Document 5Vj41aN7YpwkwK0arYgZn12V

THE TOXICITY OF CERTAIN BENZENE DERIVATIVES AND RELATED COMPOUNDS* Soit Fold Svtti, MJO., DsJML. Prrfmur af frUmtri*! Suit**, Umtmiitf 4 hmufimmim limtODCcnoii of benesas an toluene, CJXt'CH* EE title of this paper may sug Tgest a very vide range of com* pounds, about, the toxicity of and xylene, CJEL,-(CHi)i, in which one or two methyl radicals replace one or two hydrogens (1). The most important bensene deriva tome information of which but about wtheathaovfeocthoenrssideratairvbeelesthiendnuisttrreia, llyamamnod, toxieologieally diamino, and we know little or nothing. I was chlor compounds of bensene and tolu recently appealed to by an ineuianee ene. Danger to health from these company to outline a program for safe compounds depends not only on their handling of a compound that I did not chemical structure bet also largely on know was used in industry and about the toxicity of which nothing has been their physical state and the method of tK-wi Tbon published so far as I know. responsible for the greatest amount of However, though tbs derivatives of industrial sirfaw are not neoeaearily bensene are legion, yet they group themselves into certain main dimes, the most toxic. ' about certain membersofwhich we have Bomologua of Betuene information. In most cases members of a class act on the system in a similar manner and differences in action are differsoes of degree rather than of kind. `There are exceptions to this general rule, however, aome of which will be pointed out later. Considering first the homologues of bensene, toluene end xylene, we find somewhat conflicting reports. Selma Meyer (2) states that regardless of which poison is acting, whether bensene, toluene, xylene, (naphthalene, aromatie nitro compounds, etc., the Gsnxiuj. Conditions Bensene, CJI*, 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 lymphocytes an increased in the Mood stream and the neutrophils are forced back or repiemsd. American findings do not agree with this. Neither Gieenburg (3) nor we (4) have found toluene or xylene presenting * Read before the Stetfoa m Industrial Hypn of the Americas Publie Health Asaociatioo, Fort Worth, Texas, Oet. 2S, 1930* Rtesivsd for publication Dee. IS, 1930. any chamcteristie blood picture in experimental Greenburg found that with continuous exposures for up to seven days, high eonceatim- vaa K*.I SBRN001909 TOWOLDMONOOQ1474 88 TEE JOURNAL OF INDUSTRIAL HYGIENE tiooa of toiueos killed all exposed {a forty-eight to vnBtytfo hours with osteosis. Animals sur viving lower concentrations showed evidences of narcosis, irritation or deprrasinn, with irritability. Our own taste with four-hour ezpoeuiee over kneer periods showed evidsaoes of hag inflammation sad of tone degen eration ia internal organa. We both found toluene to be leas torio than benaene, and the National Safety Council recommended it as a substitute for benaene where poorible (3). In addition to being leas toxic, it is leas volatile and is lees likely to exist in a plant as vapor of toxic concentra tion. Xylene we have found alao to be quite toxie, but agiin it is even leea volatile than toluene and therefore bee hazardous. Neither of these two substances seems to he readily absorbed through the elan in toxic amounts sad I know of no can of poisoning from skin absorption due to them. Nitre and Amtno Group Compounds Nitro and amino groups, aromatics, in general produce much the earns eiinieal pictures, differing ia some details sad with a few string excep tions. The latter in general are simple blood poisons, while the former in addition exert a direct action on the central nervous system. Floret (5) says that all aromatic and aliphatic compounds are fat solvents and there fore particularly apt to affect the central nervous system. Is light eases of poisoning from nitro or amino compounds there is flushing of the face, with a sense of fulness end throbbing pain in the bead, burning sensation in the throat, and a feeling of