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May 10, 1994 OVERNIGHT MAltI
Document Control Office - Office of Poflution Prevention and Toxacs< Environmental Protection Agency 401 M Street SW N \Vashington, DC 210460 Attention: 8(d)i R.,pcrting
Dear Sir/Madam-
OPPTS-82042: FRIL-4745-5
In response to the subject final ule published in the Federal Register on February 9, 1994 (59FR 5956) and effect le on March 11, 1994, DuPont Speciaty Chemicals submits the enclosed toxicity reports under TSCA section 81d) Health and Safety Data Reporting on the following chemicals: Dimethyl sulfate, p- Chloronitrobenzene ,m-Toluidine, I ,3-Dinitrobenizene, Diphanylamine. .2.4.- Dinitrotoluene, o-Anisidine, Chlorobenzene, Tetrahydrofuran, o-Nitrotoluene. Xyiidine. p-Nitroaniline and Phenylhydrazine. Additionally, we are aware of the following ongoing studies on Tetrahydrofuran (TH-F). Under a TSCA section 4 (a) test rule THIF is being evaluated for neuroroxicity potential. The testing is being conducted by DuPont on behalf of an industry consortium, the TI-F Task Force umbrellaed under the Synthetst Organic Chemrical Manufacturers Association (SOCMA). To date the in-life phase of an acuite neurotoxicity Study has been completed. Subchrenec neurotoxicity testing incluonrg neuropathology and evaluations for Motor Activity and Functional Observat~on Bat'ery will be conducted in the near future. A two-generation reproduction ioxicity stud) is underway at BASF's toxicology laboratories in Germany to determne the reproductive toxicity potentia of THF through the oral route of exposure (compound adm'inistered in drinking water) The tn-life phase of the one generation rangefinder ',fcr the main study) has been completed. The main study is expected to begin late' this year. The studies are teng conducted by BASF on behalf of an industry consortium of which DuPont is a rnember Final reports from both studies will be submitted to EPA when they issue, the tnral report frcm the reproductive toxicity rangefirider has been submitted to EPA under the 8(d) rule by BASF, you may contact me on 302/774- 6467 if there are any quertions regarding this submission. Yours truly,
K. 0. Dastur Manager. Product Toxicology and Chemical Regulations
/pmnt Enclosure LUEhLE SLLMIID TlU I /_ /XC0- The Report4 Dirnethyl Sulfate (GAS #77-78-i',o
1. Industrial Hyqiene Survey rjt DM5 Manufacture and Use- ( CZ1 ) Rant HLR# 203-77 .2 industrial Hygiene Survey of DM5I Manufacturing Facilities - ( C81 ) Plani HLR# 202-77 3. Acute Inhalation Toxicity and Antidote Study HLP# 318- 71 4. Preliminary Tests on the Toxicity of Diethyl Sulfate and Diethyl Peroxide (DM5I data included) NA 5. Primary Skin Irrjtation and Sensitization Tests on Guinea Pigs HLR# 22-72 6. Mutagenicity Evaluation in Sa~ronslla Typhimurium HLR# 348-81 7. Dimethyl Sulfate Permeation Testing HLR# 261-81 8. Dimethyl Sulfate Permeation Testing HLR# 538-81 9. Teratogenicity Study of Dimethyl Sulfaie in Rats HL.R# 535-91 10. Carcinogenicity and Chronic Toxicity of Inhaled Dimethyl Sulfate NA 1-Chloro-4-nitrobenzene (p-N itruchloro benzene) (CAS#1 00-00-5) 1. Inhalatio' Median Lethal Concentration (LCSO) HLR# 751-81 2. Subchronic Inhalation Toxicity Study of p-Ghtoronrtrobenzene (PCNB) in Rats ALR# 429-84 3. 96-Hour L050 to Fathead Minnows HLR#6S2-79 4. Toxicity of Compounds Used in ( C1)Building HLR* 13-49 5 Eye Irritation Test in Rabbits HLP$ 57-82 6. In Vitro Microbial Mutagen;city Studies of p-Nitrochto robenizene HLR$ 4C4-75 7. Mutagenic Activity of Mixed Nitrcchloroberzene [o-. 