Part 1 book “Pesticide toxicology and international regulation” has contents: Pesticides - An overview of fundamentals, toxicology of organochlorine insecticides, anticholinesterase insecticides, toxicology of pyrethrins and synthetic pyrethroids, toxicology of miscellaneous insecticides, toxicology of fungicides.
Pesticide Toxicology and International Regulation Edited by Timothy C Marrs and Bryan Ballantyne Copyright 2004 John Wiley & Sons, Ltd.TISBN: 0-471-49644-8 Pesticide Toxicology and International Regulation Current Toxicology Series Series Editors Diana Anderson Michael D Waters Timothy C Marrs Department of Biomedical Sciences University of Bradford, UK Consultant Chapel Hill NC, USA Food Standards Agency London, UK Toxicology is now considered to be a topic worthy of study and research in its own right, having originally arisen as a subsection of pharmacology This rapid growth in the significance of toxicology necessitates specialised yet comprehensive information that is easily accessible both to professionals and to the increasing number of students with an interest in the subject area Comprising professional and reference books, primarily aimed at an academic= industrial=professional audience, the Current Toxicology Series covers a variety of ‘core’ toxicology topics, suitable for use both as an updating tool and as a reference source Published titles Nutrition and Chemical Toxicity Edited by C Loannides (0 470 974453 0) Toxicology of Contact Dermatitis: Allergy, Irritancy and Urticaria Edited by D Basketter, F Gerberick, I Kimber and C Willis (0 471 97201 0) Food Borne Carcinogens: Heterocyclic Amines Edited by M Nagao and T Sugimura (0 471 98399 3) Enzyme Systems that Metabolise Drugs and Other Xenobiotics Edited by C Loannides Pesticide Toxicology and International Regulation Edited by Timothy C Marrs and Bryan Ballantyne (0 471 49644 8) Pesticide Toxicology and International Regulation Edited by Timothy C Marrs Food Standards Agency, London, UK and Bryan Ballantyne Formerly, Director of Applied Toxicology, Union Carbide Corporation, Connecticut, USA; Adjunct Professor, Department of Pharmacology and Toxicology, West Virginia University, USA; Adjunct Professor of Toxicology, University of Pittsburgh, USA Copyright # 2004 by John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, England Telephone (ỵ44) 1243 779777 E-mail (for orders and customer service enquiries): cs-books@wiley.co.uk Visit our Home Page on www.wileyeurope.com or www.wiley.com All Rights Reserved No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning or otherwise, except under the terms of the Copyright, Designs and Patents Act 1988 or under the terms of a licence issued by the Copyright Licensing Agency Ltd, 90 Tottenham Court Road, London W1T 4LP, UK, without the permission in writing of the Publisher Requests to the Publisher should be addressed to the Permissions Department, John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, England, or emailed to permreq@wiley.co.uk, or faxed to (ỵ44) 1243 770620 This publication is designed to provide accurate and authoritative information in regard to the subject matter covered It is sold on the understanding that the Publisher is not engaged in rendering professional services If professional advice or other expert assistance is required, the services of a competent professional should be sought Other Wiley Editorial Offices John Wiley & Sons Inc., 111 River Street, Hoboken, NJ 07030, USA Jossey-Bass, 989 Market