Document Qk6eX8kgMKrvk24aojOEv31e4

LE MONDE (French Paris paper) AFTER D.D.T. - THE USE OF March 14, 1973 POLYCHLORINATED DIPHENYLS IS TO BE REGULATED For the first time, an International accord has been reached among country members of the OECD (Organization of European Economic Development) toward limiting the production and use of certain chemical products deemed dengerous for the environment and for human beings. Already the use of DDT Is severely controlled and that of PCB's shall be regulated In the coming years. The polychlorinated diphenyls have not achieved the notoriety of D.D.T,. The PCB's in fact have not found as many uses as DDT especially In the underdeveloped countries, especially In the past but also at present. These chemicals used as heat-transfer agenta figure In the production of paints, adhesives, glues, lubricants, pesticides and hydraulic fluids. Actual production is still rather limited: while DDT output still reached 200,000 to 250,000 T/yr In 1971, the producers of the OECD countries (the European countries, the U.S., Canada and Japan) manufactured only 48,400 Tons of PCB in 1971. Revealed In 1966, the toxicity and persistency of these products in the blo^ihere have been worrying the environmentalists ever since. The PCB's are In fact, like DDT very stable and carried by water and air, they can easily spread. They have been found on the North American Continent, in Europe, In the North Sea. Once they have been disseminated throughout nature, they are ab sorbed by certain animals, and as they are soluble In the fats, they pass from fish to sOa-blrds and the seals and finally to man (See Le Monde article of Feb 23, 1972). Their concentration may reach 200 to 400 parts per million In eagles, a few parts or dozens of parts per million In fish of the Baltic Sea. Laboratory studies have revealed their toxicity toward the liver, the skin, and undoubtedly the brain. MUMS 082424 -2 In 1971, the American company Monsanto, sole producer of PCB in the United States and In the U.K., recognized the danger In volved and volontarlly limited Its production. Thereupon, the'Council of the OECD following recommendations by the Environ mental Committee, followed the policy established by Monsanto between controllable and uncontrollable usage of PCBS.. In fact, these products can be used In closed systems (transformers, condensers, vacuum pumps) which makes It possible to recuperate the material following usage. In other cases, they are In contact with the environment (lubrication oils, cutting oils, pesticides, plasticizers, prlntlnk InkB, palntes) and It Is then Impossible to prevent their expansion into the biosphere. SUBSTITUTE PRODUCTS In order not to create unnecessary problems, the OECD decided not to forbid the use of PCB's In closed systems where a substantial amount of material Is put to work making Its recu peration worthwhile. On the other hand, PCB's shall not be used anymore In other applications: small condensers, heat-transfer fluids, food Industries, pharmaceuticals, plasticizers. Inks, vacuum pumps, cutting oils, pesticides. These measures will be enforoed In combination with control of production. Imports and exports of the products as well as their recuperation. A uniform system of labelling will be established and certain standards will be set up for recipients. The various countries' members of the OECD will exchange Information on quantities produced. Imported and exported, as well as on substitute products and their toxicity, the destruction of excess PCB. The countries will report to the Organisation In 1974, 1975 and 1976. It appears that the replacement of the PCBs by other less toxic products should not pose serious economic problems. Studies con ducted by the OECD have shown that they could easily be removed from pesticide oils (where they are still present), and that they Btlll represent about |30 MM In the production of printing Inks (in all OECD countries). On the other hand, the paints Industry Btlll uses great quantities and these paints are made by numerous small firms, which will force them to find suitable replacement products. This first International agreement - and this should be emphasized is not a recommendation, but a decision of the OECD Council; It will undoubtedly be a precendent for other similar agreements. It remains to be seen whether all members will respect it and follow up with the measures as decided upon. S.E. Johnson 5/31.1973. MONS 0B2425 T rr Sii<r>rr<* tf Ur T `/it! Cm irufuotnt S'uOlislung Cofl>pJii), Arwvicruin* -- Primed in Bvlyium POTENTIAL ENVIRONMENTAL CHEMICAL HAZARDS PART III. INDUSTRIAL AND MISCELLANEOUS AGENTS L riSiJUniN and W C. FLAMM Niinunaf liiinniie of Cat trtmmenuil Henhlt Snetieet, fJiihaiiul Iasuntret of Hi tilth, Cnhlie Hnilth \,nirr oml Oeptirtatrtn of Health, Ldueasson and Welfare, Mrimrrh Tnuonh !\,rk, Snnh Carolina 277UV {USA) (Received May 19th, 1971) INTRODUCTION in die previous paper, (he potential environmental chemical hazards related to drugs1 and feed medicunts and pesticides3 were considered via an a-priori consider ation of their chciinc.ii siructure, nature of metabolites and degradation products with relation to known and hazardous insults and the inter-relationships and com monality of hazards present in various use categories. The present section focuses on industrial and miscellaneous agents in analagous consideration. Polymer ami plastic ingredients A wide variety of organic derivatives are used in the polymers and plastics industry as pljsticizers, modifiers, emulsifiers, stabilizers and solvents, a.td their inertness and/or safety is far from being established. Polychlorobiphenyls. Polychlorinated biphenyls (PCB's) are produced by various manufactures and are represented as "a senes of inert, chemically resistant, ftre-rctarding plasticizers compatible with a wide variety of resins, varnishes, waxes and paints, they vary from mobile, oily liquids to white crystals and hard transparent resins"3 The senes of Aroclors (Monsanto) are marketed under various numbers and consist of mixtures of chlorinated biphenyls and terphenyls. The 1200 scries reljtcs to the biphenyls, the 5400 series to the terphenyls, and the 4400 scries to a mixture of bi- and terphenyls. The annual production of PCB's in the Western world nil most recently was estimated at I(X) million pounds. In the commercial