Phthalate Ester Plasticizers Research Articles

Analysis of Phthalate Ester Plasticizers in Polyvinyl Chloride Children's Toys, after 1998

Analysis of Phthalate Ester Plasticizers in Polyvinyl Chloride Children's Toys, after 1998

Solid Phase Extraction Method for Selective Determination of Phthalate Esters in the Aquatic Environment

The use of solid phase extraction and capillary GLC provides thebasis for the selective determination of phthalate ester plasticizers in rivers and marine water samples. Of the severalsolvent ratios (methanol in dichloromethane) used for selective elution of phthalate esters from the C18 solid phase glass catridge, the 50/50 ratio, CH3OH in CH2Cl2 (v/v)gave the best result. The method was tested on river and marinewater samples that receive effluent from industries that use phthalate esters. The rivers and marine water samples were grossly polluted as several phthalate esters, for example, dimethyl (DMP), diethyl (DEP), dibutyl (DBP) and diethylhexyl (DEHP)were present at 0.03–2306±9.4 μg L-1. A study on uncontaminated water was done to establish background levels.

The effect of phthalate ester plasticisers tested as surfactant stabilised dispersions on the reproduction of the Daphnia magna

The phthalate ester plasticisers, di-2-ethylhexyl phthalate (DEHP), di-iso-nonyl phthalate (DINP), DINP produced by the “polygas” process (DINP-PG), di-n-nonyl/n-undecyl phthalate (L911 P), di-n-octyl/n-decyl phthalate (L810P), di-iso-decyl phthalate (DIDP), di-iso-heptyl phthalate (DIHP), di-n-hexyl/n-decyl phthalate (L610P), di-undecyl phthalate (DUP), di-heptyl/nonyl phthalate (L791), di-iso-undecyl phthalate (DIUP) and di-iso-tridecyl phthalate (DTDP) have been tested for acute and chronic toxicity to Daphnia magna. In addition, di-2-propylheptyl phthalate (DPHP) has been tested for chronic toxicity to Daphnia magna. The test organisms were exposed at a nominal concentration of 1 mg phthalate per litre presented as a dispersion with either “Tween 20” or “Marlowet R40”. For the chronic studies, the nominal concentrations were verified by analysis, except for the L911P where, due to chromatographic difficulties, the test concentration could not be determined and this was estimated as 56% of nominal by analysis of the stock. The exposure period for the acute studies was 48 hours and the test organisms were monitored for flotation in the surface layer and mortalities. The chronic studies were conducted over 21 days. The end points were the numbers of young produced, survival of the parent animals and the length of the parent animals at the end of the 21 day exposure period. No significant negative effects, relative to the controls, were seen in either the acute or the chronic studies.

Migration of a phthalate ester plasticizer from polyvinyl chloride blood bags into stored human blood and its localization in human tissues

Abstract A plasticizer, di-2-ethylexyl phthalates, was found to be extracted from polyvinyl chloride plastic blood bags by both human and dog blood at 4°C at a rate of 0.25±0.03 mg per 100 ml per day. Plasticizer was found in both the lipid-containing and lipid-free fractions of plasma whereas red cells contained only minor amounts. Seven of 12 lung-tissue samples taken at autopsy from patients who had received transfusions of stored blood contained detectable amounts of plasticizer. One patients, after open-heart surgery, excreted a urinary metabolite of the plasticizer in excess of the amount calculated to have been received in the transfused blood. The additional metabolite possibly came from plasticizer extracted from the polyvinyl chloride tubing of the cardiopulmonary unit. Although the toxicology implications of these observations are not currently known, it is suggested that tractable materials to blood or its fractions be developed.

Migration of a phthalate ester plasticizer from polyvinyl chloride blood bags into stored human blood and its localization in human tissues

Migration of a phthalate ester plasticizer from polyvinyl chloride blood bags into stored human blood and its localization in human tissues

The plasticizer benzyl butyl phthalate (BBP) inhibits 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary DNA adduct formation and tumorigenesis.

