RESUMEN
The transplacental passage of monomethylphtalate (mMP) and mono (2-ethylhexyl) phthalate (mEHP) was studied using an ex vivo placental perfusion model with simultaneous perfusion of fetal and maternal circulation in a single cotyledon. Umbilical cord blood and placental tissue collected both before and after perfusion were also analyzed. Placentas were obtained immediately after elective cesarean section and dually perfused in a recirculation system. mMP or mEHP was added to maternal perfusion medium to obtain concentrations at 10 and 25 microg/L, respectively. The placental transfer was followed analyzing samples from fetal and maternal perfusion media by liquid chromatography-mass spectrometry-mass spectrometry (LC-MS-MS). Four perfusions with mMP indicated a slow transplacental transfer, with a feto-maternal ratio (FM ratio) of 0.30 +/- 0.03 after 150 min of perfusion. Four perfusions with mEHP indicated a very slow or nonexisting placental transfer. mEHP was only detected in fetal perfusion media from two perfusions, giving rise to FM ratios of 0.088 and 0.20 after 150 min of perfusion. Detectable levels of mMP, mEHP, monoethylphthalate (mEP), and monobutylphthalate were found in tissue. Higher tissue levels of mMP after perfusions with mMP compared to perfusions with mEHP suggest an accumulation of mMP during perfusion. No tendency for accumulation of mEHP was observed during perfusions with mEHP compared to perfusions with mMP. Detectable levels of mEHP and mEP were found in umbilical cord plasma samples. mMP and possibly other short-chained phthalate monoesters in maternal blood can cross the placenta by slow transfer, whereas the results indicate no placental transfer of mEHP. Further studies are recommended.
Asunto(s)
Dietilhexil Ftalato/análogos & derivados , Intercambio Materno-Fetal , Ácidos Ftálicos/farmacocinética , Placenta/efectos de los fármacos , Dietilhexil Ftalato/sangre , Dietilhexil Ftalato/farmacocinética , Femenino , Sangre Fetal/metabolismo , Humanos , Técnicas In Vitro , Modelos Biológicos , Perfusión , Ácidos Ftálicos/sangre , Placenta/metabolismo , EmbarazoRESUMEN
Fetal exposure to phthalates may be associated with adverse reproductive effects, including cryptorchidism and decreased semen quality. Information about human placental transfer is needed to qualify the hypotheses. A dual recirculating placenta perfusion system to monitor concentrations of eight phthalate monoesters in fetal and maternal perfusates was established. In addition to perfusate background measures of phthalate monoesters, the concentrations in umbilical cord plasma and placenta tissue were measured. Monomethyl phthalate (mMP), monoethyl phthalate (mEP), monobutyl phthalate (mBP), and mono (2-ethyl-hexyl) phthalate (mEHP) were detected in both maternal and fetal perfusate, demonstrating a release of compounds from tissue or blood to perfusates. The distribution of compounds between perfusate, umbilical cord plasma, and tissue was in accordance with the physical-chemical properties of the compounds. Results from the present study of compounds residing in the tissue are essential before studying human transplacental transfer, storage, and metabolism of selected phthalate monoesters.
