@article{coleman_linderman_hodgson_rose_2000, title={Comparative metabolism of chloroacetamide herbicides and selected metabolites in human and rat liver microsomes.}, volume={108}, ISSN={["0091-6765"]}, DOI={10.2307/3434827}, abstractNote={Acetochlor [2-chloro-N-(ethoxymethyl)-N-(2-ethyl-6-methyl-phenyl)-acetamide], alachlor [N-(methoxymethyl)-2-chloro-N-(2,6-diethyl-phenyl)acetamide], butachlor [N-(butoxymethyl)-2chloro-N-(2,6-diethyl-phenyl)acetamide], and metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl) acetamide] are pre-emergent herbicides used in the production of agricultural crops.These herbicides are carcinogenic in rats: acetochlor and alachlor cause tumors in the nasal turbinates, butachlor causes stomach tumors, and metolachlor causes liver tumors.It has been suggested that the carcinogenicity of these compounds involves a complex metabolic activation pathway leading to a DNA-reactive dialkylbenzoquinone imine.Important intermediates in this pathway are 2-chloro-N-(2,6-diethylphenyl)acetamide (CDEPA) produced from alachlor and butachlor and 2-chloro-N-(2-methyl-6-ethylphenyl)acetamide (CMEPA) produced from acetochlor and metolachlor.Subsequent metabolism of CDEPA and CMEPA produces 2,6-diethylaniline (DEA) and 2-methyl-6-ethylaniline (MEA), which are bioactivated through para-hydroxylationand subsequent oxidation to the proposed carcinogenic product dialkylbenzoquinone imine.The current study extends our earlier studies with alachlor and demonstrates that rat liver microsomes metabolize acetochlor and metolachlor to CMEPA (0.065 nmol/min/mg and 0.0133 nmol/min/mg, respectively), whereas human liver microsomes can metabolize only acetochlor to CMEPA (0.023 nmol/min/mg).Butachlor is metabolized to CDEPA to a much greater extent by rat liver microsomes (0.045 nmol/min/mg) than by human liver microsomes (< 0.001 nmol/min/mg).We have determined that both rat and human livers metabolize both CMEPA to MEA (0.308 nmol/min/mg and 0.541 nmol/min/mg, respectively) and CDEPA to DEA (0.350 nmol/min/mg and 0.841 nmol/min/mg, respectively).We have shown that both rat and human liver microsomes metabolize MEA (0.035 nmol/min/mg and 0.069 nmol/min/mg, respectively) and DEA (0.041 nmol/min/mg and 0.040 nmol/min/mg, respectively).We have also shown that the cytochrome P450 isoforms responsible for human metabolism of acetochlor, butachlor, and metolachlor are CYP3A4 and CYP2B6.}, number={12}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Coleman, S and Linderman, R and Hodgson, E and Rose, RL}, year={2000}, month={Dec}, pages={1151–1157} }
 @article{coleman_liu_linderman_hodgson_rose_1999, title={In vitro metabolism of alachlor by human liver microsomes and human cytochrome P450 isoforms}, volume={122}, ISSN={["0009-2797"]}, DOI={10.1016/S0009-2797(99)00107-6}, abstractNote={Alachlor (2-chloro-N-methoxymethyl-N-(2,6-diethylphenyl)acetamide) is a widely used pre-emergent chloroacetanilide herbicide which has been classified by the USEPA as a probable human carcinogen. The putative carcinogenic metabolite, 2,6-diethylbenzoquinone imine (DEBQI), is formed through a complex series of oxidative and non-oxidative steps which have been characterized in rats, mice, and monkeys but not in humans. A key metabolite leading to the formation of DEBQI is 2-chloro-N-(2,6-diethylphenyl)acetamide (CDEPA). This study demonstrates that male human liver microsomes are able to metabolize alachlor to CDEPA. The rate of CDEPA formation for human liver microsomes (0.0031±0.0007 nmol/min per mg) is significantly less than the rates of CDEPA formation for rat liver microsomes (0.0353±0.0036 nmol/min per mg) or mouse liver microsomes (0.0106±0.0007). Further, we have screened human cytochrome P450 isoforms 1A1, 1A2, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, and 3A4 and determined that human CYP 3A4 is responsible for metabolism of alachlor to CDEPA. Further work is necessary to determine the extent to which humans are able to metabolize CDEPA through subsequent metabolic steps leading to the formation of DEBQI.}, number={1}, journal={CHEMICO-BIOLOGICAL INTERACTIONS}, author={Coleman, S and Liu, SM and Linderman, R and Hodgson, E and Rose, RL}, year={1999}, month={Aug}, pages={27–39} }
 @article{hodgson_cherrington_coleman_liu_falls_cao_goldstein_rose_1998, title={Flavin-containing monooxygenase and cytochrome P450 mediated metabolism of pesticides: from mouse to human}, volume={2}, number={1998}, journal={Reviews in Toxicology}, author={Hodgson, E. and Cherrington, N. and Coleman, S. C. and Liu, S. and Falls, J. G. and Cao, Y. and Goldstein, J. E. and Rose, R. L.}, year={1998}, pages={231–243} }