tightness in the chest. More marked eases of poisoning dsvelop violent throbbing headache, dinimm, rearing in the can, and visual disturbances. With still more revere poisoning the face faeeomea livid, the lips and tongue blue, the knees weak, and the gait staggering. Tbs bhae color of the face may persist for several days. In extreme ease* cyanosis increases, muscular tremors develop, there is extreme weakness, cold akin, nausea and vomiting, ab dominal cramps, quick, shallow respi ration, lowered blood pressure, and late unoonseiousaeas. Coma develops, the respirations beooms progressively slower and shallower, involuntary urination and defecation may occur, and convuMoDS usually eoma on just before death. Not infrequently attaeka an delayed, eoma coming on even hours after cessation of exposure. The blood picture is characteristic, with reduction in the red oell count and the hemoglobin, pdkiloeytoeia, anisocytosia, and some fragmentation of red oella with polychromatophilia. The blood becomes ehoeolate colored owing to the development of methemoglobin, the spectroscope showing absorption bands between those of pure methemoglobin and oxyhemo globin. Evidences of blood regenera tion are seen after a few days in nonfatal esses, with the appearance of stippled oella and nucleated red ceils. There is an early polymorphocytosis followed later by a relative.lymphoeytosia. In slow poisoning from con tinued low exposures there may be an increase in the red oell count. The urine becomes brown, port wine col ored, or smoky red, and shows bile and blood pigments, methemoglobin or hemoglobin. At times albuminuria } r. a. Kink. HU 6BRN001910 1 l TOWOLDMONOOQ1475 BENZENE DEWTATTVEB AND BELATED C0MP0UND8 89 ocean cad the aria* may ndoee tinned exposure is said to produce Fehiiac'a solution. For moat of thia bladder turnon whieh may become group the akin ia the moat important malignant. entry port. The avenge lethal dose is 23 gm.; iwin Compounds 0.4 to 0.6 mg. per liter of air may be bene without mueh ham for ana- While the amino compounds aa a half to one hour but 0.1 to OB mg. elaaa produoe a deeper eyaaoeis than per liter for several boon produces do the nitro compounds, yet -with alight symptoms (6). Tests made by them, poieoning ia leea aarioaa and Iasard (7), in 1920, ia the aniline recovery osuaily naolta la a few days boon at a plant while reducers were if exposure ia not continued. Then being discharged, gave the following an exeeptiona to this, however. They amounts hi milligrams per liter at air: an all very readily absorbed through 0.5,1.01, LIS, 2.43, and 3.4--sD bat the akin aa well aa through the lungs. the first one well above the toxie con Aniline poisoning is fint manifested centration*. Men wen exposed to aa aa intense eymnoaia, the victims of then eoneentratione for periods of poisoning being referred to aa "blue from twenty to forty minutes. One boys." In an aniline plant Tinted workman at the pleat developed during the war, eases at poisoning eyaaoeis from wearing aa old pair of occurred daily and blue boys wen a gloves found lying in a pod at aniline common sight. Following cyanosis water on a drumhead. Changes is then develop headache, diasineaa, design at apparatus and method dysphagia, nausea, vomiting, weak relieved this condition end reduced the ness, restleameas, palpitation, and number at poisonings 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 perature ia subnormal. Then h an indigo, end new eases began to appear aniline odor on the breath and to the in men discharging the phenylgiyciae sweat.' The urine ia dark in color driers, ea the finely powdenu pheayi- owing to the presence of hemoglobin. giyeine carried more or leas absorbed In severe eases then may be a lorn of aniline. Here the poisoning was due sphincter controls and also pulmonary to dust inhalation. Two testa taken edema. Mon eaaea and more seven by Iasard, in the indigo house while the poiaonings occur in hot weather. vacuum driers wen being