Document zbG0876825By4wVyj8dnyqwkn

THE TOXICITY OF CERTAIN BENZENE DERIVATIVES AND RELATED COMPOUNDS* Edit Fold Sim*, MJO., DsJML. idindant PrHtutr ! imdmtrisi Bni***i Vmimiitf 4 . IrmtooccRow f | 1HE title of this paper may *ug I geet a 7 vide range of com* *** pounds, about, the toxicity of tome of which we have oo&adermble information but about that of others we know little or nothing. I was recently appealed to by an ineuianee company to outline a program for safe handling of a compound that I did not know was used in industry and about the toxicity of which nothing has been published so far as I know. However, though ths derivatives of bensene are legion, yet they group themselves into certain main classes, about certain members ofwhich we have information. In most eases members of a class act on the system in a similar manner and differences in action are differsces of degree rather than of kind. * There are exceptions to this general rule, however, some of which will be pointed out later. Gomut Cosmmowa Bensene, CA, is the simplest com pound of all, and the bensene ring is the basis on which all the others are formed. The so-called homologues Rtad before the Sretfoa ra Industrial Hyfiu* of the American Publie Health AaMciation, Fort Worth, Texas, Oct. 2S, 1990* Btesivsd for publication Dee. IS, 1930. of bensene ere toluene, CA-CH* and xylene, CA-(CH*),, in which one or two methyl radicals replace one or two hydrogens (1). The most important bensene deriva tives industrially and toxicoiogically are the nitre, ammo, diamino, and chlor compounds of bensene and tolu ene. Danger to health from these compounds depends not only on their eheminel structure but also largely on their physical state and the method of handling them. Thom compounds responsible for the greatest amount of industrial sirhw are not necessarily the most toxic. ' Homologua of Sentene Considering first the homologues of bensene, toluene end xylene, we find somewhat conflicting reports. Selma Meyer (2) sates that regardless of which poison is acting, whether ben* sene, toluene, xylene, (naphthalene, aromatie nitre compounds, etc., the lymphocytes are increased in the Mood stream and the neutrophils are forced back or repteewd. American findings do not agree with this. Neither Greenberg (3) nor we (4) have ' found toluene or xylene presenting any characteristic blood picture in experimental Greenburg found that with continuous exposures for up to seven days, high concentra- VAU mi GBRN001909 LEXOLDMONOOI780 88 TEE JOURNAL OF INDUSTRIAL HYGIENE tiooa of toluene killed all exposed More marked case* of poiaoning >wifii>h is forty-sight to aeventy-two develop violent throbbing headache, hours with narcosis. *ur- ditiinws, rearing in tbs ears, and viving lower concentrations ahowed visual disturbances. With still more evidences of narcosis, irritation or severe poisoning the face becomes daprearioa, with irritability. Our own livid, the lips and tongue blue, the tests with four-hour ezpoeuna over knees week, and the gait staggering. longer periods ahowod evidences of The bine color of the face may persist hag inflammation and of tone degen* for several day*. In extreme ease* ration in internal organa. Wa both cyanosis increases, muscular tremors found toluene to be leas torio than develop, than is extreme weakness, benaene, and the National Safety cold akin, nausea and vomiting, ab Council recommended it aa a substi- dominal cramps, quick, shallow respi tuts for benaena where poerible (3). ration, lowered blood pressure, and lata In addition to being leaa toxic, H ia uneonaeiousneas. Coma develops, the leas volatile and ia leea likely to exist respirations become progressively in a plant as vapor of toxic concentra slower and shallower, involuntary tion. Xylene we have found alao to urination and defecation may occur, be quite tozie, but spin it ia even leaa and convulsions usually come on volatile than toluene and therefore just before death. Not infrequently leaa basardoua. Neither of theee two attacks are delayed, eoma coming on substances aeema to be readily abaorbed