Relative Inhibitory Potencies of Chlorpyrifos Oxon, Chlorpyrifos Methyl Oxon, and Mipafox for Acetylcholinesterase Versus Neuropathy Target Esterase
Abstract
The relative inhibitory potency (RIP) of an organophosphorus (OP) inhibitor against acetylcholinesterase(AChE) versus neuropathy target esterase (NTE) is [ki(AChE)/ki(NTE)], where ki is the bimolecular rate constant of inhibition. RIPs>1 correlate with the inability of ageable OP inhibitors or their parent compounds to produce OP induced delayed neurotoxicity (OPIDN) at doses <LD50. The RIP for chlorpyrifos oxon (CPO) is >>1 for enzymes from hen brain homogenate, and the parent compound, chlorpyrifos (CPS), cannot produce OPIDN in hens at sublethal doses. This study was done to test the hypothesis that the RIP for chlorpyrifos methyl oxon (CPMO), is >>1 and >RIP for CPO. Mipafox (MIP) was included for comparison. Hen brain microsomes were used as the enzyme source, and ki (mean SE, M^ 1min^- 1) determined for AChE and NTE (n = 3, 4 experiments, respectively). ki values for CPO, CPMO, and MIP against AChE were 17.8 0.3, 10.9 0.1, and 0.00429 0.00001, respectively, and for NTE were 0.0993 0.0049, 0.0582 0.0013, and 0.00498 0.00006, respectively. Corresponding RIPs for CPO, CPMO, and MIP were 179 9, 187 4, and 0.861 0.011, respectively. Thus, RIPs for CPO and CPMO are comparable, markedly different from that for MIP, and >>1, indicating that CPS methyl, like CPS, could not cause OPIDN at sublethal doses.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2003
- Accession Number
- ADA471136
Entities
People
- Robert J. Richardson
- T. J. Kropp
Organizations
- University of Michigan