Street, San Francisco, CA 94103-1741, USA Wiley-VCH Verlag GmbH, Boschstr 12, D-69469 Weinheim, Germany John Wiley & Sons Australia Ltd., 33 Park Road, Milton, Queensland 4064, Australia John Wiley & Sons (Asia) Pte Ltd., Clementi Loop #02-01, Jin Xing Distripark, Singapore 129809 John Wiley & Sons Canada Ltd., 22 Worcester Road, Etobicoke, Ontario, Canada M9W 1L1 Wiley also publishes its books in a variety of electronic formats Some content that appears in print may not be available in electronic books British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library ISBN 471 49644 Typeset in 10=12pt Times by Thomson Press (India) Ltd., Chennai Printed and bound in Great Britain by Antony Rowe Ltd., Chippenham, Wilts This book is printed on acid-free paper responsibly manufactured from sustainable forestry in which at least two trees are planted for each one used for paper production Contents Preface List of Contributors Frequently Used Abbreviations Toxicity Classifications and Hazard Ratings Pesticides: An Overview of Fundamentals Bryan Ballantyne and Timothy C Marrs Definition and introductory generalizations Major historical features Classification and nomenclature Exposure to pesticides; routes, monitoring, and protection Health issues Regulation of pesticides References xi xv xvii xxiii 1 16 19 Part I Insecticides Toxicology of Organochlorine Insecticides Andrew G Smith Overview Lindane=hexachlorocyclohexane (HCH) Cyclodiene and related insecticides Toxaphene DDT and its analogues DDT Mirex and chlordecone Regulatory aspects Summary References Anticholinesterase Insecticides Charles M Thompson and Rudy J Richardson Introduction AChE 27 27 32 39 45 46 48 59 64 65 65 89 89 90 vi CONTENTS Major classes of anti-AChE insecticides Toxicological consequences of AChE inhibition Therapy for cholinergic toxicity Regulatory aspects of anti-AChE insecticides Acknowledgements References Toxicology of Pyrethrins and Synthetic Pyrethroids David E Ray Usage and human exposure Mechanisms of toxicity Systemic poisoning Pathology Paraesthesia and local irritation Developmental neurotoxicity Reference values for synthetic pyrethroids References Toxicology of Miscellaneous Insecticides Roland Solecki Introduction Neuroactive insecticides Insect growth regulators Plant insecticides Biochemical insecticides References 95 107 108 110 117 118 129 129 131 139 144 145 146 147 149 159 159 161 174 180 185 186 Part II Fungicides, Herbicides and Growth Regulators Toxicology of Fungicides Bryan Ballantyne Introduction Halogenated substituted monocyclic aromatics Dithiocarbamate fungicides Dithiocarbamates Ethylene bisdithiocarbamates Benzimidazole=thiabendazole fungicides Chloroalkylthiodicarboximides Azoles Morpholines Carboxanilides (oxathiins) Organophosphates Piperazines Metallic fungicides 193 193 196 217 217 225 231 242 248 261 265 268 271 272 CONTENTS Miscellaneous Aliphatic aldehydes Thiocarbonates Antibiotics Cinnamic acid class Appendix: Complete listing of fungicides by chemical classes References Toxicology of Herbicides Timothy C Marrs Herbicides Inorganic herbicides Bipyridylium herbicides Phenoxy acid herbicides Substituted anilines Ureas and thioureas Nitriles Triazines and triazoles Organic phosphorus herbicides Defoliants and dessicants, and plant growth regulators References vii 274 274 278 279 281 282 292 305 305 305 305 320 327 328 329 329 331 334 334 Part III Special Types of Pesticide Microbial Pesticides Ian C Dewhurst Introduction Regulatory approaches Toxicity