DOCSLIB.ORG

Strychnine Human Health and Ecological Risk Assessment FINAL REPORT

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Strychnine Human Health and Ecological Risk Assessment FINAL REPORT SERA TR-052-17-03b Strychnine Human Health and Ecological Risk Assessment FINAL REPORT Submitted to: Paul Mistretta, COR USDA/Forest Service, Southern Region 1720 Peachtree RD, NW Atlanta, Georgia 30309 USDA Forest Service Contract: AG-3187-C-06-0010 USDA Forest Order Number: AG-43ZP-D-08-0011 SERA Internal Task No. 52-17 Submitted by: Patrick R. Durkin Syracuse Environmental Research Associates, Inc. 8125 Solomon Seal Manlius, New York 13104 Fax: (315) 637-0445 E-Mail: [email protected] Home Page: www.sera-inc.com March 27, 2010 Table of Contents LIST OF TABLES ......................................................................................................................... vi LIST OF FIGURES ....................................................................................................................... vi LIST OF APPENDICES ............................................................................................................... vii ATTACHMENT ........................................................................................................................... vii ACRONYMS, ABBREVIATIONS, AND SYMBOLS .............................................................. viii COMMON UNIT CONVERSIONS AND ABBREVIATIONS .................................................... x CONVERSION OF SCIENTIFIC NOTATION ........................................................................... xi EXECUTIVE SUMMARY .......................................................................................................... xii 1. INTRODUCTION ...................................................................................................................... 1 2. PROGRAM DESCRIPTION ..................................................................................................... 4 2.1. OVERVIEW ........................................................................................................................ 4 2.2. CHEMICAL DESCRIPTION AND COMMERCIAL FORMULATIONS ....................... 4 2.3. APPLICATION METHODS ............................................................................................... 6 2.4. MIXING AND APPLICATION RATES ............................................................................ 6 2.5. USE STATISTICS ............................................................................................................... 7 2.6. RESTRICTIONS ON APPLICATION SITES .................................................................... 8 3. HUMAN HEALTH RISK ASSESSMENT .............................................................................. 10 3.1. HAZARD IDENTIFICATION ........................................................................................ 10 3.1.1. Overview ..................................................................................................................... 10 3.1.2. Mechanism of Action .................................................................................................. 10 3.1.3. Pharmacokinetics and Metabolism ............................................................................. 11 3.1.3.1. General Considerations ........................................................................................ 11 3.1.3.2. Dermal Absorption............................................................................................... 13 3.1.3.3. Excretion .............................................................................................................. 15 3.1.4. Acute Oral Toxicity .................................................................................................... 16 3.1.4.1. Effects in Humans ............................................................................................... 16 3.1.4.2. Effects in Experimental Mammals...................................................................... 18 3.1.4.2.1. Sex Difference in Sensitivity ........................................................................ 19 3.1.4.2.2. Age Difference in Sensitivity........................................................................ 20 3.1.5. Subchronic or Chronic Systemic Toxic Effects .......................................................... 22 Section 3.1.5.1. Multiple Doses in Mammals ................................................................... 22 3.1.5.2. Other Information ................................................................................................ 25 3.1.6. Effects on Nervous System ......................................................................................... 27 3.1.7. Effects on Immune System ......................................................................................... 27 3.1.8. Effects on Endocrine System ...................................................................................... 28 3.1.9. Reproductive and Developmental Effects .................................................................. 28 3.1.10. Carcinogenicity and Mutagenicity ............................................................................ 29 3.1.11. Irritation and Sensitization (Effects on the Skin and Eyes) ...................................... 29 3.1.11.1. Skin Irritation ..................................................................................................... 29 3.1.11.2. Skin Sensitization............................................................................................... 30 3.1.11.3. Ocular Effects .................................................................................................... 30 ii 3.1.12. Systemic Toxic Effects from Dermal Exposure ....................................................... 30 3.1.13. Inhalation Exposure .................................................................................................. 