghyphosnte,
chemicals, for example, strongly impede the activation of models and methodologies of intervention used in other working activities. For this reason, more thorough health education of all those who handle pesticides, informing them about possible cutaneous and systemic damage, is necessary. The illnesses and injuries are related mainly to incorrect use of hazardous chemicals; lack of use of adequate protective clothing (eg, hoods, glasses, face shields, sleeves, gloves, aprons, chemical-resistant shoes or boots) and barrier creams when mixing, loading, and spraying pesticide formulations; and unsuitable skin cleansing, to be carried out immediately after work with water and soap but not with solvents and diluents. Gloves should be made of nitrile rubber and butyl rubber, because these are more resistant to pesticide permeation than those of natural rubber, polyvinyl chloride, and polyethylene.92 In addition, other protective measures such as automatic equipment, closed processes, an efficient ventilation system, and environmental hygiene should be taken in pesticide plants. Primary prevention should also be aimed at identifying potential irritants and allergens through predictive tests in experimental animals prior to registration of a pesticide for sale and through multicenter epidemiologic studies. Thus, it will be possible to remove irritants from the formulations replacing them with substances less damaging to the skin. Moreover, it would be opportune to use preplacement questionnaires and examinations to reveal past and/or present cutaneous disorders that could limit a worker’s employability and placement,93 and periodic health screenings to check early alterations caused
phenmedipham,
and metham sodium in water; and nitrofen
by pesticides. Unfortunately, inspection of the entire skin is rarely part of the physical examination! The aim of secondary prevention is to eliminate or at least reduce relapses of occupational cutaneous diseases. In cases of pesticide contact dermatitis there is an imperative need to discover the allergen responsible because its removal is almost always followed by a permanent recovery. In fact, the causative agent is generally a specific chemical that can be completely avoided in and outside the work environment. Only when the contact allergens are present as dust or vapor in a factory, they cannot be removed and occasional recurrences of lesions are possible. In any case, however, it will be enough to give the patient the common name of the incriminated pesticide with its synonyms and, if possible, a list of commercial products in which it is contained.
Conclusions In our opinion, the incidence of occupational pesticide contact dermatitis is more frequent than reports by several authorities have indicated, because its clinical manifestations, often limited for extension, transitory, and seasonal, are undervalued by farmers and therefore not reported. Pesticide contact dermatitis can be caused by many active ingredients but positive patch test reactions are almost always attributable to thiophthalimides and, perhaps, bisdithiocarbamates and benomyl, used as fungicides. Health hazards from pesticides depend not only on the toxicity of these chemicals, but also on other factors such as environmental conditions (eg, hot weather, dampness,
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wind), modalities of application, incorrect use of formulations, failure to use adequate skin protection when pesticides are employed, and lack of personal and environmental hygiene. In this context, educational efforts to promote awareness of potential cutaneous and systemic damage among factory workers involved in the production of pesticides, farmers, and nonagricultural consumers should be intensified.
References 1. Savage EP, Keefe TJ, Wheeler HW, et al. Household pesticide usage in the United States. Arch Environ Health 1981;36:304-9. chemicals. In: 2. Hogan DJ. Pesticides and other agricultural Adams RM, editor. Occupational skin disease. 2nd ed. Philadelphia: WB Saunders, 1990:546-77. 3. Wolfe HR. Protection of workers from exposure to pesticides. In: WHO information circular on the toxicity of pesticides to man. VBC/Tox/73.11. Pest control, pp 17-42. 4. Lisi P. La dermatite da contatto per uso di pesticidi. Ann Ital Dermatol Clin Sper 1986;40:67-81. 5. Lisi I’. Patologia cutanea da pesticidi. Giorn Ital Dermatol Venereol 1987;122:175-82. 6. Fregert S, Hjorth N. The principal irritants and sensitizers. In: Rook A, Wilkinson DS, Ebling FG, editors. Textbook of dermatology. Oxford: Blackwell Scientific, 1968:18881904. 7. Kleinman GD, West I, Augustine MS. Occupational disease in California attributed to pesticides and agricultural chemicals. Arch Environ Health 1960;1:118-24. 8. Matsushita T, Nomura S, Wakatsuki T. Epidemiology of contact dermatitis from pesticides in Japan. Contact Dermatitis 1980;6:255-9. 9. Crippa M, Misquith L, Lonati A, et al. Dyshidrotic eczema and sensitization to dithiocarbamates in a florist. Contact Dermatitis 1990;23:203-4. dermatitis. Contact Dermatitis 10. Camarasa G. Difolatan 1975;1:127. 11 Svindland HB. Subacute parathion poisoning with erysipeloid-like lesion. Contact Dermatitis 1981;7:177-9. 12. Bhargaya RK, Singh V, Soni V. Erythema multiforme resulting from insecticide spray. Arch Dermatol 1977; 113:686-7. 13. Lisi P, Caraffini S. Pellagroid dermatitis from mancozeb with vitiligo. Contact Dermatitis 1985;13:124-5. 14. Brancaccio RR, Chamales MH. Contact dermatitis and depigmentation produced by the herbicide Carbyne@. Contact Dermatitis 1977;3:108-9. 15. Ducombs G, Felix B, Duboscq MF, et al. Allergic contact dermatitis and depigmentation due to a herbicide (Lasso@ : alachlore). Contact Dermatitis 1990;23:271. 16. George AO. Contact leucoderma from paraquat dichloride? Contact Dermatitis 1990;20:225.
Clinics in Dermatology 1992;10:175-184 17. Joost Th, De Jong G. Sensitization to DD soil fumigant during manufacture. Contact Dermatitis 1988;18:307-8. 18. Samman PO, Johnston ENM. Nail damage associated with handling of paraquat and diquat. Br Med J 1969;1:818-9. 19. Hearn CED, Keir W. Nail damage in spray operators exposed to paraquat. Br J Ind Med 1971;28:399-403. 20. Baran RL. Nail damage caused by weed killers and insecticides. Arch Dermatol 1974;110:467. 21. Botella R, Sastre A, Castells A. Contact dermatitis to paraquat. Contact Dermatitis 1985;13:123-4. 22. Wahlberg JE. Yellow staining of hair and nails and contact sensitivity to dinobuton. Contact Dermatitis Newslett 1974;16:481. pesticide incidents in 23. Heam CED. A review of agricultural man in England and Wales 1952-71. Br J Ind Med 1973;30:253-8. 24. Hayes WJ. Pesticides studied in man. Baltimore: Williams & Wilkins, 1982. 25. Flannigan SA, Tucker SB, Calderon V. Irritant dermatitis from tetrachloroisophthalonitrile. Contact Dermatitis 1986; 14:258-9. 26. Takamatsu M, Futatsuka M, Arimatsu Y, et al. Epidemiologic survey on dermatitis from a new fungicide used in tangerine orchids in Kumamoto prefecture. J Kumamoto Med Sot 1968;42:854-9. Contact Dermatitis Newslett 1972; 27. Cottel WI. Difolatan. 11:252. dermatitis. Contact Dermatitis 28. Camarasa G. Difolatan 1975; 1:127. 29. Stoke JCJ. Captafol dermatitis in the timber industry. Contact Dermatitis 1979;5:284-92. 30. Horiuchi Y, Ando K. Contact dermatitis due to pesticides for agricultural use. Jpn J Dermatol 1980;90:289-93. 31. Bruynzeel DP, Ketel WC. Contact dermatitis due to chlorothalonil in floriculture. Contact Dermatitis 1986;14: 67-8. 32. Rycroft JG. Contact dermatitis from organophosphorus pesticides. Br J Dermatol 1977;97:693-5. dermatitis. JAMA 33. Cronce PC, Alden HS. Flea-collar 1968;206:1563-4. 34. Farber GA, Burks JW. Flea-collar dermatitis. Cutis 1972; 9:809-12. 35. Fregert S. Allergic contact dermatitis from two pesticides. Contact Dermatitis Newslett 1973;3:367. 36. Mathias CGT. Persistent contact dermatitis from the insecticide dichlorvos. Contact Dermatitis 1983;9:217-8. durch das 37. Stoermer D. Beruflich bedingtes Kontakekzem Pestizid Dichlorvos. Dermatol Monatsschr 1985;171: 245-9. WF, Davies JE. Occupational dermatitis from 38. Edmundson naled. A clinical report. Arch Environ Health 1967;15:8991. 39. Jung H-D, Ramsauer E. Akute Pestizid-Intoxication kombiniert mit epikutaner Sensibilisierung durch den organis-
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40.