Asunto(s)
Contaminantes Ambientales/farmacocinética , Sangre Fetal/metabolismo , Intercambio Materno-Fetal/efectos de los fármacos , Ácidos Ftálicos/farmacocinética , Placenta/metabolismo , Adulto , Contaminantes Ambientales/análisis , Femenino , Sangre Fetal/química , Humanos , Intercambio Materno-Fetal/fisiología , Perfusión , Ácidos Ftálicos/análisis , Placenta/irrigación sanguínea , EmbarazoRESUMEN
UNLABELLED: Phthalates adversely affect the male reproductive system in animals. We investigated whether phthalate monoester contamination of human breast milk had any influence on the postnatal surge of reproductive hormones in newborn boys as a sign of testicular dysgenesis. DESIGN: We obtained biologic samples from a prospective Danish-Finnish cohort study on cryptorchidism from 1997 to 2001. We analyzed individual breast milk samples collected as additive aliquots 1-3 months postnatally (n = 130; 62 cryptorchid/68 healthy boys) for phthalate monoesters [mono-methyl phthalate (mMP), mono-ethyl phthalate (mEP), mono-n-butyl phthalate (mBP), mono-benzyl phthalate (mBzP), mono-2-ethylhexyl phthalate (mEHP), mono-isononyl phthalate (miNP)]. We analyzed serum samples (obtained in 74% of all boys) for gonadotropins, sex-hormone binding globulin (SHBG), testosterone, and inhibin B. RESULTS: All phthalate monoesters were found in breast milk with large variations [medians (minimum-maximum)]: mMP 0.10 (< 0.01-5.53 microg/L), mEP 0.95 (0.07-41.4 microg/L), mBP 9.6 (0.6-10,900 microg/L), mBzP 1.2 (0.2-26 microg/L), mEHP 11 (1.5-1,410 microg/L), miNP 95 (27-469 microg/L). Finnish breast milk had higher concentrations of mBP, mBzP, mEHP, and Danish breast milk had higher values for miNP (p = 0.0001-0.056). No association was found between phthalate monoester levels and cryptorchidism. However, mEP and mBP showed positive correlations with SHBG (r = 0.323, p = 0.002 and r = 0.272, p = 0.01, respectively); mMP, mEP, and mBP with LH:free testosterone ratio (r = 0.21-0.323, p = 0.002-0.044) and miNP with luteinizing hormone (r = 0.243, p = 0.019). mBP was negatively correlated with free testosterone (r = -0.22, p = 0.033). Other phthalate monoesters showed similar but nonsignificant tendencies. CONCLUSIONS: Our data on reproductive hormone profiles and phthalate exposures in newborn boys are in accordance with rodent data and suggest that human Leydig cell development and function may also be vulnerable to perinatal exposure to some phthalates. Our findings are also in line with other recent human data showing incomplete virilization in infant boys exposed to phthalates prenatally.
Asunto(s)
Criptorquidismo/inducido químicamente , Hormonas Esteroides Gonadales/sangre , Leche Humana/química , Ácidos Ftálicos/envenenamiento , Efectos Tardíos de la Exposición Prenatal , Adulto , Estudios de Cohortes , Dinamarca , Femenino , Finlandia , Humanos , Recién Nacido , Estudios Longitudinales , Masculino , Ácidos Ftálicos/análisis , EmbarazoRESUMEN
Degradation of two mycotoxins: zearalenone (ZON) produced by species of Fusarium and ochratoxin A (OTA) produced by species of Penicillium were followed in pot experiments using agricultural topsoils from Danish experimental farms: a sandy soil, a sandy clay soil and a gyttja soil with a high content of silt. Experiments with unplanted soil and pots planted with barley were included. Soil samples were withdrawn during a period of 225 days and analysed for the content of OTA and ZON. The degradation of both toxins consisted of an initial fast degradation followed by a slower transformation step and was described well by a sum of two first-order kinetic equations. The decay first-order rate constants for the first step (k1) were in the range 0.73-2.91 d(-1) for OTA and 0.0612-0.108 d(-1) for ZON, respectively. Half-lives (t0.5) for ZON using data from the first phase were between 6.4 and 11 days, whereas the half-lives for OTA were about 0.2-1 day. The slowest degradation was measured in soil rich in clay. After 225 days, neither OTA nor ZON was detected in any of the soil types. Generally, the degradation of ZON and OTA was faster in planted soil than in unplanted soil, probably due to higher microbial activity. Due to the fast degradation of ZON and OTA in surface soil leaching as soluble substances appears to be limited.
Asunto(s)
Agricultura , Contaminación Ambiental/análisis , Ocratoxinas/análisis , Contaminantes del Suelo/análisis , Zearalenona/análisis , Dinamarca , Monitoreo del AmbienteRESUMEN
Daily exposure of humans to phthalates may be a health risk because animal experiments have shown these compounds can affect the differentiation and function of the reproductive system. Because milk is the main source of nutrition for infants, knowledge of phthalate levels is important for exposure and risk assessment. Here we describe the development and validation of a quantitative analytical procedure for determination of phthalate metabolites in human milk. The phthalate monoesters investigated were: monomethyl phthalate (mMP), monoethyl phthalate (mEP), mono-n-butyl phthalate (mBP), monobenzyl phthalate (mBzP), mono-(2-ethylhexyl) phthalate (mEHP), and monoisononyl phthalate (mNP). The method is based on liquid extraction with a mixture of ethyl acetate and cyclohexane (95:5) followed by two-step solid-phase extraction (SPE). Detection and quantification of the phthalate monoesters were accomplished by high-pressure liquid chromatography using a Betasil phenyl column (100 mmx2.1 mmx3 microm) and triple tandem mass spectrometry (LC-MS-MS). Detection limits were in the range 0.01 to 0.5 microg L(-1) and method variation was from 5 to 15%. Analysis of 36 milk samples showed that all these phthalates were present, albeit at different concentrations. Median values (microg L(-1)) obtained were 0.11 (mMP), 0.95 (mEP), 3.5 (mBP), 0.8 (mBzP), 9.5 (mEHP), and 101 (mNP). We also analysed seven samples of consumer milk and ten samples of infant formula. Only mBP and mEHP were detected in these samples, in the ranges 0.6-3.9 microg L(-1) (mBP) and 5.6-9.9 microg L(-1) (mEHP).
