Integration of Neurotoxicity data for handling pesticides. Clive Campbell

Size: px
Start display at page:

Download "Integration of Neurotoxicity data for handling pesticides. Clive Campbell"

Transcription

1 Integration of Neurotoxicity data for handling pesticides Clive Campbell

2 Acknowledgements Although I have an MSc in applied toxicology, I am essentially an Occupational Physician. In preparing this talk I have had help and advice from a number of card carrying toxicologists. My thanks to - Kevin Ledgerwood Occupational Toxicologist, UK - Sara Lloyd Senior Technical Expert, UK - Dan Minnema Technical Expert, US 2

3 Neurotoxicology The field of neurotoxicology has emerged from the integration of toxicology, pharmacology, psychopharmacology and experimental psychology. It involves study of changes in the function and / or structure of the nervous system as a result of chemical exposure, and interpretation of the consequences of such changes. (Moser 2011) 3

4 The nervous system The nervous system is complex with different: - cell types (e.g. neuron, glia) - anatomy (central, peripheral), - structural characteristics (e.g. size, spatial configuration), - synaptic function (inhibitory, excitatory) - neurotransmitters (e.g. acetylcholine, GABA) and has high energy requirements (ion channels, action potentials) this conveys unique vulnerabilities to toxic compounds (Mosier 2008) 4

5 Neurotoxicology Originally histopathological changes considered the Gold Standard until it was realised that toxicants can also affect nervous system function e.g. behaviour. Effects in behaviours may be due to changes in nerve cell communication and integration sensitive indicator / ultimate assay of neuronal function, particularly for CNS For PNS and lower CNS look at reflexes, innate responses and survival behaviours. 5

6 Behavioural tests Testing of pesticides guided by EPA section 870, or OECD guidelines Types of behavioural tests used in first and second tier (examples, not inclusive of all tests that could be used) Type of test Behaviours evaluated Specific test/endpoint Tier 1 - Screening FOB, Irwin Screen Activity, excitability, sensorimotor, neuromuscular Arousal, rearing, reactivity, gait, posture, responses, reflexes, landing foot splay, grip strength, excretions Motor activity Spontaneous activity Open field, figure 8, cage rack chambers Tier 2 - hazard characterisation Cognition Motor Sensory Learning, conditioning, memory, attention Quantitative measures: Coordination, equilibrium, strength Quantitative measures: stimuli specific responses Passive/active avoidance, water maze, T-maze, operant schedules of reinforcement Gait analysis, rotarod, grip strength, landing foot splay, motor activity Acoustic startle response, prepulse inhibition. 6

7 Histopathology Gross examination of the NS (linked to any clinical observations) Sections of the following reviewed (H&E stain) Tissues forebrain centre of cerebrum midbrain cerebellum pons gasserian ganglia Cross sections of the following reviewed (toluidine blue O, luxol fast blue stain) : - proximal sciatic nerve - sural nerve - tibial nerve cervical and lumbar dorsal root ganglia cervical dorsal root and ventral root fibres Medulla oblongata lumbar dorsal root and ventral root fibres spinal cord at cervical swellings spinal cord at lumbar swellings 7

8 Neurotoxicity studies conducted for active ingredients with mechanism of action mediated via the nervous system (e.g. some insecticides) or for AIs with findings from other toxicity studies suggest a potential adverse effect to the nervous system. include an acute NT study (single oral dose) followed by neurobehavioral assessments (functional observational battery, motor activity) at various times after dosing (time of peak effect, 1 week, and 2 weeks). Two weeks after dosing the animals are euthanized, specific nervous tissues are collected, processed, staining, and examined microscopically. 8

9 Neurotoxicity studies Subchronic NT studies are similar, except that the AI is administered continuously (usually in diet) for 13 weeks, after which neuropathology is assessed. Neurobehavioral examinations are performed during the 2 nd, 5 th, 9 th, and 13 th weeks of treatment. Developmental neurotoxicity (DNT) studies involve exposure early in gestation (via the mother) and continuously during development (to at least postnatal day 21). In addition to standard neurobehavioral assessment, DNT studies also include assessments of learning and memory. In addition to the standard neurohistopathology, CNS morphometric assessments in the brain are performed. 9

10 Establishing NOAEL / PoD all repeated-dose studies reviewed to determine lowest no-observableadverse-effect level (NOAEL). - studies are reviewed to determine which species and assessment paradigm is most sensitive to an adverse effect, the lowestobservable-adverse-effect level (LOAEL). - Once a species/studies has been identified as to having the lowest dose level (usually mg/kg/day) at which an adverse effect is seen, the next lowest dose in that same study is used to define the NOAEL. - That NOAEL is defined as the point of departure (PoD). 10

11 Regulatory Using the NOAEL/PoD, the agency will usually add uncertainty (safety) factors (UF). - 10X UF is added to extrapolate from the test species to human - another 10X UF is added to account for variable susceptibility with the human population - In some cases an additional factor (FQPA) of 3X or 10X is added for special concerns (e.g., selective sensitivity of children, steep doseeffect curve, severity of toxicity at the LOAEL) After applying the UF factors the Reference Dose (RfD) is obtained, which is usually 100 to 1000 times less than the PoD. - This reference dose is then used to regulate the use (amounts) of products to ensure that exposure does not exceed the RfD. 11

12 The Avermectins Avermectins (macrocyclic lactones isolated from the soil actinomycete, Streptomyces avermitilis) are structurally similar: IVERMECTIN Drug EMAMECTIN Pesticide ABAMECTIN Pesticide 12

13 Avermectins: Mammalian Toxicity Broad-spectrum anti-parasitic agents used to kill: parasitic worms (filariae), athropods (mites), & insects (bedbugs) Mammalian Target Site: Neurons (activation of GABA-dependent chloride channels) Neurotoxicity dependent on the concentration at the neuronal site. Access of avermectins to neurons within the CNS of mammals is dependent on a specific P-glycoprotein (P-gp) transporter: MDR1 (man) (also known as ABCB1) or mdr1a (rodent) 13

