4
H. Wyman Dorough and Sue K. Ballard
pounds, as in the case with the conversion of parathion to paraoxon. Fortunately,
the more active compounds are usually further metabolized to nontoxic forms
and eventually eliminated from the body.
Most data available indicate that the ability of different animal species to
metabolize a pesticide vary quantitatively rather than qUalitatively. For this reason
the present discussion will center around the metabolism of parent pesticide
molecules that occur within animal systems generally. The term metabolite will
be used here to denote any derivative of the parent molecule, and bioalteration
reactions that lead to metabolites will be divided into two broad categories: phase
I (primary) metabolism and phase II metabolism, referred to as secondary or
conjugation metabolism.
Phase I metabolism involves the production of a free metabolite through
biotransformation reactions such as dehydrohalogenation, dehalogenation, desulfuration, epoxidation, hydrolysis, hydroxylation-isomerization, oxidation,
reduction, and nitrosation (Menn and Still, 1977). The term free metabolite
refers to metabolites which are derived from the parent pesticide and have not
reacted further with natural components of a biological system. These can normally be extracted from the substrate and partitioned from water into an organic
solvent. Thus, free metabolites are often referred to as organosolubles.
Phase II metabolism involves the formation of conjugates through glycoside
formation, sulfoconjugation, glutathione conjugation, amino acid conjugation,
acetylation, and methylation (Dorough, 1979a). Thus, conjugated metabolites
are derivatives of the pesticide that have reacted with a natural component of
the organism to form a new material. Generally, this type of reaction involves
the formation of a free metabolite, followed by a second step converting the
metabolite to a conjugate. These conjugates are usually extractable from the
substrate with polar solvents but do not partition from water into organic solvents.
Components of the pesticide that cannot be removed from the substrate by
thorough extraction are called bound residues. In this case, conjugation may
have occurred with endogenous portions of the organisms such as proteins or
cell membranes. However, little is actually known about the chemical nature of
the bound residues.
Further information on general pesticide degradation can be found in the
works of Wilkinson (1976), Matsumura (1975), and Melnikov (1971). A more
detailed review of conjugation metabolism of pesticides was recently reported
by Dorough (1979a).
1.2. PHASE I METABOLISM
1.2. 1. Dehydroha/ogenation and Deha/ogenation
One of the more familiar dehydrocholorination reactions in animals is the
enzymatic conversion of DDT to DDE (Fig. 1.1). DDT also undergoes reductive
H. Wyman Dorough and Sue K. Ballard
pounds, as in the case with the conversion of parathion to paraoxon. Fortunately,
the more active compounds are usually further metabolized to nontoxic forms
and eventually eliminated from the body.
Most data available indicate that the ability of different animal species to
metabolize a pesticide vary quantitatively rather than qUalitatively. For this reason
the present discussion will center around the metabolism of parent pesticide
molecules that occur within animal systems generally. The term metabolite will
be used here to denote any derivative of the parent molecule, and bioalteration
reactions that lead to metabolites will be divided into two broad categories: phase
I (primary) metabolism and phase II metabolism, referred to as secondary or
conjugation metabolism.
Phase I metabolism involves the production of a free metabolite through
biotransformation reactions such as dehydrohalogenation, dehalogenation, desulfuration, epoxidation, hydrolysis, hydroxylation-isomerization, oxidation,
reduction, and nitrosation (Menn and Still, 1977). The term free metabolite
refers to metabolites which are derived from the parent pesticide and have not
reacted further with natural components of a biological system. These can normally be extracted from the substrate and partitioned from water into an organic
solvent. Thus, free metabolites are often referred to as organosolubles.
Phase II metabolism involves the formation of conjugates through glycoside
formation, sulfoconjugation, glutathione conjugation, amino acid conjugation,
acetylation, and methylation (Dorough, 1979a). Thus, conjugated metabolites
are derivatives of the pesticide that have reacted with a natural component of
the organism to form a new material. Generally, this type of reaction involves
the formation of a free metabolite, followed by a second step converting the
metabolite to a conjugate. These conjugates are usually extractable from the
substrate with polar solvents but do not partition from water into organic solvents.
Components of the pesticide that cannot be removed from the substrate by
thorough extraction are called bound residues. In this case, conjugation may
have occurred with endogenous portions of the organisms such as proteins or
cell membranes. However, little is actually known about the chemical nature of
the bound residues.
Further information on general pesticide degradation can be found in the
works of Wilkinson (1976), Matsumura (1975), and Melnikov (1971). A more
detailed review of conjugation metabolism of pesticides was recently reported
by Dorough (1979a).
1.2. PHASE I METABOLISM
1.2. 1. Dehydroha/ogenation and Deha/ogenation
One of the more familiar dehydrocholorination reactions in animals is the
enzymatic conversion of DDT to DDE (Fig. 1.1). DDT also undergoes reductive