Although the risk for cancer is multifactorial, a substantial portion of cancer incidence rates is related to environmental factors, including diet and environmental chemicals. The magnitude of the contribution to cancer of the breast from exposure to environmental chemicals remains unclear. The phthalate ester plasticizers are abundantly-produced industrial chemicals that have become widely-dispersed environmental pollutants. The present studies were conducted to determine the effect of the phthalate ester, benzyl butyl phthalate (BBP) on mammary gland carcinogenesis induced in the female rat by the polycyclic aromatic hydrocarbon (PAH) 7,12-dimethylbenz[a]anthracene (DMBA). Exposure to BBP (i.p. injection) at 100 and 500 mg/kg doses for 5 days resulted in a significant 72 and 92% inhibition, respectively, in the in vivo formation of mammary DMBA-DNA adducts, compared to controls. Treatment with BBP (i.g. intubation) for 7 days resulted in a significant (48%) inhibition in mammary DMBA-DNA adduct formation only for those animals receiving the 500 mg/kg dose, compared to controls. Administration of BBP (i.g.) at 500 mg/kg for 7 days also was associated with a significant 8.5-fold increase in the liver activity of 7-ethoxyresorufin-O-deethylase. No change in liver glutathione-S-transferase activity was observed for animals treated with both BBP (i.g.) doses. Treatment with BBP (i.g.) at 250 and 500 mg/kg doses for 7 days prior to DMBA administration resulted in a significant 37% decrease in mammary tumor incidence for both doses, compared to controls. The number of mammary adenocarcinomas per rat was significantly inhibited by 60 and 70% for rats exposed to BBP at the 250 and 500 mg/kg doses, respectively, compared to controls. Therefore, the present studies indicate that BBP acts as a blocking agent toward DMBA-induced rat mammary DNA adduct formation and mammary carcinogenesis. This effect partly may be due to increased metabolism of BBP in the liver. These results underscore the need to further examine the effect of BBP and other phthalates on the various stages of mammary carcinogenesis, as well as on the metabolism of mammary carcinogens.

The effect of phthalate ester plasticisers on the emergence of the midge ( Chironomus riparius) from treated sediments

Sediment toxicity tests with the midge, Chironomus riparius, were carried out in a natural river sediment spiked with either di-2-ethylhexyl phthalate (DEHP) or di-isodecyl phthalate (DIDP). The phthalates were each dosed at three levels in the sediment up to 10000 mg phthalate/ kg (dry weight basis) and the test organisms were introduced as larvae (< 24 hours post-hatch). No effects, in any of the treatments, were found on the development of the midge based on a comparison with the controls of the numbers and sex of the emerging adults. Sediment concentrations were measured at the start and finish of the study (28 day period) and good agreement with the nominal levels was found. Accumulation of the phthalates and any metabolites was determined on a sample of the emerging adults by measuring their radioactivity from the 14C-labelled test substances. A biota to sediment accumulation factor of 1.5 and 0.6 was found for DEHP and DIDP, respectively.

