Page 592 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Toxicity of Herbicides Chapter | 44 557

VetBooks.ir Paraquat OUT IN Hexose monophosphate shunt 3

+
CH 3 + N NCH +
3 NADPH NADP
0.702 nm
>0.5 nm PQ 2+ PQ +2
1 Receptor 2

+
O 2 O 2
+ + 2H +
2
Then O 2 + O 2 H O 2
3+ + 2+
Fe + O Fe + O
5 2 . 2
2+
Putrescine Fe + H O − 3+
+ + 2 2 OH + OH + Fe
NH (CH ) NH3 H O
3 2 4 2 2
0.622 nm Glutathione 4
peroxidase
GSSH GSH
Glutathione Lipid peroxidation
reductase
Alveolar
epithelial NADPH NADP +
cell wall Cell death
Hexose
monophosphate shunt
FIGURE 44.3 Schematic representation of mechanism of toxicity of paraquat. (1) Structure of paraquat and putrescine; (2) putative accumulation
receptor; (3) redox cycling of paraquat utilizing NADPH; (4) formation of hydroxyl radical (OH ) leading to lipid peroxidation; and (5) detoxication
of H 2 O 2 via GSH reductase peroxidase couple, utilizing NADPH. Reproduced with permission from Smith, L.L., 1997. Paraquat. In: Sipes, I.G.,
McQueen, C.A., Gandolfi, A.J. (Eds.), Comprehensive Toxicology: Toxicology of the Respiratory System, vol. 8. Pergamon, New York, NY,
pp. 581 589.

affinity for the lung and does not appear to involve the also affects at least some form of development and/or
same mechanism that selectively concentrates paraquat in reproduction in one or more species of animals. Some
the lung (Rose and Smith, 1977). herbicides have been associated with birth defects in
Glyphosate, a member of the phosphonomethyl humans. For example, 2,4-D in combination with
amino acid group, selectively inhibits the enzyme 2,4,5-T or dioxin, oryzalin, butiphos, picloram, Silvex
5-enolpyruvoylshikimate 3-phosphate synthetase. The (2-(2,4,5-trichlorophenoxy) propionic acid) and TCDD
enzyme plays a key role in the biosynthesis of the inter- (2,3,7,8-tetrachlorodibenzo-p-dioxin) are known to cause
mediate, chorismate, which is necessary for the synthesis reproductive problems/malformations in humans. A non-
of the essential amino acids phenylalanine, tyrosine and exhaustive list of herbicides that cause developmental
tryptophan. This aromatic amino acid biosynthesis path- toxicity in experimental animals is presented in Table 44.1.
way is found in plants as well as in fungi and bacteria but
not in insects, birds, fish, mammals and humans, thus pro- Inorganic Herbicides and Organic Arsenicals
viding a specific selective toxicity to plant species (Franz
et al., 1997). Substances such as sodium arsenite, arsenic trioxide,
sodium chlorate, ammonium sulfamate and borax were
formerly used on a large scale. The disadvantage of such
TOXICITY
herbicides from an agricultural standpoint is that they are
More than 200 active ingredients are used as herbicides; nonselective; thus, their use has declined due to the avail-
however, some are believed to be obsolete or have been ability of better and selective organic preparations (Marrs,
discontinued. Of these, several have been evaluated for 2004; Gupta, 2016a,b).
their toxic potential, and acceptable daily intake has been
recommended by the Joint Meeting on Pesticide Residues Phenoxy Acid Derivatives
(IPCS, 2002). In general, with a few exceptions, most of
the newly developed chemicals have a low order of toxic- This class of herbicides includes 2,4-D, 2,4,5-T, 2,4-DB,
ity to mammals. However, there is increasing experimen- dalapon, dichlorprop or 2,4-DP, mecoprop or MCPP,
tal and anecdotal evidence that exposure to herbicides MCPA and Silvex. Some of the phenoxy derivatives are