1-Chloro-2,4-dinitrobenzene (2,4-Dinitro-1-chlorobenzene, DNCB) [MAK Value Documentation, 1999]
Documentations and Methods
Published Online: 31 JAN 2012
Copyright © 2002 by Wiley-VCH Verlag GmbH & Co. KGaA. All rights reserved.
The MAK Collection for Occupational Health and Safety
How to Cite
2012. 1-Chloro-2,4-dinitrobenzene (2,4-Dinitro-1-chlorobenzene, DNCB) [MAK Value Documentation, 1999]. The MAK Collection for Occupational Health and Safety. 1–115.
- Published Online: 31 JAN 2012
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1 Allergenic Effects
1.1 Effects in man
1-Chloro-2,4-dinitrobenzene (2,4-dinitro-1-chlorobenzene, DNCB)—like the closely related substances 1-fluoro-2,4-dinitrobenzene (2,4-dinitro-1-fluorobenzene, DNFB) and 1-chloro-2,4,6-trinitrobenzene (picryl chloride, PCl)—belongs to the group of contact allergens with the highest sensitizing potential. Inflammatory lesions of the skin and mucous membranes were already described in the original publication in which the synthesis of 1-chloro-2,4-dinitrobenzene was first reported (Jungfleisch 1868).
Soon after 1-chloro-2,4-dinitrobenzene was first used industrially in large quantities— for example in the production of certain dyes or explosives—an increased incidence of contact dermatitis was observed. The first description of nine cases in a chemical factory (Bernstein 1912) was followed in the first three decades of this century by a series of other communications. As the great sensitizing capacity and therefore the risk associated with contact were hardly known at the time, 1-chloro-2,4-dinitrobenzene was not handled with due care. There are striking reports from Russian factories. Up to 40 % of the workers were affected in some factories (Hausen and Kiehn 1990, Wedrow 1928). In a ceramics factory concentrations of 1-chloro-2,4-dinitrobenzene as low as 0.005 % in a glaze still caused contact dermatitis in some workers (Smirjagin and Schapiro 1926, Wedrow 1928).
The gradual spread of knowledge about the risk associated with contact with 1-chloro-2, 4-dinitrobenzene led to a reduction in the number of new cases of sensitization and therefore also in the number of publications, but individual cases were still observed. In the 1970s 1-chloro-2,4-dinitrobenzene was used in some countries as an algicide in cooling systems, which resulted in contact sensitization often being detected in employees engaged in repair and maintenance work (Adams et al. 1971, Malten 1974, Zimmermann 1970). Also affected were chemists, laboratory personnel, persons employed in rubber production and also transport workers (Hausen and Kiehn 1990, Zina et al. 1987).
Clinically, sensitization to 1-chloro-2,4-dinitrobenzene is almost always seen as contact dermatitis. Cases of contact urticaria have, however, also been reported (van Hecke and Santosa 1985, Valsecchi et al. 1986).
The marked sensitizing capacity was also demonstrated in experiments on men. The application of one drop of a 10 % solution of 1-chloro-2,4-dinitrobenzene to the skin induced contact allergy of the dermatitis type in about 70 % of the test persons. When a 30 % solution was used, all test persons could be sensitized (Wedroff and Dolgoff 1935). In a more recent study of dose-response relationships in which 132 persons took part, reactions were found to be clearly dose-dependent: 62.5 µg led to sensitization in 8 % of the test persons, and 500 µg in 100 % of the test persons (Friedman et al. 1983).
Structure-effect relationships for sensitization by nitro-substituted and chloro-substituted benzenes were studied with 15 test persons by epicutaneous application of the substances (10 % solutions for induction, 0.1–0.01 % solutions for elicitation of a reaction); the results agreed with those previously found by Landsteiner and Jacobs (1935, 1936) with guinea pigs (see below). Of the five substances investigated, 1-chloro-2, 4-dinitrobenzene produced a severe reaction and 1,2,4-trinitrobenzene a weak reaction. 1,2-Dichloro-4-nitrobenzene, 2-chloro-1,4-dinitrobenzene and 1,3,5-trinitrobenzene had no effect (Sulzberger and Baer 1938).
