Document rprG5b1Vw49x1DOVRedd7j4yE

CONFIDENTIAL: Not to be released outside UCCwithout the written consent of the C&P Medical Director, Occupational Health Team Operations Manager or Product Safety Director. Project Report 41-70. 6 Pages April 24, 1978 Tel: (412) 327-1020 CHEMICAL HYGIENE FELLOWSHIP Carnegie-Mellon Institute of Research Carnegie-Mellon University 4400 Fifth Avenue Pittsburgh, Pa. 15213 UCAR Resin LPCA-5011 (80% in CELLOSOLVE Acetate) Range Finding Toxicity Studies Sponsor: Union Carbide Corporation ***** Summary Stomach Intubation, rat - LD50 * 14.9 ml/kg; dosed as received. Skin Penetration, rabbit - LD50 > 16.0 ml/kg; dosed as received. Inhalation, rat Substantially saturated vapor, static conditions at 24C. 8 hours killed 0 of 6. Uncovered Skin Irritation, rabbit - None, Grade 1. Covered Skin Irritation, rabbit FHSA test - Primary irritation score - 0.0; not an "irritant". Eye Injury, rabbit - Moderate, Grade 5. Eye Injury, rabbit FHSA test - 6 of 6 eyes "positive"; an "irritant". Interpretation UCAR Resin LPCA-5011 (80% in CELLOSOLVE acetate) was slightly toxic following single stomach intubation and had an extremely low order of toxicity following single covered dermal application. Administration of the undiluted material resulted in no irritation to uncovered rabbit skin and in moderate corneal injury, with Iritis, in rabbit eyes. When tested by Federal Hazardous Substances Act (FHSA) conditions (Draize scoring), it was not an "irritant" to covered rabbit skin but was an "irritant" to the eyes. No hazard is anticipa ted from the infrequent inhalation of substantially saturated vapor evolved at room temperature under normal handling conditions. With the exception of eye irritation, the LPCA-5011 in CELLOSOLVE acetate was no more toxic or irritating than CELLOSOLVE acetate alone (tested previously). The present study indicates somewhat more severe eye Injury than noted for CELLOSOLVE acetate alone. Samples Quantity: 0.5 pt; 1 pt Date Received: 12-19-77; 2-1-78 CHF Sample No.: 40-485; 41-33 Submitted By: H. G. France Division: Chemicals and Plastics South Charleston, WV Identification: 511-01-6642; 511-01-0414 (viscous yellow liquid) Charge No.: 03986 IIQC 0^6 f* ' 494 Report 41-70 Page 2 Peroral, Single Dose to Rats LD50 - 14.9 (10.1 to 22.1) ml/kg; dosed as received. Conditions - Standard. See attached page of standard test procedures. Dosage; Dead ml/kg .'"Dosed Days to Death Weight Change 64.0 32.0 16.0 8.0 4.0 5/5 5/5 3/5 0/5 0/3 1,1,1,1,1 1,1,1,1,1 2,2,2 " - - 115 to 119 gm 86 to 138 gm 111 to 129 gm Signs Heavy breathing, sluggish 2 min. - Coughing 1 min. Gross Pathology - In victims, petechiae of the lungs; livers mottled, visceral surfaces pale; stomachs transparent, distended, gas or fluidfilled; kidneys mottled, sections congested; adrenals congested intestines transparent, yellow or white, fluid-filled. In sur vivors, nothing remarkable. Conclusions - Slightly toxic following acute peroral intubation. Skin Penetration. Single Dose to Rabbits LD50 > 16.0 ml/kg; dosed as received. Conditions - Standard. Dosed under polyethylene sheeting. Dosage; Dead^^ Days to ml/kg ^'"Dosed Death Weight Change Skin Irritation 16.0 1/7 12 135 to 340 gm - Signs !I 1 i i Gross Pathology - In victim, lungs with dark red areas; liver dark purple; in testines hemorrhaged; mucous discharge from anus. In survivor*, kidneys pale. Conclusions - Extremely low order of toxicity following acute covered dermal application. ucc 062707 435Report 41-70 Page 3 Inhalation, Single, by Rats Conditions - Static exposure at 24C. Procedure B of standard test procedures. Proce dure Time Concen tration Dead^^^ Weight Death Change B 8 hr Substantially 0/6 saturated vapor - 53 to 82 gm Signs - Gross Pathology - Nothing remarkable. Conclusions - No hazard is anticipated from the infrequent inhalation of sub stantially saturated vapor evolved at room temperature under normal handling conditions. Skin Irritation, Rabbit, Uncovered Conditions - Standard. Applied undiluted. Conclusions - No irritation on 5 rabbits. Grade 1. Skin Irritation, Rabbit, Covered Conditions - FHSA procedure; 24-hour contact. Conclusions - Primary irritation score 0.0. Not an "irritant" by FHSA definition. Eye Irritation, Rabbit Conditions - Standard. Instilled undiluted. Conclusions - Moderate corneal injury, with iritis, from 0.02 ml per eye; trace corneal injury on one of 5 eyes from 0.005 ml per eye. Grade 5. Eye Irritation, Rabbit Conditions - FHSA procedure. Conclusions - See separate sheet. Six of 6 eyes "positive" for corneal, irldal and conjunctival injury. An "irritant" by FHSA definition. } i, . 