41. 42. 43.
44. 45. 46.
47. 48. 49. 50. 51.
52. 53. 54.
PESTICIDES
then Phosphorsaureester Mevinphos (I’D 5@). Akt Dermato1 1987;13:82-3. Jung H-D. Berufsdermatosen in der Landwirtschaft des Agrar-Industriebezirkes Neubrandenburg. Dtsch Gesundh-Wesen 1975;30:1540-4. Pevny I. Pestizid-Allergie. Allergisches Kontaktekzem bei einer Winzerin. Dermatosen 1980;28:186-9. Ketel WG. Allergic dermatitis from a new pesticide. Contact Dermatitis 1975;1:297-300. Joost Th, Wiemer GR. Contact dermatitis from tetrachloroacetophenone (TCAP) in an insecticide plant. Contact Dermatitis 1991;25:66-7. Peachey RDG. Skin hazards in farming. Br J Dermatol 1981;105(suppl 21):45-50. Howard JK. A clinical survey of paraquat formulation workers. Br J Ind Med 1979;36:220-3. Edmiston S, Maddy KT. Summary of illnesses and injuries reported in California by physicians in 1986 as potentially related to pesticides. Vet Hum Toxic01 1987;29:3917. Spencer MC. Herbicide dermatitis. JAMA 1966;198:13078. Nishioka K, Kozuka T, Tashiro M. Agricultural miticide (BPPS) dermatitis. Skin Res 1970;12:15-9. Yang RS. 1,3-Dichloropropene. Residue Rev 1986;47:1935. Nater JP, Gooskens VHJ. Occupational dermatosis due to a soil fumigant. Contact Dermatitis 1976;2:227-9. Nater JP, Terpstra H, Bleumink E. Allergic contact sensitization to the fungicide maneb. Contact Dermatitis 1979;5:24-6. Cronin E. Contact dermatitis. Edinburgh: Churchill Livingstone, 1980:391-413. Adams RM, Manchester RD. Allergic contact dermatitis to maneb in a housewife. Contact Dermatitis 1982;8:271. Manuzzi P, Borrello P, Misciali C, et al. Contact dermatitis due to ziram and maneb. Contact Dermatitis 1988;19:1489.
55. Piraccini BM, Cameli N, Peluso AM, et al. A case of allergic contact dermatitis due to the pesticide maneb. Contact Dermatitis 1991;24:381-2. F. La dermatite da ditiocarbammati, 56. Scarpa C, Ippolito nuova entita clinica. Dermatologia 1959;10:257-64. 57. Laborie F, Laborie R, Dedieu EH. Allergie aux fongicides de la gamme du manebe et zinebe. Arch Ma1 Prof Med Travail Securite Sot (Paris) 1964;25:419-24. 58. Burry JN. Contact dermatitis from agricultural fungicide South Australia. Contact Dermatitis 1976;2:289. 59. Kleibl K, Rhilkova M. Cutaneous carbamates. Contact Dermatitis
in
allergic reactions to dithio1980;6:348-9.
60. Perez-Chacbn Espino V, Valerbn Martel P, Hemlndez HemPndez B. Dermatitis de contact0 por vondozeb (pesticida de1 grupo de 10s carbamatos). Actas Dermo-Sif 1985;76(suppl 1):53-4.
AND CONTACT
LISI DERMATITIS
183
61. Savitt LE. Contact dermatitis due to benomyl insecticide. Arch Dermatol 1972;105:926-7. 62. Ketel WG. Sensitivity to the pesticide benomyl. Contact Dermatitis 1976;2:290-1. 63. Joost TH, Naafs B, Ketel WG. Sensitization to benomyl and related pesticides. Contact Dermatitis 1983;9:153-4. 64. Larsen AI, Larsen A, Jepsen JR, et al. Contact allergy to the fungicide benomyl? Contact Dermatitis 1990;22:27881. 65. Fregert S. Allergic contact dermatitis from the pesticides captan and phaltan. Contact Dermatitis Newslett 1967; 2:28. sensitivity. Contact Dermatitis 66. Calnan CD. Dithianone Newslett 1969;6:119. 67. Schulz KH, Hermann WP. Tetramethylthiuramdisulphide, ein Thiohamstoffderivat als Ekzemnoxe bei Hafenarbeitern. Berufsdermatosen 1958;6:130-5. 68. Shelley WB. Golf-course dermatitis due to thiram fungicide. Cross-hazards of alcohol, disulhram, and rubber. JAMA 1964;188:415-7. 69. Iden DL, Schroeter AL. Allergic contact dermatitis to herbicides. Arch Dermatol 1977;113:983. 70. English JSC, Rycroft RJG, Calnan CD. Allergic contact dermatitis from aminotriazole. Contact Dermatitis 1986; 14:255-6. 71. Hogan DJ, Lane PR. Allergic contact dermatitis due to a herbicide (barban). Can Med Assoc J 1985;132:387-9. 72. Bruze M, Fregert S. Allergic contact dermatitis to chloridazon. Contact Dermatitis 1982;8:427. 73. Nishioka K, Asagami C, Kurata M, et al. Sensitivity to the weed killer DNA-nitralin and cross-sensitivity to dinitrochlorobenzene. Arch Dermatol 1983;119:304-6. 74. Solomons B. Sensitization to nitrofen. Contact Dermatitis Newslett 1972;12:336. 75. Nater JP, Grosfeld JCM. Allergic contact dermatitis from Betanal (phenmedipham). Contact Dermatitis 1979;5:5960. 76. Mitchell JC, Dupuis G, Towers GHN. Allergic contact dermatitis from pyrethrum ~Chysanthemum spp). The roles of pyrethrosin, a sesquiterpene lactone, and of pyrethrin II. Br J Dermatol 1972;86:568-73. 77. Jung H-D, Wolff F. Berufliche Kontakdermatiden durch Nematin (Vapam) in der Landwirtschaft. Dtsch GesundhWesen 1970;25:495 -8. 78. Richter G. Allergic contact dermatitis from methylisothiocyanate in soil disinfectants. Contact Dermatitis 1980; 6:183-6. 79. Milby TH, Epstein WL. Allergic contact sensitivity to malathion. Arch Environ Health 1964;9:4347. 80. Kligman AM. The identification of contact allergens by human assay. III. The maximization test: A procedure for screening and rating contact sensitizers. J Invest Dermatol 1966;47:393-409. 81. Behrbohm P, Brandt B. Allergisches Kontaktekzem durch technische und gereinigte Hexachlorcyclohexanpraparate
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82.
