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Patty's Industrial Hygiene and Toxicology THIRD REVISED EDITION In Three Volumes Volume 1 GENERAL PRINCIPLES Volumes 2A, 2B, and 2C TOXICOLOGY Volume 3 THEORY AND RATIONALE OF INDUSTRIAL HYGIENE PRACTICE Contributors B. D. Astill L. W. Hazleton /. L. O'Donoghue R. R. Beard Gary V. Katz V. K. Rowe G. D. DiVincenzo W. J. Krasavage H. E. Stokinger Derek Guest S. B. McCollister Robert /. Weir Rolf Hartung R. Montgomery Mark A. Wolf (deceased) Geo2GE !~ CLA-1TaN F~OR~~GE E. Cu1-'/ToK ~~(EARS ~-~ i807 (VIV) ig8z I Eb I -rD RS A WILEY•INTERSCIENCE PUBLICATION JOHN WILEY & SONS New York • Chichester • Brisbane • Toronto • Singapore

-PA7Ty S 3852 V. K. ROWE AND M. A. WOLF barbital, salicylic acid, and y-hexachlorocyclohexane were very poorly absorbed from solutions of the glycol. Polyethylene glycol E-300 (PEG-300) and PEG-300/methylated spirits (PEG IMS) (6:1 v/v ratio of PEG-300 to methylated spirits (95 percent ethanol, 5 percent methanol)) have been reported to be superior to water when used as decontaminants of the skin of rats exposed to phenol (248, 249). Other similar studies using the skin of swine, believed to be more similar to the skin of humans than is the skin of rats, indicates that a water shower for 15 min is practically equivalent to decontamination with PEG-300 or PEG-IMS. Both ; treatments were effective in reducing mortality, skin injury, and plasma concentration and retention time of absorbed phenol as compared to animals exposed to phenol but not decontaminated. These data plus the universal ; availability of water indicates that water is the decontaminant of choice (29). 6.4.13 Human Experience There are no reported human injuries or adverse effects from the handling of these polyethylene glycols. 6.5 Hygienic Standards of Permissible Exposure No hygienic standard is believed necessary. 7 PROPYLENE GLYCOL; 1,2-Propanediol; Methyl Ethylene Glycol; 1,2- Dihydroxypropane; CAS No. 57-55-6 CHsCHOHCH2OH 7.1 Source, Uses, and Industrial Exposure Propylene glycol generally is synthesized commercially by starting with propyl- ene, converting to the chlorohydrin, and hydrolyzing to propylene oxide, which is then hydrolyzed to propylene glycol. It can also be prepared by other methods (108). Propylene glycol is used in antifreeze formulations, heat exchangers, and brake and hydraulic fluids; in the manufacture of resins, which accounts ferr a large portion of its use, polypropylene glycols, and propylene glycol ethers and esters; as a solvent in pharmaceuticals, f'oods, cosmetics, and inks: as a plasticizer for resins and paper; and as a humectantiin textiles, tobacco. and pet foods. It is also used in the vapor form as an air sterilizer for hospitals and public buildings. Industrial exposures are from direct contact, or from inhalation of vapors and of mists where the material is heated or violently agitated. Other exposure is by ingestion resulting from its use in foods and drugs. t• , i t I

PAT7y 3 K. ROWE AND M. A. WOLF GLYCOLS 3853 re ve• --oorly absorbed ,iethylated spirits (PEG (95 percent ethanol, 5 to water when used as 248, 249). Other similau- similar to the skin of r shower for 15 min is M or PEG-IN1S. Both in injury, and plasnta is compared to animals lata plus the universal iinant of choice (29). ts from the handling of vcol; 1,2- -w starting with propyl- propylene oxide, which ;)ared by other methods heat exchangers, and !s, which accounts for a 1Ylene glycol ethers and tnd inks; as a plasticizer )acco, and pet foods. It ,r hospitals and public :n inhalation of vapors : itated. Other exposure 7.2 Physical and Chemical Properties Propylene glycol is a colorless, almost odorless, slightly viscous liyuid with a slightly acrid taste. It imparts no odor or taste of its own when used in food colors and flavors. Additional physical and chemical properties are given in Table 50.1. 7.3 Determination in the Atmosphere The determination of propylene glycol in air can be accomplished by several of the methods noted under ethylene glycol, although it would seem unnecessary for industrial hygiene purposes. A method for detection of propylene glycol in body fluids is described by Lehman and Newman (142). 