even hour* after ceeaation of exposure. through the eldn in toxic amounts and The blood picture ia characteristic, I know of no caac of poisoning from with reduction in the red oell count and skin absorption due to them. the hemoglobin, pdkiloeytoeia, ani- socytosia, and some fragmentation of ATtfro and Amtno Group Compound* red ocUa with polychrometophilia. Nitre and amino groups, aromatics, The blood beeomea ehoeolate colored in general produce much the asms owing to the development of methem- eiinieal pictures, differing ia some oglobin, the spectroscope showing details and with a few (truing excep absorption bands between those of tions. The latter in general are simple pure methemoglobin and oxyhemo blood poisons, while the former in globin. Evidences of blood regenera addition exert a direct action on the tion are seen after a few days in non- central nervous system. Floret (6) fatal eases, with the appearance of saye that all aromatic and aliphatic stippled cells and nucleated red cells. compounds are fat solvents and there There is an early polymorphocytoeis fore particularly apt to affect the followed later by a relative.lympho- central nervous system. eytosia. In alow poiaoning from con In light eases of poisoning from tinued low expoauwa there may be an nitre or amino compounds there ia increase in the red oell oount. The flushing of the face, with a sense of urine beeomea brown, port wine col fulness end throbbing pain in the ored, or smoky red, and shows bile and head, burning sensation in the throat, blood pigments, methemoglobin or and a feeling of tightness in the chest. hemoglobin. At times albuminuria 11. s. (ink. mi 6BRN001910 l LEXOLDMONOOI781 BENZENE DEWTATTVEB AND BELATED COMPOUNDS oeenn cad the aria* may ndoee tinned expoeun ia mid to produce Fehiiaf'i aolution. For moat of thia bladder turnon whieh may become group the akin ia the moat important malignant. entry port. The average lethal dose is 23 gm.; Amine Campowdt 0.4 to 0.0 mg. per liter of air may be bon* without mueh ham for ana- While the amino componada aa a half to one hour but 0.1 to lit mg. daaa produoa a deeper eyaaoris thaa pv Star for several boon produces do the aitro compounds, yet with alight symptoms (6). Tests made by them, poieoaiag ia leea serious aad Issaid (7), In 1920, la the aniline recovery oaaally naolta la a few days boom of a plant while rsduccn wen if exposure ia not continued. Then being discharged, gave the following an exception* to this, however. They amounts in milligrams per liter of sir: an all very readily absorbed through 0.5, L01, LIS, 2.43, and 3.4-all bat the akia aa well as through the lungs. the fint one well above the tome con Aailiae poisoning is first manifested centration*. Men wen exposed to as aa intense eyaaoeis, the victims of them eoneeatratioes for periods of poisoning being referred to as "blue from twenty to forty minutes. One boys." In an aniline plant Tinted workman at the plant developed during the war, eases of poisoning cyanosis from wearing an old pair of occurred daily aad blue boys wen a gloves found lying in a pod of common eight. Following cyanosis water on a drumhead. Changes is then develop headache, diasineaa, design of apparatus and method dysphagia, nausea, vomiting, weak relieved this condition sad reduced the ness, restleaeneas, palpitation, and number of poisoning* in this depart- irregular alow respirations with rapid meat almost to the vanishing point; feeble heart action. Pupils an con later, however, the plant started to tracted but respond to light. Tem- develop the production of synthetic ' pentun ia subnormal. Then ia aa indigo, and new ease* began to appear aniline odor on the breath aad to the in men discharging the phenylglyeine sweat.'