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Dibutyl phthalate: maternal effects versus fetotoxicity.

Dibutyl phthalate (DBP), a plasticizer, is a teratogen in mice and rabbits but produces fetal loss in the rat. Long-term dosing studies indicating reduced fertility in the rat suggested a maternal effect of the compound. The decidual cell response (DCR) and pregnant rats were used to examine whether DBP affects maternal physiological parameters independent of the compound's fetotoxic effect. DBP has no effect on the DCR, pregnant uterine weight, number of implantation sites, ovarian weight, or serum progesterone concentration during early pregnancy or pseudopregnancy. These data show that short-term dosing with DBP has no direct maternal effect in the rat and suggest that the viability of preimplantation embryos is not compromised.

Animals

Mutagenic and lethal effects of alpha-benzene hexachloride, dibutyl phthalate and trichloroethylene in Saccharomyces cerevisiae.

Saccharomyces cerevisiae strain XV185-14C for reversion studies was used to investigate the genetic activity of alpha-benzene hexachloride dibutyl phthalate and trichloroethylene. The results indicate that none of the three compounds was genetically active when yeast cells were treated in phosphate buffer (pH 7.0) in the absence of metabolic conversion. However, in the presence of the 9000 g supernatant of mice liver homogenate, NADP, glucose-6-phosphate, phosphate buffer (PH 7.4), MgCl2, KCl, the components which were used for the metabolic conversion, trichloroethylene porved to be a powerful mutagen. It increases the frequency of homoserine, histidine and lysine revertants over those of the control levels. Trichloroethylene appears to induce frameshift as well as base substitution mutations.

Animals

Biochemical studies on phthalic esters. III. Metabolism of dibutyl phthalate (DBP) in animals.

The excretion, distribution and metabolism of DBP were studied in rats. More than 90% of the dose was excreted in the urine within 48 h following intravenous or oral administration, but the faecal excretion was low. Biliary excretion was remarkably higher than that in the faeces when DBP was given orally. No significant retention was observed in organs and tissues at 24 h after dosing. In vitro experiments showed that DBP was hydrolysed very rapidly to MBP by the esterase of rat liver microsome. DBP was found to be a strong inhibitor for the succinate dehydrogenase of rat liver. DBP and its metabolites, MBP and phthalic acid, did not produce any striking effect upon hepatic and serum enzyme activities in vitro. Urinary metabolites of orally ingested DBP were investigated in 3 species, namely, rats, hamsters and guinea pigs. MBP was a common major metabolite in all 3 species. A further increment was apparently excreted as the glucuronide in the rat, hamster and guinea pig together with a small amount of phthalic acid and unchanged DBP. Omega- or omega-1 oxidation products of MBP were also detected in the urine.

Animals

Health bill beneath the plastic feast: A phthalate contamination alert from takeout food containers.

The rapid growth of takeout food consumption in China has raised concerns regarding exposure to phthalic acid esters (PAEs) from food packaging. This study investigated the presence, source, contribution, and health risk of PAEs in commonly used takeout containers. Widespread contamination was observed, with total PAE concentrations ranging from below the limit of detection to 222,000 ng/g. Diisobutyl phthalate (DIBP), dibutyl phthalate (DBP), and bis(2-ethylhexyl) phthalate (DEHP) were identified as the predominant compounds, accounting for 7.50 %, 14.7 %, and 18.7 % of the total concentration, respectively. These PAEs may originated from additives during manufacturing and potential contamination of raw materials. Human exposure assessment showed that daily exposure doses of DIBP, DBP, and DEHP via container ranged from 0.00 to 2340 ng/(kg·day) among frequent takeout consumers, contributing substantially to overall PAE body burdens. To further assess exposure and associated risks, a nationwide online questionnaire survey was conducted across China. Based on this national-scale behavioral dataset, the health risks among Chinese residents were evaluated. Although the modeled non-carcinogenic risks of DIBP, DBP, and DEHP remained within acceptable limits, the simulation suggested that approximately 70 % of participants may experience potential exceedance of the carcinogenic risk threshold for DEHP. The frequency of takeout food consumption was identified as the most important factor affecting PAE exposure. These findings underscore the importance of limiting takeout frequency and reducing reliance on plastic containers to mitigate health risks. This study provides scientific evidence to support the development of safer packaging materials and informs public health strategies.

Phthalic Acids

Mechanism of chemical-induced toxicity. I. Use of a rapid centrifugation technique for the separation of viable and nonviable hepatocytes.