emptied, Workers may develop a degree of hawed 0.7 and 1.7 mg. of aniline per tolerance but the eyanosia may persist. liter of sir. Continued exposure may result in Toluidines produoe the seme symp headaches, irritability, poor appetite, toms as does aniline, with less eyaaoeis neurasthenia, visual disturbances and but more strangury and hemoglobin itching of the eyee which may lead to uria. They produee subnormal tem injury and ulceration of the cornea perature and anemia. Exposure oo- from rubbing. There ia anemia, with eun from splashes from centrifuges decreased hemoglobin. Long-con- andwhissen. voL a n.s . GBRNQ01911 J TOWOLDMONOOQ1476 90 THE JOURNAL OF INDUSTRIAL HYGIENE Beta-naphthyUmine produce* cyan- tios available in the literature. Muy oas end eleo frequent urination ee e of theee prepantions wen for use is remit of irritation doe to overaad the rubber industry ss aeceleraton or onne. retarden. Moat of theee testa have Dieminu The may be decidedly toxie. Phenyienediaminee ere need been assembled for comparative pur poses and are here pmented in the hope that they may be of interest and of help to others called upon to use a* dye intennediatee in dyeinc hair and these materials or to mike unilsr for*. They have been reeponaible for tests. a number of eaeee of poisoning from In many cases all that was desired hair dyee and from cheap dyed fun. by those requesting information was Symptom* produced are dermatitis, the determination of the minimum aleeplessneee, dissinw, and weaknes*; and epileptiform convulsions, coma, and death may result. The reaction may develop very suddenly and be of anaphylactic type. Some writers have lethal dose, as an indication of the possibility of accidental acute poi soning. With othen the effects of repeated sublethal doses were studied. All experimental work was done with that it was a true anaphylaxis, small animals, it being the custom in tad Cunchmann has suggested cal* our laboratory to use at least two eium therapy with the inhalation of types of animal, often three, for such prayed solution* of calcium salt*. work. The animals of choice, for Most writers, however, now attribute convenience in handling, are white the poisoning to quinone intermediates rats, guinea-pip, and rabbits. Dos resulting from incomplete oxidation, ages are alwayi given as grams per and state that care to secure eomplete kilo of body weight of the <""* at the oxidation and careful, thorough wash time of administration. It ia custom ing of dyed fun will prevent the ary to interpret the results of such trouble from developing. Phenylen* tests in terms of grams per kilo of body diamine should never be used in hair weight of mam, 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 methemoglobin, and toxic jaundiee toxicity for man, rather than an actual with liver degeneration, but i* les* measurement of it. When used for toxic than the phenyl salt. comparison of the toxicity of different Anneal. Ezreanrerm compounds, however, we feel that such testa are a very fair indication of rela At various times in the past few tive harmfulness. 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 leas com scopic evidence of toxic organ degener plex, about whose effects on the ation, and in these cases we report only system there was little or no informs- dose, time of death, symptoms, and i. r. a. Man*. IWI GBRN001912 TOWOLDMONOOQ1477 BENZENE DERIVATIVES AND RELATED COMPOUNDS 91 greet changes noted at autopsy. When ample of this substance u found to ourriva more then twenty* be 0.3 gm. per kilo when dimolved in e foor hours, in addition to gross changes week add eolation end fed as e hydro* we always look for histologie ehencea chloride. With this dose, death oe- In internal arcane, --p--the Brer, coned in from three to twelve boon, kidney and epleen, and other organs aa preceded by twitehinp, convulsions, indicated. When animate surrivs a collapee. and gasping inspirations, week or more, we usually include urine Diphenylguaaidine, CuHuN, or