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v u Z I Clinical Toxicology of Commercial Products ACUTE POISONING ROBERT E. . GOSSELIN, M.D., Ph.D. Irene Heinz Given Professor. of Pharmacology. Dartmouth Medical School. Hanover, New Hampshire HAROLD C. HODGE, Ph.D., D.Sc. Professor and Chairman Emeritus of Pharmacology and Toxicology, School of Medi- cine and Dentistn•. The Unieersit.• of Rochester. Rochester, New York: Professor in Residence of Pharmacology and Oral BioloRy, University of California. San Fran- cisco: of Environmental Toxicolop-, and of Pharmacology and Medical Therapeutics, Universit.• of California. Irvine. California. ROGER P. SMITH, Ph.D. Professor of ToxicoloRti•, Dartmouth Medical School. Hanover, New Hampshire. MARION N. GLEASON, M.Sc. (h.c.) Honorary Associate Fellow, American Academy of Pediatrics; FormerlY Research Associate in PharmacoloRy. School of Medicine and Dentistry. The Universih• of Rochester, Rochester, New York. Fourth Edition WILLIAMS & WILKINS Baltimore/London

TABLE I-1 Pmbable Oral LETHAL 1)oce 4 Human I D4we F<.r 7U kK. perum 4U.0 I b. i 6 Super toxic lessthan i mg./kg. A taste (less than 7 drops/ 5 Extremely toxic 5-511 mg./kg. Between 7 drops and 1 teaspamful 4 Very toxic 50-500 mg./kg. Between I tsp. and I ounce I . 3 Moderately toxic 0.5 5 gmJkg. Between I oz. and 1 pint (or I Ih.) 2 I Slightly toxic Practically 5-1Ci above 15 RmJkg. RmJkR. Between I pt. and 1 quart More than 1 quart (2.2 lb.) nontoxic ~ ~ estimates may be useful in prognosis (Jones and Work, American Journal of Diseases of Children. 102: 427, 1961). If the toxicity rating implies a poor or equivocal prognosis (with respect to mortality or morbidity), even the asympto- matic person should be examined as soon as possible. This is important even if the alleged exposure occurred many hours before. Some toxic agents produce severe sequelae after long periods of latency. A situation like this represents a challeng- ing opportunity to the therapist. 2. Has the patient vomited? If not, and if the poison is thought to have been ingested. suggest one of the following emetic stimuli. None of these procedures should be attempted if the patient is unconscious or semiconscious, or if' the ingested poison is thought to have been a strong alkali, a mineral acid, or kerosene. Severe heart disease and pregnancy are sometimes valid contraindications. If successful, any one of the first three measures (a-c) should induce vomiting within 2 to 3 minutes. a. Tickle or gently stroke the back of the patient's throat Induce vomiting with a finger. With a child (who may bite) use a blunt probe like the handle of a teaspoon. Mechanically induced emesis is seldom extensive enough to be_ ade- - quate. b. Have the patient drink one or more glasses of warm water containing a teaspoonful of mustard powder. Mix the dry mustard with water just before drinking. c. Repeat procedure (a) above after the stomach has been distended with fluid (see 3 below). d. If available, ipecac syrup (USP) may be administered by mouth. The conventional emetic dose is said to be 8 ml., but a single dose of 15 to 20 ml. has been given without untoward effects to many young children who had ingested potentially toxic substances. Vomiting under these circumstances is not immediate, but 56% of the patients vomit within 15 minutes and 88% within 30 minutes. (Robertson, American Journal of Diseases of SECTION 1. FIRST All) AND EMERGF:NCI' THF.ATMEtiT

120 SECTION II: D. INGREDIENTS INDEX 401 401 Triethylene Glycol Toxicity rating: 2(?). This compound has a lower acute toxicity than diethylene glycol but a higher toxicity than propylene glycol. Symptoms are presumably like those due to ethylene glycol, but there is no evidence of decomposition to ethylene glycol in vivo. See also: Ethylene Glycol, Reference Congener in Section IIl. Ref.: Karel et al., 1947; Latven and Molitor, 1939; Lawter and Vrla, 1940. 402 402 Polyethylene Glycols Toxicity rating: 1& 2. If a numeral is included in the name, it represents the approximate mean molecular weight. Fractions with molecular weights of 600 (and below) are liquid, of 1000 (and above) are solid. The higher the molecular weight the lower the toxicity, perhaps partly because the long polymers are so incompletely absorbed from the bowel. Very large doses are required to kill animals and deaths are renal in origin (not due to primary central nervous depression). See also: Ethylene Glycol, Reference Congener in Section III. Ref.: Carpenter and Shaffer, 1952; Smyth et al., 1950, 1955. 