Diisononyl Phthalate (DINP)

Project ID

2247

Category

IRIS

Added on

June 3, 2013, 7:35 a.m.

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Journal Article

Abstract  Phthalates were commonly used in high quantities mainly as plasticizers. As a consequence humans are complexly exposed through different pathways. The purpose of INES (Integrated Exposure Assessment Survey) was to est. the total exposure of adults by quantifying the target substances in duplicate diet portions collected daily over 7 consecutive days. Furthermore, indoor air and dust samples were measured in 34 flats of the participants. The study population comprised 50 healthy adults (27 females and 23 males) living in Munich, Germany. They were between 14 and 60 years old. The median (95-percentile) daily dietary intake of DEHP, DnBP, and DiBP was 2.4 ?g/kg body wt. (4.0 ?g/kg b.w.), 0.3 ?g/kg b.w. (1.4 ?g/kg b.w.), and 0.6 ?g/kg b.w. (2.1 ?g/kg b.w.), resp. Median concns. in indoor air were 2.2 ?g/m3 for DEHP, 0.59 ?g/m3 for DnBP, and 0.66 ?g/m3 for DiBP. In dust the median readings for DEHP, DiNP, DiBP, and DnBP were 670 mg/kg, 155 mg/kg, 18 mg/kg, and 17 mg/kg, resp. Overall, dietary exposure is the dominant intake pathway. Our estd. 95-percentile of total daily intake from diet, dust ingestion, and inhalation contributed to 11.1% (DEHP), 17.3% (DnBP), and 23.9% (DiBP) of the tolerable daily intake (TDI). We suggest that the recent exposure of an adult population to DEHP is unlikely to pose a significant health risk. The higher share of DiBP and DnBP in the TDI indicates that other important sources are present which should be reduced under precautionary principles.

Journal Article

Abstract  In human metabolism studies we found that after oral application of di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DiNP) and di(2-propylheptyl) phthalate (DPHP), at least 74, 44 and 34%, respectively, are excreted via urine. In contrast to the short chain phthalates, their oxidized products, not the simple monoesters, were found to be the main metabolites. Based on urinary phthalate metabolite concentrations we estimated in 102 German subjects between 6 and 80 years of age median daily intakes (microg/kg/day) of 2.7 for DEHP, 2.1 for di-n-butyl phthalate, 1.5 for diisobutyl phthalate, 0.6 for DiNP, and 0.3 for butylbenzyl phthalate. In general, children have higher exposures compared to adults and seem to have a more effective oxidative metabolism of phthalates. For individual phthalates tolerable daily intake (TDI) values have been deduced. However, in rats some phthalates have been shown to act as endocrine disrupters via a common mechanism of action in a dose-additive manner. Therefore, the concept of a cumulative TDI value may be more appropriate for the consideration of the overall exposure and the potential human health risks resulting from everyday and simultaneous exposure to several phthalates.

Journal Article

Abstract  Organic bee pollen (BP, n = 22) harvested from the Douro International Natural Park (DINP, Portugal) was studied. Nine botanical families were found in the mixture of the samples. The water activity and pH ranged 0.21-0.37 and 4.3-5.2, respectively. The BP analyses averaged 67.7% carbohydrates, 21.8% crude protein, 5.2% crude fat and 2.9% ash. The energy ranged from 396.4 to 411.1 kcal/100 g. The principal fatty acid found was linolenic, followed by linoleic acid, palmitic acid and oleic acid. The phenolic and flavonoid contents varied from 12.9 to 19.8 mg of gallic acid equivalents/g of extract and from 4.5 to 7.1 mg of catechin equivalents/g of extract, respectively. The scavenger activity and β-carotene bleaching assays values (EC₅₀) were 3.0 ± 0.7 mg/mL and 4.6 mg/mL ± 0.9 mg/mL, respectively. E. coli, sulphite-reducing Clostridia, Salmonella and S. aureus were not found. Since there are studies indicating appreciable differences among BPs from different regions, the full characterization of BP from diverse origins still appears to be a sound research priority in order to obtain reliable data about this beehive product.