14 The P-glycoprotein (P-gp) Transporter P-gp are cell membrane transport proteins (mainly efflux transporters) There are 49 different P-gp transporters varying expression and function in different tissues varying affinities for a variety of substrates The MDR1 P-gp transporter high affinity for the avermectins highly expressed in blood capillary endothelial cells comprising the blood-brain and blood-nerve barriers Mectin Nerve Cell? Abluminal Side (parenchyma side) Mectin Mec Endothelial Cells (BBB, BNB) Capillary (blood circulation) Luminal Side (blood side) Mectin Mec Endothelial Cells (BBB, BNB) P-pg Efflux Transporter The localization of P-gp suggests its physiological role for the outward transport of toxic agents (protective mechanism) 14

15 Regulatory History: Merck Merck developed and registered the avermectins Merck conducted screening toxicity studies using the CF-1 mouse Some CF-1 mice were extremely sensitive to avermectin-inducted toxicity and that this increased sensitivity was due to a mdr1a P-gp deficiency. Approximate Oral LD 50 (mg/kg BW) in Genotyped CF-1 mice mdr1a(+/+) mdr1a(-/-) Ivermectin Abamectin Merck proposed that CF-1 mouse studies should not be used for human health risk assessment since no functional deficiency of MDR1 P-gp had been identified in humans. EPA agreed that results of the CF-1 mouse studies were not appropriate for abamectin human risk assessment. However, data from CF-1 mouse toxicity studies were used for emamectin human risk assessment. 15

16 Revised RfD EPA Human Health Risk Assessment for Emamectin released May 2016 EPA now agrees that the CF-1 mouse is not an appropriate species for emamectin human health risk assessment Acute and chronic endpoints (Points of Departure) for emamectin exposure are now based on the NOAEL from the canine study. No extra (FQPA) safety factors have been applied. Previously PoD = mg/kg/day (CF-1 mouse) Acute Dietary RfD = mg/kg UF A =10x UF H =10X FQPA=3x Chronic Dietary RfD= mg/kg/day UF A =10x UF H =10X FQPA=10x Currently PoD = 0.25 mg/kg/day (canine) Acute Dietary RfD = mg/kg UF A =10x UF H =10X Chronic Dietary RfD= mg/kg/day UF A =10x UF H =10X 16

17 Worker protection Syngenta OEL panel - CMO - Occ Toxicologist - Lead Occ hygienist - Lead global toxicologist - Product toxicologists Use NO(A)EL and UF approach for systemic tox - UF 3, 10, 30, 100 (dependant on severity of end point, steepness of dose response, and quality of data) - Calculate to mg/m3 assuming a bodyweight of 70kg and an inhalation volume of 10m3 per shift. - Also consider acute effects if relevant and address empirically 17

18 Syngenta OELs 4 products with NT end points as basis for OEL - Lambda cyhalothrin based on 1 year dog study with a NOEL of 0.5 mg/kg bw/day. A safety factor of 100 is regarded as appropriate. This results in an exposure limit of mg/kg bw/day and can be recalculated to an OEL of 0.04 mg/m3 - Abamectin / emamectin based on 1 year dog study with a NOEL of 0.25 mg/kg bw/day. A safety factor of 100 is regarded as appropriate. This results in an exposure limit of mg/kg bw/day and can be recalculated to an OEL of 0.02 mg/m3. - Pirimiphos methyl Based on cholinesterase inhibition from subchronic rat study with NOEL 0.4mg/kg bw/day. An UF of 1 is regarded as appropriate as similar results obtained from oral study in man. This recalculates to an OEL of 3mg/m3. 18

5.3 AZINPHOS METHYL (002)

5.3 AZINPHOS METHYL (002) 5.3 AZINPHOS METHYL (002) TOXICOLOGY Azinphos-methyl is the ISO approved common name for S-3,4-dihydro-4-oxo-1,2,3-benzotriazin-3- ylmethyl O,O-dimethyl phosphorodithioate (IUPAC) or O,O-dimethyl S-[(4-oxo-1,2,3-benzotriazin-

More information

CHAPTER 48: NERVOUS SYSTEMS

CHAPTER 48: NERVOUS SYSTEMS CHAPTER 48: NERVOUS SYSTEMS Name I. AN OVERVIEW OF NERVOUS SYSTEMS A. Nervous systems perform the three overlapping functions of sensory input, integration, and motor output B. Networks of neurons with

More information

N-Methylneodecanamide (MNDA)

N-Methylneodecanamide (MNDA) United States Prevention, Pesticides EPA-730-F-99-008 Environmental Protection And Toxic Substances July 1999 Agency (7505C) New Pesticide Fact Sheet Description of the Chemical N-Methylneodecanamide (MNDA)

More information

Nervous Systems. Brain Development

Nervous Systems. Brain Development Nervous Systems Brain Development 2007-2008 Nervous system Central nervous system Peripheral nervous system Brain Spinal cord Sensory pathways Motor pathways Sympathetic arousal & energy production fight

More information

SUPPLEMENTAL MATERIAL

SUPPLEMENTAL MATERIAL SUPPLEMENTAL MATERIAL A Critical Review of Neonicotinoid Insecticides for Developmental Neurotoicity by LP Sheets, AA Li, DJ Minnema, RH Collier, MR Creek and RC Peffer Critical Reviews in Toicology, 2015

More information

Nervous Systems: Diversity & Functional Organization

Nervous Systems: Diversity & Functional Organization Nervous Systems: Diversity & Functional Organization Diversity of Neural Signaling The diversity of neuron structure and function allows neurons to play many roles. 3 basic function of all neurons: Receive

More information

8.3 The Central Nervous System. SBI4U Ms. Ho-Lau

8.3 The Central Nervous System. SBI4U Ms. Ho-Lau 8.3 The Central Nervous System SBI4U Ms. Ho-Lau The Central Nervous System the structural and functional centre for the entire nervous system the site of neural integration and processing The Central

More information

5.24 TRIAZOLE FUNGICIDE METABOLITES

5.24 TRIAZOLE FUNGICIDE METABOLITES Triazole metabolites 355 5.24 TRIAZOLE FUNGICIDE METABOLITES TOXICOLOGY 1,2,4-Triazole, triazole alanine, triazole acetic acid, triazole pyruvic acid and triazole lactic acid are the common metabolites

More information

Chapter 17. Nervous System Nervous systems receive sensory input, interpret it, and send out appropriate commands. !