process for PCB manufacture, biphenyls are chlorinated with anhydrous chlorine with either iron filings or feme chloride as the catalyst, the byproduct is hydrogen chloride and the product is a mixture of several PCB's. In the process of replacing hydrogen atoms with chlorine atoms, a large number of sub stitution combinations arise, vis., ' i a Set. Telaf Cfturoi,, 1 (197J) 117 MQNS For example, three monnchlorohiphcnyl isomers are possinie, 12 dichlorobiphcnyl isomers, 21 irichlorobiphcnsl isomers and so on T.ieorcuca'K, 210 compounds can be prepared by this substitution process (a tj pica] PCB example would be 2.4,6,2\4'- pcnuclilorobiphcnyl) -. The chemical properties lh,u make poKchlorohipheinls desirable industrial materials are their excellent thernij! stability, lltcir strong resistance to both acidic and basic hydrolysis and their genera! inertness The largest single use of PCO's is related to their electrical properties, as coolant insulation fluids in transformers Other uses of PCS s include impregnation of cotton and asbestos for braided insula tions of clcctric.il wiring, plasticizers of vinyl chloride polymer freons, a plasticizer in wire and cable coatings and in ballasts for fluorescein fixtures. Bccjusc of their thermal stability and fire resistance, the PCB`s also find application in high-pressure hydraulic fluids, heal transfer agents, machine tool cutting oils, specialized lubricants and gasket sealers Miscellaneous uses include; formulation into epoxy paints, protective coatings for wood, metal and concretes, adhesives and in carbonless re pro- due.ng paper: and as pl.istuucrs in plants, resin and chlorinated rubber and have been recommended for improving lindane residues4; they have also been shown to increase the insecticidal properties of DDT. Polychlorinated biphenyls along with DDE [l.l-dichloro-2,2-bis (/j-chloro- phcnyl) ethane] are reported to be the most abundant of the chlorinated aromatic pollutants in the global ecosystem*. Extracts from tissues of sea eagles, pike and salmon1 as well as in various species of British wildlife* contained PCB's and in the latter instance a was found that tn birds' liver and eggs the PCB residues were greater than the organochlorine pesticide residues. PCB's have also been found in fish, mussels and birds front the River Rhine and the Netherlands costal areas1, tn marine animals in Sweden. England and the U.S.A.1-* and in other wildlife samples*'*"". Polychlorinated hiphcnyls have been found in human adipose tissue11, samples of human milk" and in foods (margarine, vegetable oils and particularly fish)1*. Essentially, the same type of residue pattern is becoming apparent for the polychlorinated biphenyls that has been found for the persistent organochlorine insecticides. The PCB's are extremely stable; chemically, fat soluble and hence persis tent in the environment. Polychlorinated biphenyls and polychlorinated tnphenyls have been found to be estrogentcally active11 -- in a sene* of PCB's the compounds containing up to 48% chlorine were active On a weight basts polychlorinated biphenyl preparations (Aroclor 1221) have been shown to have an estradiol-degrading potential about five times that of p^i'-DDE or technical grade DDT1. PCB's are inducers of hepatic enzymes and together with other chlorinated compounds may be responsible for aberrations in calcium metabolism in certain species of birds1 and are generally considered to be more of a potent threat than DDT to our declining bird populations, especially for predatory birds that accumulate fairly high levels of PCB's. Hydropericardium, occasionally accompanied by abdominal edema was 118 Sri. Total Eanron. 1 11971) HONS 0 found in chicks1*' " and Japanese quail1 aficr ingestion of PCB of American (Aroefor) jnd French (Phenoclor) origin respectively The occurrence of lesions resembling those of chick-cdcma in birds fed PCO'* '* has a!>o been reported In most rccem work, Vos et jjl.ia described ihe identification and toxicological csalujiion of chlorinaicd dibenzofuran and chlonnaicd naplululenc m two commer cial polychlorinated biphenyls. A combination of toxicological. pathological and chumcal-an.il) tical data (ntvluding mass spectroscopy) strongly suggested the identity of tetra- and pentachlo.o..>enzofurans (1 and 2, respectively) as toxic factors in the PC3's Clophcn A-60 and Phenoclor DP6, ta The occurrence of dibenzofuran derivatives was suggested via a consideration of the manufacture of PCB's and particularly in the procedure for the distillation of crude PCB in which sodium hydroxide can be used11 PCD can react with sodium hydroxide at elevated temperatures to yield phenolic compounds and can for example yield polychlorohydroxybiphenyls via saponification by sodium hydroxide m a polyhydric alcohol medium11, subsequent loss of hydrochloric acid could then produce chlorinated dibenzofuran derivatives. The biological interactions of polychlorinated biphenyls and insecticides was reported by Lichtenstein et at. 11 who showed that many of the PCB's were toxic to Drosophila melanogaster Meigen and houseflies Alusca domestka L. (but to a lesser extent than dieldrm or DDT: their toxicity increased with a decrease in their chlorine contents). Moreover, subleihal dosages of several of the plasticizer PCB's increased the toxicity of dieldnn and DDT, Although PCB's are not pesticides per se, they are included in about three dozen pesticide products registered by the USDA14. Because of their similarity in structure and chemical properties, PCB's, if present m a sample, are carried through the usual pesticide extraction and screening procedures and are frequently mistaken for DDT in monitoring tests. ci a ODD DOS Phihalale rsier plaslinztrs, Phthalate esters are among the most widely used compounds as plasticizers in a variety of lacquers, varnishes, paints, co-polymers and plastics. Scl. Total Enttrun.' t (1972) 119 HONS 082428 C.ir [n gcncr il. phthr.Iaic estcs hj\ c been rcporied to have a Icmcr order of tov.cuy for experimental anmuls35 *' and thus have been approved lor use in packaging materials for food miended for human consumption However. Guess and coverhers11'30 have dcmonsirdiedjhc subtly toxicmes ([issue culture cell deaih or enhanced growth, changes in an11body rcacliviiy and irriiauon as evidenced by dye cviravasation) ol plasticizers and stabilizers used in the