0(52763 4P6 Report 41-70 Page 4 Wwf1.. VI Mi: Roy C.'Myers, B.S.J Associate Scientist Eicon R. Homan, Ph.D. Group Leader t Approved: Director Acknowledgments: Single Peroral Tests Skin Penetration, Irritation Tests Inhalation Studies Date: April 24, 1978 Typed: sac Robin A. Turney, B.S. Technologist Naomi I. Condra, B.S. Scientist Donald J. Nachreiner, B.S. Assistant Scientist 062709 t * Standard Test Procedures 497Report 41-70 Page 5 _ In all tests, the nonfasted animals are maintained on appropriate Wayne [diets and water ad lib except during period of manipulation or confinement. Dosage levels differ by a fact r f 2 in a geometric series. LD50s or LC50s are calculated by the moving average method based on a 14-day observation period. Toxicity Terminology for Peroral and 24-Hr Dermal LD50s (A)/Inhalation 4-Hr LC50 (B) A.-&m/kg B. PP> A, gm/kg B, _E Extremely low order I Slightly f Moderately > IS 5-15 0.5-5 > 100M 10M-100M 1M-1QM Highly Seriously Dangerously 0.05-0.5 0.001-0.05 < 0.001 100-1M 10-100 < 10 Peroral. Compounds administered by stomach Intubation to Wistar derived |Mle rats, 90-120 grams In weight and 3 to 4 weeks of age. Skin Penetration. Hale albino rabbits, 3 to 5 months of age, are Immobil ized during the 24-hour contact period with the compound retained under impervious iheeting on the clipped intact skin of the trunk. Thereafter, excess fluid is re lived to prevent ingestion. Maximum dosage that can be retained is 16 to 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 j la 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 to 100 grams cf | chemical over 200 cm^ area on shallow tray placed near the top of a 120-liter glass j chamber which is then sealed for at least 16 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. I 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 j surface of a minimally heated one-inch Pyrex tube, through which metered air is passed, lesultant vapor is delivered as in A. [Procedure E. Spray - Solutlona or suspensions are atomized in a glass VAP0NEFRIN nebulizer using dried compressed air at 9 liters/min (corrected) and 22 psi. The resultant aerosol of droplets averaging 2 microns in diameter is conducted directly I 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 Feed through Iwhlch air is passed at 14 liters/min (uncorrected) at 5 psi. The dust is delivered 1 directly to a 120-liter plexiglas chamber containing rats. Airborne dust concenjtrations are measured gravimetrically every half hour. Skin Irritation. Chemical is applied in 0.01 ml amounts to clipped, uniicovered intact skin of 5 rabbit bellies either undiluted or in progressive dilutions 1 10, 1, 0.1, and 0.01Z in solvent. Ten grades are recognized based on appearance |o moderate or marked capillary injection, erythema, edema or necrosis within 24 hours, injury from undiluted Grade 1. Eye Irritation. Eyes not staining with 5Z fluorescein in 20 seconds conCf accePted* Single instillation of 0.005, 0.02, 0.10 or 0.5 ml undiluted or Ifeaii i ^ f and ** dilutions are made into conjunctival sac of 5 rabbits. I immediately unstained and after fluorescein at 24 hours, with ten grades recog- *ed. Trace or no injury from 0.5 ml undiluted Grade 1. ucc 062710 1 l t Material EYE LRRITAT10N - URAIZE (I'llSA) SCORING UCAR Resin LPCA-5011 (80% in CELLOSOLVE Acetate) Sample Number &n-48S Rabbit Number Time After Dose (Hours) T^221*U___ - 77-7209f1 __ 77-72130 __ 77-72109 __ 77-7104' 24 48 72 24 48 72 24 48 72 24 46 72 24 48 72 77-71055 24 48 72 Observation (1) Cornea Opacity Area Involved Subtotal (2) Iris Subtotal (3) Conjunctlvae * Redness Chemosi8 Discharge Subtotal CoT><-- 38 T tel Score 22211 221 21 20 20 10 10 5 0 0 0 500500 322211 211210 322210 16 10 10 12 6 2 41 30 20 27 11 2 24 Hours 48 Hours 72 Hours Comments: 6 of 6 eyes "positive" for corneal, iridal and conjunctival injury; an - SCORE 22 122211122* 44 34 33432431 40 40 15 40 30 30 20 15 10 40 30 10 5 0 0 5 5 5 -5 5_ 5 5 5 5 2212222 2222 % 31032?2212 1 310322 2 322 2 2 16 8 2 W ;2 12 1? 14 IQ 12 10 10 61 48 17 61 47 47 37 34 25 57 45 25 Cornea Median Score Iris Conjunctlvae Total 30 5 25 2.5 10 2.5 14 49.0 10 37.5 10 22.5 I 11 nm J . Conroy________ Date Applied i^iQ_-7a Report 41-70 Page 6 4S8 1