Chapter 17. Nervous System Nervous systems receive sensory input, interpret it, and send out appropriate commands. ! Chapter 17 Sensory receptor Sensory input Integration Nervous System Motor output Brain and spinal cord Effector cells Peripheral nervous system (PNS) Central nervous system (CNS) 28.1 Nervous systems

More information

Neurons, Synapses and Signaling. Chapter 48

Neurons, Synapses and Signaling. Chapter 48 Neurons, Synapses and Signaling Chapter 48 Warm Up Exercise What types of cells can receive a nerve signal? Nervous Organization Neurons- nerve cells. Brain- organized into clusters of neurons, called

More information

Abamectin Product-type 18 (insecticides, acaricides and products to control other arthropods)

Abamectin Product-type 18 (insecticides, acaricides and products to control other arthropods) SCBP24-Doc.2a Rev.1 Directive 98/8/EC concerning the placing biocidal products on the market Inclusion of active substances in Annex I to Directive 98/8/EC Assessment Report Abamectin Product-type 18 (insecticides,

More information

All questions below pertain to mandatory material: all slides, and mandatory homework (if any).

All questions below pertain to mandatory material: all slides, and mandatory homework (if any). ECOL 182 Spring 2008 Dr. Ferriere s lectures Lecture 6: Nervous system and brain Quiz Book reference: LIFE-The Science of Biology, 8 th Edition. http://bcs.whfreeman.com/thelifewire8e/ All questions below

More information

Biology 3201 Quiz on Nervous System. Total 33 points

Biology 3201 Quiz on Nervous System. Total 33 points Biology 3201 Quiz on Nervous System Total 33 points Name: Circle the best response to the following: (33 points) 1. What do we call the long fibre that carries impulses away from the nerve cell body? A.

More information

Rationale for TEL, WES and NOAEC values for ethanedinitrile, Draft 1

Rationale for TEL, WES and NOAEC values for ethanedinitrile, Draft 1 Rationale for TEL, WES and NOAEC values for ethanedinitrile, Draft 1 Prepared by Adam Jonas, Ph.D. A) Summary of relevant chronic studies 1) Ethanedinitrile: In Lewis et al. 1984 study, they exposed animals,

More information

DIAZINON (addendum) First draft prepared by U. Mueller 1 and R. Solecki 2

DIAZINON (addendum) First draft prepared by U. Mueller 1 and R. Solecki 2 DIAZINON (addendum) First draft prepared by U. Mueller 1 and R. Solecki 2 1 Offi ce of Chemical Safety, Therapeutic Goods Administration, Canberra, Australian Capital Territory, Australia; and 2 Safety

More information

The nervous system regulates most body systems using direct connections called nerves. It enables you to sense and respond to stimuli

The nervous system regulates most body systems using direct connections called nerves. It enables you to sense and respond to stimuli The nervous system regulates most body systems using direct connections called nerves. It enables you to sense and respond to stimuli The basic function of nervous system are: Receive sensory input internal

More information

Outline. Animals: Nervous system. Neuron and connection of neurons. Key Concepts:

Outline. Animals: Nervous system. Neuron and connection of neurons. Key Concepts: Animals: Nervous system Neuron and connection of neurons Outline 1. Key concepts 2. An Overview and Evolution 3. Human Nervous System 4. The Neurons 5. The Electrical Signals 6. Communication between Neurons

More information

Nervous System C H A P T E R 2

Nervous System C H A P T E R 2 Nervous System C H A P T E R 2 Input Output Neuron 3 Nerve cell Allows information to travel throughout the body to various destinations Receptive Segment Cell Body Dendrites: receive message Myelin sheath

More information

The Nervous System An overview

The Nervous System An overview Nervous System The Nervous System An overview Includes Nerve tissue Sense organs Functions to Sense environment Process information it receives Respond to information 1 Copyright 2009 Pearson Education,

More information

Function of the Nervous System

Function of the Nervous System Nervous System Function of the Nervous System Receive sensory information, interpret it, and send out appropriate commands to form a response Composed of neurons (functional unit of the nervous system)

More information

Case Study Summary: Appendix: Evaluation of Hazard Range for Three Additional Chemicals: Tetrachloroethylene, Chromium (VI) and Arsenic.

Case Study Summary: Appendix: Evaluation of Hazard Range for Three Additional Chemicals: Tetrachloroethylene, Chromium (VI) and Arsenic. Case Study Summary: Practical Guidance on the Development of a Non-cancer Hazard Range for Effective Risk Assessment and Risk Management of Contaminated Sites: A Case Study with Trichloroethylene and Other

More information

Chapter 12 Nervous System Written Assignment KEY

Chapter 12 Nervous System Written Assignment KEY Chapter 12 Nervous System Written Assignment KEY 1. Describe, in correct order, the events that occur during the transmission of a nerve impulse (action potential) as it travels from point X to point Y.

