2791. More on phthalate metabolism

2791. More on phthalate metabolism

146 Processingand packagingcontaminants Stevens, J. J. (1974). Meat-wrapper's asthma. J. Am. med. Ass. 227, 1005. Jaeger, R. J. & Hites, R. A. (1974...

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Processingand packagingcontaminants

Stevens, J. J. (1974). Meat-wrapper's asthma. J. Am. med. Ass. 227, 1005. Jaeger, R. J. & Hites, R. A. (1974). Pyrolytic evaporation of a plasticizer from polyvinyl chloride meat wrapping film. Bull. env. contam. & Toxicol. (U.S.) 11, 45. The first paper cited above describes three cases of respiratory distress, including breathlessness, wheezing and coughing, experienced by workers employed as meat wrappers. This syndrome apparently followed exposure to fumes produced during the cutting of PVC film with a hot wire. There were no personal or family histories of eczema, hay fever or asthma, and skin tests for common allergens were negative in all cases. Blood tests and chest X-rays were normal but there was some impairment of pulmonary function, which improved with bronchodilation. Symptoms developed after periods of exposure varying from 20 min to 5 hr and disappeared when use of the hot wire ceased. Two more cases of workers who experienced similar symptoms under comparable conditions are described by Stevens (cited above). In.these cases, however, a reaction to either grass or dust antigens was recorded. All sufferers from this syndrome were cigarette smokers. Similar complaints from other workers involved in the manufacture or use of PVC foodwrapping materials led the Bureau of Occupational Safety and Health in the USA to investigate the pyrolytic products of PVC film, and it appears that an unpublished preliminary communication on this work has identified chlorobutane, benzene, toluene, 1-chloro2-ethylhexane, 2-ethyl-l-hexanol, benzyl chloride and hydrogen chloride as products of the pyrolysis of PVC film at about 400°F. This information is given in the third paper cited above, the authors of which also describe the case of a worker who, in addition to suffering from complaints similar to those already described, noted an oily material in the vicinity of the meat-wrapping machinery. In subsequent laboratory investigations, samples of the PVC film were heated for 1.5 hr at 275 350°F. The oily condensate obtained was extracted with acetone and subjected to gas chromatography and mass spectrometry, which indicated that the material in question was diethylhexyl adipate, the compound originally employed in the PVC film as a plasticizer. 2791. More on phthalate metabolism

Albro, P. W. & Thomas, R. O. (1973). Enzymatic hydrolysis of di-(2-ethylhexyl) phthalate by lipases. Biochim. biophys. Acta 360, 380. Di-(2-ethylhexyl) phthalate (DEHP) has been reported in the tissues of patients transfused with blood that had been stored in PVC packs (Cited in F.C.T. 1971, 9, 910; ibid 1973, 11,914), but there has been some controversy over whether such findings are due to accidental contamination during the tissue-extraction procedures involved in the analyses. Work in rats has indicated that low doses of DEHP given iv are rapidly metabolized and excreted within 24 hr, although larger doses may be retained for much longer periods (Schulz & Rubin, Phthalic Acid Esters Conference, NIEHS, Pinehurst, N.C., (~7 September 1972). After oral administration of labelled DEHP, a significant percentage of tissue radioactivity was at no time associated with the intact diester (Schulz & Rubin, Envir. Hlth Perspec. 1973, 3, 123). DEHP given orally has been shown to be degraded by the contents of the rat caecum or small intestine to a single metabolite, tentatively identified as mono-(2-ethylhexyl) phthalate (MEHP) (Rowland, Fd Cosmet. Toxicol. 1974, 12, 293). The presence of five other metabolites in rat urine has suggested that this initial hydrolysis is followed by m-oxidation and (~o-1)-oxidation of the remaining ester group, probably in the liver (Cited in F.C.T. 1973, 11,915). Further information on possible sites of hydrolysis has been obtained from the present

Processing and packagingcontaminants


in vitro study, in which DEHP was incubated with 15 tissue lipases and several heparin-

activated lipoprotein lipases, chiefly derived from the rat. Hydrolysis to MEHP was found to occur in all preparations except those containing glycerol-ester hydrolase (pancreatic lipase; EC and sterol-ester hydrolase (cholesterol esterase; EC Rat pancreatic hydrolase was able to convert DEHP completely to MEHP, and high activity was also demonstrated by homogenates of rat liver and intestinal mucosa, while preparations of rat kidney, lung, plasma lipoprotein and adipose tissue showed lower degrees of potency. A comparison of intestinal homogenates from rats, mice, hamsters and guineapigs revealed no great differences between species, although there were considerable variations between different mouse strains. No difference was found between young and old rats, but male rats had a higher activity than females. Of all the tissues examined, only the alkaline lipase of rat liver was able to hydrolyse MEHP further to phthalic acid, at 2% of the rate at which it hydrolysed DEHP. The findings suggested that while dietary DEHP would have little opportunity to be absorbed intact, injected DEHP would probably survive long enough for all the tissue lipases and lipoprotein lipases tested to play some part in its hydrolysis.

2792. Phthalates and the aquatic life Williams, D. T. (1973). Dibutyl- and di-(2-ethylhexyl)phthalate in fish. d. agric. Fd Chem. 21, 1128. Sanders, H. O., Mayer, F. L., Jr. & Walsh, D. F. (1973). Toxicity, residue dynamics, and reproductive effects of phthalate esters in aquatic invertebrates. Envir. Res. 6, 84. Phthalic acid esters, of which the most widely used are di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DBP), have been identified as contaminants of certain inland and coastal waters in North America, particularly in areas contiguous to industrial centres. To put the problem as it may exist in Canada into perspective, Williams (cited above) has made a preliminary survey of the levels of these two major phthalates in fish available to the Canadian consumer. The highest concentrations recorded were 160 ppb (b = 109) for DEHP and 78 ppb for DBP found in a sample of processed canned tuna fish. These esters were not, however, detected in more than trace amounts in the varieties of processed frozen fish examined (trout, ocean perch, mackerel, sole, oyster and scallop) or in unprocessed catfish or pickerel. A relatively high level of DEHP (104 ppb) was found in a sample of unprocessed eel, and lower levels, sometimes with DBP, were found in salmon but not in sardine, crab, shrimp or baby clams. The number of samples studied in this work was small but the findings are not in conflict with a recent report (Stalling et al. Envir. Hlth Perspec. 1973, 1 (3), 159) that DFHP and DBP are metabolized by fish, since this indicates that high residue levels would only be expected in organisms continuously exposed to phthalate esters. The highest phthalate levels have, in fact, been recorded in fish from waters near industrial areas and in hatchery fish fed diets contaminated with these esters. In an extension of previous observations, Sanders et al. (second paper cited above) have demonstrated that invertebrates (several species of crustacea and insects) exposed to 14C-labelled DEHP and DBP exhibit a rapid uptake initially, so that within 2wk body residues ranged from 70 to 13,600 times that of the water concentration. All but about 6% of these residues were lost again after the organisms had been in phthalate-free fresh water for a period of 10 days. These workers have also pioneered studies on the biological significance of these phtha-