and often blood findinp in the reports. (CJI*NH)*C:NH, with taro substi- With moot of the testa here reported toted phenyl radicals, also fed as a on for minixaam lethal doee detennin* hydrochloride, killed in from one to ationa, no mioooeopic findwip are three hours in a does of &25 cm. per included. The tecta to be reported kilo, with the came train of symptoms, were mads ss parts of six different Triphenyicuanidine, CtiHNt or (Cr investigations on materials supplied by ILNHVCiNCJTt, 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, sa it would not co compounds are purposely omitted, but completely into eolation, killed in empirical and line structural formulas from three to four hours in a dose of are given when known. In some 0.35 cm* per kilo; death was preceded instances, however, there are differ* by violent trembling, convulsions, cnees of opinion as to the structural gaspinc, violent chewing motions, and formula of the compounds reported characteristic rolling over, always in upon. When materiab to be tested the same direction, were water soluble, they were fed by The addition of the phenyl radicals pipettein watery solution. When not io the guanidine molecule definitely, water soluble, if soluble in dilute add increased toxicity. The apparent lee* they were fed as hydrochlorides with sening of toxidty of the tri over the di ae little ae pomible excess add. product was no doubt due to its liquids not mixable with crater were busrnmi solubility; even though it fad as a starch paste. Solids insoluble required a larger dose to kill, the pre in Veteror dilute add were fed ee a lethal symptoms were more violent, paste in olive oil or water. In all Diorthotolyiguanidine, Ci*HN or eases, animals being dosed were hdd in (CJLCHiNH)* C :NH, killed in forty- the hand of the operator and it was five minutes in a dote of 0.12 gm. per made sure by personal observation that halo; this also wss fed as a hydro* aD the material wss actually cwal* chloride in solution. Prostration lowed. Except as noted, all materials developed rapidly, with twitchings, were of the technical grade of purity. irregular ahallow breathing, gasping, and cyanosis. Znrger doses him in Gvanidint and Gvanidin* Dervaiivet Here the tolyl radi- Guanidine,CHtNior(NHi)i'C:NB, is not in itself a bensene derivative but it enters into compounds that are. The mfoitwiimt fatal doee for a pure eal produced a marked increase in toxicity.. That the tolyl radical does not always insure toxicity is seen in the ease of diorthotolylthiourea, CuHuNS V*B Jb.1 GBRNOO1913 TOWOLDMONOOQ1478 f < r" .4 s 92 THE JOUENAL OF INDUSTRIAL HYGIENE or (GACHiNHVCS, la which it is man in doom at 0.35 to 1.43 gm. per combined with a harnilcm sulphur kilo (ea a pure preparation), killed compound. Her* no cjmptomf wen guinea-pigs in doees at L75 gm. per observed with t don of 4 (8L per kilo, Jdlo when fed as pun aniline though the am tendency, in * alight Thiocarfaamlide, CnHoNyS or degree, was eeen to the development (CtHiNHVCS, a thiourea deriva of hug hemorrhage aa wu observed in tive, proved aonfatal in doees of 4 gm. almost all of thaee aeries. Doaagea per kilo, fed aa a paste in dive oO, wen not menaced beyond 4 gm. per though the animals seemed weak and kilo because the eomapoading dose depreend and petechiae wen seen in for man would be tremendous and it the lungs. Lack at solubility les was extremely difficult to feed larger sened toxicity, ss did also the entrance doees to animals. of sulphur. With the materials of the guanidine Methylenediaailide, CuH,*N or series then was a very sharp line (CJLNHVCHt, was also aonfatal in between the fatal dose killing in at doees of 4 gm. per kilo, and no symp moat a few hours and the doae from toms wen observed. This material which then was apparent complete also was fed as a paste in dive oil, and recovery. No animal that survived insolubility probably was the reason overnight died. The behavior of the for nontoxicity. animals dying from