Journal Article

Abstract  Approximately 2.7% of a collection of Salmonella enterica var. Typhimurium promoter-lux reporter strains showed altered transcriptional patterns when exposed to low concentrations of nine different fluoroquinolones (FQs). Even at the subinhibitory concentrations employed, all nine FQs upregulated genes involved in the SOS response, umuD, lexA, sbmC and dinP. In addition, transcriptional regulators, genes putatively associated with membrane integrity (spr), virulence (sicA) and metabolism (plsB) were affected. Using the Ames test with Salmonella strain TA102, increased mutagenicity was demonstrated in response to all the FQs tested: ciprofloxacin, moxifloxacin, levofloxacin and gatifloxacin. Transcriptional effects were largely specific to the FQ antimicrobials. Such responses are consistent with the primary mechanism of action of this class of inhibitor, namely, the introduction of DNA damage. This work provides support for the notion that small molecules can have functions other than growth inhibition that may affect the establishment and maintenance of community dynamics in complex environments.

Journal Article

Abstract  The here-reported identification of the LexA-binding sequence of Bdellovibrio bacteriovorus, a bacterial predator belonging to the delta-Proteobacteria, has made possible a detailed study of its LexA regulatory network. Surprisingly, only the lexA gene and a multiple gene cassette including dinP and dnaE homologues are regulated by the LexA protein in this bacterium. In vivo expression analyses have confirmed that this gene cassette indeed forms a polycistronic unit that, like the lexA gene, is DNA damage inducible in B. bacteriovorus. Conversely, genes such as recA, uvrA, ruvCAB, and ssb, which constitute the canonical core of the Proteobacteria SOS system, are not repressed by the LexA protein in this organism, hinting at a persistent selective pressure to maintain both the lexA gene and its regulation on the reported multiple gene cassette. In turn, in vitro experiments show that the B. bacteriovorus LexA-binding sequence is not recognized by other delta-Proteobacteria LexA proteins but binds to the cyanobacterial LexA repressor. This places B. bacteriovorus LexA at the base of the delta-Proteobacteria LexA family, revealing a high degree of conservation in the LexA regulatory sequence prior to the diversification and specialization seen in deeper groups of the Proteobacteria phylum.

Journal Article

Abstract  The particulates in a room warmed with a radiant kerosene heater were collected, extracted and fractionated into diethyl ether-soluble neutral, acidic and basic fractions. The mutagenicity of these fractions was measured with Salmonella typhimurium strains TA98, TA98NR, TA98/1,8-DNP6 and TA100 in the presence and absence of S9 mix. Room air without the heater showed very low mutagenicity. However, a sample from a room at the beginning of the burning period showed very high mutagenicity (237 His+ revertants/plate/m3 of air in strain TA98 in the absence of S9 mix). In contrast, emissions from the heater after it was burning stably showed low mutagenicity (9 His+ revertants/plate/m3). The crude extract of particulates from the heater at the beginning of the burning period was analyzed by high-pressure liquid chromatography (HPLC) and showed a considerable amount of nitropyrenes (NPs); the concentrations of 1-NP and 1,6-diNP were 1.62 ng and 0.149 ng/m3 of air, respectively, and accounted for 1.2% and 17.6%, respectively, of the mutagenicity in strain TA98 in the absence of S9 mix. In addition, an HPLC-Ames histogram showed that peaks of mutagenicity corresponding to 1-NP and diNPs accounted for 75.7% (1-NP, 4.9%; 1,6-diNP, 17.1%; 1,8-diNP, 46.3%; 1,3-diNP, 7.4%) of the HPLC-recovered mutagenicity for strain TA98 without S9 mix. These results that kerosene heaters, especially immediately after ignition, create mutagenic substances such as NPs.