of particular organisms References Biocides Bryan Ballantyne and Susan L Jordan Introduction Chemistry of biocides 2,2-Dibromo-3-nitrilopropionamide (DBNPA) Methylenebisthiocyanate (MBT) Quarternary ammonium compounds (quats) 2-Bromo-2-nitropropane-1,3-diol (bronopol; BNP) iso-Thiazolones Tetra-(hydroxymethyl)-phosphonium sulphate (THPS) Peracetic acid (PAA) Glutaraldehyde (GA) References 349 349 351 353 361 365 365 367 368 371 372 375 377 384 385 388 401 viii CONTENTS Part IV Residues 10 Variability of Residues in Unprocessed Food Items and its Impact on Consumer Risk Assessment Caroline A Harris and Alan R C Hill Variability of pesticide residues Maximum residue limits Minor crops Derivation of MRLs Discovery of residue variability in UK crops Further studies on variability Implications of variability and derivation of the variability factor Calculation of acute dietary exposure Refinement of the variability factor Consumption data in assessing acute dietary exposure Toxicology in the derivation of an acute reference dose Calculating consumer exposure The impact on availability of pesticides References 413 413 414 415 415 416 417 418 419 422 423 424 425 426 426 Part V Human Aspects 11 Occupational Aspects of Pesticide Toxicity in Humans Angelo Moretto Occurrence of occupational pesticide poisoning Acceptable occupational exposure levels (AOELs) and estimate of levels of pesticide exposure Generalities on biological monitoring of pesticide exposure Toxicological effects of occupational exposure to pesticides References 12 Treatment of Pesticide Poisoning Gregory P Wedin and Blaine E Benson Introduction General treatment guidelines Insecticides Herbicides Rodenticides References 431 431 432 435 436 458 473 473 473 476 481 486 492 CONTENTS ix Part VI Regulation 13 Regulation of Pesticides and Biocides in the European Union Deborah J Hussey and Graham M Bell Background Data requirements Evaluation and decision-making process Progress with implementation of the Directives Classification and labelling Maximum residue levels (MRLs) Harmonization References 14 Regulation under NAFTA Cheryl E A Chaffey and Virginia A Dobozy History and legislation NAFTA and harmonizing the approach to pesticide regulation Data requirements Hazard identification Dietary risk assessment Occupational=bystander risk assessment Science policy issues raised by the FQPA References 15 The Regulatory System in Japan Kannosuke Fujimori Introduction Safety assessment of pesticides and establishment of the ADI Establishment of maximum pesticide residue levels (MRLs) Data requirements for registration of pesticides in Japan Conclusion References Index 501 501 504 505 508 509 510 511 511 513 513 515 516 517 519 521 523 524 527 527 528 530 531 533 534 535 -propylphenethyl)-1H-1,2,4-triazole CAS name: 1-[2-(2,4-dichlorophentyl)pentyl]-1H-1,2,4-triazole CAS no.: 66246-88-6 EEC no.: 266-275-6 Uses and mechanism Penconazole is a sterol demethylation inhibitor and is a systemic fungicide with protective and curative actions It is used in the control of powdery mildew on pome fruit and scab It is also used to control Ascomycetes, Basidomycetes, and Deuteromycetes on vines, fruits, vegetables, and ornamentals Penconazole is formulated as emulsifiable concentrate, emulsion, and wettable powder Toxicology Acute toxicity The oral LD50 in rats is 2125 mg=kg and in mice is 2444 mg=kg The percutaneous rat LD50 is >3000 mg=kg and the rat inhalation 4-h LC50 is >4000 mg=m3 Figure 6.32 Penconazole AZOLES 257 