83.
84.
85.
86. 87.
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bei der Anwendung im Pflanzenschutz und in der Schldlingsbekampfung. Berufsdermatosen 1960;8:95 - 101. Hegyi E, St’ota Z. Zur Frage der Allergen-spezifitat der Komponenten des technischen Hexachlorzyklohexans. Berufsdermatosen 1965;13:193-207. Palminteri G. Sulla sensibilizzazione eczematosa spenmentale da dietilparanitrofeniltiofosfato (Parathion). Ann Ital Dermatol Clin Sper 1964;18:123-5. Matsushita T, Arimatsu Y, Nomura S. Experimental study on contact dermatitis caused by dithiocarbamates maneb, mancozeb, zineb, and their related compounds. Int Arch Occup Environ Health 1976;37:169-78. Maibach HI. Irritation, sensitization, photoirritation and photosensitization assays with a glyphosate herbicide. Contact Dermatitis 1986;15:152-6. Lisi I’, Caraffini S, Assalve D. A test series for pesticide dermatitis. Contact Dermatitis 1986;15:266-9. Lisi I’, Caraffini S, Assalve D. Irritation and sensitization potential of pesticides. Contact Dermatitis 1987;17:212-8.
Clinics in Dermatology 1992;10:275-184 88. Ketel WG, Berg WHHW. The problem of the sensitization to dithiocarbamates in thiuram-allergic patients. Dermatologica 1984;169:70-5. 89. Fisher AA. Occupational dermatitis from pesticides: Patch testing procedures. Cutis 1983;31:483-508. 90. Fisher AA, Adams RM. Occupational dermatitis. In: Fisher AA, editor. Contact dermatitis. 3rd ed. Philadelphia: Lea & Febiger, 1986:486-514. 91. Jung H-D, Rothe A, Heise H. Zur Epikutantestung mit Pflanzenschutzund Schadlingsbeklmpfungsmitteln (Pestiziden). Dermatosen 1987;35:43 -51. 92. Ehntholt DJ, Cerundolo DL, Bodek I, et al. A test method for the evaluation of protective glove materials used in agricultural pesticide operations. Am Ind Hyg Assoc J 1990; 51:462-8. 93. Lisi I’. L’ambiente di lavoro e le dermopatie non professionali. Ann Ital Dermatol Clin Sper 1991;45:9 - 14.
LISI, MD
P
esticides are a heterogenous group of toxic chemicals used to destroy or to prevent growth of living organisms and weeds that damage agriculture. Among the cutaneous disorders caused by chronic exposure to these chemicals, contact dermatitis and mainly irritant contact dermatitis are the most frequent. The lesions seem slightly more common in men in the fourth decade of life, and during spring and summer. Pesticide contact dermatitis can be caused by many active ingredients, but positive patch test reactions are almost always attributable to thiophthalimides (captan, difolatan, and folpet) and, perhaps, bisdithiocarbamates and benomyl, used as fungicides. Multiple sensitivity to these compounds is possible, whereas contact dermatitis to other pesticides (insecticides, herbicides, fumigants, etc) is not significant. Health hazards from pesticides depend not only on the greater or lesser toxicity of these chemicals, but also on environmental conditions, modalities of application, incorrect use of formulations, lack of use of adequate skin protection, and lack of personal and environmental hygiene. In this context, educational efforts to promote knowledge on potential damage should be intensified. Agricultural workers as well as horticulturists, floriculturists, foresters, and cattle breeders are exposed daily to a wide variety of chemical, biologic, and physical hazards during their different working activities. Because of this, the use of chemicals and especially of pesticides and fertilizers has greatly increased over the past 40 years, and they are now an accepted part of our environment. The increasingly wide utilization of pesticides in all countries of the world has undoubtedly helped to reduce losses in production but, at the same time, has induced a From the Department of Dermatology, University of Perugia, Perugia, Italy. Address correspondence to Paolo Lisi, Via XIV Settembre, 69, I 06122 Perugia, Italy.
0 1992 by Elsevier Science Publishing
Co., Inc.
l
0738-081x/92/$5.00
progressive increase in incidence of illnesses and injuries caused by these compounds among factory workers involved in producing them, farmers, nonagricultural consumers, and the general population. In a study of 10,000 U.S. households, Savage et al’ found that 9 of 10 subjects used some type of pesticides; more recently, Hogan2 reported that 15% of pesticides sold were used in homes and gardens.
Definition and Classification of Pesticides Pesticides are a heterogenous group of toxic chemicals used to destroy or to prevent growth of living organisms and weeds that damage agriculture. According to their prevalent action, they may be classified as fungicides, insecticides and insect repellents, rodenticides and animal repellents, acaricides, nematicides, mulluscides, and herbicides. There are different formulations of these compounds, such as liquids, wettable powders, and dusts. Fumigants are volatile substances that are dispersed in the air to kill insects, fungi, bacteria, and rodents present in soil and on trees and stored grain. More than 5000 pesticide products, which contain one or more of the approximately 300 active registered ingredients, are on the market in Italy today. Their complete chemical classification is not easy; on the other hand, we believe that it is more useful to list only the substances more commonly sold in our country (Table 1). Among the fungicides, inorganic compounds (sulfur, copper sulfate) and bisdithiocarbamates (zineb, mancozeb) are the most frequently sold, whereas among the insecticides and acaricides, organophosphate compounds and white liquid petrolatum are still widely employed. Also in Italy, the use of herbicides and, above all, thiocarbamates, atrazine, and dipyridinium compounds has increased in recent years, whereas the sale of fumigants is not remarkable. Organic mercurials (phenylmercuric acetate, phenylmercuric chloride, etc), chlorobenzols (pentachloronitrobenzene), and dichlorodiphenyl-trichloroeth-
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Clinics in Dermatology 1992;10:175-184
Table 1. Chemical Classification Pesticide
of
Pesticides and Repellents More Commonly Sold in Italy
Chemical Group
Fungicides
Inorganic
compounds*
Dithiocarbamates (DTCs)
Organostannics Thiophthalimides
Organonitrogens
Insecticides acaricides
and
Dinitrophenols Organophosphate compounds*