7.4 Physiologic Response 7.4.1 Summary The hazards to health in the industrial handling and use of propylene glycol would seem to be negligible. Its systemic toxicity is especially low and, since 1942, it has been considered a.proper ingredient for pharmaceutical products (143). The Food and Drug Administration does not object to its use in food products or in cosmetics (144). The inhalation of atmospheres containing propylene glycol vapor presents no hazard to health. Exposures created by operations producing hot vapors, or by high-speed mechanical action in which a fog of propylene glycol is produced, have not been studied. However, it is difficult to visualize how this condition could create a hazard, since the material is so extremely low in systemic toxicity. The toxicology of propylene glycol has been reviewed extensively (20, 145, 146). 7.4.2 Single-Dose Oral The single-dose oral toxicity of propylene glycol has been studied by a number of investigators (142, 145, 147, 148, 139, 99, 17). The single-dose oral LD5o values range, for rats, from 21.0 to 33.7 g/kg; for mice, from 23.9 to 31.8 g/kg; for guinea pigs, from 18.4 to 19.6 g/kg; for rabbits, from 15.7 to 19.2 g/kg; and for dogs, from 10 to 20 g/kg. Laug et al. (17) report observing minimal kidney changes from large doses. From one-fourth to one-half of an oral dose given to rats, dogs, or human beings appears unchanged in the urine within 24 hr (142, 148, 149, 150). 7.4.3 Repeated-Oral Dose Seidenfeld and Hanzlik (151) gave groups of rats drinking water containing 1.0, 2.0, 5.0, 10.0, 25.0, and 50.0 percent propylene glycol over a period of 140 E

3$54 V. K. ROWE AND M. A. WOLF days. Animals receiving water containing either 25.0 or 50 percent propylene glycol died in 69 days, whereas those receiving either 1.0, 2.0, 5.0, or 10.0 percent appeared normal throughout the observation period. The average daily intakes for the latter four groups were calculated to be about 1.6, 3.7, 7.7, and 13.2 g/kg/day of propylene glycol, respectively. Histopathologic examination of the tissues from these animals revealed no renal or other pathologic disturb- ances. Weatherby and Haag (147) confirmed the fact that rats will tolerate 10.0 percent propylene glycol in the drinking water without physiologic impairment. Hanzlik and associates (148) found that rats could tolerate up to 30 m]/kg daily of propylene glycol when fed in the diet over a 6-month period. This is equivalent to 1.8 lb daily for a 70-kg person. Morris et al. (19) fed rats 2.45 and 4.9 percent propylene glycol in the diet, allowing, respectively, average daily intakes of 0.9 to 1.77 mUkg over a 24-month period without significant effect on growth rate. Microscopic examination of the tissues revealed very slight liver damage, but no renal pathology. Whitlock et al. (152) found that a diet containing 30 percent of propylene glycol was not well tolerated by young rats, and that producing females were unable to bring their young to weaning. Glycerin at 30 percent in the diet was well tolerated. Diets containing 40, 50, or 60 percent of propylene glycol were lethal after a few days. Gaunt et al. (153) fed both male and female rats propylene glycol in their diet at levels of 6,250, 12,500 and 50,000 ppm for a period of 2 years. They found no significant ill effects based upon mortality, body weight, food consumption, hematology, urinary cell excretion, urine-concentrating ability of the kidneys, organ weights, or histopathology, including tumor incidence. They suggest that the acceptable daily intake for man would be 25 mg/kg/day. (The 50,000 ppm level is equivalent to 2.5 g/kg/day for the rat.) Van Winkle and Newman (155) showed that propylene glycol, when given in concentrations of 5 or 10 percent in the drinking water of dogs for 5 to 9 months, caused no adverse effects. Criteria employed were liver function, kidney function, and histopathologic examination of the visceral organs. Fur- ther, they found no alterations in the serum calcium levels of cats and dogs fed large doses of propylene glycol. Weil et al. (154) found that male and female dogs fed diets providing propylene glycol at a dose level of 2.0 g/kg for 2 years were unaffected as judged by mortality, body weight change, diet utilization and water consumption, histopathology, organ weights of liver, kidney, and spleen, and measurement of blood, urine, and biochemical parameters. At a daily dose of 5 g/kg, the dogs GO gained more weight than the controls, especially during the early part of the GO experiment, owing to the higher caloric intake. An increase in the rate of Q~ erythrocyte hemolysis and a slight increase in total bilirubin was also noted. iD Hemoglobin, packed cell volume, and total erythrocyte count were lowered Go slightly, whereas the incidence of anisocytes, poikilocytes, and reticulocytes was 00 increased, suggesting that erythrocytes were being destroyed accompanied by 0