Hypolipidemic agents alter hepatic mitochondrial respiration in vitro

The direct effects of three different classes of structurally diverse hypolipidemic agents on respiration were studied in mitochondria isolated from donor Sprague-Dawley rats. Two classes of peroxisome proliferators (i.e. plasticizers and hypolipidemic hormones and drugs) and one class of peroxisome inhibitors (i.e. anti-psychotic drugs) were studied. The phthalate ester plasticizers dibutylphthalate, ethylhexanoic acid and di(2-ethylhexyl) adipate, the hypolipidemic hormones or drugs dehydroepiandrosterone (DHEA), thyroxine (T4), triiodothyronine (T3), gemfibrozil, clofibrate and naphthoflavone, and the anti-psychotic drugs chlorpromazine, thioridazine and fluphenazine were studied. As the dose of the plasticizer dibutylphthalate increased from 8 to 200 μ mol/l, there was a decrease ( P < 0.05) in state 3 (+ ADP) respiration and in the respiratory control ratio for both substrates tested. The anti-psychotic drug chlorpromazine decreased state 3 malate + pyruvate-supported respiration and increased state 3 succinate-supported respiration. As the concentration of all three anti-psychotic drugs increased, there was a linear increase in state 4 respiration (−ADP) and a decrease in the respiratory control ratio for both substrates tested. As the dose of the hypolipidemic agents DHEA, gemfibrozil and T4 increased, there was a linear reduction in state 3 malate + pyruvate-supported respiration. However, when succinate was used as the substrate to support respiration, only the thyroid hormones significantly decreased state 3 respiration. Gemfibrozil, T4 and T3 increased state 4 respiration, regardless of the substrate used. As the dose of clofibrate, gemfibrozil, and the thyroid hormones increased, there was a linear reduction in the respiratory control ratio for both substrates tested. These data indicate that the hypolipidemic effects of the plasticizer dibutylphthalate could be due to a decrease in ADP-stimulated mitochondrial respiration. In contrast, the hypolipidemic effects of the anti-psychotic drugs could be due to increased uncoupling of respiration from ADP phosphorylation. Lastly, the lipid-lowering effects of the hypolipidemic drug gemfibrozil and the thyroid hormones could be due to a combination of decreasing ADP-stimulated mitochondria! respiration and uncoupling respiration from ADP phosphorylation.

Levels of di-(2-ethylhexyl)phthalate and total phthalate esters in milk, cream, butter and cheese.

Di-(2-ethylhexyl)phthalate (DEHP) and total phthalate ester plasticizer levels were determined in milk, cream, butter and cheese samples from a variety of sources from three European countries (UK, Norway and Spain). Samples of milk (from Norway) obtained at various stages during collection, transportation and packaging operations showed no apparent trends in phthalate contamination with total phthalate levels (expressed as DEHP equivalents) in the raw milk of between 0.12 and 0.28 mg/kg. On processing the DEHP was concentrated in the cream at levels up to 1.93 mg/kg, whereas low fat milk contained from < 0.01 to 0.07 mg/kg. Retail dairy products (from Spain) were contaminated with < 0.01-0.55 mg/kg DEHP with a maximum total phthalate level of 3.0 mg/kg in cream samples. UK pooled milk samples from doorstep delivery (obtained from different regions of the country) contained low levels of DEHP (< 0.01-0.09 mg/kg) and total phthalate (0.06-0.32 mg/kg). Retail UK samples of cheese, butter and other fatty products varied considerably in their levels of contamination, the highest being cheese samples containing 17 mg/kg of DEHP and 114 mg/kg total phthalate. However, the majority of samples contained 0.6-3.0 mg/kg DEHP and 4-20 mg/kg total phthalate. UK cream samples contained levels of 0.2-2.7 mg/kg DEHP and 1.8-19.0 mg/kg total phthalate. The level found in these products was too high to have resulted solely from milk by concentration in the fat phase and must therefore have arisen in other ways.

Genetic toxicology testing of di(2-ethylhexyl) terephthalate.

Di(2-ethylhexyl) terephthalate (DEHT) is a commercially produced chemical (Kodaflex DOTP) that is used as a general purpose, low-volatility plasticizer for polyvinyl chloride and other polymeric materials. Less than 30 million kilograms of DEHT are produced annually. DEHT is isomeric with di(2-ethylhexyl) phthalate (DEHP), a nongenotoxic rodent carcinogen whose mode of action has been suggested to derive from its ability to produce hepatocellular proliferation and/or hepatic peroxisome proliferation. Thus it is important to know the behavior of DEHT in genotoxicity assays in order to compare it with that of DEHP and other phthalate ester plasticizers. It is known from previously published studies that rats fed DEHT in the diet at 2,000 mg/kg produce urine that is negative in the Ames Salmonella bacterial mutagenicity assay in the presence and absence of induced rat liver S-9 and in the presence and absence of beta-glucuronidase/aryl sulfatase. Reported here are the results of direct testing of DEHT in the Ames plate incorporation assay, the Chinese hamster ovary/hypoxanthine guanine phosphoribosyl transferase (CHO/HGPRT) in vitro mammalian cell mutagenicity assay, and an in vitro chromosome aberrations assay using CHO cells. The results for mono(ethylhexyl) terephthalate (MEHT), a metabolite of DEHT, in the Ames Salmonella bacterial mutagenicity assay are also presented. All test results for both DEHT and MEHT were found to be negative, and it is therefore concluded that DEHT, like its isomeric relative DEHP, is not genotoxic.

