Pesticide involving carcinogenic

Table V. Chemical classes of Pesticides Involving Carcinogenic Interactions...

Some important representative carcinogens involving carcinogenic interactions with a number of pesticides and other chemicals are listed in Table VI. 

L-Tyrosine metabohsm and catecholamine biosynthesis occur largely in the brain, central nervous tissue, and endocrine system, which have large pools of L-ascorbic acid (128). Catecholamine, a neurotransmitter, is the precursor in the formation of dopamine, which is converted to noradrenaline and adrenaline. The precise role of ascorbic acid has not been completely understood. Ascorbic acid has important biochemical functions with various hydroxylase enzymes in steroid, dmg, andhpid metabohsm. The cytochrome P-450 oxidase catalyzes the conversion of cholesterol to bUe acids and the detoxification process of aromatic dmgs and other xenobiotics, eg, carcinogens, poUutants, and pesticides, in the body (129). The effects of L-ascorbic acid on histamine metabohsm related to scurvy and anaphylactic shock have been investigated (130). Another ceUular reaction involving ascorbic acid is the conversion of folate to tetrahydrofolate. Ascorbic acid has many biochemical functions which affect the immune system of the body (131). 

Many activations involve compounds which are used as pesticides. In the case of N-nitrosation, the precursors are secondary amines and nitrate. The former are common synthetic compounds and the latter is an anion found in nearly all solid and aqueous phases. The N-nitrosation of a secondary amine [R-NH-R ] occurs in the presence of nitrite formed microbiologically from nitrate. The product is an N-nitroso compound (i.e., a nitrosamine [RR -N-N=0]). The reason for concern with nitrosamines is their potency, at low concentrations, as carcinogens, teratogens, and mutagens. 

Most of the data located concerning the health effects of heptachlor and heptachlor epoxide in humans come from case reports and occupational epidemiology studies of workers engaged either in the manufacture or application of pesticides. There is some information on people who have consumed heptachlor-contaminated food or dairy products, but no adverse health effects have been related to these exposures. The occupational studies involve exposures that are predominantly inhalation with contributions from dermal exposure, whereas all the animal studies were conducted using oral or intraperitoneal exposures. The occupational and case reports provide no quantitation of dose or duration of exposure, which makes it impossible to determine with any precision the effect levels for humans. There are no data that indicate that heptachlor or heptachlor epoxide are carcinogenic to humans. However, human studies are limited by the long latency period of carcinogenesis and by ascertainment and follow-up biases. 

D. J. Hunter and R. T. Relsey, Pesticide Residues and Breast Cancer The Harvest of a Silent Spring, J. Natl. Cancer Inst. 85 (1995) 598-99 R. El-Bayoumy, Environmental Carcinogens That May be Involved in Human Breast Cancer Etiology, Chem. Res. Toxicol. 5 (1995) 585-90 R. M. Sharpe and N. F. Skakkebaek, Are Oestrogens Involved in Falling Sperm Counts and Disorders of the Male Reproductive Tract Lancet541 (1995) 1592-95. 

A daminozide (DZ) pesticide, a plausible carcinogen, has been determined using an MIP-QCM chemosensor [150]. Preparation of MIP particles used for fabrication of this chemosensor involved thermo-radical co-polymerization, in methanol... 

Cutaneous biotransformation is mostly associated with the stratum basale layer where there can be phase I and phase II metabolism. However, the skin is not very efficient, compared to the liver. The epidermal layer accounts for the major portion of biochemical transformations in skin, although the total skin activity is low (2-6% that of the liver). Where activity is based on epidermis alone, that layer is as active as the liver or, in the case of certain toxicants, several times more active. For some chemicals, metabolism can influence absorption, and transdermal delivery systems of drugs utilize this activity. For example prodrug such as lipid esters are applied topically, and cutaneous esterases liberate the free drug. These basal cells and extracellular esterases have been shown to be involved in detoxification of several pesticides and bioactivation of carcinogens such as benzo(a)pyrene. For rapidly penetrating substances, metabolism by the skin is not presently considered to be of major significance, but skin may have an important first-pass metabolic function, especially for compounds that are absorbed slowly. 

Cytochrome P-450 and hemoproteins are known to be involved in the oxidation of a broad variety of drugs, pesticides, carcinogens, steroids and fat soluble vitamins [18, 184, 185]. Amine oxidation by P-450 has been proposed to proceed either via electron/proton transfer mechanism or via hydrogen-atom abstraction mechanism (Scheme 23). 

There is evidence that long-term phosphine exposure by individuals involved in the application of pesticides resulted in chromosome damage. Chronic exposure to very low levels of phosphine may result in altered motor, visual, and speech skills. Neither aluminum phosphide nor phosphine gas exhibit carcinogenicity in humans, or result in reproductive or developmental effects. Although definitive evidence is lacking, it is assumed that phospine is an in vivo inhibitor of oxidative phosphorylation. 

Another major difference between the current approach and the previous approach for evaluating the adverse effects of pesticide exposure involves the way in which the toxicity data are interpreted. In the current system, the carcinogenicity data from the chronic rodent studies are extrapolated using mathematical models which provide a numerical estimate of the upper bound of the cancer risk, and these numbers (Q values) are then used for a variety of regulatory purposes. In essence, this approach substitutes mathematical guidelines for the scientific judgement that was the key element in the earlier approach. 

The most potent interaction of toxicological significance reported to date involves two known animal carcinogens (2). Whether this interaction between chlordecone and CCl results in amplified carcinogenicity has not been tested. The interaction represents a sequential exposure to a halogenated pesticide, chlordecone and a haloalkane, both at individually nontoxic doses (10). 

The carcinogenicity of genotoxic procarcinogens can be increased or decreased by modification of the enzyme systems involved in their biotransformation (18-21). Several pesticidal compounds known to Induce drug metabolizing enzymes of the liver have been reported to influence the outcome of carcinogenic effect of known carcinogens (Table II). 

Table VI. Pesticides and Other Chemicals Involved in Carcinogenic Interactions...

Table VIII. Proximal Mechanisms Involved in Carcinogenic Interactions of Pesticides...

Detoxification of organophosphorus pesticides before they can reach their target sites is probably the main reason for poor correlation between carcinogenicity and electrophilicity/mutagenicity. The problem is further complicated by the fact that several different enzymes are involved in the metabolic detoxification of organophosphorus pesticides. For example, paraoxon, tetrachlojTvinphos and dimethoate are preferentially detoxified by A-esterase (paraoxonase), GSH-dependent S-alkyltransferase and carboxyesterase (aliesterase), respectively whereas chlorfenvinphos is mainly detoxified by NADPH-dependent oxidative dealkylation... 

It is estimated that 18% of all new Wilms tumours, affecting the kidneys of Brazilian children, are attributable to pesticide exposure of their parents. Consistently elevated risks were seen among children whose fatlier or mother carried out farm work which involved the frequent use of pesticides. As elsewhere, many pesticides are used in Brazil and researchers estimated that 73 insecticides, 42 fungicides and 59 herbicides are in use. Atrazine and dichlorvos are particularly widely used and both are rated as possibly carcinogenic by the International Agency for Research in Cancer. 

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