~ K ROWE AND M. A. WOLF r 50 -cent propylene r 1.0, _.0, 5.0, or 1(.0 .riod. The average dailv about 1.6, 3.7, 7.7, and thologic examination of her pathologic disturb- ,at rats will tolerate 10.0 physiologic impairment. iolerate up to 30 ml/kg i-month period. This is ,l. (19) fed rats 2.45 and pectively, average daily ithout significant effect -evealed very slight liver 0 percent of propylene )roducing females were percent in the diet was f propylene glycol were ropylene glycol in their )eriod of 2 years. They ity, body weight, food -concentrating ability of ; tumor incidence. They be 25 mg/kg/day. (The 'at.) ne gly...,., when given in ater of dogs for 5 to 9 °d were liver function, he visceral organs. Fur- vels of cats and dogs fed )gs fed diets providing ,ars were unaffected as and water consumption, ~leen, and measurement dose of 5 g/kg, the dogs ng the early part of the increase in the rate of •ilirubin was also noted. vte count were lowered es, and reticulocytes was stroyed accompanied by PR77y "S GLYCOLS 3855 accelerated replacement from the bone marrow. This effect was not sufficient, however, even at the 20 percent dietary level to result in any irreversible changes and there was no evidence of damage to the bone marrow or spleen. They state that dogs fed propylene glycol at approximately 8 percent in their diet (equivalent to 2 g/kg/day) can utilize it as a carbohydrate energy source with no adverse effects. The utilization of propylene glycol as a source of carbohydrate energy in animal feed has led to other dietary feeding studies involving cattle, sheep, chickens, and cats. It is used in pet foods as a humectant as well as a source of energy. I n lactating cattle, there is a tendency for the cow to develop hyperketosis which may be due to low carbohydrate stores in the body which are used to produce lactose excreted in the milk. Fisher and co-workers (156, 157) have summarized much of the work done to determine the usefulness of propylene glycol as a dietary supplement to alleviate this condition. Fisher et al. (156) reported on studies in lactating cows in which propylene glycol was added to food concentrates at levels of 3, 6, and 9 percent. The concentrate was fed to cows for 8 weeks during the early stages of lactation and it was found that there was no consistent effect on feed intake, body-weight change, or efficiency of ration utilization. Propylene glycol, at the 3 and 6 percent levels, appeared to increase the yield of milk but caused a slight decrease in milk fat and an increase in milk lactose content. There was also a significant decrease in hyperketosis in the propylene glycol treated animals as compared to the level in the control animals. Sauer et al. (157), in the study of 120 cows over a 2-year period in which propylene glycol was added to the diet at 3 and 6 percent levels for 8 weeks postpartum, substantiated the suitability of propylene glycol as a food additive for such cattle. It depressed the blood ketone and free fatty acids slightly below the control cattle level when the cows were not stressed by either high lactation yield or low concentrate food intake. However, if the cows were stressed by adverse environmental factors and slightly reduced food concentrate intake, the addition of propylene glycol at 3 and 6 percent to the concentrate ration caused a significant reduction of blood ketones and plasma fatty acids and increased the blood glucose concentration. They suggest that propylene glycol used as a feed additive at 3 and 6 percent of the concentrate should be desirable because of its ability to significantly decrease the incidence of clinical and subclinical ketosis in cows during early lactation when they are most susceptible to such metabolic disorder. Shiga et al. (158) fed male lambs propylene glycol at levels of 0.5 and 1.0 g/ kg in the feed every other day for 104 days. Neither level produced any adverse effects. They did increase the weight gain, especially in the early part of the experiment (about 30 days). Evaluation of the rumen liquor revealed an increase in propionate and total fatty acid concentrations. The weight percentage of wool, dressed carcass, and red meat-fat ratios were also greater than those of the controls. Propylene glycol has been shown by short-term feeding tests with chicks and E