Chemical Name Sulfur Copper (sulfate, oxychloride, etc) Iron sulfate Barium polysultide Zinc ethylene-bis-DTC Zinc and manganese ethylene-bis-DTC Zinc dimethyl-DTC Bis(dimethylthiocarbamoy1) disulfite Manganese ethylene-bis-DCT Triphenyl-tin(l+) hydroxide Triphenyl-tin(l+) acetate N-[(Trichloromethyl)thio]-4-cyclohexene-2-~carbo~mide N-(Trichloromethylthio)phthaliide N-(1,1,2,2-Tetrachloroethylthio)-3a,4,7,7otetrahydrophthalimide Methyl-1-(butylcarbamoyl)-2-benzimidazole Monoacetate dodecylguanidine 2-(1-Methylheptyl)-4,6dinitrophenyl ester O,O-Diethyl-S-(ethylthio)methylphosphorodithioate O,O-Diethyl-0-p-nitrophenyl
Common Name
Zineb Mancozeb Ziram Thiram Maneb Fentin hydroxide Fentin acetate Captan Folpet or phaltan Captafol or difolatan carbamate
thiophosphate
0,0-Diethyl-0-(2-isopropyl-6-methyl-4pyrimidinyl)phosphorothioate O,O-Dimethyl-S-[4-oxo-1,2,3-benzotriazin-3(4H)-ylmethyl]phosphorodithioate 0,0-Dimethyl-0-4nitrophenylphosphorothioate 0,0-Dimethyl-S-(N-methyl carbamoylmethyl)phosphorodithioate O,O-Dimethyl-S-(l,2-dicarbethoxyethyl)phosphorodithioate 2-Carbomethoxy-1-methylvinyldimethyl phosphate 0,0-Dimethyl-2,2dichlorovinyl phosphate O,O-Dimethyl-0-1,2-dibromo-2,2dichloroethyl phosphate Mineral oils* MethylcarbamateP Organochlorates
Natural
compounds
Pyrethroids Herbicides
Thiocarbamates* Organonitrogens Triazines Anilides Phenylureas
Nitroanilines Others
1-Naphthyl-N-methylcarbamate 1,2,3,4,5,6-Hexachlorocyclohexane 6,7,8,9,10,10-Hexachloro-1,5,5a,6,9,9~-hexahy~o-6,9methano-2,4,3-benzodiaxathiepin-3-oxide Pyretrins cu-Cyano-3-phenoxybenzyl-2-(4chlorophenyl)3methylbutyrate S-Ethyl-hexahydro-lH-azepine-1-carbothioate 2-Chloro-4-ethylamino-6-isopropylamino-s-triazine 2-Chloro-4,6-bis(ethylamino)-s-triazine N-(3,4-Dichlorophenyl) propionamide 2-Chloro-2’,6-diethyl-N-(methoxymethyl)acetanilide 3-(3,4-Dichlorophenyl)-1-methoxy-l-methylurea 3-(3-Chloro-4-methoxyphenyl)-l,l-dimethylurea 3-(3,4-Dichlorophenyl)-1,1-dimethylurea N,N-Di-n-propyl-2,6-dinitro-4-(trifluoromethyl)aniline 5-Amino-4-chloro-2-phenylpyridazin-3-one 2,6-Dichlorobenzonitrile 2,4-Dichlorophenyl-p-nitrophenyl ether
Benomyl Dodine Dinocap Phorate Parathion-ethyl diazinon Diazinon Azinphos-methyl Parathion-methyl dimethoate Dimethoate Malathion Mevinphos Dichlorvos or DDVP Naled or dibrom White liquid petrolatum Carbaryl Lindane or HCH Endosulfan Pyretrins Nicotine Fenvalerate Molinate Atrazine* Simazine Propanil Alachlor Linuron Metoxuron Diuron Trifluralin Chloridazon Dichlobenil Nitrofen Continued
or pyrazon
on next page
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1992;10:175-184
PESTICIDES
AND
CONTACT
177
DERMATITIS
Table 2. Chemical Classification of Pesticidesand Repellents More Commonly Sold in Italy (continued) Pesticide
Chemical Group Dipyridinium compounds*
l,l’-Dimethyl-4,4’-dipyridinium
Aliphatic chloroacids Phenoxycarboxylic
Fumigants
Molluscides Rodenticides l
Chemical Name
Dinitrophenols Halogenated hydrocarbons
acids
dichloride
l,l’-Ethylene-2,2’-dipyridinium dibromide Natrium trichloroacetate 2,4-Dichlorophenoxyacetic acid 2(2,4-Dichlorophenoxyl)propionic acid 4-chloro-2-methylphenoxyacetic acid 4,6-Dinitro-o-cresol 1,3-Dichloropropene + 1,2dichloropropane
Dithiocarbamates Thioazo compounds
Methyl bromide Carbon tetrachloride Dichloroethane Sodium N-methyldithiocarbamate Tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione
Coumarin
3-(a-Acetonylbenzyl)-4-hydroxycoumarin
compounds
Common Name Paraquat Diquat TCA sodium 2,4-D 2,4-DP MCPA DNOC DD
Metham sodium Dazomet Metaldehyde Warfarin’
The most widely used compounds
ane (DDT) have been banned, as have several chlorocyclodienes (aldrin, dieldrin), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), and 2-(2,4,5+ichlorophenoxy)propionic acid (2,4,5-TP).
Incidence of Skin Diseases Caused by Pesticides The skin, with its extensive surface directly exposed to the environment, is particularly susceptible to damage induced by pesticides, which may be introduced into the body by ingestion, inhalation, and skin contact. Among these ways of penetration, skin contact is by far the most important and, according to Wolfe,3 over 97% of pesticides is deposited on the cutaneous surface, especially when liquid formulations are used. Present laws that fix the highest limits of exposure to agricultural chemicals have significantly helped to reduce the incidence of acute intoxication among manufacturers, formulators, and farmers; however, the widespread use of these compounds has caused a progressive increase in chronic systemic effects and cutaneous disorders, but the real incidence of the latter (eg, contact dermatitis, chloracne, porphyria cutanea tarda, dyschromia, keratosis, non-Hodgkin’s lymphoma) still remains unknown.4*5 Until more than two decades ago, contact dermatitis has been regarded as rare, 6 but several large studies on patients who were diagnosed and treated as having pesticide poisoning by physicians in California (749 cases)’ and Japan (815 cases)a show a high incidence of contact dermatitis (55 and 26.5%, respectively).
Clinical Features of Contact Dermatitis Irritant contact dermatitis is more frequent than allergic contact dermatitis. The clinical spectrum may range from a mild reaction with erythema, scales, or chapping to a more florid dermatitis with edema, papules, vesicles, bullae, and, sometimes, eschars. Lichenification and fissures are very frequent in the chronic phase. The circumscribed or diffuse but mostly ill-defined patches develop on the skin areas more commonly subjected to occupational exposure, usually on the hands, forearms, face, and neck. Also, allergic contact dermatitis is generally located on these sites, but its clinical features are more often characterized by papulovesicles, exudation, and intense itching. Allergic dyshidrosiform contact dermatitis,9 morbilliform or urticarial eruptions,‘O erysipeloid-like lesions,” erythema multiforme,12 pellagroid dermatitis,13 as well as depigmentation following the resolution of dermatitis and/or on patch-tested areas, have been reported.“-l6 The very rare cases of contact leukoderma are produced by some herbicides, such as barban,14 alachlor,15 and, probably, paraquat dichloride,16 and by DD, which is a soil fumigant.” Nail damage associated or not with periungual irritant contact dermatitis is possible in workers whose fingernails are exposed to the weed killer paraquat,18-21 but it has been observed also in some subjects following contact with the acaricide dinobuton (2-(l-methyl-2-propyl)4,6dinitrophenyl isopropylcarbonate) and the insecticide 4,6-dinitro-o-cresol (DNOC).20 The most common lesions are softening and/or gross deformity of the nail
178
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plate, yellow or whitish and loss of the nails.