31 3.1.14. Inerts and Adjuvants ................................................................................................. 31 3.1.15. Impurities and Metabolites ....................................................................................... 31 3.1.16. Toxicological Interactions ........................................................................................ 31 3.2. EXPOSURE ASSESSMENT .......................................................................................... 33 3.2.1. Overview ..................................................................................................................... 33 3.2.2. Workers ....................................................................................................................... 34 3.2.2.1. General Exposures ............................................................................................... 34 3.2.2.1.1. Hand Baiting ................................................................................................. 34 3.2.2.1.2. Burrow Builder Applications ........................................................................ 39 3.2.2.2. Accidental Exposures........................................................................................... 40 3.2.3. General Public ........................................................................................................... 41 3.2.3.1.1. Likelihood and Magnitude of Exposure ....................................................... 41 3.2.3.1.2. Summary of Assessments ............................................................................. 41 3.2.3.2. Consumption of Bait by a Child .......................................................................... 42 3.2.3.3. Dermal Exposure from Contaminated Vegetation ............................................... 43 3.2.3.4. Contaminated Water ............................................................................................ 43 3.2.3.4.1. Accidental Spill ............................................................................................. 43 3.2.3.4.2. Accidental Direct Spray/drift for a Pond or Stream ...................................... 44 3.2.3.4.3. GLEAMS Modeling...................................................................................... 44 3.2.3.4.4. Other Modeling Efforts ................................................................................. 46 3.2.3.4.5. Monitoring Data ............................................................................................ 47 3.2.3.4.6. Concentrations in Water Used for Risk Assessment .................................... 49 3.2.3.5. Oral Exposure from Contaminated Fish .............................................................. 51 3.2.3.6. Dermal Exposure from Swimming in Contaminated Water ................................ 52 3.2.3.6. Oral Exposure from Contaminated Vegetation.................................................... 52 3.3. DOSE-RESPONSE ASSESSMENT ................................................................................. 54 3.3.1. Overview ..................................................................................................................... 54 3.3.2. Acute RfD ................................................................................................................... 54 3.3.3. Chronic RfD ................................................................................................................ 55 3.3.4. Dose-Severity Relationships ....................................................................................... 56 3.4. RISK CHARACTERIZATION ....................................................................................... 59 3.4.1. Overview ....................................................................................................................
Load more

Recommended publications
  • Electrophysiologic Evidence for Increased Endogenous Gabaergic but Not Glycinergic Inhibitory Tone in the Rat Spinal Nerve Ligation Model of Neuropathy Vesa K
    Anesthesiology 2001; 94:333–9 © 2001 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Electrophysiologic Evidence for Increased Endogenous GABAergic but Not Glycinergic Inhibitory Tone in the Rat Spinal Nerve Ligation Model of Neuropathy Vesa K. Kontinen, M.D., Ph.D.,* Louise C. Stanfa, Ph.D.,† Amlan Basu,‡ Anthony H. Dickenson, Ph.D.§ Background: Changes in the inhibitory activity mediated by There is evidence that both GABA and glycinergic inter- ␥-aminobutyric acid (GABA) and glycine, acting at spinal GABA A neurons are preferentially associated with the control of receptors and strychnine-sensitive glycine receptors, are of in- 6–9 terest in the development of neuropathic pain. There is ana- low-threshold afferent input to the spinal cord. Con- Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/94/2/333/402482/0000542-200102000-00024.pdf by guest on 29 September 2021 tomic evidence for changes in these transmitter systems after sistent with this, intrathecal administration of the 10 nerve injuries, and blocking either GABAA or glycine receptors GABAA-receptor antagonist bicuculline or the glycine- has been shown to produce allodynia-like behavior in awake receptor antagonist strychnine10,11 produces segmen- normal animals. tally localized tactile allodynia-like behavior in conscious Methods: In this study, the possible changes in GABAergic and glycinergic inhibitory activity in the spinal nerve ligation rats and increased responses to mechanical stimulation 12 model of neuropathic pain were studied by comparing the in anesthetized cats. Intrathecal strychnine has also effects of the GABAA-receptor antagonist bicuculline and the been shown to produce in anesthetized rats reflex re- glycine-receptor antagonist strychnine in neuropathic rats to sponses similar to those produced by nociceptive stim- their effects in sham-operated and nonoperated control rats.