chickens to be a suitable source of energy, the suggested level acceptable being ` in the range of 2.5 to as much as 8 percent in their diet. However, most authors feel that the level should be no more than 2 to 3 percent. Bailey et al. (159) fed ' chicks from 1 to 26 days of age with diets containing 8 and 16 percent of propylene glycol. The 8 percent level was considered to cause no significant ill effects as judged by live weight gain, food consumption, and carcass analysis. The 16 percent level caused growth depression and lower fat and higher protein content in the carcass. Persons et al. (160) also fed chicks from day 1 for 3 weeks with levels of 5 and 10 percent of propylene glycol in the diet. Both levels showed adverse effects such as depressed body-weight gains at the 5 percent level, and depressed body-weight gains and decreased food efficiency, but no mortality at the 10 percent level. They also fed hens for two periods of 28 days each with diets containing propylene glycol at levels of 2.5 and 5.0 percent. The 2.5 percent level decreased food consumption owing to the hens compensating for the change in energy intake, but there was no effect on egg production or general health. The 5 percent level caused decreased food and epergy intake and reduced egg production. The authors suggest that a level of 2.5 percent of propylene glycol is tolerated well by both chicks and hens. Based upon 21 to 28 day feeding studies on chicks of diets containing 2.5, 5.0, and 10.0 percent of propylene glycol, Waldroup and Bowen (161) found that chicks can utilize 5.0 percent of propylene glycol in their diet without ill effects. The 10 percent level caused depressed body-weight gains, reduced efficiency of feed utilization, diarrhea, and the development of deformed toes. Yoshida et al. (34) also found that chicks fed 5 percent of propylene glycol in their diet for 27 days were without ill effects. Higher levels caused inferior well being and diarrhea. Harnisch (162) feels that the no-effect level is in the range of 2 to 3 percent of propylene glycol. This resulted from his 8-week feeding studies on 4- to 5- week-old broilers in which he found that a diet containing 5 percent propylene glycol depressed food intake and reduced feed conversion efficiency. Because of the use of propylene glycol as a humectant as well as a source of energy in prepared cat food, a study (29) was conducted in which groups of two male cats each were maintained for 94 days on diets containing various amounts of propylene glycol. Two groups of two male cats each served as controls. The average calculated doses of propylene glycol cnnsumed, based on food intake and body weights, were 0, 80,443, 675, 1763. ur 4239 mglkg/day. The primary treatment-related effect was noted in the red blood cells (RBC), which eshibited Heinz body formation. This effect in the RBC was accompanied by iucreased amounts of hemosiderin pigment in the Kupffer cells of the liver and reticu- loendothelial cells of the spleen. The formation of Heinz bodies and increased hemosiderin occurred in a dose-related manner at doses of 675 mg/kg/day and higher. A daily dose level of 443 mg/kg/day appeared to cause averv slight increase in Heinz body formation without detectable increased liemosiderin present in the liver or spleen when compared to the incidence in the controls. 88698188

V. K. ROWE AND M. A. WOLF -sted -el acceptable briug ict. FL-wever, most autliors cent. Bailey et al. (159) led ning 8 and 16 percent of :I to cause no significant ilI )tion, and carcass anaIVsis. nver fat and higher proteiti I chicks from day I fM- 3 ,e glycol in the diet. Roth ody-weight gains at the 5 decreased food efticiencv, ed hens for two periods of )I at levels of 2.5 ancl 5.0 imption owing to the he.ns there was no effect on egg, aused decreased food and hors suggest that aa level of ,oth chicks and hens. ks of diets containing 2.5, p and Bowen (161) found ~:ol in their diet without ill )dy-weight gains, reduced lopment of deformed toes. •ercent of propylene glN-col ;her levels caused int'erior he rr ° of 2 to 3 percent feedii.t, studies on 4- to 5- iining 5 percent propylene ersion efficiencv. ctant as well as a source of ted in which groups of two ontaining various amounts ich served as controls. The ned, based on food intake ;9 mg/kg/day. The primarv ells (RBC), which exhibited accompanied by increased ,Ils of the liver and reticu- leinz bodies and increased oses of 675 mg/kg/day and tred to cause a very slight ble increased hemosiderin - incidence in the controls. f A_77y 5 GLYCOLS 3857 No treatment-related effects of any type were observed in the group ingesting 80 mg/kg/day. Other hematologic parameters which were evaluated and found to be unaffected by any level of treatment included packed cell volume, RBC count, hemoglobin, RBC morphology to evaluate polychromasia, RBC reticu- locyte count, RBC osmotic fragility, methemoglobin, total and differential white blood cell counts, and light microscopic examination of tissue bone marrow. In addition, serum