- The urine is dark ia color driers, as the finely powdered phenyl- owing to the presence of hemoglobin. giyeine carried more or lea* absorbed In seven eases then may be a lorn of aniline. Here the poisoning was due sphincter controls sad also pulmonary to dust inhalation. Two tests taken edema. Mon cases and mon seven by Iatard, in the indigo house while the poisonings occur ia hot weather. vacuum driers were being emptied, Worker* may develop a degree of showed 0.7 aad 1.7 mg. of aniline per tolerance but the eyaaosia may persist. liter of air. Continued exposure may result ia Toluidinee produoe the same symp headaches, irritability, poor appetite, toms as does aniline, with km cyanosis nearasthenia, visual disturbances aad but more strangury sad hemoglobin Hehiag of the eyes which may lead to uria. They pioduee subnormal tem injury and ulceration of the cornea perature and anemia. Exposure oo- from rubbing. Then is anemia, with eurs from splashes from centrifuges decreased hemoglobin. Long-oon- and whixsen. voL n n.s . GBRNQ01911 LEXOLDMONOOI782 90 THE JOURNAL OF INDUSTRIAL HYGIENE Bets-naphthyiamine produce* cyan tion available in the literature. Many osis end tlao frequent urination m * of theee preparations were for nee in result of iriiution due to overbad the rubber industry ss accelerators or urine. Diamina retarders. Most of these testa have been assembled for comparative pur poses and are here presented in the The may be decidedly hops that they may be of interest and toxie. Phesyienediuunci we need of help to others called upon to use ** dye intermediate* is dyeing hair end these materials or to make rimilar fun. They have been responsible for tests. a number of cue* of poisoning from In many cases all that was desired heir dye* sad from cheep dyed fun. by those requesting information was Symptom* produced ere dermatitis, the determination of ths wiiimm tleeplesaneaa, ditriae--, end weakneac; lethal dose, as an indication of the sad epileptiform convulsions, come, possibility of accidental acute poi sad death may result. The reaction soning. With others the effects of may develop very suddenly and be of repeated sublethal doses were studied. anaphylactic type. Some writers have' All experimental work was done with T"****4 that it was a true anaphylaxis, null inixoils, it being the custom in and Cunchmann has suggested cal* our laboratory to use at least two eium therapy with the inhalation of types of often three, for such sprayed solutions of calcium salts. work. The animals of choice, for Most writers, however, now attribute convenience in handling, are white the poisoning to quinone intermediate* rats, guinea-pigp, and rabbits. Dos resulting from incomplete oxidation, ages are alwayi given as grams per and state that care to secure eomplete kilo of body wedght of the at the oxidation and careful, thorough waab- time of administration. It ia custom* ing of dyed fun will prevent the ary to interpret the results of such trouble from developing. Phenylene- tests in terms of grams per kilo of body <iimiw should never be used in hair weight of man, but we always give dyes. such interpretation with considerable Tolylenediamine is a blood poison, reserve, and feel that at best it indi producing destruction of red cells, cates an approximation to the range of methemoglobm, and toxic jaundiee toxicity for man, rather than an actual with liver degeneration, but ie lose measurement of it. When used for toxic than the phenyl salt. comparison of the toxicity of different Annul. EzmtxiNTi compounds, however, we feel that such testa are a very fair indication of rela At various times in the past few tive humfulnees. yean our laboratory has been called When death occurs within a com upon to determine the toxicity of a paratively few hour* from a single dose number of bensene derivatives and of a chemical, we rarely find micro allied substances, more or leae com* scopic evidence of toxie organ degener plex, about whose effects on the ation, and in these eases we report only system there was little or no informs* dose, time of death, symptoms, and i. r. a. Man*, ml GBRN001912 v LEXOLDMONOOI783 BENZENE DERIVATIVES AND RELATED COMPOUNDS 91 gross changes noted at autopsy. When ample at this sabstanee was found to gurriTS more than twenty* be 0.3 gm. per kilo when diiwjlved in a four hours, in addition to gross changes weak add aohitioa and fed as a hydro* we always look for histologic