manufacture of poiyvinyl plastics Curate and phtli.il.e.. c>icr plasticizers such tts bis (2-cihjIhewDpinhahitc and acctylatcd tri-butyl citrate were found to be leached from plasticized polyvinyl chloride (PVC)31 The sigmJtcuncc nf exposure time on the leaching of these plastici zers from PVC is important since the plastic is commonly used in in-dwelling surgical devices, eg. cailteiers, and in pharmaceutical containers Callcy ft a/.30 described the toxicology of a series of phthalate esters. It has been previously shown that certain plastic devices used medically can release one or more ingredients into tissue or solvent systems31*34. The four curie acid esters used as plasticizers {eg tricthyl. accivl trielhyiributyl- and acetyl inbutyl curate) have well defined and marked pharmacological activity when administered parenterally (all Tour have local anesthetic action and can block neural transmission when they come tn direct contact with a nerve trunk, and also stimulate the nerve trunk)30, Phthalate ester plasticizers were found to be extracted by blood from plastic tubing and from plastic bags used for blood storage. Butylglycolbutyl phthalate (BGBP) was found to be metabolized by isolated perfused rat liver to glycolyl phtha late. A second phthalate ester plasticizer di(2-ethylhex>l)phihalaie (DEHP) which is commonly used m plastics in biological and medical practice was found accumulated in the liver unchanged. In addition, it was identified in samples of human tissue (spleen, liver, lung and abdominal fat) taken from patients who had received trans fusions of blood stored in plastic bags33. o-c4m. C-OCHjC-C.M, 66 BOBP ocC.OOH OCH,COOH Giytotyi pnuatt COOCHjCHtC.MjKCMjljCH, j^j-COOCH,CHtC,MsHCH, J^CH, OEH* ' The isolation of plasticizers such as DEHP from the anticoagulant curie acid-dextrose solutions stored in disposable polyvinyl chloride blood bag assemblies has also been documented30-37. In addition to evidence of phthalate ester plasticizers in certain foodstuffs such as milk30, there has been evidence concerning the presence of these plasticizers in animal tissues such as beef pineal gland3* and heart40. The teratogenic effects in the chick embryo caused by esters of phthalic acid was described by Bower e: at*1. Dibutoxyethyl phthalate caused tcaiogencsis tn the 120 Set. Tulal Enuron., 1 (1972) MQNS 082429 developing chick cmhrjo and also di-2-nic:ho\\eth\l- and ocia-isodccyi phihaiatc were capable of causing damage to ihc ccniral nervous system of the dc'dopnig chick embryo Toxigenic efTm.:, m dilTcrcni mammals caused by scieral osiers of phih.tiic acid have been well documented1' *1-1J ^ _ The clTcct of chemical sterilization of phsiic items and iheireomcms \\ uh prim arily alkj laimg agents such as cihj lene- ai'.c ?> op> lene oxide adds yei anoiher dimen sion io the lOMcmes and pcnciui.il hazards that might occur Tins is especially true in ihc interaction of iheso gas sterilization agents svuh rubber and polyvinyl com ponents of many deuces. For example, the ethylene oxide reaction product [2-{2- hydroxycthy!-mcrcapto)benzothiazo!c) of the vulcanization accelerator 2-mcrcapto- bcnzoihuuole was found to be more toxic than the precursor using cells in culture mice and rabbits**, O'Leary and Guess*7 demonstrated the homolyzing ability of known amounts of cihylcne oxide to that of freshly gas-sterilized plastic pharma ceutical products as well as the effects of ester type plastics upon the sorption of ethylene oxide into polyvinyl chloride products. Organo fin compownft Orcano tins are compounds which contain at least one un-carbon bond and if all radicals attached to tin through carbon arc designated R, and all other substituents X, the following series are obtained: RjSn, R3SnX, RjSnXj and RSnX,. (R may be simple aliphatic or aromatic hydrocarbon radicals and X halide, hydroxide, OR. SH, SR or acyl radicals). Most of the organo tins of industrial and pcsticidal utility are the derivatives of quadrivalent tin. Organo tin compounds are used in plastics and polymers as stabilizers of vinyl resins and oxygen-containing polymers and polyamides against degradation by heat and/or u.v. light; to control pore structure in polyurethane films, preserve the trans parency of polyvinyl chloride. Compounds used for this purpose arc of the type RjSnX (e g. dioctyl tin and dibutyi tin dilaurates, nulcaies, oxides, etc.), and are generally present to the extent of 1-2% of the finished polymer. The increased use of PVC in the food packaging and disposable medical articles fields has focused the need to elicit both the amount, and nature, of tin stabil izer residues. Organo tin compounds used to stabilize poly (vinyl chloride) during container-forming operations can migrate into foodstuffs packaged in such containers. The FDA permits the presence tn certain foodstuffs, as a result of such migration of two organo tin compounds, namely di-octyl SS-b (iso-octylmercaptoacetate) and di-octyi tin maleate polymer. The concentration of either, or any combination of both, may not exceed I p.p.m. which represents 0-128 or 0,259 p p.m, of tin (as organo tin), respectively, in the foodstuff. Organo tins are employed in a host of other applications that include: (fl) Tn rubber products and paints: as antioxidants and anticracking agents, to retard rubber deteriorations and as stabilizers of chlorinated rubbers or chlorinated paints; (5) Tn transformers, capacitors and cables: to prevent corrosion by serving as scavengers for HO formed if a short circuit occurred in transformers, etc., using pyranols or ihlonnated diphenyls (tetraphenyl tin is usefully employed for this purpose); (r) In lubricants and textile oils: as acute oxidants and corrosion-reducing adjuvants for lubricants; as antt-oxidanu for texuie c-ls; (d) As activators and catalyst* in oxida- Sci. Total Eitaro*., I (1972) 121 HONS 082^30 C.W. non, pol>mcri7.T!ion (polyesters and silicone customers) as Zw'glor-N.ina type catalysis for poly men/ation of olefins, (c) Tin-cont.iinmi oolynicrs numerous tm- contatning polymers and mucrotnolccules base been prepared unh tin in the main chain or as substituent as as :m analogs of silicons (m winch carbon and tin alternate) (f) Miscellaneous uses of ora.mo tins include treatment of fibreglass with alkyl and aryl tin compounds for adhesion 10 resins, curing caul) ms for application of silicons to