clinical chemistry values of blood urea nitrogen, glutamic pyruvic transaminase activity, alkaline phosphatase activity, glutantic oxaloacetic transaminase activity, glucose concentration, and total bilirubin as well as routine urinalysis were unaffected by treatment. The clinical appearance and demeanor, body weights, organ weights, gross pathology, and histopathology of tissues other than liver and spleen were unaffected by treatment at any of these levels of propylene glycol. It appears that the cat is much more sensitive than other species to the formation and/or retention of Heinz bodies. Even so, their presence in significant numbers does not seem to adversely affect the cats. 7.4.4 Injection Toxicity Table 50.8 gives the LD,o values by injection of various routes to a number of animal species. Brittain and D'arcy (165) found that when propylene glycol was injected intravenously in rabbits, there were no effects on blood other than decreased clotting time, increased platelet count, and an increase in polymorphs accom- panied by a decrease in lymphocytes. High doses in rats by intramuscular and subcutaneous injections resulted in profound depression, analgesia, and coma (146). There was no anticholinergic effect in dogs but temporary increased urinary flow, peripheral vasodilatation, and a temporary vasoconstriction of the spleen when propylene glycol was injected intravenously (167). Repeated subcutaneous injection of propylene glycol to rats at a dose of 2.5 ml/kg (2.6 g/kg) every other day for 1 month caused an increase in oxygen consumption even though there was no kidney or liver histopathology found (167). 7.4.5 Eye Contact Propylene glycol is not injurious to the eyes of rabbits (39, 168) and has not caused any eye injury in human beings, nor would such be expected, but it may cause transitory stinging, blepharospasm, and lacrimation (108, 139). 7.4.6 Skin Irritation and Absorption Propylene glycol generally produces no significant irritant action upon the skin. From the results of extensive studies by Warshaw and Herrmann (169) on some

Table 50.8. Acute Toxicity of Propylene Glycol by Injection to Laboratory Animals Route of LD,, Species Administration (g/kg) Ref. Mouse Subcutaneous 19.2 146 15.5 36 Intraperitoneal 9.73 146 12.9 139 13.6 36 6.8 163 10.9 145 11.4 166 Intravenous 8.3 146 7.6 139 Rat Subcutaneous 22.0,25.0 145 22.5, 21.7, 29.0 146 Intraperitoneal 14.7, 13.5 146 Radiated PG 14.2 (13.7 ml/kg) 164 Unradiated PG 14.7 (14.2 ml/kg) 164 Intraperitoneal 13.0 139 16.8 (16.25 ml/kg) 99 Intravenous 12.7 (12.3 ml/kg) 99 6.2 139 6.8 146 Intramuscular 14.0, 20.7 146 15.0, 13.0, 20.0 145 Guinea pig Subcutaneous 13.0-15.5 146 Rabbit Intravenous 5.0 145 6.5 146 Intramuscular 6.0 145 Dog Intravenous 25.9 146 866 human subjects with various dermatologic backgrounds, it appears that propylene glycol may cause primary skin irritation in some people, possibly due to dehydration, but the material does not appear to be a sensitizer. Because of the very low systemic toxicity of propylene glycol, no problem from percutaneous absorption can be anticipated. Propylene glycol has been used widely in preparations for topical application and no evidence of systemic injury to humans has been reported. These findings are substantiated by other workers (99, 168, 170-175, 177). One of the many medicinal uses of' propylene glycol is .ts a solvent in eardrops. Morizono and Johnstone (176) E'ound that a concentration of 10 percent or more or propylene glycol in Ringer's solution when instilled into the inner ear cavity of guinea pigs caused apparent irreversible deafness. They recommend that if propylene glycol is used in eardrops the concentration should be less than 10 percent. 88698190

_r, .. ROWE AND M. A. WOLF Injec' I to Ref. 146 36 146 139 36 163 145 166 146 139 145 il 146 146 ;g) 164 ;g) 164 139 lkg) 99 ;g) 99 139 146 146 0 145 146 145 146 145 146 ounds, it appears that ne people, possibly due k sensitizer. Because of' lem from percutaneous been used widely in of systemic injury to iated by other workers col is as a solvent in a concentration of 10 when instilled into the ersible deafness. They .ops the concentration GLYCOLS 3859 7.4.7 Vapor Inhalation Robertson et al. (119) exposed sizable groups of rats and monkeys for periods of 12 to 18 months to atmospheres saturated with propylene glycol vapor and produced no ill effects. Human beings also have been exposed to saturated and supersaturated atmospheres for prolonged periods in the air-sterilization pro- gram without adverse effect. The uptake of propylene glycol mist by humans was studied using a 10 percent solution in labeled deionized water nebulized into a mist tent (178). Less than 5 percent of the mist entered the body, and of this 90 percent lodged in the nasopharynx and rapidly disappeared into the stomach. Very little was found in the lungs. 