    [Show full text]
  • Activated Carbon in Sediment Remediation
    ACTIVATED CARBON IN SEDIMENT REMEDIATION. BENEFITS, RISKS AND PERSPECTIVES Darya KUPRYIANCHYK Thesis committee Promoter Prof. dr. A.A. Koelmans Professor Water and Sediment Quality Co-promoter Dr. ir. J.T.C. Grotenhuis Assistant professor Environmental Technology Other members Prof. dr. R.N.J. Comans, Wageningen University Prof. dr. ir. W.J.G.M. Peijnenburg, RIVM, Leiden University Prof. dr. ir. A.J. Hendriks, Radboud University Nijmegen Dr. ir. M.T.O. Jonker, Utrecht University This research was conducted under the auspices of the Graduate School for Socio-Economic and Natural Sciences of the Environment (SENSE). ACTIVATED CARBON IN SEDIMENT REMEDIATION. BENEFITS, RISKS AND PERSPECTIVES Darya KUPRYIANCHYK Thesis submitted in fulfilment of the requirements for the degree of doctor at Wageningen University by the authority of the Rector Magnificus Prof. dr. M.J. Kropff, in the presence of the Thesis Committee appointed by the Academic Board to be defended in public on Friday 1 February 2013 at 4.00 p.m. in the Aula Darya Kupryianchyk Activated carbon in sediment remediation. Benefits, risks and perspectives 264 pages. Thesis, Wageningen University, Wageningen, The Netherlands (2013) With references and summaries in English and Dutch ISBN 978-94-6173-431-0 To my mother “who told me songs were for the birds, then taught me all the tunes I know and a good deal of the words.” Ken Kesey Contents Chapter 1. General introduction....................................................................................... 9 Chapter 2. In situ remediation of contaminated sediments using carbonaceous materials. A review......................................................................................... 17 Chapter 3. In situ sorption of hydrophobic organic compounds to sediment amended with activated carbon.....................................................................................
    [Show full text]
  • Toxicology Mechanisms Underlying the Neurotoxicity Induced by Glyphosate-Based Herbicide in Immature Rat Hippocampus
    Toxicology 320 (2014) 34–45 Contents lists available at ScienceDirect Toxicology j ournal homepage: www.elsevier.com/locate/toxicol Mechanisms underlying the neurotoxicity induced by glyphosate-based herbicide in immature rat hippocampus: Involvement of glutamate excitotoxicity Daiane Cattani, Vera Lúcia de Liz Oliveira Cavalli, Carla Elise Heinz Rieg, Juliana Tonietto Domingues, Tharine Dal-Cim, Carla Inês Tasca, ∗ Fátima Regina Mena Barreto Silva, Ariane Zamoner Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil a r a t i b s c l t r e a i n f o c t Article history: Previous studies demonstrate that glyphosate exposure is associated with oxidative damage and neu- Received 23 August 2013 rotoxicity. Therefore, the mechanism of glyphosate-induced neurotoxic effects needs to be determined. Received in revised form 12 February 2014 ® The aim of this study was to investigate whether Roundup (a glyphosate-based herbicide) leads to Accepted 6 March 2014 neurotoxicity in hippocampus of immature rats following acute (30 min) and chronic (pregnancy and Available online 15 March 2014 lactation) pesticide exposure. Maternal exposure to pesticide was undertaken by treating dams orally ® with 1% Roundup (0.38% glyphosate) during pregnancy and lactation (till 15-day-old). Hippocampal Keywords: ® slices from 15 day old rats were acutely exposed to Roundup (0.00005–0.1%) during 30 min and experi- Glyphosate 45 2+ Calcium ments were carried out to determine whether glyphosate affects Ca influx and cell viability. Moreover, 14 we investigated the pesticide effects on oxidative stress parameters, C-␣-methyl-amino-isobutyric acid Glutamatergic excitotoxicity 14 Oxidative stress ( C-MeAIB) accumulation, as well as glutamate uptake, release and metabolism.
