Document KGJzKZRnxxGb8yRNrLvq68gy0

. \ Chemical Hazards of the Workplace Nick H. Proctor, Ph.D. M anager of M edical Surveillance and Toxicologist Kaiser A lum inum and Chemical Corporation O akland, Cali/ornia James P. Hughes, M.D. M edical Director Kaiser A lum inum and Chemical Corporation Oakland, Cali/ornia }. B. Lippincott Company Philadelphia Toronto Ex S'3 ? Copyright 1978 by J. B. Lippincott Company This book is fully protected by copyright, and, with the excep tion of brief excerpts for review, no part of it may be repro duced in any form, by print, photoprint, microfilm, or any other means without written permission from the publisher. ISBN 0-397-50398-9 Library of Congress Catalog Card Number 78*57614 Printed in the United States of America 3564 Library of Congress Cataloging in Publication Data Proctor, Nick H. Chemical hazards of the workplace. Bibliography: p. Includes index. 1. Industrial toxicology. I. Hughes, James P., joint author. II. Title. [DNLM: 1. Occupational dis eases--Chemically induced. 2. Poisons. 3. Poisoning. WA465 C517] RAI229.P76 615.9*02 78-57614 ISBN 0-397*50398-9 naap iv ; ig ( a transverse white ion to loss of nail. lugeson of the gastrointestinal and kidney damage; acute natory reaction. By analaused in animals* severe e pulmonary edema. -nosh: Differentiate from oqjunctivitis and mucous n, such as viral infection of Hand allergies, ronchial tree becomes inytoms and signs must be m cardiogenic pulmonary iral or bacterial pneumonia, f severe, exposure is susic studies - should include i; sputum gram stain and Ferential white blood cell nary edema occurs* there s ofarterial blood gas. stitute appropriate proceemoval from exposure and ig of eyes and skin with wa* occurs, see the section in eatment of Contact Dermae is severe, hospitalization for 72 hours for delayed onnoTg* ' edema are advisable. >eir\ Maneuvers in Treatary **itants, Chapterfi. al: Preplacement and annual ation with emphasis on the m and skin; 14' x 17' chest FVCandFEV(l sec.). References .. B.: Exposure of spray opaaraquat. Br. J. Ind. Med., i. E. D., and Keir, W.: Nail spray operators exposed to r .J . Ind. Med., 25:399, 1971. and Lewis, D. R. H.: Ocular i to paraquat and diquat. Br. 2 4 ,1968. A.: Toxicology of the Eye. ed. -787. Springfield; Charles C '74. G., McElligotl, T. F., and Parathion 399 - Hurst, E. W.: The toxicity of paraquat. in the chest and wheezing due to broncho- Br. J. Ind. Med.,25:126,1966. constriction and excessive bronchial secre 6. Gage, J. C.: Toxicity of paraquat and di tion; laryngeal spasms and excessive sali quat aerosols generated by a size-selec vation may add to the respiratory distress; tive cyclone: effect of particle size dis cyanosis may also occur. Ocular effects in tribution. Br. J. Ind. M ed.,25:304,1968. clude miosis, blurring of distant vision, tear 7. Bullivant, C. M.: Accidental poisoning ing, rhinorrhea, and frontal headache. by paraquat: report of two cases in man. After ingestion, gastrointestinal effects, * Br. Med. J .,/ : 1272,1966. such as anorexia, nausea, vomiting, abdomi 8. Toner, P. G., Vetters, J. M., Spilg, nal cramps, and diarrhea, appear within 15 W. G. S., and Harland, W. A.: Fine minutes to two hours. After skin absorption, structure of the lung lesion in a case of localized sweating and muscular fascicula paraquat poisoning. J. Pathol., 102:182, tions in the immediate area usually occur 1970. within 15 minutes to four hours; skin absorp 9. Pickersgl, J., et al: Paraquat ingestion tion is somewhat greater at higher ambient and pulmonary iiyury, West. J. Med., temperatures and is increased by the pres 128:26,1978. ence of dermatitis. With severe intoxication by all routes, an Supplemental excess of acetylcholine at the neuromuscular .10. A.C.G.I.H.: Paraquat. Documentation of junctions of skeletal muscles causes weak the TLVs for Substances in Workroom ness aggravated by exertion, involuntary Air. ed. 3, p. 195. Cincinnati, 1976. twitchihgs, fasciculations, and eventually paralysis. The most serious consequence is paralysis of the respiratory muscles. Ef fects on the central nervous system in PARATHION clude giddiness, confusion, ataxia, slurred speech, Cheyne-Stokes respiration, convul (C2H50 )2P(S)0C6H4N 6 i sions, coma, and loss of reflexes. The blood 1977 TLV 0.1 mg/m9 pressure may fall to low levels, and cardiac irregularities, including complete heart block, Synonjms: 0,0-Diethyl O-p-nitrophenyl may occur. phosphorothioate; Akron; Niran; Amer. Complete symptomatic recovery usually Cyan. 3422; BAY E-605; BLADAN; occurs within one