Human and occupational toxicology ADI (JMPR): 0.03 mg=kg WHO toxicity class: III Environment and ecotoxicology Plant metabolism includes hydroxylation of the propyl side chain, conjugation to glucosides, and metabolism to triazolylalanine and triazoylacetic acid The soil DT50 is 133–343 days The photolysis DT50 is days In avian species, the 8day oral LD50 for Japanese quail is 2424 mg=kg, for Peking duck is >3000 mg=kg, and for mallard duck is >1590 mg=kg For the mallard duck, the 8-day LC50 is >5620 ppm and for the bobwhite quail >5620 ppm In aquatic species 96-h LC50s are for rainbow trout 1.7–4.3 mg=L, for carp 3.8–4.6 mg=L, and for bluegill sunfish 2.1–2.8 mg=L For Daphnia the 48-h IC50 is 7–11 mg=L, for Scenedesmus subspicatus the 48-h IC50 is mg=L, while for Selenastrum capricornutam the 5-day EC50 is 0.83 mg=L For bees, the oral and contact LD50 values are >5 mg=bee In worms the 14-day LC50 is >1000 mg=kg Tebuconazole Chemical identification Class: triazole Structural formula: see Figure 6.33 Molecular weight: 307.8 Common name: tebuconazole IUPAC name: (RS)-1-p-chlorophenyl-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl) pentan-3-ol CAS name: ( Ỉ )- -[2-(4-chlorophenyl)ethyl]- -(1,1-dimethylethyl)-1H-1,2,4-triazole-1-ethanol Synonyms: fentrazole; terbuconazole; terburazole; ethyltrianol CAS no.: 107534-96-3 EEC no.: 403-640-2 Figure 6.33 Tebuconazole 258 TOXICOLOGY OF FUNGICIDES Uses and mechanism Tebuconazole is a sterol demethylation inhibitor and a systemic fungicide with protective, curative, and eradicant actions It is effective against a wide range of pathogenic fungi in fruit, vegetables, and ornamentals and is formulated as flowable concentrate, grease, seed treatment emulsion and gel, suspension concentrate, water dispersible granules, and powders Toxicology Acute toxicity The oral LD50 in the rat is 4000 mg=kg (males) and 1700 mg=kg (females) and in mice is 3000 mg=kg The percutaneous rat LD50 is >5000 mg=kg and the rat 4-h inhalation LC50 is 0.37 mg=L (aerosol) and >5.1 mg=L (dust) Primary irritation Tebuconazole is not irritating to rabbit skin but slightly so to the rabbit eye Human and occupational toxicology ADI (JMPR): 0.03 mg=kg WHO toxicity class: III EC hazard rating: Xn, R22 Environment and ecotoxicology Avian acute toxicity values include for the Japanese quail an oral LD50 of 4438 mg=kg (males) and 2912 mg=kg (females) and for bobwhite quail 1988 mg=kg For bobwhite quail, the 5-day dietary LC50 is > 5000 mg=kg (feed) and for mallard duck >4816 mg=kg (feed) For aquatic species the 96-h LC50 for rainbow trout is 4.4 mg=L and for bluegill sunfish 5.7 mg=L For Daphnia the 48-h LC50 is 4.2 mg=L and for Scenedesmus subspicatus 4.01 mg=L For bees, the 48-h peroral LD50 is 175.8 mg=bee and the contact LD50 is 0.6 mg=bee For worms (Eisenia foetidia) the 14-day LC50 is 1381 mg=kg (soil) Triadimefon Chemical identification Class: triazole Structural formula: see Figure 6.34 Molecular weight: 293.8 Common name: triadimefon AZOLES 259 Figure 6.34 Triadimefon IUPAC name: 1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one CAS name: 1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)-2-butanone CAS no.: 43121-43-3 EEC no.: 256-103-8 Uses and mechanism Triadimefon is a steroid demethylation inhibitor It is a systemic fungicide with curative, protective, and eradicant properties, used to control powdery mildew on cereals, fruit, and vegetables Triadimefon is available as dispersible powder, emulsifiable concentrate, water