More information

The neurvous system senses, interprets, and responds to changes in the environment. Two types of cells makes this possible:

The neurvous system senses, interprets, and responds to changes in the environment. Two types of cells makes this possible: NERVOUS SYSTEM The neurvous system senses, interprets, and responds to changes in the environment. Two types of cells makes this possible: the neuron and the supporting cells ("glial cells"). Neuron Neurons

More information

Chapter 48-49: The Nervous System & Neurons

Chapter 48-49: The Nervous System & Neurons Invertebrates Chapter 48-49: The Nervous System & Neurons Radial Symmetry - Nerve net Cnideria Bilateral Symmetry double, ventral, solid nerve cord brain (cephalization) Vertebrates Dorsal, single, hollow,

More information

Lesson 14. The Nervous System. Introduction to Life Processes - SCI 102 1

Lesson 14. The Nervous System. Introduction to Life Processes - SCI 102 1 Lesson 14 The Nervous System Introduction to Life Processes - SCI 102 1 Structures and Functions of Nerve Cells The nervous system has two principal cell types: Neurons (nerve cells) Glia The functions

More information

Risk Assessment of Chemicals in Foods- WHO Principles and Methods

Risk Assessment of Chemicals in Foods- WHO Principles and Methods Risk Assessment of Chemicals in Foods- WHO Principles and Methods Presented by Dr Debabrata Kanungo DK 31-07-2018 Seminar on Food Additives: A Global Perspect on Safety Evaluation and Use July 19-20, 2018

More information

Nervous System and Brain Review. Bio 3201

Nervous System and Brain Review. Bio 3201 Nervous System and Brain Review Bio 3201 Dont worry about: glial cells Oligodendrocytes Satelite cells etc Nervous System - Vital to maintaining homeostasis in organisms - Comprised of : brain, spinal

More information

The Scientific Rationale for Deriving Database and Toxicodynamic Uncertainty Factors for Reproductive or Developmental Toxicants

The Scientific Rationale for Deriving Database and Toxicodynamic Uncertainty Factors for Reproductive or Developmental Toxicants 1 2 3 4 6 7 The Scientific Rationale for Deriving Database and Toxicodynamic Uncertainty Factors for Reproductive or Developmental Toxicants 8 9 1 11 12 13 Prepared by Bernard Gadagbui Jay Zhao Andy Maier

More information

Chapter 7. The Nervous System: Structure and Control of Movement

Chapter 7. The Nervous System: Structure and Control of Movement Chapter 7 The Nervous System: Structure and Control of Movement Objectives Discuss the general organization of the nervous system Describe the structure & function of a nerve Draw and label the pathways

More information

Axon Nerve impulse. Axoplasm Receptor. Axomembrane Stimuli. Schwann cell Effector. Myelin Cell body

Axon Nerve impulse. Axoplasm Receptor. Axomembrane Stimuli. Schwann cell Effector. Myelin Cell body Nervous System Review 1. Explain a reflex arc. 2. Know the structure, function and location of a sensory neuron, interneuron, and motor neuron 3. What is (a) Neuron Axon Nerve impulse Axoplasm Receptor

More information

Chapter 7. Objectives

Chapter 7. Objectives Chapter 7 The Nervous System: Structure and Control of Movement Objectives Discuss the general organization of the nervous system Describe the structure & function of a nerve Draw and label the pathways

More information

Primary Functions. Monitor changes. Integrate input. Initiate a response. External / internal. Process, interpret, make decisions, store information

Primary Functions. Monitor changes. Integrate input. Initiate a response. External / internal. Process, interpret, make decisions, store information NERVOUS SYSTEM Monitor changes External / internal Integrate input Primary Functions Process, interpret, make decisions, store information Initiate a response E.g., movement, hormone release, stimulate/inhibit

More information

Nervous System: Part IV The Central Nervous System The Brain

Nervous System: Part IV The Central Nervous System The Brain Nervous System: Part IV The Central Nervous System The Brain Can you survive when part of your brain is destroyed? 2 Essential Knowledge 3.D.2 2. Cells communicate with each other through direct contact

More information

Establishing the Relevance of Health Hazard Data for GHS Classification: Adverse vs. Non-Adverse

Establishing the Relevance of Health Hazard Data for GHS Classification: Adverse vs. Non-Adverse Establishing the Relevance of Health Hazard Data for GHS Classification: Adverse vs. Non-Adverse Robert Roy, Ph.D. SCHC Fall Meeting Diplomate, American Board of Toxicology September 30, 2014 1 Disclaimer

More information

Shift 1, 8 July 2018, 09:30-13:00

Shift 1, 8 July 2018, 09:30-13:00 Shift 1, 8 July 2018, 09:30-13:00 CNS patterning A001-A014 Stem cells: basic biology and postnatal neurogenesis - part I Development of neural systems: Molecular and genetic characterisationa Epigenetic

More information

Presenting Uncertainty in the Context of Toxicological, Biological Monitoring and Exposure Information. William H.

Presenting Uncertainty in the Context of Toxicological, Biological Monitoring and Exposure Information. William H. Presenting Uncertainty in the Context of Toxicological, Biological Monitoring and Exposure Information William H. Farland, PhD, ATS Presenting Risk Information and Uncertainty Concerns regarding how uncertainty

More information

ACTIVITY2.15 Text:Campbell,v.8,chapter48 DATE HOUR NERVOUS SYSTEMS NEURON

ACTIVITY2.15 Text:Campbell,v.8,chapter48 DATE HOUR NERVOUS SYSTEMS NEURON AP BIOLOGY ACTIVITY2.15 Text:Campbell,v.8,chapter48 NAME DATE HOUR NERVOUS SYSTEMS NEURON SIMPLE REFLEX RESTING POTENTIAL ACTION POTENTIAL ACTION POTENTIAL GRAPH TRANSMISSION ACROSS A SYNAPSE QUESTIONS:

More information

Week 2 Psychology. The Brain and Behavior

Week 2 Psychology. The Brain and Behavior Week 2 Psychology The Brain and Behavior In this lesson, we will focus on the nervous system. We will learn about the Nervous System and its Command Center the Brain Characteristics and Divisions of the

More information

Risk Assessment Report on Tris (nonylphenyl)phosphite (TNPP)

Risk Assessment Report on Tris (nonylphenyl)phosphite (TNPP) EUROPEAN COMMISSION HEALTH & CONSUMER PROTECTION DIRECTORATE-GENERAL Directorate C - Public Health and Risk Assessment C7 - Risk assessment SCIENTIFIC COMMITTEE ON HEALTH AND ENVIRONMENTAL RISKS SCHER

More information

The Nervous System PART A

The Nervous System PART A 7 The Nervous System PART A PowerPoint Lecture Slide Presentation by Jerry L. Cook, Sam Houston University ESSENTIALS OF HUMAN ANATOMY & PHYSIOLOGY EIGHTH EDITION ELAINE N. MARIEB Structural Classification

More information

1. NERVOUS SYSTEM FUNCTIONS OF THE NERVOUS SYSTEM. FUNCTION The major function of the nervous system can be summarized as follows (Figure 1-1).

1. NERVOUS SYSTEM FUNCTIONS OF THE NERVOUS SYSTEM. FUNCTION The major function of the nervous system can be summarized as follows (Figure 1-1). 1. NERVOUS SYSTEM FUNCTION The major function of the nervous system can be summarized as follows (Figure 1-1). Sensory input. Multiple signals from both, internal and external environment are detected

More information

biological psychology, p. 40 The study of the nervous system, especially the brain. neuroscience, p. 40

biological psychology, p. 40 The study of the nervous system, especially the brain. neuroscience, p. 40 biological psychology, p. 40 The specialized branch of psychology that studies the relationship between behavior and bodily processes and system; also called biopsychology or psychobiology. neuroscience,

More information

Texas Commission on Environmental Quality

Texas Commission on Environmental Quality Roberta L. Grant, Susan L. Santos, Mike L. Dourson, Stephanie Shirley, Neeraja K. Erraguntla, R. Jeffrey Lewis, and Nancy B. Beck Society of Toxicology, March 22-26, 2015 San Diego, CA Texas Commission

More information

Human Nervous System. The nervous system has three functions

Human Nervous System. The nervous system has three functions Chapter 37 Human Nervous System The nervous system has three functions 1) Receive sensory input from both external and internal stimuli 2) Perform integration. (Coordinating all of the various inputs of

More information

Module H NERVOUS SYSTEM

Module H NERVOUS SYSTEM Module H NERVOUS SYSTEM Topic from General functions of the nervous system Organization of the nervous system from both anatomical & functional perspectives Gross & microscopic anatomy of nervous tissue

More information

Homeostasis Practice Quiz 20 Questions SBI 4UI

Homeostasis Practice Quiz 20 Questions SBI 4UI Homeostasis Practice Quiz 20 Questions SBI 4UI Question 1 Which system reverses a change in a variable, bringing it back to within a normal range? a. negative feedback system b. positive feedback system

More information

Neural Basis of Motor Control

Neural Basis of Motor Control Neural Basis of Motor Control Central Nervous System Skeletal muscles are controlled by the CNS which consists of the brain and spinal cord. Determines which muscles will contract When How fast To what

More information

COMMITTEE FOR VETERINARY MEDICINAL PRODUCTS

COMMITTEE FOR VETERINARY MEDICINAL PRODUCTS The European Agency for the Evaluation of Medicinal Products Veterinary Medicines Evaluation Unit EMEA/MRL/546/99-FINAL January 1999 COMMITTEE FOR VETERINARY MEDICINAL PRODUCTS EMAMECTIN SUMMARY REPORT

More information

Zinc: Issues and Update. Craig Boreiko, Ph.D. Ottawa May 2008

Zinc: Issues and Update. Craig Boreiko, Ph.D. Ottawa May 2008 Zinc: Issues and Update Craig Boreiko, Ph.D. Ottawa May 2008 Topics Basics of zinc deficiency and essentiality Nutrition vs Toxicology Effects of elevated zinc intake Comparison of risk assessments Concluding

More information

NERVOUS SYSTEM C H A P T E R 2 8

NERVOUS SYSTEM C H A P T E R 2 8 NERVOUS SYSTEM C H A P T E R 2 8 CAN AN INJURED SPINAL CORD BE FIXED? Injuries to the spinal cord disrupt communication between the central nervous system (brain and spinal cord) and the rest of the body

More information

Warm-Up. Label the parts of the neuron below.

Warm-Up. Label the parts of the neuron below. Warm-Up Label the parts of the neuron below. A B C D E F G Warm-Up 1. One neuron transmits a nerve impulse at 40 m/s. Another conducts at the rate of 1 m/s. Which neuron has a myelinated axon? 2. List

More information

GENERAL PRINCIPLES OF TOXICOLOGY

GENERAL PRINCIPLES OF TOXICOLOGY GENERAL PRINCIPLES OF TOXICOLOGY Laboratory of toxicology Department of Pharmacology and Toxicology College of Pharmacy, University of Baghdad 2015 TOXICOLOGY - PRACTICAL SYLLABUS 2015 General Principles

More information

Chapter 9. Nervous System

Chapter 9. Nervous System Chapter 9 Nervous System Central Nervous System (CNS) vs. Peripheral Nervous System(PNS) CNS Brain Spinal cord PNS Peripheral nerves connecting CNS to the body Cranial nerves Spinal nerves Neurons transmit

More information

The world of chemicals

The world of chemicals Integration of Data for Risk Assessment: The RISK21 Philosophy and Methodology in Data Integration for Risk Assessment Timothy Pastoor, PhD, DABT, ATS 1 The world of chemicals Drugs Cosmetics Agrochemicals

More information

Pesticides used for vector control in drinking-water sourcesand containers.