Clinics in Dermatology 1992;10:175-184
nail discoloration,
onycholysis,
Epidemiologic Features of Contact Dermatitis There are a reasonable number of case reports on contact dermatitis from pesticides, but little is known about the epidemiology of this disorder. Contact dermatitis seems slightly more common in men than in women, in the fourth decade of life, and during spring and summer.s The lesion onset is closely related to the percutaneous absorption of pesticides which is influenced by some characteristics of formulation active ingredients, such as chemical structure, lipid solubility, dispersion in organic solvents (eg, xylene, alcohols, and ketones), concentration, and adhesive properties; however, other environmental and occupational factors are important. The relapses of clinical manifestations in farmers and agricultural workers, in fact, are more frequent after the application of pesticides, primarily when these are sprayed in the air or scattered in the atmosphere in the form of gas by helicopters and airplanes. The other possible sources of contact, such as the transport of products, their preparation and transfer into spray equipment, cleaning and repair of this equipment, should not be underevaluated. On the contrary, crushing, pulverizing, and mixing of pesticides are especially dangerous for workers employed in the manufacture of these products.
Etiology of Contact Dermatitis Pesticide contact dermatitis can be caused by many active ingredients present in commercial products, but also by carrier liquids and dusts, emulsifiers, adjuvants, surfactants, propellents, and, sometimes, contaminants. Nevertheless, the real etiologic relevance of these substances is not easy to determine because epidemiologic studies on this subject are not large and often poorly documented. On the other hand, data collection is impeded by territorial dispersion of agricultural workers, by the difficulty in organizing collective preventive medicine programs, and by the fact that clinical manifestations are often mild, localized, and of short duration and seasonal course. Despite these difficulties in assessing the incidence of etiologic agents of occupational contact dermatitis in the agricultural sector, in 1960 Kleinman and co-workers’ reported that the most common causes of skin lesions attributed to pesticides in California were herbicides and defoliants (15%), halogenated hydrocarbons (lo%), and organophosphate compounds (8%). Hearnz3 analyzed 250 cases of poisoning from pesticides occurring between
1952 and 1971 in England and Wales and found that the dermatitis was ascribed to organomercurial compounds, paraquat, and thiram. More recently, Matsushita et al* pointed out that the principal chemicals responsible for the outbreak of contact dermatitis in the rural regions of Japan were captafol(28.7%), sulfurs (18.5%), highly and moderately toxic organic phosphates (18.1%), and chlorinated hydrocarbons (9.7%). In conclusion, these data show that health hazards from pesticides depend not only on the toxicity of these substances, but also on the extent of their sales.
Irritant
Contact Dermatitis
A large number of pesticides are known to cause irritant contact dermatitis, especially when the products are used too concentrated and/or without suitable protective precautions. Among fungicides, copper sulfate, barium polysulfide, thiophanat-methyl,24 chlorothalonil,25 and captafol (difolatan)24~26-2* are regarded as irritant compounds. In particular, it has been reported that at least one third of exposed subjects in the timber industry develop captafol dermatitis, 29but this risk can be minimized by appropriate worker training and industrial hygiene. Also, chlorothalonil is a potent skin irritant and, sometimes, a contact allergen in vegetable growers30 and floriculturists.3~ Irritant contact dermatitis from organophosphate insecticides, when adequate precautions are taken, is not common32 despite their massive sales throughout the world following the banning of DDT. It is quite probable that the usage concentration of these compounds and their persistence in the environment are too low to provoke skin lesions and sensitization; however, some cases of both irritant and allergic contact dermatitis caused by dichlorvos,33-37 naled,38 mevinphos,39 parathion,40,41 plondrel (ditalimfos),42 promecarb,24 tetrachloroacetophenone (TCAP),43 and thiometon24 have been published. The scanty data in the literature on irritant properties of herbicides and fumigants do not allow conclusions to be drawn. In 1981, Peachp4 stated that no cases of contact dermatitis from the herbicides paraquat or diquat have so far been reported, but a study by Howard45 revealed an acute irritant bullous dermatitis in several of the 36 workers employed in a paraquat factory. Also, glyphosate,46 propachlor,47 acaricides omite,48 dinobuton,** and fumigant DD49 may be irritating to the skin. The last is a highly toxic mixture of chlorinated hydrocarbons (1,3-dichloropropene and 1,2-dichloropropane) that causes an irritant dermatitis, but also can occasionally sensitize.*7,50
Clinics in Dermatology 1992;10:175-184
LISI PESTICIDES
Allergic Contact Dermatitis Occupational allergic contact dermatitis does not seem to have a high incidence despite the massive sales of pesticides and the strong potential of some of these for allergic sensitization (see later). The most common causes of lesions are fungicides and, above all, bisdithiocarbamates (eg, maneb51-55 and/or zineb,9*56,57mancozeb,13,5*-60 and benomy135*6*-63). Recently, Larsen and colleague@’ suggested that the earlier reported allergy to benomyl may represent cross-reactions and/or that the development of contact allergy to this compound requires previous exposure to other chemically related pesticides. In fact, the authors did not observe contact dermatitis in a group of 62 present and former pickers in a large mushroom company, where benomyl has been used regularly for more than 10 years. Sensitivity to other less widely used fungicides such as captan, 65 dithianon 66 and thiram52*67,68 and to herbicides (eg, alachlor,69 ami;role,70 barban,14*7* chloridazon,” nitralin I 73nitrofen,74 phenmedipham” has been noted, but it appears to be uncommon. Sensitization to insecticides derived from plants (pyrethrum, nicotine, rotenone) and to lindane5* is rare and that to DDT has never been convincingly proved.* On the contrary, metham sodium, a broad-spectrum soil fumigant, may cause contact dermatitis in humans.77,78 Finally, it is worth emphasizing that several cases of dermatitis can be induced by pesticide contaminants such as diethyl fumarate79*80 and &heptachlorocyclohex-
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ane *i,s* present in technical-grade da& respectively.
malathion
Opinions on irritant and/or sensitization contact potential of pesticides are varied, mainly because some experimental results often are in contrast with clinical relevance. Experimentally, the organophosphorus compounds malathion79*80 and parathions3 have been shown to be strong sensitizers in humans, but Milby and Epsteinm found that only about 3% of individuals with occupational exposure to malathion had a positive patch test reaction to this chemical (1% in petrolatum) and no worker had to change jobs because of malathion allergy. Successively, Matsushita and colleagues,84 using the guinea pig maximization test, demonstrated the strong potential of maneb, mancozeb, and zineb for allergic sensitization, whereas they did not observe allergenicity of ethylene thiourea and dimethylditiocarbamic acid sodium salt. Also, the herbicide glyphosate, extensively investigated by Maibach, 85 has been found to be a nonsensitizer. These data were not confirmed by predictive testing in subjects with or without contact dermatitis by the members of the International Contact Dermatitis Research Group (ICDRG)52 and, more recently, by us and some other members of the Italian Group for the Study of Contact and Environmental Dermatitis (GIRDCA)*6JJ7 (Table 2). Italian results,86,87 moreover, demonstrate that
Concentration (%)
Zineb Mancozeb Ziram Thiram Maneb
ICDRG 1
1
Captan
Folpet
1 0.1
Difolatan
Parathion-ethyl Parathion-methyl Malathion
0.5
and lin-
Sensitizing Potential of Pesticides
Table 2. Positive Reactionsto PesticidePredictive TestsObservedby ICDRG and GIRDCA Members
Allergen
179
DERMATITIS
GIRDCA 1 1 0.5 1 1 1 0.5 1 0.5 0.25 0.1 0.1 0.1 0.05 0.025 1 1 0.5
Positive reactions ICDRG 3/655
35/655 16/509
50/509 3/107
l/455
GIRDCA 2/389 o/149 o/149 l/348 7/442 3/389 3/386 17/442 17/389 6/279 2/279 6/442 5/389 3/279 O/282 O/280 l/294 o/351
180
Clinics in Dermatology 1992;20:175- 284
LISI
positive reactions to pesticides are not common and almost always attributable to fungicides, in particular, thiophthalimides (captan, difolatan, and folpet) which may also be irritant, as mentioned earlier.