0-I in the Salmonella Microsome Assay HLR# 539-r77 8. Mutagenic Activity of para-Chloronitrobenzene In SalmoneliaMicrosame Assay HLR# 53&-77 9. Mutageric Activity of Benrena, para-Nitrochloro-46.5c% In Sal monella/M icro some Assay HLR4 965-77 10.%4.utagen~c Acbivity of Mixed Nitrochlorobenzene in SairnaneiajMicrosome Assay HI, R* 964 7 11. Mutagrnic Activity in the SalmonellaiMicrosome Assay HLR* 392-18 12. Mutagenic Activ"t in the SalmonellaiMicrosome Assay HALR* 53b.-78 13. Mutagenrc Activity in the Salmonella/Microsomne Assay HLR* 536-78 14. Mutage'lic Activity in the Salmonella/Microsame Assay H.-LR% 70 -78 15. Mutagenic Activity in the .SaIrnonelladMicrosorne Assay HLRO 275-71 16. Mutagenic Activity tn the Chinese Hamster Ovary Assay HL i's 24-80 -2
Lito umte tde (continued)
1.3-Dinitroteflzane (CAS#99-65-O) 1. Nitrobenzene Derivatives NA DiDhanvlamine (CAS#122-39-4) 1. Para Chaor Aniine Quinaldine and ) NA 2. Results of Inorganic Lead and Djgfenyf amine Air Samples Collected at the ( )PlantiB HLR# 484-76 3. Department of Transportation Skin Corrosion Test on Rabbit Skin HLR$* 421l-75
1. Industrial -Hygiene Survey of the IfCa -) Iivo~vng Dry Chemical Handling Procecures HLP.# ' -77 2. Evaluation of Exposure to 2,4-Dinitrotoluene While Handloading Shotshell - ( Cal HL.P# 654-79 3. Class B Poison Labelling Test HLR# 26-68 4. 96-Hour LCO to Fathead Minnows HL9# 61- 79 5. Eye rntatian Test in Rabbits HLF# 713-81 6. Department of Transportation Skin Corrosion Test on Ranbit Skin HLRE ,56-73 7 Orai Bioassay Study (Dogs) HLRfl 490-76 B. The Toxicity of TNT and DNT NA 9 eratologicai and Postnatal Evaluation of Dinntrotoluene nFisc er 344 Rats RTI RC1O' RTI/i- 9,&VOOGF J3. A thirty day toxicology study in Fischer 344 rats given. dinitrotoluene-technical grade. (Study performed at Hazleton Laboratories Amer:ca. Inc. for Chemical Indus' y Institute it Toxicology, Research Trangle Park. NC- -3-
Ls o ubm.r~ittd tuasiContinu6d) Til Retport# 2-Afllsidifle (CAS#90-104-0) 1. Toxicity of Compol. ids Used in Q-ydrogen Reduction) Building NA 2. Department of Transportation Skin Corrosion Test on Rabbit Skin HILR# 532-73 3. In Vitro Microbial Mutagenicity Studies of ortha-Anisidine HLR# 247-75 4. Toxic Hazards Evaluatian of Five Atmospheric Pollutants from Army Ammunition Plants NA £hobnzann (CAS#408-90-7) I. Mutagenic Acitrvty of Monochlorobenzene in the Salmoneila/Microsome Assay HL!R# 537-77 LTetrahvdrofuran (CAS$1 09-99-9) 1. Acute Toxicity Evaluation By Aspiration and Insufflation HLH# , /4-71 2. Toxicity of Teu-ahydrofuran NA 3, Acute Inhalation Toxicity in Rats HILR# 848-79 4. 48-Hour LOSO to Daphnia Magna HLR# 744-80 5. 96-Hour LC5O to Pathead Minnows HLR# 745-80 6. Federal Hazardous Substances Act Test - Rabbit Eye Irritat;on NLR# 290-71 7. 96-Hour LCSC to Fathead Minnows HLR# 175-82 8. Tetrahydroturari (THF) Inhalation Effect on the Rat Conceptus HLR# 753-82
-Nitrotoluene (CAS#88-72-2) 1. Inhalation Class 8 Poison HLR# 98-72 2 Class B Poison Tests on Rabbit qkur. HLR# 84-72 3. Acute Oral Test HLR# 56-72 4. Departmnt ot Transportal'on SKin Irritation Test on Rabbit SIC,- HiLR#623-73 Phenvihydrazine (CAS#100-63-C}
1 Acute Skin Absorption Toxicity HLRq# 106-63 .4-
List of SubMCIiZSIL"t§c (Continued)
Xylidine (CAS#1300-73-8) 1. Crass B Poison Test HLR# 228-69 2. Class B Poison Test HLR# 172-69 3. Department of Transportation Skin Corrosion Test on Rabbit Skin HLR# 538-73