A new pharmacological function of phthalate ester plasticizer

Phthalate ester plasticizers have a new pharmacological function in selective suppression of the growth of tumor cells both in vitro and in vivo.

Peroxisome proliferators: Paradigms and prospects

Peroxisome proliferators are a structurally diverse group of chemicals. They include fibrate hypolipidaemic drugs, phthalate ester plasticisers, phenoxy acid herbicides, azole antifungal drugs, and perfluorinated fatty acids. This presentation will focus on the common pleotropic responses produced by these compounds including hepatomegaly (hyperplasia and hypertrophy), activation of cell cycle S-phase ploidy changes, cytochrome P4504A1 induction, morphometric/biochemical analysis of peroxisome proliferation and stimulation of growth factors, and oncogene activation. Consideration will also be given to the role of recently described Peroxisome Proliferator Activated Receptor in these diverse hepatic responses. Peroxisome proliferators are uniformly negative in a wide range of genotoxicity tests, but nevertheless are complete carcinogens, particularly in rodent liver. Mechanisms of nonmutagenic carcinogenesis will be discussed including the active oxygen hypothesis involving 8-hydroxydeoxyguanosine adducts and the possibility of peroxisome proliferators promoting preexisting lesions by clonal expansion, eventually resulting in frank tumorigenesis. Finally, a consideration of the risk assessment of peroxisome proliferation to humans will be discussed.

Determination of phthalate ester plasticizers in the aquatic environment of Southwestern Nigeria

Water from the Lagos, Oyo, Osun, Ondo, and Delta states of Nigeria and the cities' water treatment plants had been analized for the presence of ubiquitous phthalate esters using liquid chromatography. Extraction with CH 2Cl 2 and liquid chromatography was used for compound separation. Several phthalate esters, dimethyl- (DMP), diethyl- (DEP), and di-n-butyl- (DBP) were found present at levels of 10 mg L −1 to 1472 mg L −1 in river water and 91 mg L −1 to 1219 mg L −1 in tap water from the cities' water treatment plants. A study of uncontaminated water was done to establish blank levels.

Characterization and determination of organic compounds in the mutagenic XAD-2 extracts of drinking water

Amberlite XAD-2 extracts, which exhibit mutagenicity in the Ames assays, of drinking water sampled each month during the period from April 1988 to March 1989 were studied in order to characterize and determine the organic pollutants. The major organic pollutants were phthalate ester plasticizers such as dibutyl and di(2-ethylhexyl) phthalate. Several polynuclear aromatic hydrocarbons (PAH S) and the organochlorine pesticide oxadiazon were also identified to be present at low concentrations. The XAD extractable and chromatographable organic pollutants were found to be composed of PAH S with a mean concentration of 0.136 μg/1 ( ca. 10% of the total amount of organic compounds detected), phthalates with a mean value of 0.405 μg/1 ( ca. 30%) and other compounds with a mean value of 0.845 μg/1 ( ca. 60%). The concentrations and compositions of these organic pollutants were correlated with the effective rainfall content of the river and with the water temperature.