week; increased suscepti FOLIDOL E605 b ility to the effects of anticholinesterase Physical Form: Brown or yellowish liquid agents persists for up to several weeks after Uses: Acaracide; insecticide exposure.9 Daily exposure to concentrations Exposure: Inhalation; skin absorption; in which are insufficient to produce symptoms gestion following a single exposure may result in the Toxicology: Parathion is an anticholines onset of symptoms. Continued daily expo terase agent. sure may be followed by increasingly severe Signs and symptoms of overexposure are effects. caused by the inactivation of the enzyme The minimum lethal oral dose of parathion cholinesterase, which results in the accumu for humans has been estimated to range from lation of acetylcholine at synapses in the less than 10 mg up to 120 mg.7 In a study of nervous system, skeletal and smooth mus 115 workers exposed to parathion under cles, and secretory glands. The sequence of varying conditions, the majority excreted sig the development of systemic effects varies nificant amounts of p-nitrophenol (a metabo with the route of entry. The onset of signs lite of parathion) in the urine, while only and symptoms is usually prompt but may be those with heavier exposures had a measur delayed up to 12 hours.1"4 After inhalation, able decrease in blood cholinesterase.1 respiratory and ocular effects are the first to Parathion itself is not a strong cholines appear, often within a few minutes after ex terase inhibitor, but one of its metabolites, posure. Respiratory effects include tightness paraoxon, is an active inhibitor. Paraoxon in- 400 The Chemical Hazards activates cholinesterase by phosphorylation ent set of normal values and a different set of of the active site of the enzyme to form the reporting units. The laboratory report of a " diethylphosphoryl enzyme.*' Over the fol cholinesterase determination should state the lowing 24 to 48 hours there is a process, units involved along with the appropriate called aging, of conversion to the "m ono normal range. Based on the Michel method, ethylphosphbryl enzyme." Aging is of clin the normal range of red blood cell cholines ical interest in the treatment of poisoning terase activity (delta pH/bour) is 0.39 to 1.02 because cholinesterase reactivators such as for men and 0.34 to 1.10 for women.11 The pralidoxime (2-PAM, Protopam) chloride are normal range of the enzyme activity (delta ineffective after aging has occurred. pH/bour) of plasma is 0.44 to 1.63 for men The TLV was set at a level to prevent sys and 0.24 to 1.54 for women. temic intoxication.10 Treatment: Treatment of organophosphate Diagnosis: Initial signs and symptoms in poisoning ranges from simple removal from clude headache, blurred vision, pallor, weak exposure in very mild cases to the provision ness, sweating, abdominal pain, nausea, vom of very rigorous supportive' and antidotal iting, and diarrhea. The signs of moderate to measures in severe cases.**1 In the moder- severe intoxication are miosis, lacrimation, ate-to-severe case, because of pulmonary excessive salivation, muscle fasciculadon, involvement, there may be need for artificial dyspnea, cyanosis, convulsions, shock, car respiration using a positive-pressure method. diac arrhythmias, and coma. Careful attention must be paid to removal of Differential Diagnosis: Diagnosis is based secretions and to maintenance of a patent primarily on a history of exposure and clinical airway. Anticonvulsants such as thiopental evidence of diffuse parasympathetic stimula sodium may be necessary. Maintenance of tion.4 Careful observation of the effect of at respiration is critical, since death usually re ropine and pralidoxime may be valuable. Pa sults from weakness of the muscles of respi tients with organophosphate poisoning are ration and accumulation of excessive secre resistant to the action of atropine; failure of 1 tion in the respiratory tract. to 2 mg of atropine administered parenterally As soon as cyanosis has been overcome, 2 to produce signs of atropinization (flushing, to 4 mg of atropine should be given intraven mydriasis, tachycardia, or dryness of mouth) ously.' (Atropine may induce ventricular indicates organophosphate poisoning. In fibrillation in the presence of cyanosis.) This travenous injection of 1 g. pralidoxime gener dose o f atropine is approximately ten times ally causes some recovery from signs and the amount which is administered for other symptoms of organophosphate poisoning. conditions in which atropine is considered Special Testst The following two types of