Abstract  The toxicological profiles of monopropylene glycol (MPG), dipropylene glycol (DPG), tripropylene glycol (TPG) and polypropylene glycols (PPG; including tetra-rich oligomers) are collectively reviewed, and assessed considering regulatory toxicology endpoints. The review confirms a rich data set for these compounds, covering all of the major toxicological endpoints of interest. The metabolism of these compounds share common pathways, and a consistent profile of toxicity is observed. The common metabolism provides scientific justification for adopting a read-across approach to describing expected hazard potential from data gaps that may exist for specific oligomers. None of the glycols reviewed presented evidence of carcinogenic, mutagenic or reproductive/developmental toxicity potential to humans. The pathologies reported in some animal studies either occurred at doses that exceeded experimental guidelines, or involved mechanisms that are likely irrelevant to human physiology and therefore are not pertinent to the exposures experienced by consumers or workers. At very high chronic doses, MPG causes a transient, slight decrease in hemoglobin in dogs and at somewhat lower doses causes Heinz bodies to form in cats in the absence of any clinical signs of anemia. Some evidence for rare, idiosyncratic skin reactions exists for MPG. However, the larger data set indicates that these compounds have low sensitization potential in animal studies, and therefore are unlikely to represent human allergens. The existing safety evaluations of the FDA, USEPA, NTP and ATSDR for these compounds are consistent and point to the conclusion that the propylene glycols present a very low risk to human health.

Abstract  Dipropylene glycol (DPG) is a component of many commercial products such as antifreeze, air fresheners, cosmetic products, solvents, and plastics. Male and female F344/N rats and B6C3F(l) mice were exposed to DPG in the drinking water for 2 weeks, 3 months, or 2 years. In the 2-week and 3-month studies, rats and mice were exposed to 0, 5000, 10,000, 20,000, 40,000, or 80,000 ppm DPG. There was no mortality in the 2-week studies. In the 3-month rat study, all animals survived to the end of the study. Liver weights of rats exposed to 10,000 ppm or greater and kidney weights of rats exposed to 40,000 and 80,000 ppm were greater than those of the controls. The incidences of liver and kidney lesions were significantly increased in males exposed to 20,000 ppm or greater and females exposed to 80,000 ppm. Focal olfactory epithelial degeneration was present in all rats exposed to 80,000 ppm. In males, the incidences of testicular atrophy, epididymal hypospermia, and preputial gland atrophy were significantly increased in the 80,000 ppm group. In the 3-month mouse study, three males and one female exposed to 80,000 ppm died. Liver weights were increased, as was the incidence of centrilobular hypertrophy in males exposed to 40,000 ppm and males and females exposed to 80,000 ppm. In the 2-year studies, exposure groups were 0, 2500 (rats only), 10,000, 20,000 (mice only) or 40,000 ppm DPG. Survival of male rats exposed to 40,000 ppm and mean body weights of males and females exposed to 40,000 ppm were significantly less than controls. In male rats, exposure to DPG resulted in increased incidences and severities of nephropathy and secondary lesions in the parathyroid and forestomach. Increased incidences of focal histiocytic and focal granulomatous inflammation of the liver were also observed. In male and female rats, there were increased incidences of bile duct hyperplasia and changes in the olfactory epithelium of the nose. In mice, survival of males and females was similar to controls. Mean body weights and water consumption of males exposed to 40,000 ppm were less than that of the controls. Treatment-related nonneoplastic lesions did not occur in mice. Treatment-related neoplastic lesions did not occur in rats or mice. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Abstract  The effects of various cosmetic ingredients, including preservatives, humectants, ultraviolet absorbents and solvents, on the electrical properties of neuronal cells were investigated using rat phaeochromocytoma PC12 cells and cultured rat dorsal root ganglion (DRG) neurons. When membrane current was measured under whole-cell voltage-clamp, all nine test compounds inhibited voltage-activated K super(+) current in PC12 cells. With the five compounds selected for further experiments with DRG neurons, two types of current responses were observed, namely inhibition of K super(+) current by methyl or butyl p-hydroxybenzoate (MPHB or BPHB) and resorcinol, and induction of a cationic inward current by MPHB, BPHB, ethanol and dipropylene glycol. The order of potency of these chemicals to inhibit the K super(+) current in PC12 cells was similar to that of their cytotoxicity, which was determined by MTT assay. Capsaicin, BPHB, MPHB and resorcinol, however, inhibited the K super(+) current at concentrations lower than those required for cytotoxicity. These results suggest that these cosmetic ingredients exert significant effects on the electrical properties of cultured neuronal cells. This electrophysiological method may be useful in prescreening test systems to detect stinging, and also to clarify mechanisms underlying the irritation induced by a variety of compounds.