4flxnirailnf (p-Nitroaniline) (CAS#100-O1-6) 1. Subchronic Inhalation, Toxicity Study ot p-Nitroaniline (PNA) in Rats HLR# 3t2-84 2. Toxicity of Compounds Used in Hydrogen Reduction Building NA 3. Inialation Median L-ethal Concentration (LC5O) HLR# 856-81 4. Micronucleus assay with p-Nitroanilina MSL-9283 m-Toluidine (CAS#1 08-44-1) 1. Oral Class B Poison Test HLF4# 543-74 2. Oral LO5O Test in Rats HLR# 955-80 3. Eye Irritation Test in Rabbits HLP - 945-8C 4. Skin Irritation rest in Rabbits HLR# 948-80 5. DOT Skin Corrosion Test HLR# 527-713 MMi
TOXICITY 0? COMPOUNDS TIE INl au ri Gt1l9
Preizcav rs tcxicA ytudies havi-~en carried cutA urder Medica R ac Pro feat L1i4 on a isries or compounds used1 in the( JAuiding ?oC5.The eleven compounds
tested vezt urtncantaidtne,-nn-But!N;-sm42-cpbcnol, 2-Chlcr-azl-no- r- toluoe,olne, e-;-tcnl .p-N.trodichloobenzeane, ;- I trc;nane tole, Alvtha naphthol, U;h.rc ac~d, PiperIdine, and Diagen A.
Acute oral toxicity was tested by deterrnnzing the approximate - lethal dose (ALD) ,C or ratsn The metncd of De~cizann. and LaBlac~vas k used vherctn sir~gle doses/6k! Increalsing amounts Were given to * uc3rieSS- of rats by sta--ch tube .7/The minimum dose 6::cU killed vao considered ths ALD.- Chronic or c 1.u Ictitxicitf was tested t7 adminis taring orally t3 rats apprcXiaatL2by' 1/5 tho AID fiv t" -es a week for 2 weeks tO that I total cf twice the 1e.a2.a dcae '. administered. The rats wore checked tcz change in weight and any r-us'zal clinlzaL Symptoms. 701 Ing tl'$final treatmnent they ut, i- observed for' a1 perod t fomc..4Kt,two weeks prior tc being :.AiCrff104. Tissues of all rnts were noinmed for gross ard micropatholocy.
uctaila of the tests performed for sach compound were - as follows:>
0Acu,-ta Oral Taxicity: The ALD for rats was found to be < 1OO mg/kg. _Th. material vaa administered by atomach . tube as a 5C a olution In peanut oil. The rat rees.4ving 7 the 1503 mg/kg dose died v~.thin 48 houns after treatment; The lungs were found to be congested and edematous.z 1
*dafl~c~:~nand T. J. Le~lano, J. Ind. Hyg. & Tox-t 4~D15,- 1943. F ]-2- May 9, 1949
Chronit Oral Toxicity.: Ten does& of 300 mg/kg a-- solution in peanut ±1 were admin~tsned to 6 rats over> a period of two weeks. The rats shoved an inititil lcur or vogigbt but a subasquent normal gain. Wheti acrificed, no pathology was found which could be attributed to o-anlsidine. Conclusions: Prom the standpoint of -al toxicity, o an f aynsis not a very toxic compt. - 1500 ms/kg were required to produce death In the rat. Izr'addition, cumulative toxicity did not occur unwlrthe conditions described.
n-But, l-p-aininopbenol
Acute Oral Toxioitv: The ALO was found to be 450 mg/cg. The compounca ra--ministdre-d as-e 40% aolution in peanut oil heated to 50* C. The animals died within 21 hours. The only pathology noted was th.s presence of albumin La the Lldne"s. - Chronic Oral Toxicity7: Ten treatments of 90 mg/g each as a 5A solution in peanut oil containing 10% acetone were given. The'zrsts were uncomfortable following the treatments. Th@6 also shoved a detirite slowing of the rate of gain id' weight, until a week after the f Inal treatment, alth~ough tbiy did not go below the original weight at any tImt*-.' They were killed two weeks after thi final treatm6ntand no pathology attributable to the F material Vi3 detected.