Asunto(s)
Ésteres/análisis , Fórmulas Infantiles/química , Leche Humana/química , Ácidos Ftálicos/análisis , Espectrometría de Masas en Tándem/métodos , Cromatografía Liquida/métodos , Cromatografía Liquida/normas , Ésteres/normas , Femenino , Humanos , Lactante , Recién Nacido , Ácidos Ftálicos/normas , Valores de Referencia , Sensibilidad y Especificidad , Espectrometría de Masas en Tándem/normas , Factores de TiempoRESUMEN
Moisture affects bioavailability and fate of pollutants in soil, but very little is known about moisture-induced effects on pollutant toxicity. We here report on a modifying effect of moisture on degradation of linear alkylbenzene sulfonates (LASs) and on their toxicity towards ammonia-oxidizing bacteria (AOB) in agricultural soil. In soil spiked with two LAS levels (250 or 1,000 mg/kg) and incubated at four different moisture levels (9-100% of water-holding capacity), degradation was strongly affected by both soil moisture and initial LAS concentration, resulting in degradation half-lives ranging from 13 to more than 160 d. Toxicity towards AOB assessed by a novel Nitrosomonas europaea luxAB-reporter assay was correlated to total LAS concentration, indicating that LAS remained bioavailable over time without accumulation of toxic intermediates. Toxicity towards indigenous AOB increased with increasing soil moisture. The results indicate that dry soil conditions inhibit LAS degradation and provide protection against toxicity within the indigenous AOB, thus allowing for a rapid recovery of this population when LAS degradation is resumed and completed after rewetting. We propose that the protection of microbial populations against toxicity in dry soil may be a general phenomenon caused primarily by limited diffusion and thus a low bioavailability of the toxicant.
Asunto(s)
Ácidos Alcanesulfónicos/toxicidad , Nitrosomonas/metabolismo , Contaminantes del Suelo/toxicidad , Suelo/análisis , Agua/química , Biodegradación Ambiental , Bioensayo , Disponibilidad Biológica , Dinamarca , Cinética , Compuestos de Amonio Cuaternario/análisisRESUMEN
Linear alkylbenzene sulfonates (LAS) often occur in sewage sludge that is applied to agricultural soil. Here LAS may affect the microbial activity, which is an important basis for nutrient cycling. Previous studies have shown that single bacterial species and specific soil processes can be very sensitive to LAS. Here we report that two levels of LAS, 22 and 174 mg/kg dry weight soil, had little or no significant influence of the functional diversity of bacteria in a sandy soil, as tested by community-level physiological profiles. Briefly, these profiles are a characterization of the microbial communities based on the pattern of substrate utilization in 96-well microtiter plates (Biolog EcoPlates). Sandy agricultural soil was incubated in duplicate 1-L mesocosms with or without LAS, and bacteria were extracted after one, two, and four weeks. During incubation, more than 98 and 93% of LAS added to 22 and 174 mg/kg dry weight soil was degraded, respectively. The presence of LAS at 174 mg/kg dry weight caused a higher number of bacteria in the soil extracts, maximally corresponding to 2.5 times the numbers in LAS-free soil (1.8 x 10(7) cells/g dry wt soil) after four weeks of incubation. No inhibitory effect of LAS was observed when the substrate utilization data were analyzed for substrate richness and diversity (Shannon-Weaver indices). Principal component analysis, however, showed that the pattern of substrate utilization in soil with the highest LAS content (174 mg/kg dry wt) could be distinguished from control soil and soil with 22 mg LAS/kg dry weight. Yet the overall conclusion was that the functional diversity of the aerobic, heterotrophic bacterial community was rather insensitive to LAS.