textiles, paper. The biocidal applications of organo tin include (c) agricultural fungicides iriphcnyl tin acetate (Brestan, fennn acetate) and tnphcnyl im hydroxide (Du-tcr, fentin hydroxide) and bis(tri-n-butyl tin) oxide (TBTQ); --Sn-O-So C4h(^ 1BTO () General fungicidal action (e g. tnphenyl tin chloride): in paints, preservation of mantla and sisal ropes, leather, textiles, to confer mildew resistance to fabrics, for protection of juie and jute bags; wood presenattse, shmicide, paper production process paper; (c) Bactericides and biostats: disinfectant (tnantyl tin), bactericides for seeds; (</) Anthelmintics: against worms in poultry (dibutyl tin laurate, tin oleate, tctraisobuiyl tin), {c) Nemaioctde. y-bromophenoxy triethyi tin, (f) Herbicides, vinyl tin compounds (irtvinyl tin chloride); (g) Rodent repellants. protecting food in treated bags (tnbuiyl tin chloride, tnphenyl tin chloride and acetate), (/i) Molluscides. tnphcnyl uns, (i) Ovicides: trialkyl and iriaryl tin chloride* {e.y. R3SnCI, R being methyl, ethyl or propyl) as insecticides and ovicides in combination with DDT or pyrethrum. The mode of action of organo tins in mammals can be delineated as ihe degree of alkylation of the tin compound perse In general, in the whole animal, pharmacol ogical and toxicological effects of tnalkyl tins are confined to the nervous system** *'. For rats, the oral toxicities10 of the trialkyl tins are in the order triethyl > tnnneihyl > ir;isopropyl> tn-n-butyl, (The decrease of toxicity with increasing length of alkyl chain is analogous to that observed with di- and tetraalkyl tins). The conversion of tetraalkyl tins to trialkyl tins"*13 m two (as demonstrated for tetraelhyl tin) accounts for the latent toxicity of the tetraalkyl tins, with the sue of the conversion being the liver*1,From the toxicological point of view, the tetraal kyl tins can thus be considered to behave in a manner analogous to their trialkyl tin counterparts'* (This conversion of a tetraalkyl to a trialkyl metal has also been shown for tetraethyl lead**13 **, and may be a general phenomena). Once tetraethyl tin 122 Sd- Tout Em'ton., 1 (1972) MONS 03^31 has been convened to tnethyl tin n appears io persist m the bod> m that form uiihoui apparent further reaction to the dmlkyl dcrixame The irmlkyl im ion is a stable entity which ts toxic per sc and persists for some time tn the tissues'2 Long-term feeding experiments smih ir,cth) I tin hate disclosed some testicular jtroph) tn addition to lesions confined lo ihc central nervous s\stem'`,, Triclh>I tins and diethyl tins ionize in aqueous solution'1 '* with production of llie univalent (C2Hs)Sn' ,md divalent (C:Hjl:Sn'* canons, respectively It is reasonable to assume that trialkyl and inary! uns exert ihetr biological action as RjSn* ions or as the undissociated hydroxide RjSnOH formed on dissociation. The dcjlkylniton of diethyl tin by the rat has been reporied'', with diothylntion occurring in both the gul and tissues The induction of biliary and hepatic lesions by dibuiyi tm salts in rats has also been desenDed0. Tnphcnyl tins (C6Hj)2SnX, (where X was halide, hydroxide, alkyl or alkenyl, aryl or aiicydic radicals and ester groups or organic acids) have been found io be chemostcrilants41 *' when fed to adult houseflies. Many of the tnphcnyl tins were found to be superior as chemostcnlnnss, io the aziridincs, if both groups were administered orally. The highest chemosienlumg activity was shown by inphenyl tins tn which X is mobile and the inphcnyl ion is obtained, eg halides, hydroxide, sulphide, alkenyl and ester derivatives (but not phenyl or butyl). Trtphcnyl tins are mainly used tn agriculture as fungicides (e.g. Bresian, TBTO) In the finely-divided state in which trtphenyl tins are applied to plants, they are susceptible to light and oxygen*'. Phenyl groups are gradually split off with step-by-step loss in toxictly. T nphenyl tins decompose slowly into diphenyl tins and the final stage of non-toxic inorganic quadrivalent tin compounds is probably reached through the unstable intermediate monophcnyl tins**, m.. \(C.JI,),Sn/ [C.H.SiV/ J \ --Sn--" Pate and Hays*' described several degenerative changes in testicular tissue of male albino rats treated with iriphenyl tin acetate and chloride Complete sterility was achieved after 19 days of treatment following oral administration of triphenyl tin acetate, a decrease in the number of cell layers per seminiferous tubule, a decrease in tubule diameter and overall testicular size, a depletion of the more advanced cell forms from the tubules and a closing of tubule lumtna. Tricyclohexyl (in hydroxide is used as a mutetde (Plictran, muicide) for apples, pears and citrus fruits, Exposure of tricyclohexyl tin hydroxide to u.v light has indi cated that the compound degrades to cyclohcxyl tin and inorganic tin**. Also, it has been found that when fruit is harvested at varying periods after the final spray treatmeni, the ratio of tricyclohexyl tin to total tin decreases with time. Residue half-lives for tricyclohexyl tin hydroxide in apples and pears were. 5-6 weeks for the apples and 2 weeks for pears following application of Plictran (0.84-1.00 ppm for apples and 0 40-0 99 ppm for pears). Sri. Tetat Environ., 1 (1971) 123 MQNS 082432 Bnphcttol Bisphenol A[(2 2-bi'.f/-hydrox>phcn\l> propane] as a copolymer is an important monomer in several resins used as food packaging materials for industrial processing and consumer use. 3ch Biion*no< A The metabolic f.iic and properties of huphcnoJ A arc of importance since some unreacted monomer docs migrate to food. The metabolism of bisphenol A m the rut following oral administration*'7 indieaics that less than IV# of the material present in urine was free btsphcnol A while the feces contained 35% free bisphenol A and an additional 35% was identified as a hydroxjlaied product of bisphenol A U is important to also note the marked extrogentc activity of bisphenol A19 (ihe minimum effective subcutaneous dose was 0.25 mg in thesensmve ISh-glycogen response of the rat uterus), Rubber additives More than 600 different compounds are employed in ruhber technology. Genetically, however, the organic additives could be grouped into a dozen or so chemical classifications Among these are the thiurams, dithiocarbamaics, thiazolcs, sulfonamide*, thioureas, guanidines, amines, amides, quinolines and phenols. The