Conelansa ';-8utyl-p-aminopheno1 is a moderately toxic comp)oun vheribsorbed through the gastro-intestinal- tract . "thoto% was no evidence of cumulative toxicity under- the conditidna of' our experiment. V , Xlnfoxtatton on the toxicity of this compound in parti4ular has not been reported but the auinophenol. .tIn general are known to cause skin sensitization among * workers in the dye and photographic industries anid to V * cause the formation of methemoglobin.
2 -Cblor-4-Aminotoluene Acute Oral 7oict-:The material was given as a 50% soluion n pau oil. 1500 mg/kg wag found to be the * A=. Pain and weakness occurred 10 minutes after the dose was given And was followed by unoonsdiouunesa. and L 1 -3-May 9, 19249
death within 22 hcurs. Both rata showed 3Ii&'bt 3'.agaatiefl of the lungs, and one bad ev4idenceOof gastrit. -but the cause of death was not aarent. C
ral oxtit1 )CO ing/Lcg as a 10% solution in peanutChroic oil was edten times3 to each of 6 roti. After the third end fourth treatm~ents the rats wore ,1l and c~anot.z. The reacticn3 nitinued atter."tho,.siubsequent trejatmenta but the Intensityf slackened a 4'b 7 ' the tenth they showed acme improvement. They were .ied11 day, after the final dose. Gross and miop&tholotlcal examination revealed no pathology vhflfrcould be attributed to 2 -Chlcr--4-amino toluene, but foco'b'lood formation were. conUi3tantly found Inthe s_1_a,; O-nnlusionnt 2 -Cbbor-4-aino toluen_ t/ot highly toxic 33s 7 R3 3!Msle oral dozes are concrirrod. Sfnce other chior- dines have been shovn.to cause Cyanosis and depression, p-_ umably throug&h fornatli ofatemoglobln, it i3 probable that the same moedrsni3r Is involved with 2-Chior- 4-omlnotcluone. ThMs woufld b,3 conalaztent with the observe- tions on the chronic treatuerwi~in vhIch the decrease in c7anoais during the latter pi-rt of the treatment period was prcoabIy due to compensatory activity of' the lreMOPOietIC system, since foci of blood formation were found In the sp,1ons of the rots.
Acute Oral Toxicity: The material was admiitered asa 7,T solUtion !.n meanut oil containing 15% azeton~a. The AMD was 1000 ingAga. The material caused pain, weakness, cyafl~ia, aneteath within 21 hours. Pathological examina- t~on ± ~dca~id damage to the liver end kidneys. chrrr'c OraTOXC1~o~i Ten doses of 200 in/4g each yene R&Iven as a b* _soluton iLn peanut oil containing 19% acetone. Th.Kcta became pale and week after six treatments but re- gained&normal strenjgth and color a 'jock after trntmant < fifthended': treatmentThe rata folloe~dshoved a bymarked a slow loam gain of untilweight the wflh last thae w9>eek of cbaervccion w:,to.n they began to gain rapidly. They wer, sacrificed 12 days after the final treatment and shoved evidenc, of damage to the apleen, kidneys and liver. Conclusions' p-Toluidine is only moderately toxic by mingle acute Oreldosme. Its action is apparently mimilar to that of aniline, caui!g anel.a and formation of .ethenoglobin. Cases of industrial poisoning from toluidine have been reported and acute cases are usually characterized by r~~~-ava] 4. 1,
cyanctis and menta-l contusion vhich may be due to cerebral anoxt4a. Ir uLry' to the kcidrnyz .ins been reported In workers, and was alii observed in our rot's.