Journal Article

Abstract  Nitrated polycyclic aromatic compounds, 1-nitropyrene (1-NP) and 1,6-dinitropyrene (1,6-diNP), are environmental mutagens and carcinogens. Nitroreductases purified from an anaerobic bacterium, Bacteroides fragilis, catalyzed the metabolic activation of these compounds to produce DNA- and tRNA-bound adducts in vitro. Formation of the adducts was inhibited by p-chloromercuribenzoic acid, which is an inhibitor of nitroreductases from B. fragilis. The enzyme and coenzyme (NADPH) were essential for the adduct formation. These results suggest that nitroreduction is a necessary step in the metabolic activation of nitropyrenes. 1-NP bound specifically to poly(G) and poly(dG), and 1,6-diNP bound to poly(G), poly(dG), and poly(X). The other purine polynucleotides were weak acceptors. However, the reactive products of nitropyrenes formed by nitroreductases could not bind to pyrimidine polynucleotides. Enzymatic hydrolysis of 1-NP-bound DNA and subsequent analysis by high-performance liquid chromatography showed one major and two minor adducts in the hydrolysate. The peak of the major adduct corresponded to that of N-(deoxyguanosin-8-y1)-1-aminopyrene, which is the same as an adduct formed by xanthine oxidase, a mammalian nitroreductase. Nitroreductase activity in the various organs and intestinal contents of Sprague-Dawley rats was assayed in the presence of NADPH or NADH under nitrogen gas. Nitroreductase activity was widely distributed in the organs of the rats; in particular, that of the liver and of the small intestine was relatively high, but that of the respiratory organs such as lung and alveolar macrophages was very low. Intestinal contents had high nitroreductase activity, which was proportional to the number of bacteria, especially anaerobic bacteria, in the intestine. These results suggest that the nitroreductase activity of the normal bacterial flora is very high in rats and that the intestinal bacteria play a major role in the metabolism of nitropyrenes in vivo.

Technical Report

Abstract  The fate of diisononyl phthalate (DINP) was evaluated in three groups of male Fischer 344 rats receiving 14C-DINP (neat compound) dermally. Group 1 rats (6 animals) received a single dermal application of 14C-DINP at 0.2ml (1.2mg/kg). Group 2 rats (6 animals) were pretreated with a dermal dose of non-labelled DINP at 0.2ml for three days and then blotted clean before the application of 14C-DINP (1.2mg/kg). Group 3 rats (3 animals) received a single dermal application of 14C-DINP at 0.1ml (1.6mg/kg). Animals were placed in metabolism cages for collection of urine and feces. Two animals from each group receiving 0.2ml dose and one animal receiving the 0.1ml dose were sacrificed on post treatment days 1, 3 and 7. At termination blood was drawn and selected tissues were excised. Only 0.3% of the applied dose was recovered in the urine, feces, GI tract and tissue at 24 hours. The absorption of the test article for low and high animals at the end of the study was only 4 and 3% of the administered dose, respectively. Most of the applied radioactivity was recovered from the aplication area (skin & protective cover). Skin from non-application areas had the highest levels of radioactivity, followed by the liver, muscle and fat. Tissue levels were only sightly higher at the end of the study than at day 1 post treatment. There were no differences in the tissue levels or excretion rates of 14C-DINP in any of the rats.

Technical Report

Abstract  Diisononyl phthalate was tested for subchronic toxicity in Fischer 344 rats (5/sex/dose level) fed nominal concentrations of 0, 0.6, 1.2, and 2.5% in the diet for 21 days. Toxicity was evident by statistical differences between dosed groups and controls for: mean body weights (decreased for both sexes fed 2.5% and 1.2%), absolute and relative liver weights (increased for both sexes fed 0.6, 1,2, and 2.5%), absolute kidney weights (increased for both sexes fed 0.6, 1.2, and 2.5%), relative kidney weights (increased for males fed 0.6 and 2.5%), relative testis weights (increased in males fed 2.5%). There was a dose related decrease in the triglyceride concentrations in all treated male rats and in female rats given 1.2 and 2.5% levels. Cholesterol levels decreased for all treated groups, but no dose relationship was observed. There was a dose related increase in cyanide-insensitive palmitoyl-CoA oxidation in both sexes at 1.2 and 2.5% levels, and increases in 11- and 12-hydroxylase activities at all dose levels in males and at 2.5% in females, in hepatic protein levels in all treated groups, and in microsomal protein levels in females given 0.6 or 1.2% levels. There was a very marked and a marked increase in peroxisome proliferation in males and females fed 2.5% levels, respectively.