therapeutic. This dose should be repeated at cholinesterase are clinically significant* true five- to ten-minute intervals until signs of acetylcholinesterase, found principally in the atropinization appear (dry, flushed skin, nervous system and the red blood cell; and tachycardia as high as 140 beats per minute, pseudo- or butyTylcholinesterase, found in and pupillary dilatation). A mild degree of the plasma, liver, and nervous system. Al atropinization should be maintained for at though the action of both types is inhibited by least 48 hours. organophosphates, the level of depression of Pralidoxime (2-PAM, Protopam) chloride red blood cell cholinesterase is a better indi is a cholinesterase reactivator which com a; i cator of clinically significant reduction of plments the action of atropine. In the cholinesterase activity in the nervous system. moderate-to-severe case the dose for adults is Laboratory evidence of depression of red 1 g. injected intravenously at a rate not in ex blood cell cholinesterase to a level substan cess of 500 mg/mmute. After an hour, a sec tially below pre-exposure levels (at least 50 ond dose of 1 g. is indicated if muscle weak per cent and usually much lower) is verifica ness has not been relieved. Treatment with tion of organophosphate poisoning. pralidoxime chloride will be most effective if i :? There are many different methods for esti given within 24 hours after poisoning. Mor V 1 mation of cholinesterase content of blood, phine, aminophylline, and phenothiazines are and associated with each method is a differ contraindicated. I .~ - ' .. * ( ' h ltw .t S April 1M ( m ? tofallaat Koaej trom Armj V H irtb Otet-- Cenftronco, 8DX J . IU Key And O j ^ O lA k tr , U 9 , 81 AprU J . K. I r y , V tshlngtoa F# / W insle, besten 7 L. Oc*r*/C J . L>y, Do 1 . t , . H a r d y , Do7 too F. C. IU C f St Louis J# D. r a r ly , WasbiAgtoo mi y*f ^z * * * * W . Khlagte* / 'E. It7 end Z T l i l t H Lt. Col. Louis 0 . XXlaker Dr. Joseph fUJorviet, and Dr Cusmsv X, pora e f tbo JLtkj Ki m i m d Offlee 1a Arllngton, V irg in ia , 1 A p ril 1564 tb o p o r o s o e f tbo r i a i t as to so s ho cou Id rot r Arar funda f o r fu r th sr C o fo lia a t vrk, p resu xab lj fr e u a source o ta e r ta sa Ft P a trick . - Col. Allnker describid A technique for r t t l f l f moooy eut o f pisaos 11k tbc Licitad Var Laboratorios st Aborde a. I f s Company has a prodmet tbey thlnk can perforo a real erriet mm Id Vietuaa, t U j sa i a 4 a description (reelly a proposai) to linker, ho 111 sood i t to den. Cessa la Vietnam. Zf Cessa thlnks l t nicht e t tbo netd. ht s t i l l fa ll outsido sAj definite m ilita n sp o cifisstlo a, bo w ill sedero l t bae* te Al in1er lta s reue et tbat l t be tostod ia Vietnam t m t ^ r s l t dooaa't s m i ab o f f i c i a l l j ststod speelM eitlon er b n I , Klinker 111 tbam bo in s poaitioo te get noaey and pmission for A fie K tost 0r original nonorendan to Alink er shouit an State ment e f Otojectlre; Operational Coooepts, Justification; and Cthrr Considrations ia A form similar te tbat descrlbed en p. 10 or AA 71- 1 rrrleod U J mm U i L ,f *** r;'r. _ Klinker strossod tbat tbo eempaay so it bt v lllln g te la7 l t s rputation om tbo lise- Sais ahould be sa item hieb 1s aire ad la a state of adranoed dire le pment. Zt sooadod to me sa tbough fctls procedure 1s modo to erd*r for A A ltustioo 11km Cor sod ^Tordoa" * fear age. Tmo p e s s ib ilitla s ero diesisod bare One mas Bonssato Coepanr' t rlM s is r ila n ts , dereloped eo tlrely ea proprietary mono7 Tos. i f AjU D lrlsioe aared t e , tbsy oeuld present a preprietary ries s tc r lla a t bo tbo A n / em tb is basla . 1 dom't feol tbat XAC sheuld take an; p e t it tom pro er eom oa ta la . Xf Col. Allaker and Oem. Covsa ver aultably lmpressed, t e l s eemld resuit la a small sale e f abeni al lx ? * d l t* l? #' aod potential develepaest e f large application. j',' ,EcV'otbr p esslb U U y mas tbat mo mlght irlsb to atats l-.it en* o f sur fa s te s t le a l s si o mium ledlCes (or trialk jrltla sysao-.