    [Show full text]
  • Analgesic Effects and Pharmacologic Mechanisms of the Gelsemium
    www.nature.com/scientificreports OPEN Analgesic efects and pharmacologic mechanisms of the Gelsemium alkaloid koumine on a Received: 8 June 2017 Accepted: 13 October 2017 rat model of postoperative pain Published: xx xx xxxx Bo-Jun Xiong1, Ying Xu1,2, Gui-Lin Jin1,2, Ming Liu1, Jian Yang1,2 & Chang-Xi Yu1,2 Postoperative pain (POP) of various durations is a common complication of surgical procedures. POP is caused by nerve damage and infammatory responses that are difcult to treat. The neuroinfammation- glia-steroid network is known to be important in POP. It has been reported that the Gelsemium alkaloid koumine possesses analgesic, anti-infammatory and neurosteroid modulating activities. This study was undertaken to test the analgesic efects of koumine against POP and explore the underlying pharmacologic mechanisms. Our results showed that microglia and astroglia were activated in the spinal dorsal horn post-incision, along with an increase of proinfammatory cytokines (interleukin 1β, interleukin 6, and tumor necrosis factor α). Both subcutaneous and intrathecal (i.t.) koumine treatment after incision signifcantly prevented mechanical allodynia and thermal hyperalgesia, inhibited microglial and astroglial activation, and suppressed expression of proinfammatory cytokines. Moreover, the analgesic efects of koumine were antagonized by i.t. administration of translocator protein (18 kDa) (TSPO) antagonist PK11195 and GABAA receptor antagonist bicuculline. Together, koumine prevented mechanical allodynia and thermal hyperalgesia caused by POP. The pharmacologic mechanism of koumine-mediated analgesia might involve inhibition of spinal neuroinfammation and activation of TSPO. These data suggested that koumine might be a potential pharmacotherapy for the management of POP. Postoperative pain (POP) of varying duration is extremely common afer surgery.
    [Show full text]
  • Crews Lab Discovers Inflammatory Mechanisms Underlying Alcohol
    research alcohol actions on brain, liver, pancreas, fetus, the The Director’s Column endocrine system and the immune system, has contributed Thanks for your gifts to our Center! to Crews’ insights. Alternatively, I suspect that he A. Leslie Morrow, Ph.D. assembled this diverse group of researchers to study alcohol Dean’’’ s Club Ms. Carolyn S. Corn Mr. and Mrs. Ben Madore Associate Director, actions across so many systems of the body for the very Ms. Harriet W. Crisp Bowles Center for (annual gifts of $5000 and above) Ms. Regina J. Mahon purpose of discovering how the complex systemic and Mr. and Mrs. Ray Damerell Alcohol Studies Dr. William Maixner molecular roles of alcohol go awry in the disease of Center Line James A. Bowles Mr. Lewis A. Dancy Mrs. Melissa M. Mann Bowles Center for Alcohol Studies alcoholism. Mr. John N. Howard, Jr. Mr. F. E. Danielus Mr. and Mrs. H. J. McCarthy School of Medicine, University of North Carolina at Chapel Hill Mr. and Mrs. Robert F. Schaecher Mr. Stephen M. Dean and Ms. Patricia L. Ms. Michelle McCarthy This integration of research across systems, organs, brain Ms. Ann Lewallen Spencer Amend Mr. and Mrs. Robert H. McConville, Jr. Dr. Fulton Crews’ brilliance can be attributed in part to regions, human development and the progression to Our mission is to conduct, coordinate, and promote basic and clinical research on the causes, prevention, and treatment of alcoholism and alcoholic disease. Tennessee Medical Foundation Ms. Elizabeth L. Deaver Mr. and Mrs. Loyce L. McCormick his understanding that human beings are not just a alcoholism is the hallmark of research in the Bowles Center Ms.