403 403 Carbowax Toxicity rating: 1. Solid and semisolid polyethylene glycols. A series of waxy substances with mean molecular weights of 1000 and higher (indicated by the numeral following this trademarked name). In animals the toxicity decreases with increasing molecular weight. With massive doses some animals die from kidney injury. No human poisonings are known. See also: Ethylene Glycol, Reference Congener in Section III. Ref.: Carpenter and Shaffer, 1952; Smyth et al., 1950, 1955. ° 404 404 Propylene Glycol 1,2-Propanediol Toxicity rating: 1. Toxicity is said to be similar to that of glycerine and is therefore practically nontoxic. No untoward reactions described in man, but large oral doses in animals may produce central nervous depression and minimal kidney changes. See also: Ethylene Glycol, Reference Congener in Section III. Ref.: Davis and Jenner, 1959; Thomas et al., 1949. 405 405 Polypropylene Glycols Toxicity rating: 3. Name is often followed by a numeral which indicates approximate mean molecular weight. Unaccountably much more toxic than propylene glycol or even ethylene glycol in laboratory animals. Polymers with molecular weights of about 1000 seem to be more toxic than longer or shorter homologues. When ingested or injected in dogs, ventricular extrasystoles result. 406 406 1,3-Butanediol 1,3-Butylene glycol Toxicity rating: 2(?). Said to be slightly more toxic than propylene glycol, but has been tested as a parenteral drug solvent. Subcutaneous LD„ 16.5 ml./kg. in mice and 20.1 ml./kg. in rats. See also: Ethylene Glycol, Reference Congener in Section III. Ref.: Spiegel and Noseworthy, 1963. 407 407 Hexylene Glycol 2-Methyl-2, 4-pentaned iol Toxicity rating: 2 or 3. Used in hydraulic brake fluids, printing inks, textile dye vehicles, and recommended as a solvent for some pharmaceuticals. Lethal doses in animals produced muscular incoordination which progressed to a narcosis lasting for several hours; death was delayed for 1 to 4 days. Evidence of slight liver and kidney damage on chronic feeding. Human subjects have ingested 5 gm. daily for 5 days without apparent ill effects or urinary abnormalities. Eliminated in urine, partly (20 to 25%) in conjugated forms. Said to constitute a negligible hazard on intact skin, but when gauze impregnated with a dressing containing 80 per cent hexylene glycol was used on 483 pediatric patients with extensive burns, 36 exhibited highly variable periods of coma (hours to weeks). Almost half of this comatosed group eventually expired in renal failure. See also: Ethylene Glycol, Reference Congener in Section III. Ref.: Jacobsen, 1958; Procter, 1966; Woodward et al., 1945. 408 408 1,2,6-Hexanetriol Toxicity rating: 1. Hygroscopic viscous fluid, miscible with water and used as humectant and plasticizer for hydrophilic films. Acute oral LD„ in male rats 16 ml./kg.; intraperitoneally as a 50 per cent solution in water, 10 gm./kg.; and intravenously as undiluted material, 5.6 ml./kg. Two ml./kg. applied to shaved rabbit skin 30 times over 6 weeks was without effect. A 30 per cent solution in 0.75 per cent saline was only slightly hemolytic in vitro. Almost 80 per cent of a large dose appeared within 24 hours in the urine of rats apparently unchanged. There was a significant increase in the urine oxalate, but it accounted for less than 0.1% of the intubated dose. It is a moderately good diuretic in rats. Fed to rats over a 2 year period a 5 per ce: year and produc hexanetriol is inn of compound. See also: Ethyler Ref.: Smyth et a. Non-fatty esters Diethylene glycol Toxicity rating: : ether ( a Carbito produced by ethy more toxic by ski: See also: Ethylen Ref.: Karel et al.. Toxicity rating: 3 slightly more toxi See also: Ethylen i.e., Laurate, olea Toxicity rating: ; diethylene glycol t ' = See also: Ethylen, Ethylene glycol in ; acetate, Dowanol Toxicity rating: : corresponding mo Oral toxicity (am probably higher. See also: Ethylen. Ref.: Anon., 1947: e.g., Ethylene gly. Toxicity rating: : ethylene glycol. T Special problems . See also: Ethylent Ref.: Anon., 1947; Non-fatty ethers Diethylene glycol Toxicity rating: 3. than the ethyl deri tuxicitv and toxic See also: Ethylent Ref.: Karel et al.. Ethylene glycol in Toxicity rating: 4. as the ethyl deriv: See also: Ethylent Ref.: Smyth et al. e.g.. Crag fly repe Toxicity rating: 3