Effect of co‐additives on the flame/smoke suppression properties of zinc borates

AbstractTwo zinc borates are useful partial replacements for the antimony oxide flame retardant normally used to flame retard flexible PVC products. The effect of using various co‐additives with zinc borates on the flame retardancy and smoke formation of a model flexible PVC cable jacket was evaluated in an attempt to further improve the properties of the formulation. The use of ammonium octamolybdate with the borates yields products with improved properties. Highly flame retarded formulations that yield low levels of smoke can be prepared by using alumina trihydrate or magnesium compounds as replacements for the usual calcium carbonate filler. Replacement of part of the phthalate ester plasticizer with brominated ester, a phosphate ester, or a brominated phosphate ester also results in formulations with oxygen values as high as 39.5 which produce lower levels of smoke.

The cytochrome P450 IV family: constitutive and inducible haemoproteins

The cytochrome P450 IV family: constitutive and inducible haemoproteins

Evidence for the induction of cytochrome P-452 in rat liver by Aroclor 1254, a commercial mixture of polychlorinated biphenyls

We have examined the ability of a commercial mixture of polychlorinated biphenyls (Aroclor 1254) to induce hepatic cytochrome P-452-linked enzyme activities in rat and pigeon liver five days after its intraperitoneal injection. The results provide evidence that, at the doses used, Aroclor 1254 induces cytochrome P-452-linked enzyme activities in rats, but not in pigeons. This inductive effect was previously regarded as being specific for hypolipidemic drugs and phthalate ester plasticisers.

Poly(vinyl chloride)/plasticizer‐mixture interactions. Part I. Phthalate ester mixtures

AbstractFlory‐Huggins interaction parameters, χ, have been determined as a function of plasticizer composition for poly(vinyl chloride) in various binary mixtures of phthalate ester plasticizers using a method involving the micro‐determination of the temperature at which PVC particles in excess plasticizer appear to melt. An optimum composition at which χ goes through a minimum was found to exist for some of the systems. A good correlation between the apparent melting temperature tm and χ for the neat plasticizers with PVC was also established.

Comparison of hepatic peroxisome proliferative effect and its implication for hepatocarcinogenicity of phthalate esters, di(2-ethylhexyl) phthalate, and di(2-ethylhexyl) adipate with a hypolipidemic drug.

Peroxisome proliferation is inducible in hepatocytes of rodent and nonrodent species by structurally dissimilar hypolipidemic drugs and certain phthalate ester plasticizers. The induction of peroxisome proliferation appears to be a tissue specific response limited largely to the hepatocyte. Peroxisome proliferation is associated with increases in the activity of the H2O2-generating peroxisomal fatty acid beta-oxidation system and in the amount of peroxisome proliferation-associated 80,000 MW polypeptide (PPA-80). Chronic administration of these non-DNA damaging and nonmutagenic peroxisome proliferators to rats and mice results in the development of hepatocellular carcinomas. Comparative morphometric and biochemical data from rats treated with varying dose levels of ciprofibrate, a hypolipidemic drug, and di(2-ethylhexyl) phthalate, and di(2-ethylhexyl) adipate, the widely used plasticizers, indicate that the hepatocarcinogenic potency of these agents is correlatable with their ability to induce peroxisome proliferation, peroxisomal beta-oxidation and PPA-80. Available evidence strongly favors the role of peroxisome proliferation-associated oxidative stress in the induction of liver tumors by peroxisome proliferators.

Inhibition of alveolar macrophage killing by di(2-ethylhexyl)phthalate.

The phthalate ester plasticizer di(2-ethylhexyl) phthalate (DEHP) affected the phagocytosis and killing ofStaphylococcus aureus by rabbit alveolar macrophages. Pre-exposure to DEHP caused a slight increase in phagocytosis and a dose-dependent inhibition of alveolar macrophage killing ofS. aureus, reaching a 14-fold decrease in the killing index at a concentration of 2 mg DEHP per 100 ml of media. The significance of this inhibition is discussed with respect to the role of the plasticizer in lung disease and macrophage research.