A major obstacle in defining the mechanism of chemical-induced toxicity has been the inability to distinguish between events that cause cell death and those that result from cell death. This problem results from measuring biochemical parameters in tissues or cell pellets containing both viable and nonviable cells. In the present study, we described a method for the rapid separation of viable hepatocytes from nonviable cells and medium prior to biochemical analysis. Separation of viable hepatocytes was accomplished in a microcentrifuge tube by layering a sample of isolated hepatocyte suspension over a dibutyl phthalate oil layer and centrifuging for several seconds. As a result, greater than 90% of the hepatocytes centrifuged through dibutyl phthalate were viable while greater than 90% of the cells recovered above the oil layer were nonviable. The separation of viable hepatocytes by the dibutyl phthalate method was not affected by the presence of the hepatotoxins, adriamycin (ADR) in combination with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or ethyl methanesulfonate (EMS), though the ratio of viable to nonviable cells in the suspension was drastically reduced. The metabolic and morphological integrity of hepatocytes centrifuged through dibutyl phthalate was altered after cell suspensions were treated with the ADR-BCNU or EMS. These chemically treated viable hepatocytes showed degenerative ultrastructural changes and a greater than 80% reduction in intracellular K+ and glutathione concentrations. Because centrifugation through dibutyl phthalate does not significantly alter the concentration of intracellular constituents nor the ultrastructure of control hepatocytes, the signs of reversible injury observed in hepatocytes centrifuged through oil resulted from the chemical treatment. These data indicate that the dibutyl phthalate separation technique offers the advantage of monitoring only viable hepatocytes for changes in membrane integrity or metabolic performance during a toxic chemical insult.

Animals

Effects of diethyl phthalate and other plasticizers on laurate hydroxylation in rat liver microsomes.

Diethyl phthalate (DEP) is used in pharmaceutical coatings, cosmetics, and plastic films to wrap foods. There is a health concern associated with the exposure to certain phthalate esters because they belong to a class of compounds referred to as peroxisome proliferators which have been shown to increase the incidence of liver tumors when administered to rats. In this study, we have compared DEP to four other commonly used plasticizers, 2-diethylhexyl phthalate (DEHP), dibutyl phthalate (DBP), 2-diethylhezyl adipate (DEHA), and acetyltributyl citrate (ATBC), for their ability to induce the cytochrome P450-mediated fatty acid omega-hydroxylation system, which is one of the initial cellular responses when animals are treated with peroxisome proliferators. The administration of DEHP, DBP, and DEHA to rats increased the specific activity of laurate 12-hydroxylase from 2.8 +/- 1.1 in control rats to 30.3 +/- 11.6, 14.5 +/- 4.1, and 9.7 +/- 1.9 nmol 12-hydroxylaurate formed/min/nmol P450, respectively. In contrast, laurate 12-hydroxylase activity in DEP- and ATBC-treated rats were 4.4 +/- 1.2 and 4.4 +/- 1.0 nmol 12-hydroxylaurate formed/min/nmol P450, respectively. In addition, whereas DEHP increased peroxisomal palmitoyl-CoA oxidation 6-fold, DEP increased this activity only 1.3-fold. Two protein bands, at 51 and 52 kDa, were found to increase 6- to 12-fold in microsomes of DEHP-, DBP-, and DEHA-treated rats, but these bands were increased only 2-fold in DEP- or ATBC-treated rats.

Animals

Mutagenicity evaluation of phthalic acid esters and metabolites in Salmonella typhimurium cultures.

The mutagenic potential of dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), and di-2-ethylhexyl phthalate (DEPH), as well as metabolites of DEHP--i.e., mono-2-ethylhexyl phthalate (MEHP), 2-ethylhexanol (2-EH), and phthalic acid (PA)--were tested in Salmonella typhimurium cultures using the Ames test procedure. The compounds were tested on strains TA98, TA100, TA1535, TA1537, TA1538, and TA2637 for base-pair substitution or frameshift-type mutations. Spot tests yielded negative responses for all compounds with the strains tested. Each compound was tested for a dose-effect relationship in the TA98, TA100, TA1535, and TA1538 systems. DEP and DBP exhibited a mildly positive response in both TA100 and TA1535 cultures, and DMP showed a similar response in TA1535. Normalization of the data for cytotoxicity of DMP suggests TA100 has a mildly positive effect. The higher doses of these compounds exhibited some cytotoxic effects. The mutagenic effects were apparently abolished by the addition of S9 fraction in TA100 and TA1535 cultures, while no effect, other than cytotoxicity, was observed in the TA98 and TA1538 systems. DEHP, MEHP, 2-EH, and PA exhibited no mutagenicity in any of the strains of Salmonella typhimurium tested, with or without S9 metabolic activation. MEHP and 2-EH, however, exhibited a moderate cytotoxic effect in most cultures.

Biotransformation

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

[Studies on the efficacy of five repellents against Phlebotomus alexandri].

The efficacy of five repellents were tested against Phlebotomus alexandri both in the laboratory and in the field in Meiyaogou, Turfan City, Xinjiang Uygur Autonomous Region during 1986-1987. A total of 3,301 female Ph. alexandri were used in the laboratory and 306 man-times of volunteers were tested in the field. At a dose of 0.25 microliters/cm2, the protective durations of mosquito repellent perfume (MRP), N, N-diethyl-mtaluamide (DETA), mosquito repellent liquid (MRL), dimethyl phthalate (DMP) and dibutyl phthalate (DBP) were 7.50 h, 5.00 h, 3.75 h, 1.25 h and 1.00 h, respectively. At a dose of 0.75 mg/cm2, the protective durations of the essential balms of DETA, DMP and DBP were 5.50 h, 3.50 h and 3.00 h, respectively. The repelling effect on volunteers in the field was the same as that tested in the laboratory. The relative efficacy of the five repellents was in the order of MRP greater than DETA greater than MRL greater than DMP greater than DBP. The above-mentioned repellents may be of practical use for individual protection against kala-azar transmission in the field.

Animals