changes chloride. With this dose, death oc tal internal organs, --p--'ny the liver, coned in from three to twelve boors, Udtey and spleen, and other organs as preceded by twitching*, convulsions, indicated. When animals survive a collapse, and gasping inspirations, week or more, we usually include urine Diphsaylguanidine, CuHuNf or and often blood fiadinp in the reports. (CJLNHVC:NH, with two substi- With mast at the tests here reported tuted phenyl radicals, also fed as a on for minimum lethal dose determin- hydrochloride, killed in from one to ationa, no microscopic findfap are three hours in a dose at 035 gm. per included. The tests to be reported kilo, with the same train of symptoms, were made as parts at six different Tripbenyiguanidine, CiJSuN, or (Cr- investigations on materials supplied by ENH)i-C:NC(H*, with three phenyl three different industrial firms. Firm radicals, fed as a paste in 0.1 per eent. names and trade names of or hydrochloric add, as it would not go compounds are purposely omitted, but completely into solution, killed in empirical and fine structural formulas from three to four hours in a dose of are given when known. In some 0.35 gm. per kilo; death was preceded instances, however, there are differ* by violent trembling, convulsions, cnees of opinion as to the structural gasping, violent chewing motions, and formula of the compounds reported characteristic rolling over, always in upon. When materials to be tasted the same direction, were water soluble, they were fed by The addition of the phenyl radicals pipettein watery solution. When not to the guanidine molecule definitely. water soluble, if soluble in dilute add increased toxidty. The apparent les they were fed as hydrochlorides with sening of toxidty of the tri over the di as little as possible excess add. product was no doubt due to its liquids not mixable with water were busrnmi solubility; even though it fed as a starch paste. Solids insoluble required a larger dose to kill, the pro- in Vatevor dilute add were fed as a lethal symptoms were more violent. paste in olive oil or water. In all Diorthotolyiguanidine, Ci*HN or eases, being dosed were held in (CJLCH*NH)t-C:NH, killed in forty- the hand of the operator and it was five minutes in a dose of 0.12 gm. per made sure by personal observation that kilo; this also was fed as a hydro all the material was actually swal chloride in aohitioa. Prostration lowed. Except as noted, all materials developed rapidly, with twitching*, were of the technical grade of purity. irregular shallow breathing, gasping, and cyanosis. larger doses killed in Qvanidutt and Guanidin* Dcricaiwc* twelve minutes. Here the tolyl radi Guanidine, CHtNi or (NHiVCiNH, cal produced a marked Increase in is not in itself a bensene derivative toxidty.. That the tolyi radical does but it enters into compounds that are. not always insure toxidty is seen in the The "'"imnm fatal dose for a pure ease of diorthotolylthiourea, CuBmNS ua Jh.1 GBRNOO1913 LEXOLDMONOOI784 f 4 i i \ l 1 i a 92 THE JOURNAL OF INDUSTRIAL HYGIENE or (CJLCHNH)t C8, is which it fc combined with a harmless sulphur compound. Hero no ejmptome were observed with a doea at 4 gm. per kilo, though the aame tendency, in a alight bob in doses of 0.35 to 1.43 cm. per kilo (ea a pore preparation), killed guinea-pigs in dome of L75 gm. per kilo when fed M pun aniline Thiocarbanilids, CbHbNiS or degree, waa aeen to the development (CH*NHVCS, * thiourea derira* of lung hemorrhage u waa observed in tire, proved aonfatal in doaaa of 4 gm. almoet aO of thorn eeriea. Doaagea per kilo, fed ae a paste in dire oil, were not increaeed beyond 4 gm. per kilo became the eorreeponding doe* for man would be tremendous and it was extremely difficult to feed larger though the animaia aaemad weak and depremed and petechiae were aeen in the lungs. Inch of solubility lee* aened toxicity, aa did also the entrance doees to animate. With the materials of the guanidine series there was a very sharp line between the fatal dose killing in at of sulphur. Methylenedianilide, CuH,*N, or (CJLNHVCHt, was also aonfatal