these materials Faiaaitreeodimethylanilide, CH- stnngiy suggested cyanide poisoning, N0 or N0 CJLN(CH,),, a nitroeo as did the behavior of one factory compound fed ee a paste in water, employee whose death was poeeibly proved to be twice as toxic as aniline, the result of an accidental overdose of even though not easily dissolved. It one of the guanidine derivatives. was fatal in doses of 0.55 gm. per kilo A aeries of animals wen fed sub- in from twelve to forty-eight hours, lethal doses daily of 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. reducing Fehling'a 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 (C?H,N)* or oped mild albuminuria but no casta, (CJLN:CH0s, a combination of two and postmortem examination showed definitely toxic substances but itself early but not marked liver and kidney soluble with difficulty was not fetal in changes. Then was evidently no doses of 4 gm. per kilo. rapid cumulative effect. A trade compound, a condensation product of aniline, acetaldehyde and Aniline and Aniline Deneatinu and formaldehyde, and another made from Compound* aniline, acetaldehyde and carbon disul A number of aniline derivatives wen phide, also very slightly soluble and tested and compared with aniline. fed aa olive oil pastes, were not fatal in Aniline itself, CHtN or CtHiNHt, doeea of 4 gm. per kilo. reported in the literature as fatal for Paratoluidine, CHN orCHt-CJL* 3. L H. Umrtk. mi GBRNOO1914 )t i TOWOLDMONOOQ1479 BENZENE DERIVATIVES AND RELATED COMPOUNDS S3 KB* (pan preparation) fed u a twenty to forty hours in a doss of 2.5 paste is water, killed in a doee of 1.1 gm. per kilo, with mild eonvubioas, ta. per kilo. This was sorprisiaf as end the 4-ehloro compound killed in Hamilton (1) quotes Gibbe and Han forty hours in a dose of 35 gm. per as (trine 0.1 (a. per kilo as fatal for kilo, with no convulsions. Both were ft&isuJi* fed in pastes as they ware apparently Anhydroformaldehyde-pantolui* insoluble. Here the position of the dine, (CJB^f). or(CBrCAN:CBiU chlorine atom seemed to govern the fed as a paste in 0.1 per cent, hydro* degree of toxidty. chloric add, was lea tons, tbs fatal Two polyehlorodiphsnyla, the defi* dose being 2 gm. par kilo, killing in nits compositions of which wen unde twelve boon; death was preceded by cided, proved nontoxic in deem of 4 trembling and kicking, bat no general gm. per kilo. They wen also fed in oonvulsions occurred. This is the pastes, and wen composed of even toluidine analogue of formasiline larger molecules than the moaochloro reported previously, and the substitu compounds. . tion of toluidine for aniline markedly 4-nitrodiphenyi, CnHiNOi or increases toxicity. CiHt'CANO*, in spite of He nitration A condensation product of aniline, waa not fatal in dceee of 4 gm. per kilo, paratoluidine, butyraldehyde and car* owing probably to its insolubility. bon bisulphide was more toxic than anbydroformaldehyde-paratoluidine, but not so toxic as paratoluidine. It Nitrobenzene Nitrobensene, CJL-NO*, decidedly killed in doees of 1.7 gm. per kilo in toxie as a vapor and by skin absorp from two to six hours; death was pro* tion, the latter due to He solubility in ceded by prostration and collapse but fat, wea lees toxie (using a pun pnp there were no convulsions. This was antion) than we had anticipated, an oily iuid with presumably a smaller when fed in a stareh pasta, the fatal molecule than anhydroformaldehyde- dose being 1 gm. per kilo for animale paratoluidine, and sise of moleeule seems to bear acme inverse ratio to toxicity. Phenylnaphtkylaminu Both alpha and beta aaphthjrlamine, - Diphenyl end Diphenyl Deruatme Ci*HN or CiiHi-NHi, an decidedly toxic but their phenylated compounds, Technical grade diphenyl, CuHn or CuHuN or CuBrNH'CJSt, proved CJL-CHfc prepared by peering ben* very little toxie. The alpha com aene vapor through a red-hot iron pound fed as a paste required 4 gm. per tube, little if at all soluble in water but kilo to kill in throe days, while the readily soluble