Document G5VYpjzJN2Kp5JXBEvbk81Eex

X. 2k-*' 3. E.'TUUeillujuu Texas City Plant .TMrr-'Rr-NDr. W, R.Manning-Building2000 Tech.Center-South Chas. You may find of interest. Not warning on peroral dose rate. May wish to file will the Food ProducfiS project . ABSteele received received SEP V 1971 SEP 2 9 19TT M. E. E1SENHQUR [R. N. WHEELER UCC 065106 Confidential Special Report 34-71 Chemical Hygiene Fellowship MELLON INSTITUTE Carnegie-Mellon University Rt 9-1-71 Miscellaneous Toxicity Studies Editors C. S. Well Fori UNION CARBIDE CORPORATION, Chemicals and Plastics Operations Division SEVIN and/or Phenothiazine Samples 33-162 and 33-56 Peroral, Single Dose to Female Rats SEVIN LD50 - 0,224 (0.117 to 0.432) gm/kg; 1 ml - 0.05 gm in corn oil Phenothiazine LD50 - 2.99 <2.02 to 4.42) gm/kg; 1 ml - 0,25 gm in corn oil SEVIN plus Phenothiazine LD50 0.933 (0.631 to 1.38) gm/kg; 1 ml - 0,30 in com oil Predieted/observad " 0,978/0.933 - 1.05; additive Joint action, TEMIK Oxime 2-Methyl-2<!methylthio)propionaldahyde oxime Sample 34-113 Peroral', Single Dose to Rats LD50 - 0,707 (0.281 to 1.78) ml/kg, undiluted. UC 30948 2-Methy1-2- Jl-methyl-2-(me thylthiopropylideneaminoxyQpropionaldahyde 0"<m#thy1carbamoy1)oxime Sample 34-107 Peroral, Single Dose to Rats LD50 - 0.0238 (0.00952 to 0.0594) gm/kg; 1 ml - 0.05 gm in PEC-400 A D.O.T* Class B poison perorally. UC 44123 2 '',6' -Diisopropy 1-3' ,5' -dinitro-2,2,2-trichloroacetanilide Sample 34-112 Peroral, Single Dose to Rats LD50 > 5.0 gm/kg; 1 ml - 0.20 gm in PEG-400 Skin Irritation, Rabbit, Uncovered No irritation on 5 rabbits from 202 in PEG-400 Eye Irritation, Rabbit No, or trace, irritation from powder or 202 in PEC-400, UC 46207 2-^p-(roethylcarbamoyl)oximin^-l,4-dithlane Sample 34-128 Peroral, Single Dose to Rats LD50 - 0.0L54 (0.0114 to 0.0208) gm/kg; 1 ml 0.10 gm in corn oil A D.O.T. Class B poison perorally. R E C L i V *: O itP 23 jgy| UCC 065107 A. B. STEM'LL Report Vinvlidene Chloride Sample 32-222 Peroral, Single Dose to Rats LD50 - 0.406 (0.295 to 0.559) ml/kg undiluted. Inhalation - 4 Hour LC50 38,060 (24,940 to 58,070) ppm. Repeated Peroral Dosing Aimed at Finding any Circulatory Disturbances In Toes or Tail Groups of 10 male and 10 female Harlan Wistaiv 90 to 120 gram, weanling rats were given undiluted vlnylldene chloride by daily stomach intubation to a maximum of 29 doses. The dosage schedule was as followst Hags Oajrs 0.203 7 0.511 3 0.256 3 0.644 2 0.323 5 0.811 3 0.406 2 1.02 2 1.28 2 Animals received various dosages before death or sacrifice ensued. dosage ranged from 3.8 ml/kg to 14.5 ml/kg* Cumulative Tissues were taken from the rats that died or that were killed for histopathologlcal examination. The pathologist reported lesions related to gastritis, enteritis and esophagitis with some being sufficiently severe to become perforating ulcers. Particular attention was paid to the toes and tails based on the hypothesis that if this compound was implicated in acro-osteolysls that circulatory failure and lesions of the most distal portions of the body would be affected as is the case in man. No single lesion occurred with sufficient frequency to Implicate the compound in this regard. Detailed reports on pathology are available. Protocol sheets and Standard Test Procedures are available for each entry upon request. Approved: Typed: September 13, 1971 - md Carrol S. Well, M.A, Senior Fellow Charles P. Carpenter, Ph.D. Administrat;iivvea Fellow ucc 065A08 Vinylidene Chloride M. I. Sample No, 32-222 Date Started _ . 10-20-69 Report 34-71 Protocol Initiator A. B. Steele Sample Identification Peroral, Single Doae to Rata LD50 - 0.406 (0.295 to 0,559) ml/kg, undiluted. Conditions - standard, Dosage; Dead^-''^ Days to ml/kg ^/iSoaed Death 1.0 5/5 0,0,0,0,0 Weight Change - Signs and/or Symptoms Abdomen's distended - death In 3 hours. 0.5 0.25 4/5 2,2,3,3, +49 At autopsy intestinal irritation. One rat had blood on genitalia and one had a dark red spot on the tall. 0/5 - 81 to l04 Conclusions - highly toxic following acute peroral administration. Inhalation. Single, by Rats Conditions - Procedure D, Proce dure Time Concen tration D 1.5 hra 64,000 ppm. D 4 hrs 32,000 ppm. Deadx^ Days to Weight ^^^Dosed Death Change 6/6 All In m exposure. 