in doees of 4 gm. per kilo, and no symp* moat a few hours and the doae from which there waa apparent complete recovery. No animal that survived overnight died. The behavior of the animate dying from these materials strongly suggested cyanide poisoning, toms were observed. This material also was fed as a paste in dive oil, and insolubility probably was the reason for nontojdrity. Faranitreeodimethytenilide, CHt* N0 or NO-CH*N(CH,),, a nitroeo aa did the behavior of one factory compound fed as a paste in water, employee whose death waa possibly proved to be twice as toxic ae aniline, the result of an accidental overdose of even though not easily dissolved. It one of the guanidine derivativee. was fatal in doses of 0.65 gm. per kilo A series at animate were fed sub- in from twelve to forty-eight hours, lethal doees daily at diorthotolyl- death being preceded by prostration guanidine for up to twelve days. In and convulsions, and red staining of these traces of a substance the urine. redudng Fehling's solution appeared A series of condensation products in the urine after each feeding, but did containing aniline gave interesting not persist overnight. They all devel- results. Fonnaniline (CHjN} or oped mild albuminuria but no casts, (CJXtN:CHi)s, a combination of two and postmortem examination showed early but not marked liver and kidney changes. There waa evidently no rapid cumulative effect. definitely toxic substances but itself soluble with difficulty was not fatal in doeee at 4 gm. per kilo. A trade compound, a condensation , product at aniline, acetaldehyde and Aruhm and AntZnw Dtrioaiwu and formaldehyde, and another made from Compound* aniline, acetaldehyde and carbon disul- A number of aniline derivatives were phide, also very slightly soluble and teeted and compared with aniline, fed aa olive oil pastes, were not fatal in Aniline itself, CH>N or CtHNHi, doses of 4 gm. per kilo, reported in the literature ss fatal for Paratoluidine, CHN orCHt-CtH** J.LI. Umrtk. IB! * GBRNOO1914 , ' ! i lexoi DMnMnm7Rc; _ _____ _ __ ______ BENZENE DERIVATIVES AND RELATED COMPOUNDS S3 NHt, (pan preparation) fed u ft twenty to forty hours ia ft dose of 2.5 piste in water, killed in ft doee of 1.1 gm. per kilo, with mild eonvubioas, per kilo. This was sorprisinc aa and the 4-cUoro compound killed in Hamilton (1) quotes Gibbs and Han forty hours in a dose of 3.5 gm. per as (trine 0.1 gm. per kilo as fatal for Uo, with no convulsions. Both were fed in pastes aa they ware apparently Anhydrofonnaldehyde-paratolui- insoluble. Here the position of the dine, (CAN), oKCHiCANrCajw chlorine atom seemed to govern the fed as a paste in 0.1 per cent, hydro degree of toxicity. chloric add, was leas toxic, the fatal Two polychlorodipbsnjls, the defi dose being 2 gm. per kilo, killing in nite compositions of which were unde twelve hours; death was preceded by cided, proved nontoxic ia deem of 4 trembling and kicking, but no general gm. per kilo. They were also fed in convulsions occurred. This is the pastes, and were composed of even toluidine analogue of formuiline larger molecules than the monochloro reported previously, and the substitu compounds. . tion of toluidine for aniline markedly 4-aitrodiphenyi, CoHiNOi or increases toxicity. CA'CANO*, ia spite of its nitration A condensation produet of aniline, was not fatal ia doses of 4 gm. per kilo, paratoluidine, butyraldehyde and car owing probably to its insolubility. bon bisulphide waa more toxic than anhydroformaldehyde-paratoluidine, Nitnbenxtne but not so toxic as paratoluidine. It Nitrobensene, CA-NOi, decidedly killed in doses of 1.7 gm. per kilo in toxie aa vapor and by akin absorp from two to six hours; death was pre tion, the latter due to its solubility in ceded by prostration and collapse but fat, was leas toxie (using a pure prep there were no convulsions. This was aration) than we had anticipated, an oily fluid with presumably a smaller when fed In a stareh paste, the fatal molecule than anhydrofonnaldehyde- dose being 1 gm. per kilo for animals paratoluidine, and aise of molecule seems to bear some