Abstract  As reports of contact dermatitis in humans due to acrylate compounds have increased considerably in recent years, it was decided to investigate the ability of these chemicals to evoke contact sensitivity skin reactions in guinea pigs. 21 different acrylate and methacrylate compounds were scanned for their ability to induce contact sensitivity, using 5 different sensitization protocols. Contact reactions of varying intensities were produced to all the mono-, di- and triacrylates tested. However, it was not possible to sensitize guinea pigs to any methacrylates. It would appear that guinea pigs cannot be contact sensitized to acrylate chemicals that are substituted on carbon 2.

Abstract  The German Chemicals Act stipulates that certain existing chemicals must be reported to the competent authority, if they exhibit properties which indicate they may be hazardous, either alone or in combination with other chemicals (§ 4 (6) ChemG). In summer 1982, an Advisory Committee on Existing Chemicals of Environmental Relevance (BUA), consisting of representatives from science, chemical industry, and governmental authorities, was established at the Society of German Chemists (GDCh). Its purpose was to seek appropriate solutions for dealing with chemicals which are relevant to health and the environment through the adoption of voluntary measures. It is the responsibility of this committee to selected and examine existing chemicals for environmental or health purposes as authorized by § 4 (6) ChemG. In doing so, exclusively scientific criteria are to be applied. In view of the estimated number of about 100000 chemicals in the inventory of existing chemicals of the European Community (EINECS), a selection on the basis of strictly quantitative criteria is not feasible. Even if the necessary resources were available, reliable data for a quantitative evaluation are lacking in most cases. Consequently, a pragmatic approach had to be developed for carrying out a selection on the basis of the limited data available. For this purpose, chemicals were compiled from various priority lists: the presence of these chemicals in the environment has been proved or is highly probable; they are industrially important, or are manufactured in large quantities. Approximately 4500 substances were compiled in this manner. From this total, about 1000 chemicals were selected on the basis of their occurrence in the environment and their industrial significance. After elimination of those substances which are subject to special legal regulations, materials of natural origin, inorganic chemicals, and chemicals which are unstable in the environment, a remainder of 512 chemicals was obtained. For these chemicals data were collected in respect to eight selection criteria covering environmental exposure and effects. For selection purposes these data were scored (scoring procedure). This approach resulted in a list of 60 substances which may be of environmental relevance and which consequently should be treated with priority. In continuation with this work the Advisory Committee now presents a second list of 75 chemicals which are environmentally relevant. The production volume of these chemicals served as an additional criterion. This second selection is, again, associated with considerable uncertainty, since the data employed are partially incomplete, and because their scientific quality could not be checked individually in all cases. This means that, analogously to the chemicals of the first list, this list may also include chemicals which are not hazardous to the environment, and on the other hand, some environmentally hazardous substances may have been omitted. Again, a conclusive evaluation is not feasible until all available data have been collected in separate substance reports and possibly lacking data have been obtained by means of appropriate testing.