dispersible granules, and powder Toxicology Acute toxicity The oral LD50 in rats is 1000 mg=kg and dogs 500 mg=kg The percutaneous rat LD50 is >5000 mg=kg The rat 4-h inhalation LC50 is 3.27 mg=L (dust) Primary irritation Triadimefon is a mild irritant to skin and a moderate eye irritant in the rabbit Metabolism and toxicokinetics Following peroral dosing of triadimefon, 83–96 per cent is excreted unchanged in urine and faeces within to days Metabolism occurs in the liver mainly to triadimenol and its glucuronide conjugates The t1=2 in blood plasma is 2.5 h Human and occupational toxicology ADI (JMPR): 0.03 mg=kg WHO toxicity class: III EC hazard rating: Xn, R22, N, R51, R53 260 TOXICOLOGY OF FUNGICIDES Environment and ecotoxicology In plants the carbonyl group is reduced to a hydroxyl group with the formation of triadimenol A similar conversion occurs in soil with a DT50 of 18 days Koc ¼ 300 Avian toxicity values include in mallard duck an acute oral LD50 of >4000 mg=kg In the mallard duck, the 5-day dietary LC50 is >10 000 mg=kg (diet) and in bobwhite quail it is >4640 mg=kg For aquatic species, toxicity values include 96-h LC50s for bluegill sunfish of 11.0 mg=L, for orfe of 13.8 mg=L, and for rainbow trout of 17.4 mg=L In Daphnia the 48-h LC50 is 11.3 mg=L and in Scenedesmus subspicatus the EC50 is 1.71 mg=L For bees, the contact LD50 is >100 mg=bee Triadimenol Chemical identification Class: triazole Structural Formula: see Figure 6.35 Molecular weight: 295.8 Common name: triadimenol IUPAC name: (1RS,2RS,1RS,2SR)-1-(4-chlorophenoxy)–3,3-dimethyl–1-(1H-1,2,4trazol-yl)butan-ol {Two diastereoisomers are A-(1RS,2SR) and B-(1RS,2RS); ratio is A:B 7:3} CAS name: -(4-chlorophenoxy)- -(1,1-dimethylethyl)-1H-1,2,4-triazole-1-ethanol CAS no.: 55219-65-3 EEC no.: 259-537-6 Uses and mechanism Triadimenol inhibits gibberellin and ergosterol synthesis and interferes with mitosis It is a systemic fungicide with protective, curative, and eradicant effects Triadimenol has extensive use against powdery mildews, rusts, and Rhynchosporium in a large variety of crops and is formulated as dispersible powder, emulsion, emulsion concentrate, flowable concentrate, granule, suspension concentrate, wettable granules, and powder Figure 6.35 Triadimenol MORPHOLINES 261 Toxicology Acute toxicity The oral LD50 in rats is 700 mg=kg and in mice is 1300 mg=kg The percutaneous rat LD50 is >5000 mg=kg and the rat 4-h inhalation LC50 is >0.9 mg=L Primary irritation Triadimenol is not irritating to rabbit skin or eyes Human and occupational toxicology ADI (JMPR): 0.05 mg=kg WHO toxicity class: III EC hazard rating: Xn, R22 Environment and ecotoxicology The soil DT50 is 110–375 days (sandy loam) and 240–270 days (loam) In avian species the acute oral LD50 in bobwhite quail is >2000 mg=kg In aquatic species the 96-h LC50 in goldenorfe is 17.4–27.3 mg=L, in rainbow trout is 13–23.5 mg=L, and in bluegill sunfish is 15 mg=L In Daphnia the 48-h LC50 is 51 mg=L In Scenedesmus subspicatus the EC50 is 3.7 mg=L and in worms (Eisenia foetidia) the LC50 is 772 mg=kg (dry soil) Morpholines This group are derivatives of the basic morpholine (tetrahydro-1,4-oxazine) molecule A major example is dodemorph and its acetate compound Dodemorph Chemical identification Dodemorph Class: morpholine Structural formula: see Figure 6.36 Molecular weight: 281.5 Common name: dodemorph IUPAC and CAS name: 4-cyclododecyl-2,6-dimethylmorpholine 262 TOXICOLOGY OF FUNGICIDES Figure 6.36 Dodemorph CAS no.: 1593-77-7 EEC no.: 