    [Show full text]
  • Unnamed Document
    Mutations M287L and Q266I in the Glycine Receptor ␣1 Subunit Change Sensitivity to Volatile Anesthetics in Oocytes and Neurons, but Not the Minimal Alveolar Concentration in Knockin Mice Cecilia M. Borghese, Ph.D.,* Wei Xiong, Ph.D.,† S. Irene Oh, B.S.,‡ Angel Ho, B.S.,§ S. John Mihic, Ph.D.,ʈ Li Zhang, M.D.,# David M. Lovinger, Ph.D.,** Gregg E. Homanics, Ph.D.,†† Edmond I. Eger 2nd, M.D.,‡‡ R. Adron Harris, Ph.D.§§ ABSTRACT What We Already Know about This Topic • Inhibitory spinal glycine receptor function is enhanced by vol- Background: Volatile anesthetics (VAs) alter the function of atile anesthetics, making this a leading candidate for their key central nervous system proteins but it is not clear which, immobilizing effect if any, of these targets mediates the immobility produced by • Point mutations in the ␣1 subunit of glycine receptors have been identified that increase or decrease receptor potentiation VAs in the face of noxious stimulation. A leading candidate is by volatile anesthetics the glycine receptor, a ligand-gated ion channel important for spinal physiology. VAs variously enhance such function, and blockade of spinal glycine receptors with strychnine af- fects the minimal alveolar concentration (an anesthetic What This Article Tells Us That Is New EC50) in proportion to the degree of enhancement. • Mice harboring specific mutations in their glycine receptors Methods: We produced single amino acid mutations into that increased or decreased potentiation by volatile anesthetic in vitro did not have significantly altered changes in anesthetic the glycine receptor ␣1 subunit that increased (M287L, third potency in vivo transmembrane region) or decreased (Q266I, second trans- • These findings indicate that this glycine receptor does not me- membrane region) sensitivity to isoflurane in recombinant diate anesthetic immobility, and that other targets must be receptors, and introduced such receptors into mice.
    [Show full text]
  • Assessing Neurotoxicity of Drugs of Abuse
    National Institute on Drug Abuse RESEARCH MONOGRAPH SERIES Assessing Neurotoxicity of Drugs of Abuse 136 U.S. Department of Health and Human Services • Public Health Service • National Institutes of Health Assessing Neurotoxicity of Drugs of Abuse Editor: Lynda Erinoff, Ph.D. NIDA Research Monograph 136 1993 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health National Institute on Drug Abuse 5600 Fishers Lane Rockville, MD 20857 ACKNOWLEDGMENT This monograph is based on the papers and discussions from a technical review on “Assessing Neurotoxicity of Drugs of Abuse” held on May 20-21, 1991, in Bethesda, MD. The technical review was sponsored by the National Institute on Drug Abuse (NIDA). COPYRIGHT STATUS NIDA has obtained permission from the copyright holders to reproduce certain previously published material as noted in the text. Further reproduction of this copyrighted material is permitted only as part of a reprinting of the entire publication or chapter. For any other use, the copyright holder’s permission is required. All other material in this volume except quoted passages from copyrighted sources is in the public domain and may be used or reproduced without permission from the Institute or the authors. Citation of the source is appreciated. Opinions expressed in this volume are those of the authors and do not necessarily reflect the opinions or official policy of the National Institute on Drug Abuse or any other part of the U.S. Department of Health and Human Services. The U.S. Government does not endorse or favor any specific commercial product or company.
    [Show full text]
  • GABA Receptors
    D Reviews • BIOTREND Reviews • BIOTREND Reviews • BIOTREND Reviews • BIOTREND Reviews Review No.7 / 1-2011 GABA receptors Wolfgang Froestl , CNS & Chemistry Expert, AC Immune SA, PSE Building B - EPFL, CH-1015 Lausanne, Phone: +41 21 693 91 43, FAX: +41 21 693 91 20, E-mail: [email protected] GABA Activation of the GABA A receptor leads to an influx of chloride GABA ( -aminobutyric acid; Figure 1) is the most important and ions and to a hyperpolarization of the membrane. 16 subunits with γ most abundant inhibitory neurotransmitter in the mammalian molecular weights between 50 and 65 kD have been identified brain 1,2 , where it was first discovered in 1950 3-5 . It is a small achiral so far, 6 subunits, 3 subunits, 3 subunits, and the , , α β γ δ ε θ molecule with molecular weight of 103 g/mol and high water solu - and subunits 8,9 . π bility. At 25°C one gram of water can dissolve 1.3 grams of GABA. 2 Such a hydrophilic molecule (log P = -2.13, PSA = 63.3 Å ) cannot In the meantime all GABA A receptor binding sites have been eluci - cross the blood brain barrier. It is produced in the brain by decarb- dated in great detail. The GABA site is located at the interface oxylation of L-glutamic acid by the enzyme glutamic acid decarb- between and subunits. Benzodiazepines interact with subunit α β oxylase (GAD, EC 4.1.1.15). It is a neutral amino acid with pK = combinations ( ) ( ) , which is the most abundant combi - 1 α1 2 β2 2 γ2 4.23 and pK = 10.43.