Acute Orl.o"bi Te AID we'1 determined tryi srtar- T11d tb' coETP f is a c 0U~ n in pent oil 9q it Was found .be !375 mg/kg.Evnob-tadse utd wee .dning end cyanosis while lethal doueanZproduced tremors In additiun. The urine contained a brigbt ,s'allow pigment. Microscopic examination indicated damage to'tbe liver, and L the kidneys were dim tended with al) 4naus fluid. Chronic Oral Toxicity: p-witroat,.Mine'kn 10 -loses of 675 *~rAs each, was aomlniatored to 'rats as 'd 20% solution in peanut oil. One rat dled after the second treatment and one after the sixth, The o'ther four survived the ten dose~* and were sacrificed eftarA.ten-day observation period. flij rats were J_, pain after each' treatment. Their eyes and skin a-peared yel low a3 d~d tlz& url2,i; and there warn generalized Veakne's. The average weight or' the -four survivors showed a sharp drop until the eightZ' trestzent which was followed "by a slol, rise until the \ast,'week of lurnervation which warn4 marked b7 a rapid gain in woig~t. The original weight, hcwever, was never again attained. On microsoJ5u examl~hatlcr. the kidneys Vere observed to have granulation of tbe tubular epitheliun and oceanmional vecuolation. -
Conclus ion: The LIzutd oral toxicity of p-Nitroaniline was - ?sFairly mw, but the renults do £r- a tendency toward ctmuta tivs.'ef feots, and p-Nltroaziline has frequently been implicated In human Cases orf poisoning. Lavln (Gifts u. Ver' igltungen, 1929) states that 40 mg/kg of p -1Nitroani line by intraxanous injection kills animals, and be reports a- fatal eas(f of huran p-Nitroaniline poisoning of Industrial (o'rigin. The Encyclopedia of Occupation and Health '(Thternationai tAbr, Office) states that the fatal dose for. 46gw of o-rNitroaril". is 300 ag/cg, and "in certainlyr ,smaller for r,-Nitroanilino". The route of administrtition y.as,*' not described. It is further stated that p-Nitrvan-iline 4n: practice causes the grreatest number of poisoning oases, of dermatitis, and of conjunctivitis. Loto-Mendanca, dxnndian Med. Gat. 7Z, 673) has repcr~ed cases of' poisoning I= textile wrixers. The dye was absorbed thrOuEh the skin and caused perelyrnia of the central nervous system, marked cyanosis 91;d sometimesi death. Methemcglobin yan found In the blood and hemoglobin and hemetoporphyrin were found I' the urine.- ]-a M 3, 1949
Theae riaultS suggest that acme species, Inclua2!ng humn bDeings, may be relatively rcra uc~tbet Nitroantli-ne than the rMt. p -Nltrochlorbeimaene
Act r'ti lcitz: Trhe material was administeziod Pm3 a souto=0 ipenut oil warmed to 50* C. The AlL was 670 m;/kg. All treated rats became cyanotic. ,Tn rats treated with sublethal doses It laate&-24 hours after tree tmsnt. The rat receiving 670 mg/lg livedi near).; 48 tours after dosing. Pathological examination re':oatec" nccrobia and hemorrhage of the liver and ,inaipli.t necrosis of the convoluted tubulesi ot--the kidnoya. ?to. bladder contained blood tinged urin&. -
ChrnicOra Tolcit! Tetj chronic doses of 135 mg/kig each asa* oltin n eanut'oil wore administered to each aff six rots. One rat died after the fourth exposure and one after the eighth. Both these rota were found to have acute necrosis arm nd the heoatic veins3 of the liver and the <,resence or albumnin and Casts in the kidney tul-ulem and granular epithelium in the case of cooe ra.t. The "emasining four nt s 5urv17*d 10 treatments and wer%" sacrif-*s:d. twelve clays after the MenC treatment. The -eta were cyanotic during the early part ct the treatment period and showed a rap-id loss qivagbttrougbcut treatment and a sub)sequent gain during the,,abs.ervaticn period. However they barely exceeded their Inti:-1 weight, Tha spleens of these animals veru large and congeatec. and showed signs of increased blood- formation. This Increased activity was probably