Multiple Sensitivity Simultaneous sensitivity to pesticides has never been examined extensively but our data on irritation and sensitization potential of pesticides*’ showed multiple positive reactions to bisdithiocarbamates and/or thiophthalimides in 10 of 652 subjects patch tested with a standard series of 36 pesticides. Six of these were sensitized to two fungicides (zineb and folpet in one, captan and difolatan in three, captan and folpet in two) and four subjects were sensitized to three fungicides (zineb, maneb, and difolatan in one; maneb, thiram, and captan in one; captan, folpet, and difolatan in one; captan, folpet, and phorate in one). Nevertheless, multiple sensitivity to bisdithiocarbamate and thiuram compounds has already been described in some case reports 13,52,53,57,60,88 and considered as cross-sensitivity. Positive reactions to several thiophthalimides have not been documented, but could be the result of impurities or small amounts of cross-sensitizing materials.
Diagnosis The diagnosis of occupational contact dermatitis from pesticides is not always easy because its clinical picture is mostly of short duration and therefore not present at the
moment of physical examination, as many agricultural workers are transient and almost all centers for occupational skin diseases are located only in regional hospitals. Despite these difficulties, a careful detailed history, the observation of the dermatitis course before and after 2 weeks off work, and patch testing usually make it possible to decide whether or not a case is pesticide related. The results of patch tests must, however, be interpreted in the light of the history, and the relevance of a positive reaction must be accurately determined, especially when patch testing has not been carried out with pure active ingredients. Many pesticide formulations on the market, in fact, are dissolved in solvents that are irritating to the skin or may contain impurities that cause more problems than the active chemical. The nonirritating concentrations of analytic-grade pesticides in appropriate vehicles have been investigated by a number of authors2,52,86*87,89-91who suggested different standard test series. Tables 3 and 4 show our updated series.
Prevention and Rehabilitation As happens in other productive sectors, the incidence of pesticide contact dermatitis might at least be partly reduced by programming suitable interventions of primary and secondary prevention. Their development encounters a great amount of difficulty of different nature, which is more prevalent in agricultural workers than in pesticide factory workers. The territorial distribution of the farmers and their often seasonal exposure to different
Table 3. Patch Testing for Fungicides and Insectides* Fungicides Benomyl Captafol (difolatan) Captan Chlorothalonil Copper Sulfate Dinocap Dithianon
0.1 0.1 0.5 0.01 1 1 1
Azynphos-methyl Carbaryl Diazinon Dichlorvos (DDVP) Dimethoate Endosulfan Lindane (HCH) Malathion Mevinphos Naled (dibrom)
1 1 1 0.05 1 1 1 0.5 0.25 .I
Fentin hydroxide Folpet (phaltan) Mancozeb Maneb Thiram Zineb Ziram
0.5 0.1 1 1 1 1 1
Nicotine sulfate Parathion-ethyl Parathion-methyl Phorate Pyrethrum Rotenone Tetrachloroacetophenone White liquid petrolatum
5 1 1 1 2 5 0.01 1
Insecticides
*All in talc.
in petrolatum,
except dichlorvos,
mevinphos,
and nicotine
sulfate in water, parathion-ethyl
in alcohol, and rotenone
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1992;10:175-184
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LISI DERMATITIS
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181
Table 4. Patch Testing for Herbicides, Fumigants, Acaricides, Molluscides, and Rodenticides Herbicides Alachlor Amitrole Atrazine Barban Chloridazon Diquat DNOC
Glyphosate Molinate Nitrofen Paraquat Phenmedipham Propanil
1
(pyrazon)
1 0.1 0.1 0.1 0.5
10 1 0.5 0.1 2 1
Fumigants Dazomet
0.25
Metham
sodium
0.03
Acaricides Dinobuton
10
Omite
0.05
Warfarin
0.05
Molluscides Metaldehyde Rodenticides Antu All in petdatum, in oil.
except barban in acetone; DNOC, ghyphosnte,
chemicals, for example, strongly impede the activation of models and methodologies of intervention used in other working activities. For this reason, more thorough health education of all those who handle pesticides, informing them about possible cutaneous and systemic damage, is necessary. The illnesses and injuries are related mainly to incorrect use of hazardous chemicals; lack of use of adequate protective clothing (eg, hoods, glasses, face shields, sleeves, gloves, aprons, chemical-resistant shoes or boots) and barrier creams when mixing, loading, and spraying pesticide formulations; and unsuitable skin cleansing, to be carried out immediately after work with water and soap but not with solvents and diluents. Gloves should be made of nitrile rubber and butyl rubber, because these are more resistant to pesticide permeation than those of natural rubber, polyvinyl chloride, and polyethylene.92 In addition, other protective measures such as automatic equipment, closed processes, an efficient ventilation system, and environmental hygiene should be taken in pesticide plants. Primary prevention should also be aimed at identifying potential irritants and allergens through predictive tests in experimental animals prior to registration of a pesticide for sale and through multicenter epidemiologic studies. Thus, it will be possible to remove irritants from the formulations replacing them with substances less damaging to the skin. Moreover, it would be opportune to use preplacement questionnaires and examinations to reveal past and/or present cutaneous disorders that could limit a worker’s employability and placement,93 and periodic health screenings to check early alterations caused
phenmedipham,
and metham sodium in water; and nitrofen
by pesticides. Unfortunately, inspection of the entire skin is rarely part of the physical examination! The aim of secondary prevention is to eliminate or at least reduce relapses of occupational cutaneous diseases. In cases of pesticide contact dermatitis there is an imperative need to discover the allergen responsible because its removal is almost always followed by a permanent recovery. In fact, the causative agent is generally a specific chemical that can be completely avoided in and outside the work environment. Only when the contact allergens are present as dust or vapor in a factory, they cannot be removed and occasional recurrences of lesions are possible. In any case, however, it will be enough to give the patient the common name of the incriminated pesticide with its synonyms and, if possible, a list of commercial products in which it is contained.
Conclusions In our opinion, the incidence of occupational pesticide contact dermatitis is more frequent than reports by several authorities have indicated, because its clinical manifestations, often limited for extension, transitory, and seasonal, are undervalued by farmers and therefore not reported. Pesticide contact dermatitis can be caused by many active ingredients but positive patch test reactions are almost always attributable to thiophthalimides and, perhaps, bisdithiocarbamates and benomyl, used as fungicides. Health hazards from pesticides depend not only on the toxicity of these chemicals, but also on other factors such as environmental conditions (eg, hot weather, dampness,
182
LISI
wind), modalities of application, incorrect use of formulations, failure to use adequate skin protection when pesticides are employed, and lack of personal and environmental hygiene. In this context, educational efforts to promote awareness of potential cutaneous and systemic damage among factory workers involved in the production of pesticides, farmers, and nonagricultural consumers should be intensified.