216-474-9 Dodemorph acetate IUPAC name: N-cyclododecyl-2,6-dimethylmorphololium acetate CAS no.: 31717-87-0 Uses and mechanism Dodemorph is an inhibitor of ergosterol biosynthesis and is a systemic fungicide with protective and curative actions It is absorbed through roots and leaves and is used to control powdery mildews on roses and other ornamentals Dodemorph is formulated as an emulsifiable concentrate Toxicology Acute toxicity For dodemorph acetate the oral rat LD50 is 3944 mg=kg (males) and 2465 mg=kg (females) The percutaneous rat LD50 is >4000 mg=kg The rat 4-h inhalation LC50 is mg=L Primary irritation Dodemorph acetate is moderately irritating to rabbit skin and severely irritating to rabbit eye Environment and ecotoxicology For dodemorph acetate the soil DT50 is 73 days Koc ¼ 4200–48 000 (high adsorption) Aquatic toxicity values include for guppy a 96-h LC50 of 40 mg=L In Daphnia the 48-h LC50 is 3.34 mg=L MORPHOLINES 263 Fenpropimorph Chemical identification Class: morpholine Structural formula: see Figure 6.37 Molecular weight: 303.5 Common name: fenpropimorph IUPAC name: ( Ỉ )-cis-4-[3-(4-tert-butylphenyl)2-methylpropyl]-2,6-dimethylmorpholine CAS name: cis-4-[3-[4-(1,1-dimethylethyl)phenyl]-2-methylpropyl]-2,6-dimethylmorpholine CAS no.: 67564-91-4 EEC no.: 266-719-9 Uses and mechanism Fenpropimorph is an ergosterol biosynthesis inhibitor [by steroid reduction (sterolD14-reductase) and isomerization (D8- to D7-isomerase)] Fenpropimorph is a systemic foliar fungicide with protective and curative effects Xylem translocation occurs acropetally Fenpropimorph is used to control several fungal species in cereals, sugar beet, beans, leeks and sunflowers It is formulated as emulsifiable and suspension concentrates Toxicology Acute toxicity In the rat the oral LD50 is >3000 mg=kg, the percutaneous LD50 is >4000 mg=kg, and the 4-h inhalation LC50 is 3580 mg=m3 Primary irritation Fenpropimorph is a mild irritant to rabbit skin Figure 6.37 Fenpropimorph 264 TOXICOLOGY OF FUNGICIDES Human and occupational toxicology ADI (JMPR): 0.003 mg=kg WHO toxicity class: III EC hazard rating: Xn, R20, Xi, R38, N, R51, R53 Environment and ecotoxicology Fenpropimorph is strongly adsorbed to soil with a Kd of 22.6 (sand) and 73.9 (loamy sand) Koc ¼ 2772–5943 In avian species the acute peroral LD50 is 3900 mg=kg and the 5-day LC50 is 5000 mg=kg for mallard duck In pheasants the oral LD50 is 3900 mg=kg In bobwhite quail the 5-day LC50 is >5000 mg=kg For aquatic species, 96-h LC50s are: for rainbow trout 9.5 mg=L, for bluegill sunfish 3.2–4.6 mg=L, and for carp 3.2 mg=L For Daphnia the 48-h LC50 is 2.4 mg=L, for Chlorella fusca the 96-h EC50 is 2.21 mg=L, and for Pseudomonas putida the 17-h EC10 is >1874 mg=L The bee acute oral LD50 is >100 mg=bee For earthworms, the 14-day LD50 is 562 mg=kg Tridemorph Chemical identification Class: morpholine Structural formula: see Figure 6.38 Molecular weight: 297.5 Common name: tridemorph IUPAC name: 4-alkyl-2,6-dimethyl morpholine (originally 2,6-dimethyl-4-tridecylmorpholine) CAS name: 2,6-dimethyl-4-tridecylmorpholine CAS no.: 81412-43-3(original); 24602-86-6 (tridecyl-) EEC no.: 246-347-3 (tridecyl-) Composition: tridemorph was originally considered to consist of tridecyl C13 isomers but is now believed to be composed of C11 to C14 homologues containing Figure 6.38 Tridemorph CARBOXANILIDES (OXATHIINS) 265 60–70 per cent 4-tridecyl isomers, 0.2 per cent C9 and C15 homologues, and per cent 2,5-dimethyl isomers Uses and mechanism