due to the presence of mathemoglobin. The nuclei of the liver cells ahcvs4Q'aligb., Avsriation in staining quality and the kidneys awl dencn'off d =age. L r ~zluIon:As In aniline poisoning the nitro bensene MCoa1oun produce breakdown products which cause the farmna- tlctc,'f *ethemoglobin with subsequent heuclysis and anemia. As far S5 acuts toxicity is concerned p-Nttroehlorobmnzene is modenately toxic with an AIM foe rats at 0570 mg/kg. «CRegeneration of blood after acute poisoning Is fairly rapid. Chronic exposure to the compound caused similar blood changes and was fatal in the case of two rets. Blood ragenerstlon is slow in chronic exposure and spparently varies greatly with the Individual. 7 -'- May9 p-Nitraphenctole Acute Oral Tox~city:% p-Nitrophenotole vas adminmistered as a 25J1 solution in peanut oil containing 15% acetne-nd the AML was fcund to be 7500 majrcg. Doss. up tr#-000-, mb/cE produced Lio symptoms whatsoever. The ret roceivl g 5000 agl~cg, however, suffered try. pain, weakness, and bronchial irritation, for 24 hours after tr4qs*nt. At- the 7500 Mg/kg level the rat immediately bicam ii i, p'n- ccnacious and died within 24 hours. Autopay-4±aolobed1 congestion and edema of the langs. It Crnic G-IjT-oiity: Ten doses of 1500 mg/kj eaCh, as a !5ui&Ttinnut oil-acetone ve~administered to sIx- rats, They exhibited a slowing Wathe ratew of gain of weight up to thi seventh treatment: after which there war- a-1 n-rual gain. At no timte, hovever, did tbsy rail below thir --- pre-erpoeure weight. Three of the '-th- volded bright yellow - urine through7out the treatment period. The animals were
klled twelve days after treatment and nop athology van - detected.
r cusions: p-Nlttphceatole Is a relacively non-toxic- Cznpound. nor did a cumulativ~:t'oxicity show up under the conditions of our teat.
A~lhaNaphtholN4
Acute On&l oxit-: A.7Zh was found to be 1000 mgfrg. i The8 matra nraiiatered as a 50% solution In Peanut oil. Ra rec~tvingz'1ethal doses suffered from diarrhea, and died within I8 bouru after trectnent. Pathological J e- 4 atlon indicated congestion and edema of the lungs, albumin in the kirdhey tubules end superfioial necrosis of the %tcmach. ,- Cbroic'0~t"hxicty:Alpha naphthol as a 10% solution TH reflniut -oll was red ten times tn doses of 200 meAs. The rats were pale during the treatment period and voided an aft 1malllarge amount of urine. They shoved a marked - drop- n weight throughout treatment. but a normal guan dur- iN na Ut. observation period. Pathological examination 7/ indicated no pertinent pathology. Conclusion.: Alpha nsphthol, was not found to be a highly Ktoxic cmpound although It Is said to be more toxic than ')Beta naphthol. The frequency of urination in the rats on chronic ex- psune yan probably due to the kniown irritating effect of - Alpha naphthol on the &ldneys. The intens'ty and duration of our chronic exposure, however, did not produce a. degree- of organic kidney damage that could be detected grossly or microscopically wV"3n the rats were sacrificed 10 days after - the last treatment. Napbtkztonic Aaid
ALoxicity: Doses up to 7500 Mg/kg an a-!=. U saolution l pi~hiV Eu oil were given to rats. The' a-al 1, showed no Ill effects and all survived. They vonre sacrificed and gross and microscopic examiznation of the tissues did not reveal any pathology. Chronic Oral Toxicity.: 2500 ugAg was ftdlattiues to each of 6 rata. They were somewhat uncomfortableafe treatment and drank much water. They lost wei1ght until the fifth treatment, gained slowly until the tenth, andI gained nepidl'j during the observatialiZperiod which lasted 10 day. beorn the rats were sacrlficed .\ Do pathology which could be attributed to the pcapound was detected. C.oncluflcn-3: 5aphtbicnio acid is i~fieynon-toxicJ when takec1 under the conditions described.