    [Show full text]
  • Environmental Properties of Chemicals Volume 2
    1 t ENVIRONMENTAL 1 PROTECTION Esa Nikunen . Riitta Leinonen Birgit Kemiläinen • Arto Kultamaa Environmental properties of chemicals Volume 2 1 O O O O O O O O OO O OOOOOO Ol OIOOO FINNISH ENVIRONMENT INSTITUTE • EDITA Esa Nikunen e Riitta Leinonen Birgit Kemiläinen • Arto Kultamaa Environmental properties of chemicals Volume 2 HELSINKI 1000 OlO 00000001 00000000000000000 Th/s is a second revfsed version of Environmental Properties of Chemica/s, published by VAPK-Pub/ishing and Ministry of Environment, Environmental Protection Department as Research Report 91, 1990. The pubiication is also available as a CD ROM version: EnviChem 2.0, a PC database runniny under Windows operating systems. ISBN 951-7-2967-2 (publisher) ISBN 952-7 1-0670-0 (co-publisher) ISSN 1238-8602 Layout: Pikseri Julkaisupalvelut Cover illustration: Jussi Hirvi Edita Ltd. Helsinki 2000 Environmental properties of chemicals Volume 2 _____ _____________________________________________________ Contents . VOLUME ONE 1 Contents of the report 2 Environmental properties of chemicals 3 Abbreviations and explanations 7 3.1 Ways of exposure 7 3.2 Exposed species 7 3.3 Fffects________________________________ 7 3.4 Length of exposure 7 3.5 Odour thresholds 8 3.6 Toxicity endpoints 9 3.7 Other abbreviations 9 4 Listofexposedspecies 10 4.1 Mammais 10 4.2 Plants 13 4.3 Birds 14 4.4 Insects 17 4.5 Fishes 1$ 4.6 Mollusca 22 4.7 Crustaceans 23 4.8 Algae 24 4.9 Others 25 5 References 27 Index 1 List of chemicals in alphabetical order - 169 Index II List of chemicals in CAS-number order
    [Show full text]
  • Simvastatin Attenuates Renal Ischemia/Reperfusion Injury from Oxidative Stress Via Targeting Nrf2/HO‑1 Pathway
    4460 EXPERIMENTAL AND THERAPEUTIC MEDICINE 14: 4460-4466, 2017 Simvastatin attenuates renal ischemia/reperfusion injury from oxidative stress via targeting Nrf2/HO‑1 pathway YU ZHANG1, SHU RONG2, YI FENG1, LIQUN ZHAO1, JIANG HONG1, RUILAN WANG1 and WEIJIE YUAN2 Departments of 1Emergency Intensive Medicine and 2Nephrology, Shanghai General Hospital of Nanjing Medical University, Shanghai 200082, P.R. China Received August 31, 2016; Accepted June 15, 2017 DOI: 10.3892/etm.2017.5023 Abstract. Ischemia-reperfusion (I/R) injury of the kidneys pathway to ultimately protect the kidneys from I/R-associated is commonly encountered in the clinic. The present study oxidative damage. assessed the efficacy of simvastatin in preventing I/R‑induced renal injury in a rat model and investigated the corresponding Introduction molecular mechanisms. Rats were divided into 3 groups, including a sham, I/R and I/R + simvastatin group. The Ischemia/reperfusion (I/R) injury of the kidneys represents a results revealed that in the I/R group, the levels of blood urea challenge in the clinic and is commonly encountered in renal nitrogen, serum creatinine and lactate dehydrogenase were transplantation, hemorrhagic shock, partial nephrectomy and significantly higher than those in the sham group, which accidental or iatrogenic trauma, brining about serious injury was significantly inhibited by simvastatin pre‑treatment. to multiple organs, including renal tubules, brain and heart (1). I/R significantly decreased superoxide dismutase activity Therefore, it is urgent to find effective therapies and elucidate compared with that in the sham group, which was largely molecular mechanisms by which renal I/R injury may be rescued by simvastatin.
