Jennifer Przybyla, Melanie C Buser, Henry G Abadin, Hana R Pohl
Objectives: The Agency for Toxic Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA) derive minimal risk levels (MRLs) and reference concentrations and doses (RfCs and RfDs), respectively, for environmental contaminants to help identify potential health risks to exposed populations. MRLs, RfDs, and RfCs involve similar derivation methods, but the values sometimes differ for the same chemical. The objectives of this manuscript are to quantitatively assess similarities and differences between MRLs, RfCs, and RfDs, qualitatively describe how a number of factors can influence the development of the health guidance values (HGVs) and identify ongoing collaborations and opportunities for increased coordination of efforts.
Materials and methods: We collected MRLs and RfCs/RfDs, assessment date, and description of the derivation process from ATSDR's toxicological profiles and EPA's Integrated Risk Information System (IRIS) and Office of Pesticide Program (OPP) and identified reasons for differences between MRLs and RfCs/RfDs.
Results: The most frequent types of differences in values that we found in our analysis included use of different methodologies, use of different studies, and/or completion of a more recent chemical evaluation. These can stem from differences in scientific judgement.
Conclusion: To avoid confusion when disparate HGVs occur between government agencies, a keen understanding of these differences can be helpful for appropriate risk characterization and communication when applying HGVs.
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Shirley X Guo-Ross, Edward C Meek, Janice E Chambers, Russell L Carr
The effects of developmental exposure to two organophosphorus (OP) insecticides, chlorpyrifos (CPF) and methyl parathion (MPS), on cholinesterase (ChE) activity and muscarinic acetylcholine receptor (mAChR) binding were investigated in preweanling rat brain. Animals were orally gavaged daily with low, medium, and high dosages of the insecticides using an incremental dosing regimen from postnatal day 1 (PND1) to PND20. On PND12, PND17 and PND20, the cerebral cortex, corpus striatum, hippocampus, and medulla-pons were collected for determination of ChE activity, total mAChR density, and the density of the individual mAChR subtypes. ChE activity was inhibited by the medium and high dosages of CPF and MPS at equal levels in all four brain regions at all three ages examined. Exposure to both compounds decreased the levels of the M1, M2/M4, and M3 subtypes and the total mAChR level in all brain regions, but the effects varied by dosage group and brain region. On PND12, only the high dosages induced receptor changes while on PND17 and PND20, greater effects became evident. In general, the effects on the M1 subtype and total receptor levels appeared to be greater in the cerebral cortex and hippocampus than in the corpus striatum and medulla-pons. This did not appear to be the case for the M2/M4 and M3 subtypes effects. The differences between CPF and MPS were minimal even though in some cases, CPF exerted statistically greater effects than MPS did. In general, repeated exposure to organophosphorus insecticides can alter the levels of the various mAChR subtypes in various brain regions which could induce perturbation in cholinergic neurochemistry during the maturation of the brain regions.
{"title":"Effects of Chlorpyrifos or Methyl Parathion on Regional Cholinesterase Activity and Muscarinic Receptor Subtype Binding in Juvenile Rat Brain.","authors":"Shirley X Guo-Ross, Edward C Meek, Janice E Chambers, Russell L Carr","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The effects of developmental exposure to two organophosphorus (OP) insecticides, chlorpyrifos (CPF) and methyl parathion (MPS), on cholinesterase (ChE) activity and muscarinic acetylcholine receptor (mAChR) binding were investigated in preweanling rat brain. Animals were orally gavaged daily with low, medium, and high dosages of the insecticides using an incremental dosing regimen from postnatal day 1 (PND1) to PND20. On PND12, PND17 and PND20, the cerebral cortex, corpus striatum, hippocampus, and medulla-pons were collected for determination of ChE activity, total mAChR density, and the density of the individual mAChR subtypes. ChE activity was inhibited by the medium and high dosages of CPF and MPS at equal levels in all four brain regions at all three ages examined. Exposure to both compounds decreased the levels of the M1, M2/M4, and M3 subtypes and the total mAChR level in all brain regions, but the effects varied by dosage group and brain region. On PND12, only the high dosages induced receptor changes while on PND17 and PND20, greater effects became evident. In general, the effects on the M1 subtype and total receptor levels appeared to be greater in the cerebral cortex and hippocampus than in the corpus striatum and medulla-pons. This did not appear to be the case for the M2/M4 and M3 subtypes effects. The differences between CPF and MPS were minimal even though in some cases, CPF exerted statistically greater effects than MPS did. In general, repeated exposure to organophosphorus insecticides can alter the levels of the various mAChR subtypes in various brain regions which could induce perturbation in cholinergic neurochemistry during the maturation of the brain regions.</p>","PeriodicalId":73996,"journal":{"name":"Journal of toxicology and pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052801/pdf/nihms939301.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36334963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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