Piperidizne j, Acute OrlTxi0y The AtZfla determined to be 450 M7s wMen adinis-0-tered to rats as a 50% solution in water. The rats exhibited marked weakness and lethargy and died in from one to zWety hours depending on the size or the dose. Pcstzortsri examination revealed edema of the lungs and necrosis of /the stcmach.
Ctroanic rs Iij*9C mgAg as a 5% solution in water JA was given to rotgxzsn times over a two week period. There was a marked loss,4n weight until the third troatabent, followed b-, a rise to the original weight bry the sixth day aft.,r the final treatment. Pathological examination in- di~tA ncr~aljof tbc, liver and possible kidney changes. The r ±ndn' of the rats were killed ten days after the A4amage or"'tbe presence of hyaline casts. Coiduaicns: Piperidine Is said to be similar to 'jonline2 vhic&± s known to cause pronowicec paralysis of 1,he central 2nervous system and of siculetal muscle nerve endings. It Is amoderately toxic compound with Its ALD oftA450 mg/kg and - an thin dosage takes d relatively long time to kill.- Chronic exposure to piperidine caused a temporary loss. in weight and Vs3 the probable cause of death of on-nrt. Kidrney damage though slight, appeared In five of the six * rats Indicating that cumulative toxicity my occur. r -e-PAYy9, 19ag
DiagenA Acute OrlTziiy Diagen A was administered ,tanMta by, 1 at7os-Ech tubiS it. original form. T500 mg./g tbegingjimn feasible dose did not kill. The ret receiving this doji, however,p vhen sacrificed 10 days after treatment sate evidunce of chronic gssttitit-localized at ,.Pl~tion r squamous and glandular portions. Chronic Ori,;oxiy Ten danas of llCU-m.ga each were- givento q&Cli or a over a period or tv6i\seku. jhers was an LItIial loss of weight but It vas folibted by, a.
the -final treatment and no pat..lfi-ttibutable to Diagen - A cor'ld be detected. . Conclusions: From the standpoint intake Diagen A 1. relatively non-toxic. Diagen Bordeau vhich vas tested by this laboratory was also-Icund to be eq'zally non-toxic by ncoutb, but vas round t6 t ia mild skin irritant.
General Suriary: The results of our teats are stnarised in the following tab!e, in which- the corpounds are arranged in order of decreasing &auto toxicity./
Compound_ 7 7 ALD Cinulative Effects : Piperidine ~;, 4K-/x50 mg/kg Yea-4 n-Eutyl-p-aninophenoi'-l 450 None observed p-Nitro-dichlorobansane 670 Yes Alpha naphthol 1000 yea2 p-ou7i* 1000 yes 2-Chslo -a#vun 1500 None observed
p-Nitrcaniline , V q""rc yes P-Ni tiapkine tole 750None observed Diageni'4K 7500 None observed - * Nawthiott Acid 750None observed'
/7 While none of these materials Is highly tokic, all-but the- -1 Is tbne are probably toxic enough to cause indus trial poisoning- in 4 0, .,Since most of- the: capounds tested are eitheParcust1r-zdtro- 0r ~compounds -they -have certain oclgli.-rptstr'om . -.- One or e tinst a*uptous or poiacining to appear la-flhat- 'ot--asrn. This-is primarily -due" to the fomnation or meteutoglobdtandrnaulta 'in a reduction of- oxygt.. capacity which in'tartL affcats' those t~aaueuif trot whosa-oxygen reed is high and-especially the central nervousasytl Oxidation of 'these compounda often leads to the produationi of =,;,&Ias which are Injurious to the kidneys. -- ] -s-Nay 9, 1949
A The compounds diaoussed reach the htmn organism by skin absorption, by inhalation and by oral ingeution. The rintrtare the mor* important industrially. The tot ta perfornef give hi approiate lethal dome and ton Idea of the danger of* ocuuative toxicity. They do not exclude the posibility of psthoq,-g occurring when exposure covers very long periods of time.
XMUS TRIAL TOXZ .OG John RrlRqulgqr, N. D. /v~l'OtO?
BY., John A. pp, Jr., Ph.D.
Asaiatant Director -- JTAZ:ovf A AMTEK CORP-
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