References 1. Savage EP, Keefe TJ, Wheeler HW, et al. Household pesticide usage in the United States. Arch Environ Health 1981;36:304-9. chemicals. In: 2. Hogan DJ. Pesticides and other agricultural Adams RM, editor. Occupational skin disease. 2nd ed. Philadelphia: WB Saunders, 1990:546-77. 3. Wolfe HR. Protection of workers from exposure to pesticides. In: WHO information circular on the toxicity of pesticides to man. VBC/Tox/73.11. Pest control, pp 17-42. 4. Lisi P. La dermatite da contatto per uso di pesticidi. Ann Ital Dermatol Clin Sper 1986;40:67-81. 5. Lisi I’. Patologia cutanea da pesticidi. Giorn Ital Dermatol Venereol 1987;122:175-82. 6. Fregert S, Hjorth N. The principal irritants and sensitizers. In: Rook A, Wilkinson DS, Ebling FG, editors. Textbook of dermatology. Oxford: Blackwell Scientific, 1968:18881904. 7. Kleinman GD, West I, Augustine MS. Occupational disease in California attributed to pesticides and agricultural chemicals. Arch Environ Health 1960;1:118-24. 8. Matsushita T, Nomura S, Wakatsuki T. Epidemiology of contact dermatitis from pesticides in Japan. Contact Dermatitis 1980;6:255-9. 9. Crippa M, Misquith L, Lonati A, et al. Dyshidrotic eczema and sensitization to dithiocarbamates in a florist. Contact Dermatitis 1990;23:203-4. dermatitis. Contact Dermatitis 10. Camarasa G. Difolatan 1975;1:127. 11 Svindland HB. Subacute parathion poisoning with erysipeloid-like lesion. Contact Dermatitis 1981;7:177-9. 12. Bhargaya RK, Singh V, Soni V. Erythema multiforme resulting from insecticide spray. Arch Dermatol 1977; 113:686-7. 13. Lisi P, Caraffini S. Pellagroid dermatitis from mancozeb with vitiligo. Contact Dermatitis 1985;13:124-5. 14. Brancaccio RR, Chamales MH. Contact dermatitis and depigmentation produced by the herbicide Carbyne@. Contact Dermatitis 1977;3:108-9. 15. Ducombs G, Felix B, Duboscq MF, et al. Allergic contact dermatitis and depigmentation due to a herbicide (Lasso@ : alachlore). Contact Dermatitis 1990;23:271. 16. George AO. Contact leucoderma from paraquat dichloride? Contact Dermatitis 1990;20:225.
Clinics in Dermatology 1992;10:175-184 17. Joost Th, De Jong G. Sensitization to DD soil fumigant during manufacture. Contact Dermatitis 1988;18:307-8. 18. Samman PO, Johnston ENM. Nail damage associated with handling of paraquat and diquat. Br Med J 1969;1:818-9. 19. Hearn CED, Keir W. Nail damage in spray operators exposed to paraquat. Br J Ind Med 1971;28:399-403. 20. Baran RL. Nail damage caused by weed killers and insecticides. Arch Dermatol 1974;110:467. 21. Botella R, Sastre A, Castells A. Contact dermatitis to paraquat. Contact Dermatitis 1985;13:123-4. 22. Wahlberg JE. Yellow staining of hair and nails and contact sensitivity to dinobuton. Contact Dermatitis Newslett 1974;16:481. pesticide incidents in 23. Heam CED. A review of agricultural man in England and Wales 1952-71. Br J Ind Med 1973;30:253-8. 24. Hayes WJ. Pesticides studied in man. Baltimore: Williams & Wilkins, 1982. 25. Flannigan SA, Tucker SB, Calderon V. Irritant dermatitis from tetrachloroisophthalonitrile. Contact Dermatitis 1986; 14:258-9. 26. Takamatsu M, Futatsuka M, Arimatsu Y, et al. Epidemiologic survey on dermatitis from a new fungicide used in tangerine orchids in Kumamoto prefecture. J Kumamoto Med Sot 1968;42:854-9. Contact Dermatitis Newslett 1972; 27. Cottel WI. Difolatan. 11:252. dermatitis. Contact Dermatitis 28. Camarasa G. Difolatan 1975; 1:127. 29. Stoke JCJ. Captafol dermatitis in the timber industry. Contact Dermatitis 1979;5:284-92. 30. Horiuchi Y, Ando K. Contact dermatitis due to pesticides for agricultural use. Jpn J Dermatol 1980;90:289-93. 31. Bruynzeel DP, Ketel WC. Contact dermatitis due to chlorothalonil in floriculture. Contact Dermatitis 1986;14: 67-8. 32. Rycroft JG. Contact dermatitis from organophosphorus pesticides. Br J Dermatol 1977;97:693-5. dermatitis. JAMA 33. Cronce PC, Alden HS. Flea-collar 1968;206:1563-4. 34. Farber GA, Burks JW. Flea-collar dermatitis. Cutis 1972; 9:809-12. 35. Fregert S. Allergic contact dermatitis from two pesticides. Contact Dermatitis Newslett 1973;3:367. 36. Mathias CGT. Persistent contact dermatitis from the insecticide dichlorvos. Contact Dermatitis 1983;9:217-8. durch das 37. Stoermer D. Beruflich bedingtes Kontakekzem Pestizid Dichlorvos. Dermatol Monatsschr 1985;171: 245-9. WF, Davies JE. Occupational dermatitis from 38. Edmundson naled. A clinical report. Arch Environ Health 1967;15:8991. 39. Jung H-D, Ramsauer E. Akute Pestizid-Intoxication kombiniert mit epikutaner Sensibilisierung durch den organis-
Clinics in Dermatology
1992;10:175-184
40.
41. 42. 43.
44. 45. 46.
47. 48. 49. 50. 51.
52. 53. 54.
PESTICIDES
then Phosphorsaureester Mevinphos (I’D 5@). Akt Dermato1 1987;13:82-3. Jung H-D. Berufsdermatosen in der Landwirtschaft des Agrar-Industriebezirkes Neubrandenburg. Dtsch Gesundh-Wesen 1975;30:1540-4. Pevny I. Pestizid-Allergie. Allergisches Kontaktekzem bei einer Winzerin. Dermatosen 1980;28:186-9. Ketel WG. Allergic dermatitis from a new pesticide. Contact Dermatitis 1975;1:297-300. Joost Th, Wiemer GR. Contact dermatitis from tetrachloroacetophenone (TCAP) in an insecticide plant. Contact Dermatitis 1991;25:66-7. Peachey RDG. Skin hazards in farming. Br J Dermatol 1981;105(suppl 21):45-50. Howard JK. A clinical survey of paraquat formulation workers. Br J Ind Med 1979;36:220-3. Edmiston S, Maddy KT. Summary of illnesses and injuries reported in California by physicians in 1986 as potentially related to pesticides. Vet Hum Toxic01 1987;29:3917. Spencer MC. Herbicide dermatitis. JAMA 1966;198:13078. Nishioka K, Kozuka T, Tashiro M. Agricultural miticide (BPPS) dermatitis. Skin Res 1970;12:15-9. Yang RS. 1,3-Dichloropropene. Residue Rev 1986;47:1935. Nater JP, Gooskens VHJ. Occupational dermatosis due to a soil fumigant. Contact Dermatitis 1976;2:227-9. Nater JP, Terpstra H, Bleumink E. Allergic contact sensitization to the fungicide maneb. Contact Dermatitis 1979;5:24-6. Cronin E. Contact dermatitis. Edinburgh: Churchill Livingstone, 1980:391-413. Adams RM, Manchester RD. Allergic contact dermatitis to maneb in a housewife. Contact Dermatitis 1982;8:271. Manuzzi P, Borrello P, Misciali C, et al. Contact dermatitis due to ziram and maneb. Contact Dermatitis 1988;19:1489.