categories of utility include accelerators, activators, antioxidants, blowing agents, vulcnmrcrs. retarders, reinforcing agents, plasticizers, dusting or dipping agems and inert fillers. Table I illustrates the structures of a number of elasscs of common rubber additives. It is of interest to note that ethyl selcnac (selenium dieihvldtthiocaibamaie) which is used both as rubber accelerator and fungicide is carcinogenic in the mouse*'*, while the rubber additive polymerized A'-niiroso*2.2,4-trimeihyi-l,2-dihydroquinoiioe has rcccnily been found carcinogenic in the rat**1'0. The dithiocarbamaics and their meial salts have also wide utility as fungicides and their decomposition products include: alkyl thiourea, ethylene thiuram mono sulfide, carbon disulfide, carbonyl sulfide, hydrogen sulfide, meial sulfide salts and elemental sulfur. Both thiuram71 and thiourea are carcinogenic for the thyroid71, and 4,4'methylene bis (2>meihylanitiiie) and 4,4'-meihylene bis (2-chloroanilme) arc liver and lung carcinogens m the rat19. Brightening agents Optical brighteners or optical bleaches were first introduced into household products about 23 yean ago as detergent additives. These compounds were generally used at levels varying from a few hundredths of 1% to a maximum of 0.2*/# m such products but today's quality detergents contain optical brighteners, often at levels higher than 0.5V#. They are deposited in minute amounts on fabrics during laundering and emit a bluish fluorescence when exposed to ultraviolet radiation, thus improving the appearance of whiteness or brighteners in the fabrics. 124 Sri. Total Ennroit,, 1 (I*72j HONS 0S2433 TAHLE I COMMON R UII It f. ft ARri|T)VF5 Cuirxoty ---- -- ----- - --- -- Acccfcratort Tcirafnclhylihiunim disulfide itntcUtrt Chk = M S ,ch, & CM, TcuamclhyUlnuram monosulfide 'Vc--C-O CM, H g 'cm, DipcnUmelhylencIhiuram hexasulfide HlcVu _ ,n-C-(S1,-C-n; Mcullodtmclhyl* and dicthyldilhiocafbamaitt CH|S *Cyi '' n-CjM -S-m-S-Ci5t -nN'-C,.Nj M a Cu PQ Zft K-C-S- M / u S cMi js* J ft.a.cd " S*,T* Benzolhiazyl diaullld* CO-~QO )cm, 2* Mcrcaptobcniot htaxoW >~ yV'Ox}dKthylcnebcnztthiiiole>2'$uJfenamidc 00*0 jV.Cyctohciyl-2-bctuothiazolesolfcnamid* TnmeihyJ thiourea Diphenyl guafudlflt <J=VNvS yCN,CH, W`ST^CM,CVCH* 1 cm, >-s-< CM, g H ^MtN-CNMc,H, H NH Scl, Total Environ., I (1972) 125 HONS 082434 TAflLE 1 Continued) Category AntiOXidantt Phcnyl-/*-naphthylamine Structure -- 'QCn- Diphenyl />*/>hcnylcncU<.ifmn />-liopfopony diphinylimine Hydroquinone monobenzyl elhef HH 0-r-0-"C H* C M, - 0-^^-OM l.2-Dihyd/o-2,2,4-lnnu:ihyl quinolnw CCTc 1 cw H Aldol-a-naphlhrUmwa o6 ~ 2,2-Mclhy>cnc-bn-(`l-rolhy|-6-i*.biilyl phenol) OH QH CM, CH, AnU*oSo/ttintS /V,A'--Di(2-ocly!)-p-phenylen* diamin* HH CM, MN CM, jV-< 1 ,)-Oimthylbutyl)-A''-phenyJ-/*phcnytn* diAnuM HM CM.-C-CM.-i -N-Q-7-Q CM, CM, M M Blorirtf afMII AwdtcarboMmidt m}N-C-N=N-C-NMj 11 Jl 0o Diniirotopenumeihylenc tctraminc (3(T-Dinitroo-l,J,J,7-ietraabieye]o[J,J,l]nonanc) M.C-N--CM, III ON-N CM.N-NO 1 11 M.C -- N--CH, 126 Scl. Total Esiriron , 1 0972) HONS 082435 TABLE t (continued) Cuiugur/ Retarder! N-N iirosodiphertylamme So I icy he acid Structure 6-r-o NO COOH Aiatttrttrrt Djbutylphilulaio COOC,,Ht QrC00C<M' Dioctylphthalate [bis(2'Cthylhc*yl)phthabicJ COOCMjCMtCjMjXCMjljCM, XcOOCMjCm -(CH,),CM, Qf c,", yulrtwiziiif agent! 2,5-B(r^/-f-buty! pcroxy)>2,5-djmcihy1 heun CM* CM* CM^-C-CH* cm'-c-ch* 00 0^ CM,-c-Ch1-Cm'-C-Cm' Cm* Cm* fungicide! N~ Trichloromc thy It hio-A-cyclohexene 1 ,J. dicj/bommidc (Capun) Murellaiwotu oddllltti Polymerized N'-nnroo-2,2,4-trimethyl-1,2- dihydroquiQoluw o 0^Vs-cc.t o r NO 4.4-OumiftotliphcnrlfntihaM Set. Total E'iclfQti., I (1973) 127 HONS 082*36 TABLE f (continued) 4.4'`Mcthytcne bji'(--chloroamlmc) 4,4' Miihylcnc bij-(I-mjUiylanihne) Structurr A1 Cl NHJ Cl CH) Ch, The most commonly used cotton bnghteners, shown in Fig, IA arc bis triazinyl derivatives of 4,4'-diani>nosiilbcnc-2,2'*disulfon!C acid. These so-called CC/DAS bnghteners arc prepared from 2 moles of cyanuric chloride (CO and I mole of the disodiuni sail of diammostilbenc disulfomc acid (DAS) With the exception of brightener DMDDEA nil are reaction products of I mole of CC/DAS unit 2 moles of aniline. Bnghicner DMDDEA is the reaction product of I mole of CC/DAS and 2 moles of sulfamlic or mctamllic acid, A number of typical structures of briihicncrs that are stable to chlorine bleach in the wash liquor are shown in Fig. IB. These are benzidine sulfone disulfonic acid (brightener BS). naphthotnazoyJstiibene sulfonic acid (bnghicticr NTS, R m H) and bcnzirr.idazolyl (bnghicner BBI) derivatives. The general structures of typical nylon and woo) bnghteners arc shown in Fig I C and include the derivatives of amino coumarin (brighicner AC) and diphcnylpyrazohne (bnghicner DP), none of winch are stable to chlorine bleach The general structures of polyester bnghteners that also have alfinity for polyamide fibers are shown in Fig. ID and include btsbenzoxazoiyI (bnghtener DBO), naphihoxazotyi (briglttcner NOS) and naphihotriazolyl (brightener NTSA) derivatives. The (CC/DaS) bnghteners behave like direct, dyestuffs on cotton7* Brighte ning of hydrophobic fibers such as nylon, polyester and acetate in an alkaline deter gent liquor takes place by a procedure similar to the dyeing of these fibers by dispersed dyestuffs74. Although the solubility of the commonly used bnghteners in a detergent wash liquor is relatively low, it is still high enough to allow a sufficient amount to dissolve. The exhaust of brightener onto the fiber and migration into the fiber allow more brightener to dissolve in the liquor. It is claimed that the total concentration of brightener in the liquor of the modem American home laundry would be only J-IO mg/liter, even if all the brightener were in solution at one time7'. Of all laundering aids commonly added to the wash liquor apparently only active chlorine products affect the stability of some brighteners. The extent of attack on the so-called bleach unstable bnghteners depends on their chemical structure, temperature, amount of bleach used, etc. Differences in stability to hypochlonte and dichloroisocyanurat; bleaches ] 2J Sel. Total Enciran,. 