Pesticides used for vector control in drinking-water sourcesand containers. 12.126 Pesticides used for vector control in drinking-water sourcesand containers. In setting local guidelines or standards in the context of local storage practices and realistic insecticide application

More information

Bio 3411 Midterm Review:

Bio 3411 Midterm Review: Bio 3411 Midterm Review: Structure/Development/Systems/ Plastics/Talents/Diseases/Genes Structure General Overview Wednesday October 26, 2011 1 2 THE BRAIN ATLAS 3 rd ed, p. 8! THE BRAIN ATLAS 3 rd ed,

More information

Nervous System CHAPTER 9. Copyright 2016 by Elsevier, Inc.

Nervous System CHAPTER 9. Copyright 2016 by Elsevier, Inc. Nervous System CHAPTER 9 Copyright 2016 by Elsevier, Inc. Neurons and Supporting Cells Copyright 2016 by Elsevier, Inc. 2 Communication and Control Systems nervous system endocrine system uses chemicals

More information

Organization of The Nervous System PROF. MOUSAED ALFAYEZ & DR. SANAA ALSHAARAWY

Organization of The Nervous System PROF. MOUSAED ALFAYEZ & DR. SANAA ALSHAARAWY Organization of The Nervous System PROF. MOUSAED ALFAYEZ & DR. SANAA ALSHAARAWY Objectives At the end of the lecture, the students should be able to: List the parts of the nervous system. List the function

More information

SHORT ANSWER. Write the word or phrase that best completes each statement or answers the question.

SHORT ANSWER. Write the word or phrase that best completes each statement or answers the question. Exam Name 1) A change in the conditions in the synaptic terminal can influence the soma as a result of axoplasmic transport. 2) The nervous system is composed of the brain and spinal cord. A) efferent

More information

The Nervous System. Anatomy of a Neuron

The Nervous System. Anatomy of a Neuron The Nervous System Chapter 38.1-38.5 Anatomy of a Neuron I. Dendrites II. Cell Body III. Axon Synaptic terminal 1 Neuron Connections dendrites cell body terminal cell body cell body terminals dendrites

More information

Human Health Risk Assessment Overview [For the APS/OPP Roundtable]

Human Health Risk Assessment Overview [For the APS/OPP Roundtable] Human Health Risk Assessment Overview [For the APS/OPP Roundtable] Christina Swartz, USEPA Nov. 12, 2008 [Slides Courtesy of Mike Metzger, USEPA] The Risk Assessment Paradigm: The Red Book Hazard Identification

More information

ENV 455 Hazardous Waste Management

ENV 455 Hazardous Waste Management Risk Assessment Basic Information ENV 455 Hazardous Waste Management Environmental Risk Assessment Özgür ZEYDAN (Phd.) http://cevre.beun.edu.tr/zeydan/ Hazard: a potential source of harm to a worker. Risk:

More information

Fig Copyright 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Fig Copyright 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 48.1 Fig. 48.2 Axon endings are called synaptic terminals. They contain neurotransmitters which conduct a signal across a synapse. A synapse is the junction between a presynaptic and postsynaptic

More information

Outline: risk assessment. What kind of environmental risks do we commonly consider? 11/19/2013. Why do we need chemical risk assessment?

Outline: risk assessment. What kind of environmental risks do we commonly consider? 11/19/2013. Why do we need chemical risk assessment? Outline: Human health h and ecological l risk assessment Purpose of risk assessment Methodology for quantifying risk Case study: Children s exposure to As from CCA wood staircases Issues practical and

More information

Chapter 34 The Nervous System:

Chapter 34 The Nervous System: Chapter 34 The Nervous System: 3.5 Learning Objectives 3.5.3 Responses in the human 1. The nervous system: two-part division into the CNS and the PNS. 2. Neurons, name 3 types, give structure and function

More information

Will s Pre-Test for Exam IV

Will s Pre-Test for Exam IV Will s Pre-Test for Exam IV 1) The brain and spinal cord comprise the. (a) autonomic nervous system (b) peripheral nervous system (c) central nervous system (d) efferent nervous system (e) afferent nervous

More information

5.15 HEXYTHIAZOX (176)

5.15 HEXYTHIAZOX (176) Hexythiazox 225 5.15 HEXYTHIAZOX (176) TOXICOLOGY Hexythiazox is the ISO approved name for (trans-5-(4-chlorophenyl)-n-cyclohexyl-4-methyl-2-oxo- 3-thiazolidine-carboxamide (CAS No. 78587-05-0). Hexythiazox

More information

NEURONS ARE ORGANIZED INTO NERVOUS SYSTEMS 34.5

NEURONS ARE ORGANIZED INTO NERVOUS SYSTEMS 34.5 NEURONS ARE ORGANIZED INTO NERVOUS SYSTEMS 34.5 INTRODUCTION The cnidarians have nerve nets, the most simple type of nervous system. The sea anemone has a nerve net that serves simple behaviours such as

More information

TABLE OF CONTINENTS. PSYC1002 Notes. Neuroscience.2. Cognitive Processes Learning and Motivation. 37. Perception Mental Abilities..