7.4.8 Reproduction Guerrant et al. (179) checked the reproduction capacity of rats fed up to 30 percent of propylene glycol in their diets through six generations. No adverse effects on reproduction were found when concentrations of propylene glycol in the diet were less than 7.5 percent. At higher levels the rats receiving the propylene glycol consumed less food, grew slower, had young at an older age, produced smaller litters on the average, and weaned fewer young than did the control animals. At the 30 percent level, the females did not breed normally and when they had young they did not feed them properly. They failed to wean third generation young. Emmens (180) fed mice 0.1 ml of a 50 percent water solution of propylene glycol for several days prior to mating and found that it reduced the mating to as little as 30 percent of normal, and litters to 15 percent. The mice swelled visibly with intestinal gases and then recovered. 7.4.9 Teratogenicity Gebhardt (181) found that 0.05 ml of propylene glycol was not teratogenic when injected into the yolk sac of chick embryos. However, it caused a high mortality of the embryos when injected into the air sac on the fourth day of development and unilateral micromelia in about 20 percent of the survivors. Waldroup and Bowen (161) have reported that chicks fed high levels of propylene glycol in their diets developed a high incidence of toe deformities, 57 out of 168 chicks as compared to the control group, 9 out of 168. 7.4.10 Mutagenicity Kennedy et al. (182) studied the dominant lethal effects in mice treated with propylene glycol intraperitoneally at a level of 10 mg/kg. The results suggest that it is nonmutagenic at this level. Pfeiffer and Dunkelberg (247) found propylene glycol to be inactive when tested against S. typhimurium strains TA- 98, TA-100, TA-1535, and TA-1537. E

7.4.11 Carcinogenicity Dewhurst et al. (183) and Baldwin et al. (184) in studies on the carcinogenicity of other chemicals used propylene glycol as the solvent. As a result they tested propylene glycol alone for carcinogenic activity. Dewhurst et al. (183) used a single injection of 0.2 ml whereas Baldwin et al. (184) gave three to five subcutaneous injections, amount not specified. In neither case were tumors observed over a period of about a year (184) or 2 years (183). Wallenious and Lecholm (185) applied propylene glycol to the skin of rats three times a week for 14 months but found no tumor formation. Stenback and Shubik (186) confirmed these findings when they applied propylene glycol at undiluted strength and as a 50 and 10 percent solution in acetone to the skin of mice over their lifetime. No development of tumors has been reported in the lifetime dietary feeding studies (19, 153, 154). In fact, Gaunt et al. (153) specifically states that no tumors were found in the rats. Thus it appears that propylene glycol is without carcinogenic properties. 7.4.12 Metabolism Ruddick (145), in his review of the toxicity of propylene glycol, summarized the work done to establish its metabolism in the body. It is oxidized to lactic acid or pyruvic acid by two pathways. These two metabolites are then used by the body as a source of energy either by oxidation through the tricarboxylic acid cycle or by generation of glycogen through the glycolytic pathway. The metabolic pathways are thought to be as shown in Figure 50.2. In ruminants, such as sheep and cattle, research has shown that the metabolism of propylene glycol is carried on to a large extent by the microbial flora in the rumen (187, 158, 156, 188). The metabolite is primarily propionate. In the chick, excessive intake of propylene glycol results in its passage to the cecum, where it is metabolized by bacteria to propionaldehyde (190a). 7.4.13 Mode of Action Browning (20) states that the studies on propylene glycol indicate that about one-third is excreted via the kidneys as a conjugate with glucuronic acid and the rest is metabolized or excreted in the urine unchanged. This suggests that the organic injury and the central nervous system depressing action is probably due to the excessive presence of the propylene glycol and not to its metabolites or its glucuronide. 7.4.14 Human Experience There has been no reported injury to humans that resulted from industrial use. However, when used in large doses as a vehicle for repeated medication of a 88698192