1 (t#7I) MQNS 082^37 cmsi also jmong (he CC D\S hrtehicncrs This isould appear 10 indicate (hat (tic bleach stability of these compounds ts tl.rcciK or indirectly related to the amine sshich is used Tor the reaction suth the second rcaeusc chlorine on the inazinc ring r NH I I t. (f^) cc^V'cch, ^ M'CWCM> ' OH H Bnght*n*r C*tgnl'On TA OM DMA H,c'' ''cm, H,C" 'CM, M,c CM, 1 H,C CH, oh Oh QH Oh M so,w* D0A OmOOEA N0,S SO,w. SrigntA*r 0S R I 0 1 *ZH-Q~r **0,i BriBtiterwr NTS -A Bngmn*r BBl ;N-^0,c,0 Brt^hUft*r AC T -- N, ,CMft Brrgnt*n*r 0^ QrigMo#r BBO e-<HsCN->ft Brighten#*- NOS Br^nt#*#r NtSA Fitf. 1. Structure* of optical bnghteners, A, Bts tnazjnyl derivatives of 4,4'-dtjnunosiilbcn**2.2'dkkuironic uwid (CC/DAS cotton brtfihieners)* 0, Bleach*Mabte bnghierten. C, Nylon jnd wool brightener*, Dt polyester and polyamide brighiencn. The combined action of optical bnghteners and ultraviolet light in the produc tion of turnon hat been reponed by Bingham and Falk7*. The optical bnghteners studied were: 3-benzyl-4-methyl-7.hydroxy coumarin t3), disodtum^M'-bis (2,4-dimethoxybeniamido)-2,2'-s(ilbenedisulfonate (4), disodtum-4,4'-bit (4,6-dtamlino-S*tnazm-2-yl)-amino-2,2'-stilbeneditutfonate (5). Set* Total CtfotrQtt^ I (1972) 129 HONS 032438 VC" iOfNt i Tumors were noi found in any mice receiving topical applicaiion of the opneal bnghtener in DM SO alone, bur with addition of ultraviolet light (6 h/day on 5days/wcck to a germicidal lamp having 60% of us energy at 254 nip) a high incidence of luntors deselopcd that resembled grossly the tumors ("squamous cell carcinomas) arising from repeated application of carcinogenic poljcycltd aromatic hydrocarbons Since the use of optical brighteners is widespread m laundry products such as detergents, starchcv fabric softeners, in fabrics and paper and in miscellaneous products such as toilet soap and all-purpose cleaners, questions relating to the poten tial hazard of dermal contact and/or penetration of the above brighteners as well as those listed in Fig, I A-D, are germane. Also of importance is the recent finding7"' that the optical brightening agent (6) has been recovered from fish in Sweden suggesting a potential hazard of wash liquors containing other optical brighteners being concentrated in marine organisms and fish and hence available for human consumption. Another interesting brightening agent ts 4-mcthyl umbelliferone (7-hydroxy -4-methyl coumartn) (7) that is used as a whitener in laundry detergents as well as a brightener in dentrifnees. It is related to umbelliferone (7-hydroxy coumann) (8) which is used in sunscreen lotions and creams. Both coumann derivatives had been shown to induce chromosome breakage in allium cepa1,`1*. Miscellaneous ogenis Trichloroethylene and letrachlorotthykne. Both trichloroethylene and tetra- chloroethylene (perchloroethylene) are used extensively as industrial solvents (pri marily far dryclcaning ana degreasing), the latter has been finding increasing use since the advent of coin-operated drycleaning. Trichloroethylene is also used with other chemicals such as po.ymertzed resins of phcnol-formaldchydc, urea-formal- 130 Sci. Totaf Environ^ 1 (1972) C.W. HONS 082439 1 dciiydc and epoxides in the production of ipccul fiber glasses. Tcir.ichlorocthi lone is used in small amounts as a commodity fumijint Doth mcbloro- and tetr.u.hlorocihylcnc have been shown to be ncuroiovic10'bui icirachlorocthjienc is bcheuJ to be more hcp.itoxic than tltc tnehloro dgmative.. The metabolism of 3C-labcled tnehloro- and icimchlorcicihilcnc was studied by Daniel** who found th.n both compounds are largely cxcrctej through the lungs. It is well known that trichloroethylene is excreted in the urine as trichloroacetic acid and irichloroclhanol in all species of experimental animals studies Tn addition to these compounds, monochloroacetie acid ts also a urinary metabolite of man. A point of major importance is the nature of the rearrangement winch results tn the formation of 2,2.2-tnchlorocthanol and tnchloroaceiic acid from 1.1.2'trichlorocthyJcnc Thts has been shown to be an intra-molecular rearrangement of trichloro ethylene and no exchange of chloride with the body chloride pool. Pig. 2 illustrates the metabolic pathways of trichloroethylene and tetrachloroethylene. E0OH4Bt*6A Ci,C*CHCi 11 -- TntnfOTOBihyitn# Lntramoicutr -CMCt CGt* CKO non/ CCUCM.OH CCuCOOH I i I f i CljCsCClj CoOKiati'OO A - 1 CrtC -- CCf( * ccijcoci Tr ,ci'ioro*ciyi emonaa cct,cooH Tneworoaeat* Fig 2. Metabolic pathways of tnehlorocthylanc and tetrachloroethylene rn the rai The formation of the intermediate oxide was postulated by Powell*1, Trichloro ethylene oxide is believed to be formed in vitro when trichloroethylene is oxygenated in the presence of actinic radiation. Rearrangement of the oxide yields tnchloroace(aldehyde (chloral). The formation of chloral in men exposed to trichloroethylene vapor has been reported**. Chloral appeared in the blood within 30 mm of exposure but subsequently underwent rapid metabolism. The oxidation of chloral to trichloro acetic aetd is reporied to be carried out by an enzyme present in the liver of a variety of experimental animals"7. The reduction of chloral to tnchlorocthanol would involve alcohol dehydroge nase. The metabolism of tetrachloroethylene may also involve the intermediate oxidation formation. For example, following exposure of tetrachloroethylene vapor for 2 h in mice, the urinary metabolites included 32% trichloroacetic acid, 11% oxalic acid and traces of dichloroacetic acid. An epoxide intermediate was postulated to account for these products" as shO'n in Fig. 2. Set. Tula! Enrirun,, t (19721 131 ! i c.w. I moms Q8^aq i The acid chloride would be rapidly hvdrolycd lo tnehloroncclic acid and neither trichlorocihanol or ovalic acid would be formed In all of the above discus-ion of the metabolism of inch loro- and tetrndtlorocihylcnc it rs impoiuji 10 notg the mutagenicity of the intermediate chloral hydrate1' as well as the potential mutagenicity and carcinogenicity of cpovidcs in general with specific reicrence to tctrr.chlorocthyleno oxide postulated above. It is of added intpoitnncc to consider the similarity of types of metabolic products (10 those discussed above) of ihe important anesthetics hniorlnmc (1,1.ttrinuoroO-liroitto-2'Chloroctlt,tne) (9) and fluoioxoite (2.2.2-tnfluoroethyl vinyl ether) (10) H 1 CF.