inverse ratio to PhenylnaphAytamam toxicity. Both alpha and beta napbthjrlamine, - Diphenyl and Diphenyl Dtruatieu Ci*HN or CkHt'NHi, are decidedly toxic but their phenylated compounds, Technical grade diphenyl, CuHn or CuHuN or CtA'NH'CA, proved CA-CA, prepared by passing ben- very little toxie. The alpha com sene vapor through a red-hot iron pound fed as ft paste required 4 gm. per tube, little if at all soluble in water but kilo to kill in three days, while the readily soluble in alcohol and ether (8), same dose of the beta compound was was not toxic in doses of 4 gm. per not fatal. Here the alpha position kilo. . proved the more toxic. Two ehlorodipheeyl preparations, CbHiCI or CA-CAC1, were tested Talylenediamirui and both proved slightly toxie; the We have stated above that tolykne- 2-chloro compound killed in from diamine is a blood poison, producing vs. a JU.I GBRNOO1915 LEXOLDMONOOI786 i lt 04 THE JOCBNALOF INDUSTBIAL HYGIENE destruction ofredeeUs, methemoglobin, deaired. The minimnm fatal doaa by texie jaundice, and liver degenera mouth was found to bo about 3.6 gm. tion. It has, however, bees sug- of the pun substance per kilo- not gened aa a substitute for the phenyi- very tcude. Wo found the material snadiaminei as a hair dye, oa the toxie to this sztent by mouth and by ground of its much lower toxicity. subcutaneous injection, but could me Tan were made with both the pan no evidence of aheorption through aad the meta compounds, CtHt*N or the unbroken akin. When oaed as a C3*'CtH4'(NHi)t, the former aa aa dye ft Is oxidised with hydrogen ingredientof a hair dye tad the latter peroxide to bring out tbs full depth of aa a robber chemical color. MetatolyleBadiainiae waa fad aa a hydrochloride ia water. The fatal dose waa 3 gm. per kilo; however, 0.7 Gmui Patwoloot or Emu flams . gm. per kilo daily for nmeteea daya The one outstanding pathologic was fatal to a guinea-pig, aad 0.6 gm. lesion seen in animals of the series per kilo daily for five dayr killed a poisoned with the various rabbit Ia surviviag several derivatives wae a tendency to extrava days there waa evident definite fatty sation of blood in the hugs, whether degeneration aad also renal degenera the animal died from the drug or waa tion. The body fluids were stained killed far study. This varied from with the material and chemical testa scattered minute peteehiae to larger showed that some of it was excreted ecchymosee or even amative lobular onchanged ia the urine. When com or lobar hemorrhage, the severity of bined with unvuloaaised rubber it wee the lesion usually paraDrling the not extracted from the rubber when severity of the poisoning. In order that was applied to the skin aad held to avoid agonal congestions seen in there ss a poultice for several hours, gaaeed animals, the animals were killed though it was very slowly extracted by by rapid severing of the spinal cord. a buffered watery solution ranging By this method we practically never between a hydrogen ion concentration found such hemorrhagic hog condi of 3 aad of 7. The toxicity tecta for tion! in normal animals. In animals this produet seem to agree fairly well surviving several daya these lerions with those previously reported by wen found to be in the process of gtadeimaaa (9) though he did not absorption and they did not seem to report in grams per kilo. lead to pneumonic conditions, though Panxolylenediamine was tested as an we should mrrni-- that repeated ingredient of a hair dye. For testing, lesions of this type would lower the this catena] waa used in solutions resistance of the hmg to infection. erf three different strengths ss rec Similar lung lesions were found post ommended for dyeing, containing mortem in a fatally poisoned worker amounts of the active ingredients who may have been a victim of the ranging from 2 to 39.6 per cent., scute affects of one of the guanidine depending on the depth of color derivatives. J.LB. abe.au GBRNOO1716 LEXOLDMONOOI787 BENZENE DERIVATIVES AND RELATED COMPOUNDS 85 la animals which survived several days end then died or wen killed for tody, then wh usually