Toxicity of dinitrophenols

The concurrent use of sulfonamide drugs, which are able to bind preferentially to serum albumin, may greatly enhance the acute toxicity of dinitrophenols. 

Toxicity of Dinitrophenol Metabolites. Since dinitrophenols are metabolized in the body (Davidson and Shapiro 1934 Eiseman et al. 1972 Gisclard and Woodward 1946 Okino and Yasukura 1957 Perkins 1919 Robert and Hagardorn 1985), exposure to DNPs also results in exposure to DNP metabolites. While information on the metabolism of DNPs is limited to 2,4-DNP, it is likely that the metabolism of the other DNP isomers would also be carried out by a nitroreductase and result in aminonitrophenols and diaminophenols. Table 3-3 in Chapter 3 lists the parent DNPs and their likely metabolites. 

Brecken-Folse.l.A.. Mayer. F.L.. Pedigo. L.E.. and Marking. L.L. Acute toxicity of 4-nitrophenol. 2.4-dinitrophenol.terbufos and trichlorfon to grass shrimp (Palaemonetes spp.) and sheepshead minnows (Cyprinodon variegatosf as affected by salinity and temperature. Environ. ScL Technol, 13(l) 67-77.1994. 

DNOC (4,6 -dinitro-o-cresol) is one of a group of dinitrophenol and dinitrocresol herbicides that are highly toxic to both humans and animals. Most compounds in this class are well absorbed from the GI tract, via the skin and by the lung (as fine droplets). 

Zitko, V., McLeese, D.W., Carson, W.G., Welch, H.E. (1976) Toxicity of alkyl-dinitrophenols to some aquatic organisms. Bull. Environ. Contam. Toxicol. 16, 508-515. 

Howe, G.E., Marking, L.L., Bills, T D., Rach, J.J., Mayer, Jr., F.L. (1994) Effects of water temperature and pH on toxicity of terbufos, trichlorfon, 4-nitrophenol and 2,4-dinitrophenol to the amphipod Gammarus pseudolimnaeus and rainbow trout (Oncorhyn-chus mykiss). Environ. Toxicol. Chem. 13, 51-66. 

Picric acid (Figure 3.9) is made by dissolving phenol in sulfuric acid, then nitrating with nitric acid. Another route is from nitration of dinitrophenol, which is made from dinitrochlorobenzene. Picric acid was used extensively in World War I as a bomb and grenade filler both by itself and in mixtures with other explosives. Its major drawback (besides its toxicity) is that it reacts with metals... 

Tuovinen, O.H. and Kelly, D.P., (1974 (a) (b) (c). Studies on the growth of Thiobacillus ferrooxidans. II. Toxicity of uranium to growing cultures and tolerance conferred by mutation, other metal cations and EDTA. Arch. Mikrobiol., 95 153—164. III. Influence of uranium, other metal ions and 2,4-dinitrophenol on ferrous iron oxidation and carbon dioxide fixation by cell suspensions, ibid, 95 165—180. IV. Influence of monovalent metal cations on ferrous iron oxidation and uranium toxicity in growing cultures, ibid, 98 167—174. 

The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and other interested individuals and groups with an overall perspective of the toxicology of dinitrophenols (DNPs). It contains descriptions and evaluations of toxicological studies and epidemiological investigations and provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health. 

Anderson HH, Reed AC, Emerson GA. 1933. Toxicity of alpha-dinitrophenol. Report of case. JAMA 101 1053-1055. 

Dow Chemical Co. 1950. Initial 8e submission The comparative acute oral toxicity of several dinitrophenols used in agriculture (final report) with cover letter dated 3/18/92 (sanitized). 

Harvey DG. 1959. On the metabolism of some aromatic nitro compounds by different species of animal Part III. The toxicity of the dinitrophenols, with a note on the effects of high environmental temperatures. J Pharm Pharmacol 11 462-474. 

Kaiser JA. 1964. Studies on the toxicity of diisophenol (2,6-diiodo-4-nitrophenol) to dogs and rodents plus some comparison with 2,4-dinitrophenol. Toxicol Appl Pharmacol 6 232-244. 

Robert TA. 1986. The disposition and acute toxicity of 2,4-dinitrophenol and its mono reduced metabolites in mouse plasma and liver. In Proceedings of the 70th Federation of American Societies for Experimental Biology Annual Meeting, St. Louis, MO, April 13-18. Fed Proc 45 638. 

Efficacy and toxicity of antimelanoma immunocytokine scFvMEL/TNF in melanoma-bearing mice Exacerbation of viral hepatitis by hexachlorobenzene Decreased suppression of the humoral response to dinitrophenol (a T-independent antigen) by 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin Increased susceptibility to Coccidioides immitis Increased susceptibility to systemic Cryptococcus neoformans... 

Dinitrophenol is another highly toxic phenolic compound. All nitrophenols are toxic. Nitrophenols containing more than three nitro groups are unstable, the toxicity of which has not been invesdgated. 

Several chemicals were tested with 25 imoles EDTA and 7.4 imoles of calcium, 10 times the amount used in the experiments reported. The results of this experiment are shown in Table 15.2.2.6. In the presence of high levels of EDTA and calcium, isonicotinic acid is no longer toxic. Dinitrophenol and 3-phenoxy benzoate, in the presence of low levels of EDTA and calcium were not as toxic, in flic presence of high levels, it had the same toxicity. In presence of low levels of EDTA and calcium. Streptomycin was comparably toxic, the calcium and EDTA did not affect the toxicity. In the presence of high levels, Streptomycin was extremely toxic. Pentachlorophenol, a common soil contaminant, had reduced toxicity with low levels of EDTA and calcium, had elevated levels of toxicity with high levels of EDTA and calcium. This work shows that the effect of EDTA and specific toxins must be worked out before any conclusions as to the toxicity of the compound in the presence of EDTA and calcium can be established. 

Dinitrophenol was at one time used as a slimming agent. Explain how it acted, and describe what you would expect to observe in a person who had consumed a modest (non-toxic) amount of dinitrophenol. 

It is obvious that the slopes of the regressions in TABLE 4 vary significantly. But it was quite satisfactory that the regression equation we found for phenols (equation 3) proved to be nearly similar to the relationship given by Neely et al. (1974). Equation (3) is also valid for phenols bearing the structure element 2,4-dinitro-substitution but then a constant factor has to be subtracted as shown in equation (5). With respect to the toxicity of phenols, dinitrophenols (2,5-dinitro-phenol and 2,4-dinitro-sec-butylphenol) were only poorly fitted to a QSAR based solely upon log P (Lipnick et al. 1986). But whereas for toxicity there is an explanation for the higher toxicity of the dinitrophenols (i.e., the inhibition of oxidative phosphorylation), we cannot, as yet, explain their much smaller accumulation compared to other phenols. 

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