    [Show full text]
  • Fish Bioconcentration Data Requirement: Guidance for Selection of Number of Treatment Concentrations
    Document ID No.: EPA 705-G-2020-3708 Fish Bioconcentration Data Requirement: Guidance for Selection of Number of Treatment Concentrations [Supplement to OCSPP Test Guideline 850.1730] July 15, 2020 Disclaimer: The contents of this document do not have the force and effect of law and are not meant to bind the public in any way. This document is intended only to provide clarity to the public regarding existing requirements under the law or agency policies. Office of Pesticide Programs Office of Chemical Safety and Pollution Prevention U.S. Environmental Protection Agency I. Purpose The purpose of this document is to clarify EPA recommendations for the number of treatment concentrations needed to result in acceptable fish bioconcentration factor (BCF) studies for pesticide registration. EPA routinely requires BCF studies to determine whether pesticide active ingredients have the potential to accumulate in fish, enter the food chain, and cause adverse effects in fish-eating predators such as aquatic mammals and birds of prey. In April 2017, EPA was approached by an outside party, the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3R), with a suggestion to modify the test guideline for the BCF study to reduce the number of animals used in BCF testing, by reducing the number of concentration levels used from three (two positive doses and one control) to two (one positive level and one control). NC3R stated that this would be “[i]n the interest of international harmonization and reducing unnecessary animal testing” because “[a]t the moment the Japanese and US EPA guideline require that two concentrations are always tested, which is in contrast to the OECD Test Guideline[1]; therefore, many companies are understandably continuing to test two concentrations to ensure acceptance within these regions.” This modification has the potential to reduce the number of fish used by one-third.
    [Show full text]
  • High Throughput Determination of Multiple Toxic Alkaloids in Food By
    Application Note Food Testing & Agriculture High-Throughput Determination of Multiple Toxic Alkaloids in Food by UHPLC/MS/MS Authors Abstract Guoyin Lai, Lijian Wu, Zhongda Lin, Liyi Lin, Dunming Xu, This Application Note presents a simple sample preparation procedure followed Zhigang Zhang with an Agilent 1290 Infinity II LC combined with an Agilent 6470A triple quadrupole Technigue Center, LC/MS for simultaneous, high-throughput determination of multiple alkaloids in food Xiamen Customs, matrices. The matrix-matched calibration shows very good linear relationships for Xiamen, China the 18 alkaloids in the concentration range of 0.5 to 50 µg/L in the diluted, extracted matrices of bread, milk, wine, and rice powder. This corresponds to 5.0 to 500 µg/kg Meiling Lu in the matrices when considering the dilution factor of 10. The linear regression Agilent Technologies (China) coefficients for all the analytes are higher than 0.99. The signal-to-noise ratios Co., Ltd. (S/Ns) for all analytes are higher than 10 at the lowest calibration level of 0.5 µg/L, corresponding to 5.0 µg/kg in the samples. The recoveries for the analytes in four different matrices at 5, 50, and 250 µg/kg levels ranged from 90 to 110%, and the corresponding relative standard deviations were within 2.3 to 7.9%. The results demonstrated that the developed method has the advantages of high sensitivity, accuracy, and precision. The simple sample preparation combined with rapid LC/MS/MS detection allows high-throughput screening of alkaloid residues in food matrices. Introduction Experimental (pH 3). The tube was vortexed thoroughly for two minutes, then centrifuged Alkaloids are naturally occurring alkaline Standards and sample at 7,500 rpm for five minutes.
    [Show full text]