2/6 1 in ex +31 to posure, 1 +53 at 1 day* Signs and/or Symptoms All prostrate at 8 min. Poor coordination at 8 min* Prostrate at 45 min. Cross Pathology - Victims - scattered hemorrhage of lungs, capillary Injection in oviducts. Survivors - large, dark spleen; light brown areae on lungs. Conclusions - 4-hour LC50 38,060 (24,940 to 58,070) ppm. 4 FOR DESCRIPTION OF TESTS REFER TO STANDARD TEST PROCEDURES Ucc 065109 Standard Test Procedures In all tests, the nonfasted animals are maintained on appropriate Rockland diets and water ad lib except during period of manipulation or confinement. Dosage levels differ by a factor of 2 in a geometric aeries, LDSOs or LC50s arc calculated by the moving average method based on a 14-day observation period. Peroral. Compounds administered by stomach intubation to Wistar derived male rats, 90-120 grams in weight and 3 to 4 weeks of age, reared in our own colony. Skin Penetration. Male albino rabbits, 3 to 5 months of age, are immobil ized during the 24-hour contact period with the compound retained under impervious sheeting on the clipped Intact skin of the trunk. Thereafter, excess fluid is removed to prevent ingestion. Maximum dosage that can be retained is 20 ml./kg. Inhalation. Procedure A, Concentrated vapor is generated in a gas washing bottle by passing dried air at 2.5 liters/min. through a fritted glass disc immersed to a depth of at least 1-1/2 inches in the chemical which Is delivered to rats in a 9-liter glass exposure chamber. Mean vapor concentration is calculated from the loss In weight of the liquid or estimated from the vapor pressure at the actual temperature of the chemical during aeration. Procedure B. Substantially saturated vapor is prepared by spreading 50 grams of chemical over 200 cm,2 area on shallow tray placed near the top of a 120-liter glass chamber which is then sealed for at least 10 hours while an Intermittently operated fan agitates the internal chamber atmosphere. Rats are then introduced in a gasketed drawer-type cage designed and operated to minimize vapor loss. Procedure C. Mist, vapor and Any oxidation or decomposition products of the chemical held at 170C, are generated and delivered as in A. Procedure D. Vapor at metered concentration, not checked analytically, is generated by feeding the liquid at a constant rate down the inside of a spirally corrugated surface of a minimally heated one inch Pyrex tube, through which metered air is passed Resultant vapor is delivered as in A. Procedure E. Spray - Solutions or suspensions are atomized in a glass VAPONEFRIN nebulizer using dried compressed air at 9 liters/min. (corrected) and 22 p.s.l. The resultant aerosol of droplets averaging 2 microns in diameter is conducted directly into a 60-liter cubic glass chamber containing rats. Mean aerosol concentration is calculated from the amount of material atomized. Procedure F. Dust - Dust clouds are generated by a baffled Wright Dust Fead through which air is passed at 20 liters/min, (uncorrected) at 15 p.s.l. The dust is de livered directly to a 120-liter plexielas chamber containing rats. Airborne dust concentrations are measured gravimetrically every half hour. Skin Irritation. Chemical is applied in 0,01 ml. amounts to clipped, un covered intact skin of 5 rabbit bellies either undiluted or in progressive dilutions of 10, 1, 0.1, and 0.01X in solvent. Ten grades are recognized based on appearance of moderate or marked capillary infection, erythema, edema or necrosis within 24 hours. No injury from undiluted Grade 1. Kye Irritation. Eyes not staining with 5% fluorescein in 20 seconds contact are accepted. Single instillation of 0.005, 0,02, 0,10 or 0.5 ml. undiluted or of 0.5 ml. of 40, 15, 5 and 1% dilutions are made into conjunctival sac of 5 rnhlilLu, Uuiul lmmudlately unstained and after fluorescein at 24 hours, with ten gi'iidus recognized. Trace or no inlurv from 0,5 ml. undiluted Grade 1, ucc 065110 MAILING LIST Summary of the Miscellaneous Toxicity Studies Report is being mailed to the following List B and Agricultural Chemicals List. List B Agricultural Chemicals Medical Directors A - C. U, Dernehl 1 - E. Q. Hull 1 - R, E. Joyner 1 - T. N. Spencer 1 - R, J. Sexton Other Distributions 1 - M. B. VerNooy 2 - N. H. Ketcham 1 - P, W. McDaniel 1 - 11, R, Guest 1 - R. C. Back 1 - W, J* Bartley 1 - R. A. Bleidt 1 - J. A. Durden 1 - J. B, Harry 1 - R. A. Hensley 1 - D, L, Heywood 1 - H, E, Johnson 1 - F G Kennsdy 1 - R. L, Masker 2 - H. H, Moorefield 1 - R. H, Wellman Library Libraries 2 - Chemicals Division (1 set each Library) Building 701 and 770 Libraries! South Charleston, W, Va, 1 - Union Carbide Corporation Library - Building 7A0 P, 0. Box 8361 South Charleston, W. Va, The summary of this report will be included in the COLLECTED SUMMARXES for the month of Sept, and mailed to the following List A, List A (G. H, Daniels 1 < R. I. Hoaglln Smith 1 - T, T, Szabo 1 - T. H. Welch 1 - N. L, Zutty 1 - J, V, Murray, Jr. 1 - Leon Shechter 1 - Plastics Division Library Bound Brook, N, J. 1 - Mining and Metals Library Tuxedo, N, Y. 2 - Chemicals Division Library Bldg. 701 & 770 Libraries South Charleston, W. Va. 1 - R & D Library Tarrytown, N. Y, 1 - W, B. Ackart 1 - E, A. Barr 1 - F, W, Tauber Pertinent protocol sheets and Standard Test Procedures, along with the Summary pages, are being mailed to the following project Initiatorss Project Initiators , l J. K. Chun 1 " J. K Lncount 1 - A, B. Steele ucc 065111