Technical Report
Technical Report

Abstract  The ability of 1K [di(heptyl, nonyl, undecyl) phthalate] to induce morphological transformation in vitro was evaluated in the Balb/C-3T3 mouse cell line (Cell Transformation Assay). Based on preliminary determinations of cytotoxicity, the test compound was evaluated at concentrations of 0, 60, 190, 600, 1900, and 6000 nl/ml culture medium. Cell survival was concentration-related, ranging from 88 to 12.4% over the range of concentrations tested. The treatment did not increase the frequency of cell transformation, suggesting that 1K was not carcinogenic in the mouse under the conditions of this assay. The ability of diisodecyl phthalate to induce morphological transformation in the BALB/c-3T3 mouse cell line (Cell Transformation Assay) was evaluated. The test material was relatively nontoxic at treatment doses below and above the solubility limit in culture medium (1000 to 5000 nl/ml). Diisodecyl phthalate at concentrations of 200 to 20,000 nl/ml did not induce statistically significant increases in transforming activity, and 51 to 74% survival was observed in simultaneous colony survival assays. Diundecyl phthalate was tested in the cell transformation assay in vitro on the Balb/c-3T3 mouse cell line. Preliminary toxicity assays in plastic culture vessels did not produce a clear dose response relationship; thus five arbitrary doses at and above the test article's solubility (ranging from 4000 to 100000 nl/ml) were chosen for the transformation assay, resulting in cell survival ranging from 64 to 86% relative to the control (culture medium). Assays conducted in glass bottle culture vessels did not a produce a clear dose response; thus 5 arbitrary doses were chosen both above and below the solubility limit (ranging from 400 to 40000 nl/ml), resulting in cell survival ranging from 44 to 86% relative to the control (culture medium). None of the treatments in plastic vessels produced significantly greater transformation frequencies relative to the negative control. At a concentration of 12,650 nl/ml in the glass culture flasks, a statistically significant (.02

DOI
Journal Article

Abstract  The early stages of the penetrant behavior of a series of phthalate plasticizers into thin films of glassy, high‐molecular‐weight deuterated poly(methyl methacrylate) (dPMMA) have been studied with in situ real‐time neutron reflectivity. After an initial induction phase, both dioctyl phthalate and diisononyl phthalate penetrate the dPMMA films, as indicated by an increase in the thickness. In both cases, a fast linear rate of swelling of the polymer is followed by another behavior that is much slower. The slowdown in the velocity of the plasticizers at or near the transition point is assumed to occur because of a balancing of the misfit‐induced pressure and the osmotic pressure, which is responsible for the initial plasticizer ingress. In contrast, and unexpectedly, lower molecular weight dibutyl phthalate does not swell dPMMA, but after an initial induction period, the polymer film begins to dissolve. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 3267–3281, 2004

DOI
Journal Article

Abstract  The use of plasticizers with low environmental impact is one of the most interesting research fields in the plasticizer additives industry because of the possible toxicity of o‐phthalates. Among the wide variety of new plasticizers, it is important to note the use of di(isononyl) cyclohexane‐1,2‐dicarboxylate (DINCH), which shows a structure similar to the most commonly used o‐phthalates, that is, diisononyl phthalate and di(2‐ethylhexyl) phthalate (DEHP). It is necessary to evaluate the processing conditions (temperature and curing time) regarding the mechanical properties to study the possibilities for substituting conventional plasticizers and to determine whether changes in the processing conditions are needed for use in industrial applications. In this work, we carried out a comparative study of the optimum curing conditions and mechanical performance of DEHP and DINCH as plasticizers. The obtained results show that the viscosities of DINCH and DEHP‐based plastisols were similar. Furthermore, the mechanical properties of the flexible poly(vinyl chloride) obtained from DINCH‐based plastisols were very interesting for industrial applications. All of this favored the substitution of DEHP by DINCH as plasticizer for flexible poly‐ (vinyl chloride).