-C-Cl I Br CF,CH,OCH=CH, 9 10 Ynfluorocihanol, trifluofoacclaldehyde hydrate and tnfltioronccuc acid are the metab olites of both anesthetics and their formation may proceed vta an intermediate cpoxidanon and intramolecular rearrangement as described for inchloro- and tclrachloroclhylcnc in Fig. 2. Little is known of the chronic toxtcities of the above fluoro-mclab- olites. Triazenes. Certain In.tzenes have technical importance as intermediates in Ihe "Rapidogen" dyeing process'* and aryl dialkyl trtazenes have been palentcd for use as rodent repcllant* and hcrbicidcs',-M. Other inazencs have been evaluated as carcinosiatic agents'1-**. |-Phcnjl-3,J-dimelbyltriazcnc is both a potent carcinogen** and leratogen in rats'90 101. Ccrlatn other l-aryl*3.3-dtalkyl trtazenes of the general formula aryl-N-N-N^f I i } 'alkyl are also potent nemotroptc carcinogens in rats'01. The potency increases in the order: phenyl, 3*pvnd)l, pyndyl-A'-oxide, and methyl and ethyl, respectively. In acid medium, aryldialkyltnazenes are hydrolyzed to yield aryi dtazoruum salts and a secondary amine (it ts of importance to note that methyl phcnylnttrosa* nunc and phcnylnurosourea are boih carcinogenic101104 forming probably phenyl* diazontumion as a reactive intermediate.) Prcussmann ct a!.'ai studied the enzymatic dealkylation by rat liver and lung microsomal fraction m ntro. 1-Phcnyl-3,3-dimcthyl triazcnc was found to be oxtdaiively dcalkylated to form the corresponding aldehyde (formaldehyde) and aniline was also shown to be a metabolite The results suggest that carcinogenic aryl dialkyl inazencs are dcalkylated to form aryl-mono alkyl trtazenes as proximate carcinogens Aryl mono-alkyl trtazenes are known alkylating agents and the carcinogenic activity of mazenes was explained by alkylation of biopolymers (nucleic acids). Fig. 3 illus trates s proposed activation mechanism of carcinogenic phenyl dinelhyl tnazenc 132 Set Total nttrott*i I MGNS QSZVtl to form phenyl inonomcihyl in.izene o$ proximate carcinogen and carbonium ion as ultimate alkylating agent, The proposed reaction mechanism, however, docs not exclude that certain triazenes may act by a purcl> chemical haeroljsis to form aryl di.izomum ions as reactive iniermediaies (for example, the xery local sarcomas after subcutaneous injection of 1-phcnj 1-3,3-dimethyl iriazcne may be explained on this basis). CH, N c*> rtyqrcwyitfOft nyPahreon*yyl m*3*thy|trrH#r# PhoytrAoApnittrkyitntiM* * HjO CHO*N=N'CK,l Anum* MtnyMi*>nyere<)a* UomT i-t CM, * Carbonium n u *yi*tmg 9*nt Fig. } Proposed setivmion mechanism of carcinogenic phcnyldimcthyllnucne lo form phenylmonomeihyliriaune u proximate carcinogen, and carbonium ion as ultimate alkylating agent "*, The iti two alkylation of guanostne, RNA and DNA with aryl-monoalkyliriazenes 10 form 7*alkyiguanme was demonstrated by Preussinann and von Hodentwrg1*. Aryl nionoalkyItriazenes are alkylating agents11-11 as shown; + H* -- * Hf + CM,* The alkylaiion of biopolymers was earlier proposed as the first step in carcino genesis by aryldialkyltriazencs101. Reactions of l-phenyl-3-monomethyl- and mono ethyl triazenes, respectively, with guanostne, RNA and DNA resulted in the formation of 7-methyl and 7-ethyl guanine. It is germane to consider the closely related carcinogenic alkylating substances consisting of. A'-niiroso, hydrazo-, azo-, and azonyalkanes since, as we have discussed previously, many environmental agents either possess ihe above moieties or are trans formed via metabolic and/or degradattve pathways to them. Set. Totai EnmroU', 1 (1972) 133 HONS 032^2 The first and decisive slop in ilie aciixation of these groups in an enzymatic a-C-hydroxylmion of an alkyl residue, which is then cleaved oil' as ihc corresponding aldehyde (an alkyl diazohydro\ide or an alkyl diazonium ion is prohahly formed as an alkylating intermediate). The naiurally occurring azoxyalkane cycasin (mctliylazoxymcihano! glucundc) (11) is transformed to tts methylazoxy methanol (12). + CHj-S-N-CHjO-P-O-C.MmO, I O' II + ch,-n-n-ch,oh I 0- 12 This proximate carcinogen is then easily hydrolyzed to formaldehyde and an alkylatins agent, probably methyl dnnttne oxide, which is a tautomer of methyl- du/ohydroxidc. Azoalkanes could possibly be oxidized m mo to yield azoxyalkancs. Dealky lation of alkanes could form alkyl dumines which could possess alkylating activity. Fig 4 illustrates the proposed reaction mechanism of Uydrazo-, azo- and azoxyalkancs according to Preussmann tt a/.111. - B-CHj-KM-NH-CM,-* 0 1 n-C H,-M=N-CH,- *-C- nyor<**yi** 0 1 B-CH^-NsN-^H-B OH o * Cm,-b Fig. 4. Proposed reaction mechanism of hydrezo-, azo- and azoxyalkancs. The alkylation of nucleic acids, particularly at N-7 in guanine, and the resulting change of the genetic code in ceils ts considered as lhe initiation of their carcinogenic transformation. Since the "active forms" in all three groups of substances (ui., () nilroso compounds. (6) hydrazo, azo, and azoxyalkancs, and (c) l-aryl-3.3-dia)ky! inazcncs) are the same, e.g, alkyldiazomum compounds, the spectficity of the effects must most probably be altnbuted to the whole molecule of the "transport forms" or to their 134 Sri. Total nnrun, I 09T2} HONS Q84|43 enzymatic activation The detection of carcinogenic properties in diazomoth.imr 3nd duzo.iccuic as well as in directly acting alkyl.mng agents such as alk\l lulides, a/iridincs. dialky! sulfates and 1,3-propane sulfone gives considerable support to the alkylatton theory101. _^ A number of reported reactions of mono-nucleic acids with diazomum salts hi uiro are informative1'1-' u. For example, the arylation of guanine in the S-posMion by dijzomum salts has been demonstrated111. Typical compounds formed include <$-/>-bcnzolsuIfoguanine (J3). Guanine reacts with dtazomum salts to yield guanine 3-azo compounds which can further reduce to d-arntno guanine and arylamtne111-1'4 while adenine docs not undergo the analogous reaction. ' Kosscl111 described the reaction of mononucleotides with diazonium salts to proceed as shown: X%ntrudyJi< iCid The mononucleotides guanyl-, adenyl and cytidylic acid react with diazotized sulfa* nilic acid at pH 10-1t forming colored dyes (pigments) which absorb strongly at 370-440 mji. Guanylic acid reacts more rapidly than adenylic or cytidylic acid while undyt- and thymidylic acids show no rcation with diazonium sails. At pH 3 all the pigments decompose again to the tuning materials. The pigment formation it inhib ited in the presence of formaldehyde. The reaction products are suggested to be dia zoamino compounds. Sri. Tmal