55. Piraccini BM, Cameli N, Peluso AM, et al. A case of allergic contact dermatitis due to the pesticide maneb. Contact Dermatitis 1991;24:381-2. F. La dermatite da ditiocarbammati, 56. Scarpa C, Ippolito nuova entita clinica. Dermatologia 1959;10:257-64. 57. Laborie F, Laborie R, Dedieu EH. Allergie aux fongicides de la gamme du manebe et zinebe. Arch Ma1 Prof Med Travail Securite Sot (Paris) 1964;25:419-24. 58. Burry JN. Contact dermatitis from agricultural fungicide South Australia. Contact Dermatitis 1976;2:289. 59. Kleibl K, Rhilkova M. Cutaneous carbamates. Contact Dermatitis
in
allergic reactions to dithio1980;6:348-9.
60. Perez-Chacbn Espino V, Valerbn Martel P, Hemlndez HemPndez B. Dermatitis de contact0 por vondozeb (pesticida de1 grupo de 10s carbamatos). Actas Dermo-Sif 1985;76(suppl 1):53-4.
AND CONTACT
LISI DERMATITIS
183
61. Savitt LE. Contact dermatitis due to benomyl insecticide. Arch Dermatol 1972;105:926-7. 62. Ketel WG. Sensitivity to the pesticide benomyl. Contact Dermatitis 1976;2:290-1. 63. Joost TH, Naafs B, Ketel WG. Sensitization to benomyl and related pesticides. Contact Dermatitis 1983;9:153-4. 64. Larsen AI, Larsen A, Jepsen JR, et al. Contact allergy to the fungicide benomyl? Contact Dermatitis 1990;22:27881. 65. Fregert S. Allergic contact dermatitis from the pesticides captan and phaltan. Contact Dermatitis Newslett 1967; 2:28. sensitivity. Contact Dermatitis 66. Calnan CD. Dithianone Newslett 1969;6:119. 67. Schulz KH, Hermann WP. Tetramethylthiuramdisulphide, ein Thiohamstoffderivat als Ekzemnoxe bei Hafenarbeitern. Berufsdermatosen 1958;6:130-5. 68. Shelley WB. Golf-course dermatitis due to thiram fungicide. Cross-hazards of alcohol, disulhram, and rubber. JAMA 1964;188:415-7. 69. Iden DL, Schroeter AL. Allergic contact dermatitis to herbicides. Arch Dermatol 1977;113:983. 70. English JSC, Rycroft RJG, Calnan CD. Allergic contact dermatitis from aminotriazole. Contact Dermatitis 1986; 14:255-6. 71. Hogan DJ, Lane PR. Allergic contact dermatitis due to a herbicide (barban). Can Med Assoc J 1985;132:387-9. 72. Bruze M, Fregert S. Allergic contact dermatitis to chloridazon. Contact Dermatitis 1982;8:427. 73. Nishioka K, Asagami C, Kurata M, et al. Sensitivity to the weed killer DNA-nitralin and cross-sensitivity to dinitrochlorobenzene. Arch Dermatol 1983;119:304-6. 74. Solomons B. Sensitization to nitrofen. Contact Dermatitis Newslett 1972;12:336. 75. Nater JP, Grosfeld JCM. Allergic contact dermatitis from Betanal (phenmedipham). Contact Dermatitis 1979;5:5960. 76. Mitchell JC, Dupuis G, Towers GHN. Allergic contact dermatitis from pyrethrum ~Chysanthemum spp). The roles of pyrethrosin, a sesquiterpene lactone, and of pyrethrin II. Br J Dermatol 1972;86:568-73. 77. Jung H-D, Wolff F. Berufliche Kontakdermatiden durch Nematin (Vapam) in der Landwirtschaft. Dtsch GesundhWesen 1970;25:495 -8. 78. Richter G. Allergic contact dermatitis from methylisothiocyanate in soil disinfectants. Contact Dermatitis 1980; 6:183-6. 79. Milby TH, Epstein WL. Allergic contact sensitivity to malathion. Arch Environ Health 1964;9:4347. 80. Kligman AM. The identification of contact allergens by human assay. III. The maximization test: A procedure for screening and rating contact sensitizers. J Invest Dermatol 1966;47:393-409. 81. Behrbohm P, Brandt B. Allergisches Kontaktekzem durch technische und gereinigte Hexachlorcyclohexanpraparate
184
82.
83.
84.
85.
86. 87.
LISI
bei der Anwendung im Pflanzenschutz und in der Schldlingsbekampfung. Berufsdermatosen 1960;8:95 - 101. Hegyi E, St’ota Z. Zur Frage der Allergen-spezifitat der Komponenten des technischen Hexachlorzyklohexans. Berufsdermatosen 1965;13:193-207. Palminteri G. Sulla sensibilizzazione eczematosa spenmentale da dietilparanitrofeniltiofosfato (Parathion). Ann Ital Dermatol Clin Sper 1964;18:123-5. Matsushita T, Arimatsu Y, Nomura S. Experimental study on contact dermatitis caused by dithiocarbamates maneb, mancozeb, zineb, and their related compounds. Int Arch Occup Environ Health 1976;37:169-78. Maibach HI. Irritation, sensitization, photoirritation and photosensitization assays with a glyphosate herbicide. Contact Dermatitis 1986;15:152-6. Lisi I’, Caraffini S, Assalve D. A test series for pesticide dermatitis. Contact Dermatitis 1986;15:266-9. Lisi I’, Caraffini S, Assalve D. Irritation and sensitization potential of pesticides. Contact Dermatitis 1987;17:212-8.
Clinics in Dermatology 1992;10:275-184 88. Ketel WG, Berg WHHW. The problem of the sensitization to dithiocarbamates in thiuram-allergic patients. Dermatologica 1984;169:70-5. 89. Fisher AA. Occupational dermatitis from pesticides: Patch testing procedures. Cutis 1983;31:483-508. 90. Fisher AA, Adams RM. Occupational dermatitis. In: Fisher AA, editor. Contact dermatitis. 3rd ed. Philadelphia: Lea & Febiger, 1986:486-514. 91. Jung H-D, Rothe A, Heise H. Zur Epikutantestung mit Pflanzenschutzund Schadlingsbeklmpfungsmitteln (Pestiziden). Dermatosen 1987;35:43 -51. 92. Ehntholt DJ, Cerundolo DL, Bodek I, et al. A test method for the evaluation of protective glove materials used in agricultural pesticide operations. Am Ind Hyg Assoc J 1990; 51:462-8. 93. Lisi I’. L’ambiente di lavoro e le dermopatie non professionali. Ann Ital Dermatol Clin Sper 1991;45:9 - 14.