Abstract  The single peroral dose toxicity of 26 chemicals was estimated each year for 12 years to determine the reproducibility of the test and of commercial production. For 11 years the resultant median lethal doses were relatively unaffected by the different samples of each chemical received annually, by changes in the stock of rats, by the diluted or undiluted state of the materials, or by the change of personnel performing the tests. Only one variable, the weight of the rat, appeared to have a significant effect on the LD50.

Abstract  Based on their importance in the industrial community, information profiles were provided for the following glycols: 2-butene-1,4-diol (110645), 1,3-butylene-glycol (107880), 1,4-butylene-glycol (110634), 2-butyne-1,4-diol (110656), 1,4-cyclohexanedimethanol (105088), diethylene-glycol (111466), dipropylene-glycol (108612), ethylene-glycol (107211), 2-ethyl-1,3-hexanediol (94962), 1,6-hexanediol (629118), 2,5-hexanediol (2935446), 2-methyl-2-propyl-1,3-propanediol (78262), neopentyl-glycol (126307), 1,5-pentanediol (111295), propylene-glycol (57556), tetraethylene-glycol (112607), triethylene-glycol (112276), 2,2,4-trimethyl-1,3-pentanediol (144194), and tripropylene-glycol (1638160). The acute toxicity of these compounds was characterized by central nervous system depression. Some of the glycols have caused renal damage of varying degrees. Some of the glycols were readily absorbed through the skin. Administration of diethylene-glycol to animals has caused formation of bladder stones. Investigation of possible carcinogenic, teratogenic, reproductive, or mutagenic potentials for these compounds had been very limited.

Abstract  Butylene Glycol, Hexylene Glycol, Ethoxydiglycol, and Dipropylene Glycol are viscous liquids used in the cosmetic industry as humectants, emulsifiers, plasticizers, and solvents. The results of acute, subchronic, and chronic oral toxicity studies using a variety of animal species indicate low order of toxicity for the Glycols. Butylene Glycol, Ethoxydiglycol, and Dipropylene Glycol caused minimal to mild irritation of rabbit skin, whereas Hexylene Glycol was moderately irritating. The Glycols produced mild to severe ocular irritation when tested in rabbit, with Hexylene Glycol producing the most severe irritation. Human skin patch tests on undiluted Butylene Glycol and undiluted Hexylene Glycol produced a very low order of primary skin irritation. A repeated insult patch test on Butylene Glycol produced no evidence of skin sensitization. It is concluded the Butylene Glycol, Hexylene Glycol, Ethoxydiglycol, and Dipropylene Glycol are safe as presently used in cosmetics.

Abstract  Floor lacquerers' inhalation and total exposure to 1-alkoxy-2-propanols and 1-(2-methoxy-1-methylethoxy)-2-propanol (DPGME) were measured. The total exposure was biomonitored by urinalysis of free unchanged 1-alkoxy-2-propanols and DPGME. The floor lacquerers' 8-h inhalation exposures to 1-methoxy-2-propanol (PGME), 1-butoxy-2-propanol (PGBE) and DPGME were 1.9 +/- 1.3 (mean S.D., n = 15), 1.0 +/- 1.4ppm (n = 11) and 0.2 +/- 0.3 ppm (n = 11), respectively. The gravity-corrected urinary excretions of PGME, PGBE and DPGME were 5.3 +/- 5.4 mu mol/l, 0.9 +/- 0.9 mu mol/l and 1.5 +/- 2.8 mu mol/l, respectively. A linear relationship was found between the gravity-corrected urinary excretion of PGME (R-2 = 0.82), PGBE (R-2 = 0.93) and DPGME (R-2 = 0.93) and their preceding 8-h inhalation exposure. The correlations between the uncorrected urinary excretions and inhalation exposures to PGME, PGBE and DPGME was also calculated and found good (R-2 = 0.82-0.95). The effect of work strain on the total exposure seemed to be more relevant in the exposure to hydrophilic PGME than in the exposure to more lipophilic PGBE. (c) 2005 Elsevier Ireland Ltd. All rights reserved.