eeen hum evidence of tirijr toxic fiver sod kid* Bey degeneration. No of this eeriee survived bag enough or bed sufficient repeeled doeee to develop merited blood efaesgee. With moet of theee preperetioae the taxidty wee rather low. There i> very fittle danger of accidental in industry with any material having a minimum lethal doee of over 0.25 gm. per kilo, or 17.5 gm. far a man weigh* tag 70 kiloa. With limits under that point but over 0.1 gm. per kilo, there ie little danger in handling the prepan* tiona if their possible toadty is real ised and reasonable precautions are taken as to dust and fume removal and personal cleanliness. It must be bone in mind, however, that personal idio syncrasy may make exceptions to this rule, and also that fat soluble or lipoid soluble materials, if water insoluble, may poison by akin absorption in doses not toxic by mouth. It must be emphasised that the toxidties here reported refer only to administntion of solids or liquids by mouth. As previously stated, fat or lipoid soluble subsumes may be decidedly more toxic by skin absorp tion than by oral ingestion; also H must be borne in mind that the same may be true of vapor inhalation. Therefore theee results do not neces sarily represent the hazards of indus trial exposure to vapors or to slrin -absorption. TABUS l.-UMMABY OFTOX1CITEES BKPOBTED Oromt per fcile / My aeiffc fer mail eafstsfi (fwass-pife sad reUtts) GmtmMm mod Oomidfae Derwmee ...... o.JO Diphaayictisabiins..............................0.2S Tripheayigwaafrtiite..............................0.18 DierthotolyicuaBidiae..........................0.13 DiorthotelyUhirarns............................ 4.+ Nitrobeasens by entk....................... 1.00 Aniline................................................ 1.78 Thioearbaailide.................................... 4.-f MsthyleatdiaaiUde............................. 4.+ Paraaitroeodiaethylaailiae.................. 0.48 Faratoluidiae..................................... 1.10 Csadeaeah'oa Products FormaaBiat........................................ 4.+ Aabydrofonsaldehyds-pemtoluidiae.. 2.0 Formaldehyde) JAailiae 1................................. 4.+ Acetaldehyde Aniline 1 Acetaldehyde ^............................ 4.+ Carbon bisulphide; AailiM |. Paiatoluidiae l--....................... 1.7 Butyraldehyde [ Carbon bisulphide] ' Difksnfi ead Dipteayi Doriratims Diphenyl...............................................4.+ 2-ehlorodipheayl................................. 2.8 4blorodipheayl..................... .......... 3.8 Folyehlorodiphuyl, A.......................... 4.+ Folyehlorodipbeayl, B.......................... 4.+ pteaylaephttid--itaee Pkeayl-alpha-naphthyiaBuno................4.0 Fheoyl-beta-aaphthylaain*................. 4.+ TafpimediamtiiM Metatolylenediaxnine.......................... 3.0 Paratolylenediaaiae.......................... 3.4 B1BUOGRAPHY 1. Hamilton, A.: IadostrisJ Poisons in tbs United States. New York, Tbs Maesullen Co., 1933. Tbs chapter on "Benson* Derivativee" haa boen drawn on freely in eompilin* the tat part of this paper. V4.U DU EBRNOO1917 LEXOLDMONOOI788 M THE JOURNAL OF INDUSTRIAL HYGIENE 4 Km, L: Ckuoi ia tW Blood oo Bodwtim (adaatrial Doaaco. Two ion., ISO*, to, a. 4 Thai Boport of tko O--Htotoo Bn* ooL Nat. Safety Coaeil, Kty, 1934 4 Bktib, B. on Sara, B. F, ia.: lahalatina Bipatinaait tftk Cartaia Xnoqaar Bohraota. Tu Jowl, 190, <4 an* 4 FLosar: Goarbiieka Vatftftoaa8 dank Soklawaaaaiatofa dor aio- atiaahaa aad aHphatiaaka Boiho (Boahlorta Eoklawiawartoffa) aad ikio VartOtoac. ZaatnibL L Gowarbokyr* lar, nb. 4, at. 4 Botnar, B.: Koapaadina dar pnkt* iaekea Toxikolocfe. Btattcart, Fudi* aaad Eaka, 1912, pp. M-tf. ad aaiao Wtafeaac oaf da Tkiar* kSrpv. knk. (. oapar. Fatk. a. FkamakoL, 190, U, Ol. Braaauumr, BL: Dio Wlifcaac daa Tolayiwititwiia aaf da TkiaikArpor. /K4. p. 423. fcinuun, B.: Wottaio BoiMco aw Laka roaa lotaroa. IUL, 1B84 if, 114 GBRNOO1918 j. l a. JM.ni LEXOLDMONOOI789 THE TOXZCZTT OP CERTAIN BENZENE DERIVATIVES AND REUTED COMPOUNDS JOURNAL OF INDUSTRIAL HYGIENE 13 87-94 1931 GBRN001919 LEXOLDMONOOI790