TABLE OF CONTINENTS. PSYC1002 Notes. Neuroscience.2. Cognitive Processes Learning and Motivation. 37. Perception Mental Abilities.. TABLE OF CONTINENTS Neuroscience.2 Cognitive Processes...21 Learning and Motivation. 37 Perception.....54 Mental Abilities.. 83 Abnormal Psychology....103 1 Topic 1: Neuroscience Outline 1. Gross anatomy

More information

New Pesticide Fact Sheet

New Pesticide Fact Sheet United States Prevention, Pesticides Environmental Protection And Toxic Substances May 2005 Agency (7505C) New Pesticide Fact Sheet Picaridin Description of the Chemical Use Patterns and Formulations Generic

More information

The Nervous System IN DEPTH

The Nervous System IN DEPTH The Nervous System IN DEPTH The right half of the brain controls the left half of the body. This means that only left handed people are in their right mind. Note taking tips Make sure that you have written

More information

Captan (Pesticides) Summary. Risk assessment report. Food Safety Commission of Japan. Conclusion in Brief

Captan (Pesticides) Summary. Risk assessment report. Food Safety Commission of Japan. Conclusion in Brief 2017 Food Safety Commission, Cabinet Office, Government of Japan doi: 10.14252/foodsafetyfscj.2017003s Food Safety 2017; Vol. 5, No. 2, 61 66 Risk assessment report Captan (Pesticides) Summary Food Safety

More information

The Nervous System. The right half of the brain controls the left half of the body. This means that only left handed people are in their right mind.

The Nervous System. The right half of the brain controls the left half of the body. This means that only left handed people are in their right mind. The Nervous System The right half of the brain controls the left half of the body. This means that only left handed people are in their right mind. Central Nervous System Made up of brain and spinal cord

More information

STUDIES TO EVALUATE THE SAFETY OF RESIDUES OF VETERINARY DRUGS IN HUMAN FOOD: GENERAL APPROACH TO ESTABLISH AN ACUTE REFERENCE DOSE

STUDIES TO EVALUATE THE SAFETY OF RESIDUES OF VETERINARY DRUGS IN HUMAN FOOD: GENERAL APPROACH TO ESTABLISH AN ACUTE REFERENCE DOSE VICH GL54 (SAFETY) ARfD November 2016 For Implementation at Step 7 STUDIES TO EVALUATE THE SAFETY OF RESIDUES OF VETERINARY DRUGS IN HUMAN FOOD: GENERAL APPROACH TO ESTABLISH AN ACUTE REFERENCE DOSE (ARfD)

More information

DIETARY RISK ASSESSMENT

DIETARY RISK ASSESSMENT lambda Cyhalothrin 91 The maximum dietary burden for poultry is 1.3 ppm. No residues above the LOQ of the analytical method used were observed in the feeding study for laying hens at the lowest dose level

More information

1. Nervous System and Neurons (Chap 10&11)

1. Nervous System and Neurons (Chap 10&11) Lecture 05, 05 Sept 2006 Vertebrate Physiology ECOL 437 (MCB/VetSci 437) Univ. of Arizona, Fall 2006 Kevin Bonine & Kevin Oh 1. Nervous System and Neurons (Chap 10&11) (endocrine system later) 52 Randall

More information

Unit 3: The Biological Bases of Behaviour

Unit 3: The Biological Bases of Behaviour Unit 3: The Biological Bases of Behaviour Section 1: Communication in the Nervous System Section 2: Organization in the Nervous System Section 3: Researching the Brain Section 4: The Brain Section 5: Cerebral

More information

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460 MEMORANDUM OFFICE OF PREVENTION, PESTICIDES, AND TOXIC SUBSTANCES Date: August 30, 2004 Subject: Flumetsulam. Chronic Dietary Exposure

More information

The Nervous System. Functions of the Nervous System input gathering To monitor occurring inside and outside the body Changes =

The Nervous System. Functions of the Nervous System input gathering To monitor occurring inside and outside the body Changes = The Nervous System Functions of the Nervous System input gathering To monitor occurring inside and outside the body Changes = To process and sensory input and decide if is needed output A response to integrated

More information

NEURAL TISSUE (NEUROPHYSIOLOGY) PART I (A): NEURONS & NEUROGLIA

NEURAL TISSUE (NEUROPHYSIOLOGY) PART I (A): NEURONS & NEUROGLIA PART I (A): NEURONS & NEUROGLIA Neural Tissue Contains 2 kinds of cells: neurons: cells that send and receive signals neuroglia (glial cells): cells that support and protect neurons Neuron Types Sensory

More information

Biology 3201 Unit 1: Maintaining Dynamic Equilibrium II

Biology 3201 Unit 1: Maintaining Dynamic Equilibrium II Biology 3201 Unit 1: Maintaining Dynamic Equilibrium II Ch. 12 The Nervous System (Introduction and Anatomy) The Nervous System - Introduction Cells, tissues, organs and organ systems must maintain a biological

More information

MOLECULAR AND CELLULAR NEUROSCIENCE

MOLECULAR AND CELLULAR NEUROSCIENCE MOLECULAR AND CELLULAR NEUROSCIENCE BMP-218 November 4, 2014 DIVISIONS OF THE NERVOUS SYSTEM The nervous system is composed of two primary divisions: 1. CNS - Central Nervous System (Brain + Spinal Cord)

More information

Biopsychology. Neurons

Biopsychology. Neurons Biopsychology What is Biopsychology? The study of the physiological, evolutionary, and developmental mechanisms of behavior and experience (Kalat) Primarily focused on brain activity especially as it relates

More information

Chemical Name: Metolachlor ESA CAS: Synonyms: Ethanesulfonate degradate of metolachlor; CGA

Chemical Name: Metolachlor ESA CAS: Synonyms: Ethanesulfonate degradate of metolachlor; CGA 2011 Health Risk Limits for Groundwater Health Risk Assessment Unit, Environmental Health Division 651-201-4899 651-201-5797 TDD Web Publication Date: March 21, 2011 Chemical Name: Metolachlor ESA CAS:

More information

CHAPTER 3 THE STRUCTURE OF THE NERVOUS SYSTEM

CHAPTER 3 THE STRUCTURE OF THE NERVOUS SYSTEM CHAPTER 3 THE STRUCTURE OF THE NERVOUS SYSTEM 3.1. THE BASIC STRUCTURE OF THE NERVOUS SYSTEM. The nervous system of all animals is made up of groups of neurons that receive information from sensory systems,