Eni wh., t (1972) 135 MONS 0824^ I c.w. 1 Reactions of dia/ontum salts \Mth nucleic acids were investigated by Pochon and Michel son1 11 Diuroi. . .1 tabs obtained from 2-amino-/>-bcn/cnc disulphonic acid and 2->imslionjphtlialene-l,5-disulphonrc acid were found to be highly specific giving 8-subsiiuucd guanine residues This type of reagent lus been employed to mark DNA for studies by electron microscopy"* Polyphetnh Ceri.un polyphcnyl compounds have been used as moderator coolanis in nuclear reactors for some years and their toxicity is of importance should they be accidentally released The errome toxic.ty of polypheny) mixtures have been reported11*'110 At a daily dietary intake of 350 m;'kg or more Samowax OM. a mixture of tcrphcnyls used as a coolant, causes severe and to sonic extent irreversible chemical nephrosis and interstitial nephritis in rats following prolonged ingestion Samowax OM consists of a mixture of biphenyl (4,7%), o-terphcnyl (64 !%), mtcrphcnyl (25.1%) and p-tcrphenyl (6,1%), while OMRE High Boilers consists of high botlerj>98%. biphenyl (<0I%), o-terphenyl (0 1%), m-terphcnyl (<0.1%. p-terphcnyl (<0,7) and inorganic (<0.1%), At a daily dietary intake of 33 mg/kg or more an OMRE High Boiler Sample (consistingof tcrphcnyl and radiolytic and pyrolytic products derived thereof)induces a marked reticuloendothelial hyperplasia in rats following chrome oral adminis tration, leading to an irreversible monolobular cirrhosis. The toxicity of the above reactor coolant to fish was described by Guthrie and Acres111. The acute toxicity in rabbits of poly phenyl compounds used as atomic reactor moderator coolants was described by Haley et aA111. Ortho* and mtia tcrphcnyls were the only polyphcnyls that caused death after inhalation. Diitoc) auatts and polyurethanes. The dusocyaaates such as toluene-2,4diisoeyanate (TD1) and methylenediphenyldiisoeyanate (MDI) are representative of chemically hghly reactive moieties that will combine with many organic compounds. The industrially useful reactions involve the combination with a resin, usually an organic polyhydric alcohol, to form a high molecular weight polymer of the polyure* ethane type. Polyurethanes are used as paints and varnishes, surface coatings, flexible and rigid foams, wire coverings and in tbermal and sound insulation, ""ip MCO 701 NCO NCO MOt TD1 is usually prepared from toluene-2,4-diamine and phosgene m a solvent such as o-diehlorobenzene or toluene. In the process where TD1 is used on a very large scale in the manufacture of flexible foams, the highly exothermic reaction is controlled by the addition of appropriate caialysis (eg blowing agems such as azodicarbonamide). As a result of the exotherm, significant quantities of TDI vapor may appear in the atmosphere and in concentrations substantially above the present threshold limit value of 0 02 p p m.121 Prolonged exposure of workers to low air concentrations of TDI (0.1 p.p.m.) have been reported to produce a variety of acute and chronic respiratory effects11*'11*. Sri. Tumi Eurireu., I (1972) HONS c.w. J Crude MDI utcd in rigid urethane foam formulations is prepared by treating the condensation product of aniline and formaldehyde with phosgene Any uncondcnsed aniline initially present will be contorted 10 phenyl isocyanate, winch because of its volatility, is more tovre ihai\_the diuqeyanaics The hazards involved tn ihc decomposmon of polyurethanes hate been suggested by Paisley110 lTor example the decomposition of polyurethanes used in wire insulation occurs at 220"C-275*C, producing iso-cyanatcs and W-oudes. (The temperature of a soldering iron in no-mal soldering operations is approximaicly 300 C.) The possibility of a serious incipient hazard in combatting fires involving buildings and refrigerated compartments, etc., where large quantities of polyurethane foams are used was also raised by Paisley110 The effects of physiologically active media on polyurethanes were studied by Lipatova and VerclovsW11 to determine the poicntial use of polyurcihancs as substitutes for tissues in surgery The mechanical strength of polyurethanes were declined by 40-80*/* after a 5-month treatment in test solutions (r g, physiological solution, gastric juice and pure HCI). The degradation of polyurethane in the model solution occurred as a result of cleavage of CO-bonds in the urethane group affording RNCOOH and R'OH. The degradation rate was inversely proportional to the number of intermolccular bonds in the polyurethane. SUMMARY We have examined but a small number of selected chemical agents from a spectra of environmental areas, t drugs1, feed medicants and pesticides'; polymer and plastic ingredients, rubber additives, brightening agents and industrial chemicals with a view toward elaborating their potential hazard via a primary consideration of their structural analogies to known carcinogens, mutagens and/or teratogens. Efforts were made to cue where possible, the areas of primary environmental concern to man in terms of water, soil, air and food residues and attendant portals of entry of these agents as well as to stress their known biological and toxicological effects. Recognition was also made wherever feasible to the interrelationships and commonal ity of metabolites and degradation products from wilhtn the classes of compounds examined. We stress the fact that not only are chemical pollutants (both synthetic and naturally occurring, as well as their metabolic and/or degradation products) capable of producing any one or more ofa variety of acute and chrome toxrciues, but they may also interact tn vitro and in vivo to produce synergistic or potentiating efTccts. Clearly the problem is staggering when one considers the myriad of new agents introduced into the environment annually on top of an already staggering number of present and potential hazards, but the time may also be short in eliciting the hazards of these sgents to man. i I I I I 1 t A 1 c.w, fu/ Envircn** ! (1972) 137 MONS OAibhb I J i references 1 L. FiUibcm and 'V- G Flimm, Sel. Total Em,can.. J 097') ij 2 L. Fithbewi and ". G. J lamui, Su Tn/,,1 Cm into , I (1972) 31. 3 Monumo Tech. Hull. G Mfuclitvc !'11tie!Srr,, 1963. 4 I, HornsKin and \V S Sulinan, J Ccun. tniunio', 4b 09") 9.17. 5 R. W, Riccbrougli, P, Rciclie, O B Peakall, 5 G. Herman and M. N. 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