* --tes) tsetpled v ita a boroleide li 2 ,t-C rouit giro fas ter k o e c i '- v .p l u s a loag tors efToet. (2 berne saggssted to Detrlek last week tbat they eoold - bars rs-ersluated such a ooufelaation.) Xf ve sold tbis to krmj Pesesrob O ffice bp tbo sbore-des oribed procedure l t la at least possible that ve eould get ma mrder ter soeuKh e f tho lodlds fer a Meid tost. Zf the Mold test mero sus esaful thla mibt beooae ' -j ue? a different set of * la .atory report of a mination should state the ig with the appropriate i on the Michel method, 'red blood cell cholines* i pH/hour) is 0.39 to 1.02 5 1.10 for women.11 The e enzyme activity (delta is 0.44 to 1.63 for men vomen. nent of organopbosphate Dm simple removal from ild cases to the provision upportive and antidotal cases.4,'` In the moder- because of pulmonary may be need for artificial >ositive-pressure method, ust be paid to removal of maintenance of a patent sants such as thiopental cessary. Maintenance of il, since death usually res of the muscles of respiauon of excessive secrery tract. sis has been overcome, 2 should be given intravenma I duce ventricular est * of cyanosis.) This approximately ten times is administered for other h atropine is considered ose should be repeated at : intervals until signs of ear (dry, flushed skin, as 140 beats per minute, ation). A mild degree of ild be maintained for at *AM, Protopam) chloride reactivator which com- on of atropine. In the case the dose for adults is mously at a rate not in exute. After an hour, a sec* indicated if muscle weakrelieved. Treatment with le will be most effective if urs after poisoning. Morle, and phenothiazines are Pentaborane 401 It is of great importance to decontaminate the patient. Contaminated clothing should be Grob, D.: Poisoning due to organophosphate insecticides. Am. J. Med., 50:475, removed at once, and the skin should be 1971. washed with generous amounts of soap or de 5. Milby, T. H.: Prevention and Manage tergent and a flood of water; this is best ac ment of organophosphate poisoning. complished under a shower or by submersion JAMA,276:2131, 1971. in a pond or other body of water if the expo sure occurred in the field. Careful attention Supplemental should be paid to cleansing of the skin and 6. Hayes, W. J., Jr.; Toxicology of Pes hair. ticides. pp. 379-428. Baltimore: Williams The patient should be attended and moni &. Wilkins, 1975. tored continuously for not less than 24 hours, 7. Hygienic Guide Series: Parathion. Am. since serious and sometimes fatal relapses Ind. Hyg. Assoc. J .f50:308,1969. have occurred because of continuing absorp 8. Arterberry, J. D., Durham, W. F., El tion of the toxin or dissipation of the effects liott, J. W., and Wolfe, H.R.: Exposure of the antidote. to parathion--measurement by blood Regeneration of cholinesterase is primarily cholinesterase level and urinary by synthesis of new enzyme and takes place p-nitrophenol excretion. Arch. Environ. at the rate of approximately 1 per cent/day.4 H e a lth ,5:476,1961. A patient who has recovered from the acute 9. Murphy, S. D., Lauwerys, R. R., and phase of poisoning remains hypersusceptible Cheever, K. L.: Comparative anticho to anticholinesterases for up to several linesterase action of organophosphorus weeks. insecticides in vertebrates. Toxicol. Medical Control: Preplacement and annual Appl. Pharmacol., 72:22, 1968. physical examination with determination of 10. A.C.G.I.H.: Parathion. Documentation pre-exposure red blood cell cholinesterase of the TLVs for Substances in Workroom activity. A person whose red blood cell Air. ed. 3, pp. 195-196. 3rd printing). cholinesterase falls to or below 40 per cent of Cincinnati, 1976. the pre-exposure baseline should be removed 11. Michel, H. O.: Electrometric method for from further exposure until the activitiy re determination of red blood cell and turns to within 80 per cent of the pre- plasma cholinesterase activity'. J. Lab. exposure baseline. Clin. Med.,54:1564,1949. 12. National Institute for Occupational ... _ Safety and Health, Department of Principal 1. Koelle, G. B. (ed.): Cholinesterases and anticholinesterase agents. Handbuch der Experimentellen Pharmakologie, vol. 15, pp. 989-1027. Berlin: Springer- Health, Education and Welfare: Criteria for a_Recommended Standard. Occupa tional Exposure to Parathion, (NIOSH) 76-190. pp. 13-36. Washington. D.C.: U.S. Government Printing Office, 1976. Verlag, 1963. 2. Koelle, G. B.Anticholinesterase agents. 7n Goodman, L. S., and Gilman, A. (eds.): The Pharmacological Basis of Therapeutics, ed. 5, pp. 456-466. New York: Macmillan, 1975. B*H, PENTABORANE 1977 TLV 0.005 ppm 3. Hayes, W. J., Jr.: Clincal Handbook on Economic Poisons. Emergency Informa Synonyms: Dihydropentaborane (9); pen- tion for Treating Poisoning, U.S. Public taboron undecahydride Health Service Publication No. 476. pp. Physical Form: Volatile liquid 12-23, 35-37. Washington, D.C.: U.S. Uses: Reducing agent in propellant fuels Government Printing Office, 1963. Exposure: Inhalation; skin absorption; in 4. Namba, T., Nolle, C. T., Jackrel, J., and gestion