More information

Dichlorvos DICHLORVOS (025)

Dichlorvos DICHLORVOS (025) Dichlorvos 63 5.7 DICHLORVOS (025) TOXICOLOGY Dichlorvos is the International Organization for Standardization (ISO) approved common name for 2,2-dichlorovinyl dimethyl phosphate (International Union of

More information

TTC NON-CANCER ORAL DATABASES

TTC NON-CANCER ORAL DATABASES TTC NON-CANCER ORAL DATABASES Dr Sue Barlow Consultant in toxicology & risk assessment suebarlow@mistral.co.uk EUROTOX CEC on TTC 13 September 2015 Overview of presentation Rationale for TTC values for

More information

alternative short-chain fluorinated product technology

alternative short-chain fluorinated product technology The extensive toxicology data behind alternative short-chain fluorinated product technology SOT RASS-MISS Webinar 9 December 2015 Robert C. Buck, PhD Technical Fellow The Chemours Company Wilmington, Delaware,

More information

Portions from Chapter 6 CHAPTER 7. The Nervous System: Neurons and Synapses. Chapter 7 Outline. and Supporting Cells

Portions from Chapter 6 CHAPTER 7. The Nervous System: Neurons and Synapses. Chapter 7 Outline. and Supporting Cells CHAPTER 7 The Nervous System: Neurons and Synapses Chapter 7 Outline Neurons and Supporting Cells Activity in Axons The Synapse Acetylcholine as a Neurotransmitter Monoamines as Neurotransmitters Other

More information

The Nervous System II Neurons

The Nervous System II Neurons The Nervous System II Neurons Review Nervous System What is it? The system that receives, processes, stores and transmits information that comes from various parts of the body and the external world. Composed

More information

Autonomic Nervous System

Autonomic Nervous System Autonomic Nervous System Autonomic nervous system organization Sympathetic Nervous System division of the autonomic nervous system that arouses the body, mobilizing its energy in stressful situations

More information

CHARACTERIZING THE IMPACTS OF UNCERTAINTY AND SCIENTIFIC JUDGMENT IN EXPOSURE LIMIT DEVELOPMENT

CHARACTERIZING THE IMPACTS OF UNCERTAINTY AND SCIENTIFIC JUDGMENT IN EXPOSURE LIMIT DEVELOPMENT CHARACTERIZING THE IMPACTS OF UNCERTAINTY AND SCIENTIFIC JUDGMENT IN EXPOSURE LIMIT DEVELOPMENT Andrew Maier, Ph.D., CIH, DABT TERA Robert Sussman, Ph.D., DABT SafeBridge Consultants, Inc. Bruce Naumann,

More information

E) A, B, and C Answer: D Topic: Concept 49.1 Skill: Knowledge/Comprehension

E) A, B, and C Answer: D Topic: Concept 49.1 Skill: Knowledge/Comprehension Chapter 49 Nervous Systems Multiple-Choice Questions 1) Which of the following is (are) characteristic of a simple nervous system? A) a nerve net such as is found in cnidarians B) nerve cell ganglia C)

More information

Pesticide Risk Assessment-- Dietary Exposure

Pesticide Risk Assessment-- Dietary Exposure Pesticide Risk Assessment-- Dietary Exposure Allan Felsot Department of Entomology, WSU-TC Food & Environmental Quality Lab afelsot@tricity.wsu.edu Lecture for 11/17/03 Mandates of the FQPA All tolerances

More information

Gymnázium, Brno, Slovanské nám. 7, WORKBOOK - Biology WORKBOOK. Student:

Gymnázium, Brno, Slovanské nám. 7, WORKBOOK - Biology WORKBOOK.   Student: WORKBOOK http://agb.gymnaslo.cz Subject: Teacher: Student: Biology Iva Kubištová.. School year:../ This material was prepared with using http://biologygmh.com/ Topics: 1. 2. 3. 4. 5. Nervous system, Senses,

More information

ESTIMATION OF TOXICITY TO HUMANS

ESTIMATION OF TOXICITY TO HUMANS 240 TABLE 21-5. (continued) Mammalian bone marrow chromosome aberration test Mammalian erythrocyte micronucleus test Rodent dominant lethal assay Rodent heritable translocation assays Bacterial DNA damage

More information

PSY 215 Lecture #5 (01/26/2011) (Anatomy of the Brain) Dr. Achtman PSY 215. Lecture 5 Anatomy of the Brain Chapter 4, pages 86-96

PSY 215 Lecture #5 (01/26/2011) (Anatomy of the Brain) Dr. Achtman PSY 215. Lecture 5 Anatomy of the Brain Chapter 4, pages 86-96 Corrections: none needed PSY 215 Lecture 5 Anatomy of the Brain Chapter 4, pages 86-96 Announcements: Reminder: The first midterm is in one week! Everyone is encouraged to start studying (recommend 30/night

More information

PMT. Explain the importance of reflex actions (3) Page 1 of 19

PMT. Explain the importance of reflex actions (3) Page 1 of 19 Q1. When a finger accidentally touches a hot object, a reflex action occurs. The biceps muscle contracts, causing the arm to be flexed and the finger is pulled away. The diagram shows the arrangement of

More information

Achieving The Goals Of Toxicity Testing In the 21st Century: The TestSmart Developmental Neurotoxicology (DNT) Testing Program

Achieving The Goals Of Toxicity Testing In the 21st Century: The TestSmart Developmental Neurotoxicology (DNT) Testing Program Achieving The Goals Of Toxicity Testing In the 21st Century: The TestSmart Developmental Neurotoxicology (DNT) Testing Program Joseph Bressler and Alan Goldberg Center In Alternatives To Animal Testing

More information