Tridemorph is an ergosterol biosynthesis inhibitor, acting by inhibition of steroid reduction (sterol-D14-reductase) and isomerization (D8- to D7-isomerase) It is a systemic fungicide with eradicant action Tridemorph is absorbed by leaves and roots with protective action and is used to control Erysiphe graminis in cereals, Mycosphaerella in bananas, Corticum salmonicolor and Exobasidium vexams in tea, and Odium heveae in Hevea It is formulated as an emulsifiable concentrate Toxicology Acute toxicity In rats, the oral LD50 is 480 mg=kg, the percutaneous LD50 is >4000 mg=kg, and the 4-h inhalation LC50 is 4.5 mg=L Primary irritation Tridemorph is not irritant to rabbit skin or eyes Human and occupational toxicology ADI: 0.016 mg=kg WHO toxicity class: II EC hazard rating: Xn, R20=22, Xi, R38, N, R50, R53 Environment and ecotoxicology Metabolism in plants is by oxidation of the 4-alkyl side chain or opening of the morpholine ring The soil DT50 is 14–34 days (field) Koc ¼ 2500–10 000 The LD50 is 1388 mg=kg in quail and >2000 mg=kg in the duck In trout the 96-h LC50 is 3.4 mg=L and in Daphnia the 48-h LC50 is 1.3 mg=L Bees have a 24-h LD50 of >200 mg=bee In worms (Eisenia foetidia) the14-day LD50 is 880 mg=kg Carboxanilides (oxathiins) Carboxin Chemical identification Class: oxathiin Structural formula: see Figure 6.39 266 TOXICOLOGY OF FUNGICIDES Figure 6.39 Carboxin Molecular weight: 235.3 Common name: carboxin; carbathiin IUPAC name: 5,6-dihydro-2-methyl-1,4-oxathi-ine-3-carboxanilide CAS name: 5,6-dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-carboxamide CAS no.: 5234-68-4 Uses and mechanism Carboxin is a systemic fungicide It is a seed treatment for the control of smuts and bunts Carboxin is used to control Rhizoctonia in barley, wheat, oats, rice, cotton, nuts, and vegetables It is formulated as suspension concentrate, flowable concentrate, and water dispersible powder Toxicology Acute toxicity The rat oral LD50 is 2000–3820 mg=kg The percutaneous rabbit LD50 is >4000 mg=kg The rat 1-h inhalation LD50 is >20 mg=L Primary irritation Carboxin is moderately irritating to the rabbit eye Metabolism and toxicokinetics In rat and rabbit the principal metabolic pathway is o- or p-hydroxylation, followed by glucuronidation Human and occupational toxicology Ingestion may produce nausea, vomiting, and headache ADI: 0.01 mg=kg WHO toxicity class: III CARBOXANILIDES (OXATHIINS) 267 Environment and ecotoxicology Plant metabolism involves oxidation to the sulphoxide The soil DT50 is 24 h Koc ¼ 373 In the mallard duck the 8-day dietary LD50 is >4640 mg=kg and in bobwhite quail is >10 000 mg=kg For rainbow trout the 96-h LC50 is 2.0 mg=L and for bluegill sunfish it is 1.2 mg=L For Daphnia the 48-h LC50 is 84.4 mg=L, for Chlorella the 96-h EC50 is 2.4 mg=L, for Selenastrum the 96-h EC50 is 0.48 mg=L and for Lemna the 14-day EC50 is 0.92 mg=L Bees have an LD50 of >181 mg=bee For earthworms, the 14-day LC50 is 500–1000 ppm Oxycarboxin Chemical identification Class: oxathiin Structural formula: see Figure 6.40 Molecular weight: 267.3 Common name: oxycarboxin IUPAC name: 5,6-dihydro-2-methyl-1,4-oxathi-ine-3carboxanilide 4,4-dioxide CAS name: 5,6-dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-carboxamide 4,4-dioxide CAS no.: 5259-88-1 EEC no.: 226-066-2 Uses and mechanism Oxycarboxin is a systemic fungicide with curative action It is used by foliar application to control rust diseases on ornamentals and cereals It is formulated as emulsifiable concentrate and wettable