DOI
Journal Article

Abstract  Poly(vinyl chloride) (PVC) is one of the most commonly used plastics in the current market due to its low cost and versatility in processing, combined with its satisfactory physical and chemical properties. However, there is an important problem associated to the use of plasticized PVC. This problem is regarding to the toxicity of the most common plasticized used like DOP, DEHP, DINP, due to its possible migration. This problem limits the use of the plasticized PVC in the industry. In this work we have used epoxidized linseed oil (ELO) as a non toxic plasticizer for PVC. This type of natural oil is characterized by acting as both plasticizer and stabilizer of PVC. With this purpose, ELO have been added to PVC. The processing conditions (temperature and time of curing) are vital to determine the final properties of the material. A study of the processing conditions shows the adequate temperature and time to achieve the optimum properties.

WoS
Book/Book Chapter

Abstract  In order to clarify the mechanism of indoor air quality in vehicle cabins, it is important to measure correctly the emission rates of volatile organic compounds (VOC) and semi-volatile organic compounds (SVOC) from automotive interior materials. In this study, we measured VOC and SVOC emitted from automotive interior materials using the Thermal Desorption Test Chamber method (TDC method), which quantified emission rates (ER) of VOC and SVOC of materials at actual temperature. This method was composed of two measurement steps. First, VOC emitted from material in the glass chamber was measured. Second, SVOC adsorbed on the internal chamber surface was measured. As a result, VOC emitted (Toluene, Ethylbenzene, Xylene, Styrene, Cyclohexanone, etc.) and SVOC emitted (BHT, DEP, DBP, DEEP, DINP, DOA, etc.) were confirmed. These results indicated that measurements of VOC and SVOC emitted from automotive interior materials could be carried out effectively.

DOI
Journal Article

Abstract  The utility of carbon paste electrode modified with silver ethylmercurythiosalicylate (silver thimerosal) in both static mode and flow injection analysis (FIA) is demonstrated. The electrode was fully characterized in terms of composition, response time. thermal stability, usable pH and ionic strength ranges. It has been shown that diisononyl phthalate (DINP) acts as more suitable solvent mediator for preparation of the electrode, which exhibits linear response range to Ag(I) extending from 5.0 x 10(-7) to 1.0 x 10(-8) M with detection limit of 2.5 x 10(-7) M and Nernstian slope of 59.3 +/- 1.0mV/decade. The proposed chemically modified carbon paste electrode shows a very good selectivity for Ag(I) over a wide variety of metal ions and successfully used for the determination of the silver content of silver sulphadiazine (burning cream) and developed radiological films. The electrode was also used as an indicator electrode in the potentiometric titration of thiopental and thimerosal with AgNO3. (c) 2005 Elsevier B.V. All rights reserved.

DOI
Journal Article

Abstract  The migration of di(2-ethylhexyl) phthalate (DEHP), di-isononyl phthalate (DINP), di(2-ethylhexyl) adipate (DEHA) and 4-nonylphenol (NP) contained in polyvinyl chloride (PVC) gloves was investigated. PVC gloves released 0.005-0.416 mug/cm(2) of DEHP, DINP, DEHA and NP into water, 20% ethanol or 4% acetic acid. In n-heptane at 25 degreesC for 60 min, PVC gloves released 1,410-2,500 mug/cm(2) of DEHP; 720 mug/cm(2) of DINP, 137-841 mug/cm(2) of DEHA and 2.72-36.4 mug/cm(2) of NP. Migration levels into rapeseed oil (60 degreesC, 30 min) were 1/2-1/4 from disposable gloves and 1/4-1/10 from thicker gloves compared with that into n-heptane (25 degreesC, 60 min). The migration amount into rapeseed oil increased as the test time and temperature increased, though the levels were high even at low temperature or for only a short time. If PVC gloves come in contact with fatty food, large amounts of DEHP, DINP, DEHA and NP might migrate into the food.

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