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EC number: 200-087-7
CAS number: 51-28-5
2,4- dinitrophenol (2,4-DNP) can readily enter in the body through inhalation, through the stomach if swallowed and probably can be absorbed through the skin. It is well metabolized and the parent compounds and metabolites are excreted in the urine. 2,4-DNP is an uncoupling of oxidative phosphorylation has the potential to affect all tissues and organs.
The available data from human case reports
and experimental animal studies indicate that 2,4 -dinitrophenol
(2,4-DNP) is readily absorbed by the oral and inhalation routes. There
is some evidence suggesting significant absorption through the skin as
The half-time for absorption of 2,4-DNP
following gavage administration was 0.5 hours. Maximum values for the
plasma concentration of 2,4-DNP were seen at 0.5 and 1.0 hours after
dosing, giving additional evidence of rapid absorption (Robert et al.,
The time course of plasma concentrations
of 2,4-DNP following oral administration to dogs in Kaiser (1964) study
confirmed substantial absorption of about 0.5 hours; furthermore no
evidence of a trend towards higher plasma levels with continued daily
dosing was reported.
2,4-DNP is rapidly metabolized via
reduction of the nitro groups, in fact nitroreductase reduces 2,4-DNP to
the aminonitrophenols. The maximum metabolism activity was found in the
cytosol, which is the site of other nitroreductases, although
nitroreductases can also be located in microsomes (Eiseman et al, 1952).
In the blood, 2,4-DNP is transported both
free and bound to serum proteins. The unbound fraction of the 2,4-DNP in
the blood enters organs and tissues such as the liver, the kidneys, and especially
in the eyes.
Pharmacokinetic analysis indicated that a
two-compartment open model best characterized the disposition of 2,4-DNP
in the serum, liver, and kidney of mice given a gavage dose;
concentrations found of 2,4-DNP were much lower in liver and kidney than
in serum (Robert et al., 1983). The similar half-times for absorption
and biphasic elimination in all three tissues (except terminal
elimination phase in kidney) indicated that rapid exchange of 2,4-DNP
occurred among these sites: the authors suggested that the apparent
persistence of 2,4-DNP in the kidney could be related to tissue binding
of the compound (Robert et al., 1983).
The parent compound and metabolites are
excreted in the urine.
for the slow terminal elimination phases were 7.7 hours for serum, 8.7
hours for liver, and 76.2 hours for kidney (Robert et al., 1983).
and 4-amino-2-nitrophenol were identified as metabolic products, with
the 4-amino-2-nitrophenol present in greater abundance; an
additional ether-insoluble metabolite was tentatively identified as
Eiseman (1952) identified under optimal pH
and cofactor levels that the 81% of the 2,4-DNP was metabolized.
2-Amino-4-nitrophenol accounted for 75%, 4-amino-2-nitrophenol for 23%,
and 2,4-diaminophenol for ≈1% of the total amine metabolites produced.
Also in this case 2-amino-4nitrophenol was determined as the predominant
metabolite. A proposed metabolic pathway for 2,4-DNP is reported in the
attachment below (Eiseman et al., 1952).
Further studies investigated the
relationship between the susceptibility of cataractogenesis and the
concentrations of 2,4-DNP in the compartments of the eye. The uncoupling
of mitochondrial electron transport from oxidative phosphorylation with
resultant decreased production of ATP by 2,4-DNP is related to the
cataractogenesis of 2,4-DNP (Kuck, 1970).
The concentration of 2,4-DNP in the ocular
compartments appears to be more important than the elimination rates in
determining susceptibility of developing cataracts, showing a
correlation between local concentration of 2,4-DNP and cataract
formation (Gehring et al., 1969b).
The uncoupling of oxidative
phosphorylation has the potential to affect all tissues and organs.
Limited toxicokinetic and mechanism data
for the other DNP isomers indicate that these isomers also uncouple
oxidative phosphorylation but that, with the exception of 2,6-DNP, they
are eliminated much more rapidly than is 2,4-DNP (Harvey, 1959).
Only two studies were identified that
described the effects of human exposure (reported in 7.10.5 IUCLID
section). Both report cases of illness and death associated with
occupational exposure to 2,4-DNP. The first study (Perkins 1919) reports
findings in workers exposed via inhalation to vapour and airborne dust
of 2,4- DNP and by direct contact of the skin with the solid chemical.
Exposure may have occurred by the dermal and possibly oral routes, as
well as by inhalation. In addition, examination of the blood,
unspecified organs, and urine of workmen in this industry who died from
exposure to 2,4-DNP revealed the presence of 2,4-DNP and its
metabolites; quantitative data were not provided (Perkins 1919).
The second study reported a fatal
occupational 2,4-DNP poisoning from exposure to mists and airborne dust
of 2,4-DNP and the relative urine analysis (Gisclard and Woodward 1946).
No conclusions regarding fraction absorbed can be drawn from this study,
but it does provide additional evidence of absorption from the
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