Allergic cross-reactions with chemically related halogenated nitrobenzenes are to be expected. Positive results in epicutaneous tests are often observed with 1-fluoro-2, 4-dinitrobenzene and 1-chloro-2,4,6-trinitrobenzene (Garcia-Perez 1978). One patient, who developed eczema on the hand during the production of the herbicide “DNA-Nitralin”, produced a reaction to the intermediate product 4-chloro-3,5-dinitrophenyl-methylsulfone and to 1-chloro-2,4-dinitrobenzene (Nishioka et al. 1983). It should be pointed out that the suggestion published some 30 years ago that allergic cross-reactions between chloramphenicol and 1-chloro-2,4-dinitrobenzene can occur could not be confirmed (Djawari et al. 1980, Eriksen 1978).
As a result of its marked sensitizing capacity, 1-chloro-2,4-dinitrobenzene was used for some time in immunodiagnostics and immunotherapy for testing the function of the cellular immune system (Ahmed and Blose 1983, Burdick et al. 1975, Catalona et al. 1972), for the local treatment of alopecia areata (Happle 1979, Happle et al. 1978), of verrucae vulgares (Buckner and Price 1978) and of malignant melanomas (Burg and Braun-Falco 1977).
1.2 Animal experiments
In the 1930s 1-chloro-2,4-dinitrobenzene was first shown to be able to sensitize guinea pigs specifically. In studies of the structure-effect relationships of various halogen-substituted and nitro-substituted benzene derivatives, Landsteiner and Jacobs (1935, 1936) found that some of the compounds investigated produced distinct reactions of the skin and that others did not. The type and position of the substituents on the benzene ring were the decisive factors that determined the sensitizing effect. The most chemically labile substances were found to be the most powerful sensitizers.
The substances to produce a reaction were 1-chloro-2,4-dinitrobenzene (severe), 1-fluoro-2,4-dinitrobenzene (severe), 1-bromo-2,4-dinitrobenzene, 1-iodo-2,4-dinitrobenzene, 1,4-dichloro-2,6-dinitrobenzene, 1,3-dichloro-4,6-dinitrobenzene and 1-chloro-2, 4,6-trinitrobenzene (severe).
Sensitization was not achieved with 1,4-dichloro-2-nitrobenzene, 1,2-dichloro-4-nitrobenzene, 1,3-dichloro-5-nitrobenzene, 1-chloro-4-nitrobenzene, 1,4-dichlorobenzene, 1,2,4-trichlorobenzene or hexachlorobenzene. There were allergic cross-reactions between the benzene derivatives with sensitizing effects.
To date numerous studies have been carried out with 1-chloro-2,4-dinitrobenzene and also with 1-fluoro-2,4-dinitrobenzene and 1-chloro-2,4,6-trinitrobenzene on the pathogenesis, and in particular the immunopathogenesis of contact dermatitis; several hundred publications have been the result (see review by Storck 1962). Various methods were used (epicutaneous application, intracutaneous injection with and without Freund's adjuvant) (Christensen et al. 1984, Gad 1988, Goodwin et al. 1981). In other experiments with epicutaneous application investigating the relationships between the chemical structure and the ability to induce dermatitis-type allergy to 2,4-dinitrobenzenes, it was shown that replacing the Cl group in the 1-chloro-2,4-dinitrobenzene molecule with OH, CH3 or NH2 produces substances which are no longer effective. Replacement with SO3Na, SCl or SCN led to a weakening but not to complete suppression of the effect compared with that of 1-chloro-2,4-dinitrobenzene (Eisen 1959, Eisen et al. 1952).
2 Manifesto (sensitization)
On the basis of the observations in man and the positive results obtained in animal experiments, 1-chloro-2,4-dinitrobenzene can be regarded as one of the strongest allergens. As a contact allergen 1-chloro-2,4-dinitrobenzene is therefore designated with an “S”.
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