powder Toxicology Acute toxicity The oral rat LD50 is 5816 mg=kg (males) and 1632 mg=kg (females) The percutaneous rabbit LD50 is >5000 mg=kg The rat 4-h inhalation LC50 is >5000 mg=L Figure 6.40 Oxycarboxin 268 TOXICOLOGY OF FUNGICIDES Primary irritation Oxycarboxin is not irritant to rabbit skin, but is mildly irritant to rabbit eye Human and occupational toxicology ADI: 0.15 mg=kg WHO toxicity class: III EC hazard rating: Xn, R22, R52, R53 Environment and ecotoxicology The soil DT50 is 2.5–8 weeks (sandy loam) In mallard duck the LD50 is 1250 mg=kg and the 8-day dietary LC50 is >4640 ppm In bobwhite quail, the 8-day LC50 is >10 000 ppm In rainbow trout the 96-h LC50 is 19.9 mg=L and in bluegill sunfish 28.1 mg=L In Daphnia the 48-h LC50 is 69.1 mg=L, while in Chlorella the 96-h LC50 is 19 mg=L In bees, the contact LD50 is >181 mg=bee Organophosphates Pyrazophos Chemical identification Class: phosphorothiolate Structural formula: see Figure 6.41 Molecular weight: 373.4 Common name: pyrazophos IUPAC name: ethyl 2-diethoxyphosphinothioyloxy-5-methylpyrazolol[1,5-a]pyramidine-6-carboxylate; O,O-diethyl-O-6-ethoxycarboyl-5-methylpyrazolol[1,5-a]pymidim-2-yl phosphorothiolate CAS name: ethyl 2-[(diethoxyphosphinothioyl)oxy]-5-methylpyrazolo[1,5-a]pyrimidine-6-carboxylate CAS no.: 13457-18-6 EEC no.: 236-656-1 Figure 6.41 Pyrazophos ORGANOPHOSPHATES 269 Uses and mechanism Pyrazophos is a systemic fungicide with protective and curative actions It is absorbed by leaves and shoots, and transported acropetally It is used to control many fungi in various fruit and vegetables and is formulated as an emulsifiable concentrate and wettable powder Toxicity Acute toxicity The rat oral LD50 is 151–778 mg=kg, the percutaneous LD50 is >2000 mg=kg, and the 4-h inhalation LC50 is 1220 mg=m3 Primary irritation Pyrazophos is not irritating to rabbit skin but is slightly irritating to rabbit eye Human and occupational toxicology ADI (JMPR): 0.004 mg=kg WHO toxicity class: II EC hazard rating: Xn, R22 Environment and ecotoxicology Degradation in soil occurs by cleavage of the phosphoric acid group, saponification of the carboxylate fraction, and degradation of the heterocyclic ring The DT50 is 10–21 days, and the DT90 is 111–235 days Koc ¼ 1332–2670 In mallard duck the 14-day dietary LC50 is 340 mg=kg, while in bobwhite quail it is 300 mg=kg In aquatic species the 96-h LC50 for rainbow trout is 0.48–1.14 mg=L, for carp 2.8– 6.1 mg=L, and for bluegill sunfish 0.28 mg=L In Scenedesmus subspicatus the 72-h LC50 is 65.5 mg=L, while in bees the 72-h contact LC50 is 0.25 mg=bee For worms (Eisena foetidia) the14-day LC50 is >1000 mg=kg (soil) Tolclofos-methyl Chemical identification Class: phosphorothiolate Structural formula: see Figure 6.42 Molecular weight: 301.1 Common name: tolclofos-methyl IUPAC name: O-2,6-dichloro-p-tolyl O,O-dimethyl phosphorothiolate ... insecticides References 95 10 7 10 8 11 0 11 7 11 8 12 9 12 9 13 1 13 9 14 4 14 5 14 6 14 7 14 9 15 9 15 9 16 1 17 4 18 0 18 5 18 6 Part II Fungicides, Herbicides and Growth Regulators Toxicology of Fungicides Bryan Ballantyne... References Index 5 01 5 01 504 505 508 509 510 511 511 513 513 515 516 517 519 5 21 523 524 527 527 528 530 5 31 533 534 535 Preface Pesticides are used daily and internationally on a massive scale They... The impact on availability of pesticides References 413 413 414 415 415 416 417 418 419 422 423 424 425 426 426 Part V Human Aspects 11 Occupational Aspects of Pesticide Toxicity in Humans Angelo