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[Diethylhexyl phthalate in plastic bags and glass bottles for blood preservation].

The amount of di-(-2 ethyl hexyl) phtalate (D.E.H.P.) is measured in the liquid contained in plastic bags or glass bottles for blood storage. Comparisons between the results show that D.E.H,P. has an equal level in plastic and glass container liquid except for one blood packs series. Particular attention has been paid to obtain solvents and glassware free from D.E.H.P., and to the specificity and the sensitivity of the detection method: a mass fragmentographic technic has been used.

Blood Preservation

Diethylhexyl phthalate as a factor in blood transfusion and haemodialysis.

Di-2-ethylhexyl phthalate (DEHP), the most frequently occurring plasticiser in medical equipment manufactured from polymers of vinyl chloride, forms about 40% w/w of tubes and containers used for storing blood and for haemodialysis. The plasticiser leaches out into liquids with lipid contents, although it is very sparingly soluble in purely aqueous solutions. On infusion of 2-3 1 of stored blood, up to 200 mg DEHP may be transferred to the patient, while much higher quantities may be given during dialysis, which is moreover often repeated frequently over long periods. The acute toxicity of DEHP is very low (greater than 20 g/kg as LD50 in rats), and the ester is rapidly metabolised to products which are excreted in the urine and bile; chronic toxicity from the levels of dosage obtaining is thus very improbable. Carcenogenicity has never been demonstrable in animals, while teratological effects are of a very low order. Serious acute results observed after transfusion of neonates have not been proved to be caused by DEHP, and might be ascribable to accompanying foreign substances. Atheroma in chronic dialysis subjects is still unexplained, but hepatitis probably caused by diethylphthalate from plastic was resolved when apparatus plasticised by DEHP alone was substituted. The benefits of DEHP appear vastly to outweigh any risks. The status of DEHP as environmental contaminant is noted.

Animals

Recent progress in safety evaluation studies on plasticizers and plastics and their controlled use in Japan.

Recent experimental studies in Japan on the evaluation of potential health hazards from phthalate esters used in manufacturing poly (vinyl chloride) as well as several plastics for medical devices and for food containers and packages were introduced. Development of pulmonary granuloma formation after intravenous injection of diethylhexyl phthalate was assumed to be dependent on the particle size of the phthalate in vehicle used. Dietary administration of large amount of diethylhexyl phthalate and dibutyl phthalate produced renal cysts in mothers and in descendants in reproduction studies in mice. Cytotoxicity and mutagenicity of the phthalates and several plastics and resins were also examined by in vivo and in vitro studies. Hematological parameters examined in rabbits after repeated intravenous injection of diethylhexyl phthalate and after implantation of plastics in aorta for 3--6 months did not show any significant change. A slow decrease of radioactivity was observed in adipose tissue of rats following oral administration of 14C-labeled diethylhexyl phthalate. tthe administrative action on phthalates by the Japanese Ministry of Health and Welfare is briefly reviewed.

Animals

The influence of phthalate esters on human plasma lecithin/cholesterol acyltransferase.

The effect of various phthalate esters on the lecithin/cholesterol acyltransferase activity in man was studied in vitro. The enzymatic activity was strongly reduced with all phthalates except for the dimethyl phthalate. The inhibition rate depends on the phthalate concentration and also on the carbon number of the alkyl groups of phthalates.

Acyltransferases

Effects of phthalate esters on the latent ATPase and swelling of mitochondria.

Phthalate esters have shown to stimulate the latent ATPase [EC 3.6.1.3] activity and induce mitochondrial swelling. Among the tested phthalate esters, di-n-butyl phthalate (DBP) exhibited the greatest activity, and the activity decreased progressively as the alkyl chain was lengthened or shortened. The DBP-stimulated ATPase was oligomycin-sensitive. The degree of stimulation of the ATPase was proportional to the extent of mitochondrial swelling induced by DBP in 0.1 M Tris-HCl (pH 7.2) containing 0.25 M sucrose. However, the swelling was dependent on the tonicity of the solution or the concentration of chloride ions, while the stimulation of ATPase was independent of these factors. Swelling was strongly induced by DBP at slightly acidic rather than neutral or alkaline pH. The pH-activity curve of DBP-stimulated ATPase was in inverse correlation with that of swelling, which showed a rather flat maximum at pH 8.0. When bovine serum albumin (BSA) was added to a solution containing mitochondria before addition of DBP, swelling was no longer caused by DBP, though the latent ATPase was stimulated to the same extent in the absence of added BSA.

Adenosine Triphosphatases

[Effect of phthalic esters on lecithin cholesterol acyltransferase].

The in vitro effects of different esters of phthalic acid at increasing levels on the activity of LCAT have been studied using three currently known methods (Mickel and Foulds, Stokke and Norum, Alcindor). Inhibition from phthalates is high. It is proportional to the amounts used and in inverse ratio to the length of the carbon chains.

Dibutyl Phthalate

[Comparative evaluation of the methods of determination of the orientation reaction of rats in a toxicological experiment].

A procedure for determining orientation reaction after Boissié et al (1964) was modified for albino rats. In determining the thresholds of acute action of phthalates and carboran in comparison with summation-threshold index, registration of spontaneous motor activity and orientation reaction according to the number of risings in a jar the proposed method is shown to be 5-10 times more sensitive.

Animals

Structural requirements for the inhibition of phthalate ester hydrolysis in rainbow trout by methylenedioxyphenyl compounds.

1. The ability of a number of methylenedioxyphenyl compounds and paraoxon to inhibit the hydrolysis and oxidation of di-2-ethylhexyl phthalate by rainbow trout tissue preparations was examined. 2. In addition to paraoxon, only the methylenedioxyphenyl compounds with long side-chains (piperonyl butoxide and tropital) inhibited the hydrolysis of di-2-ethylhexyl phthalate by trout liver subcellular fractions and trout serum. 3. Paraoxon decreased the production of the major metabolite of di-2-ethylhexyl phthalate by trout liver microsomes (+ NADPH) suggesting that this metabolite arises via further metabolism of mono-2-ethylhexyl phthalate.

Animals