in alcohol and ether (8), acme dose of the beta compound waa was not toxic in doses of 4 gm. per not fatal. Hen the alpha position kilo. . proved the mon toxic. Two ehlorodiphenyl preparations, CbHiCI or CtHfCJLG, were tested and both proved slightly toxic; the Tblylenediaminez We have stated above that tolykne* 2-chloro compound killed in from diamine is a blood poison, producing VI.B JU.I GBRNOO1915 TOWOLDMONOOQ1480 i iI i 94 THE JOURNAL OF INDUSTRIAL HYGIENE dnctioaefredee]]s,methemoffobin, desired. Tbe miniinnm fatal does by texie jaundice, and ibe degenera mouth was found to be about 3.6 gm. tion. It has, however, been sug- of tbe pure substance per kilo--not feited aa a substitute for tbe phenyi- rery uude. We found tbs wnmiiM u e bair dye, on tbe toxic to this extent by mouth and by ground of its much lower toxicity. subcutaneous injection, but could ree Tan wen made with both tbe pan no evidence of absorption through and tbe meta compounds, CtHi*N or the unbroken akin. When used as a CHcCJEb*(NHi)i, tbe former aa an dye it Je oxidised with hydrogen ingredient of a bair dye and tbs latter peroxide to bring out the full depth of aa a rubber ebemieaL odor. Metatolyienediamine was fad aa a hydrochloride in water. Tbe fatal Gmui PataoLoor on Ermas dose was 3 gm. per kilo; bowerer, 0.7 gm. per kilo daily for nineteen days The one outstanding pathologic was fatal to a guinea-pig, and 0.8 gm. lesion seen in animak of tbe series per kilo daily for fire daye killed a poisoned with the various rabbit. In lurriving sereral derivatives was a tendency to extrava daye there was erident definite fatty sation of blood in the lungs, whether degeneration and also repel degenera the animal died from the drug or was tion. Tbe body fluids were stained killed far study. This varied from with tbe material and chemical testa scattered minute petechiae to larger showed that some of it was excreted ecchymosee or even maaive lobular unchanged in tbe urine. When com or lobar hemorrhage, the severity of bined with unruloanised rubber it was the leeka usually pj*iuHwg the not extracted from tbe rubber when severity of tho poisoning. In order that was applied to the skin and held to avoid agonal congestions seen in there as a poultice for sereral hours, gireed animals, tbe animals were killed though it was rery slowly extracted by by rapid severing of the spinal eord. a buffered watery solution ranging By this method we practically never between a hydrogen ion concentration found such hemorrhagic hing condi of 3 sad of 7. Tbe toxicity tests for tions in normal animals. In animals this product seem to agree fairly well surviving several days these lerions with those previously reported by were found to be in the process of Stadehnann (9) though he did not absorption end they did not seem to report in grams per kilo. lead to pneumonie conditions, though Peraxolyleaediamiae was tested as an we should that repeated ingredient of a hair dye. For testing, lesions of this type would lower tbe this material was used in solutions remstance of the lung to infection. of three different etrengths as rec Similar lung lesions were found post ommended for dyeing, containing mortem in a fatally poisoned worker amounts of tbe actire ingredients who may have been a victim of tbe ranging from 2 to 39.6 per cent., acute effects of one of the guanidine depending on tbe depth of odor derivatives. ui. GBRNOO1716 TOWOLDMONOOQ1481 BENZENE DERIVATIVES AND RELATED COMPOUNDS 85 la animals which survived several days and then died or were killed for study, then wm usually seen mom tTideoce of tirijr toxie fiver and kid* nay degeneration. No animah of thk seriee survived lone enough or had auffident repeated dcaea to develop marked blood changes. With aioat of theae praparatioaa the toxicity wm rather low. There is very little danger of aeddeatal poiaiwiiag in industry with any material having a minimum lethal dOM Of Over 0.25 gOL per kilo, or 17.5 gm. for a man weigh ing 70 kiloe. With limits under that point but over 0.1 gm. per kilo, there is little danger in handling the prepara tion if their possible toxicity is real ised and reasonable precautions are taken m to dust and fume removal and personal cleanlinen. It must be borne in mind, however, that personal idio syncrasy may make exceptions to this rule, and also that fat soluble or lipoid soluble if water insoluble, may poison by akin absorption in doses not toxic by mouth. It must be emphasised that the toxidtim here reported refer only to administration of solids or liquids by mouth. As previously stated, fat or lipoid soluble substanom may be decidedly more toxic by akin absorp tion thaw by oral ingestion; also it must be borne in mind that the same may be true of vapor inhalation. Therefore these results do not neces sarily represent the hazards of Indus trial exposure to vapors or to airin -absorption. TABUS 1.--8CMMAEY OFTOXICITEES BXPQBTED Aw per MU of tody aatffc for tmmil --Wi (rm--s-piyc and ruibiU) Cfnomidint sad fteeWw Pirimiw Oaaaidiae.......................................... 0.9 Dtphaayifusaldiii............................. 0-9 TripheoylsnanVHne............................ O.V Diorthotolyicvaaidiae....................... 0.13 Diorthotelylthiouraa...........................4.+ AmUm mod AwiUmc J Ce-.jp Nitrobeaseae by entk.................... 1.00 Aniline............................................. 1.78 Thioearbaoilida.................................4.-f Methyleatdiaailide............................4.+ Paraaittoeodimethylaailiae............... 0.48 Faratoluidiae.................................... 1.10 CendeaiaWea Product* FonaaaBiae........................................ 4.+ Aahydrofomaldehjde-peratoluidiae.. 2.0 Fernaldehydel Aailiae }................................. 4.+ Acetaldehyde j Aniline 1 Acetaldehyde f............................. 4.+ Carbon bisulphide; AeiliM 1. Fantoluidine 1.......................... 1.7 Butymldehyde I Carbon bisulphide] Dipkrofl mod Diphenyl Derteorieee Diphenyl.......................................... 4.+ 2-ehlorodipheayl............................... 2.8 4blorodipheayl........................... 3.8 FolyeUorodipboayi, A.........................4.+ Folyehlorodipbaayl, B.......................4.+ Pkmyincphikyiooanot Fheayl-alpba-naphthylaBiM...............4.0 Fheayl-bcte-aaphthylaaias...............4.+ fdlilMdlMMI Metatotyleaediaaiae......................... 3.0 ParatolyleaediaaiM......................... 3.4 BIBUOGRAPHY 1. BaiaLvoM, A.: lodnitrial Foisoas ia the United States. New York, The Mae- aaOlaa Co., 199. The chapter ea "Beareoe Derivative*" hae been drawn on freely in eompilins the Orat part ef this paper. us Ne.1 BBRND01917 TOWOLDMONOOQ1482 \ M THE JOURNAL OF INDUSTRIAL HYGIENE A Mitb, A: Ghoacoo ia ko Blood m lofloftim ladaotriol Daaoo. Tna ion., MO, 19, 30. 1 Fteol Boport of tko O--Htotoo Bn* ooL Not. Safety Cooaal, Hoy, 1KB 4. ferm, B. urn Sunn, H. F, Jo: loholotioo tepariaoott with Cortaia Inoqoar Sohrooto. Tu Jomt, 1933, 10,9a. & Vtoin: GnoUiekt Votftftaacoa dank nhlonwowwtoto dor oio> aotbekn aad olipkotiookoa Boiko (loaUnrta KohloovMwntoffa) nod ikio ToUtgaf. ZootnlbL 1. Oowtr boky*., 1037, NJI. 4,397. A Xtuti, .: Koapoadino dor pnkt* ioekto Toxikolopt. Btattfort, Fdi* aoad Boko, 1912, pp. M-t. Soso*, &.: Tokrtaoh 4m Utakt* 9mm. 0Mond odtttaa. Btattgoro, VMIooad Boko, 1909, roL 3, p. 7*. 7. Iauoo, If. S.: Dotomiasttoa of AaiUao Vopon is tko Air. Ta Boob., 1930 1931, A 399. A Beuaiu*,A.7.:ATt-BaokafOifoaio nwiolry. Nov York, Joka Wlloy A Sow, 1930. A tunuun, BL: Dm Tatayloadioaia ond nko Vhkni oaf daa ThiarkBrpv. Aiak f. oxpor. folk. a. TkomokoL, 19U, U 391. Moauumr, BL: Dio Wiifcaac doo Tafeyioodioaia oof daa TkiorkArpor. IKdL, p. 423. SrisautAira, B.: Wottoio BoiMc* oar Lobro na lotorao. Aid, 1981, 10, 11A GBRNOO1918 1.LI. MaoO. Ml TOWOLDMONOOOI483 wrtm f THE TOXICITY OP CERTAIN BENZENE DERIVATIVES AND REUTED COMPOUNDS JOUtNAL OF INDUSTRIAL HYGIENE 13 87-94 1931 GBRN001919 TOWOLDMONOOQ1484