OBJECTIVETo investigate the associations of hormone circulation with phthalate exposure in adult men.

METHODSSemen and serum samples were collected from 118 men who were suspected of infertility. Phthalate diesters including dibutyl phthalate (DBP) and diethylhexyl phthalate (DEHP) in both semen and serum samples were measured, along with serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E(2)) and prolactin (PRL).

RESULTSSerum PRL was positively associated with serum DBP and DEHP and semen DEHP in all models of Spearman correlation, linear regression and binary logistic regression. In linear regression models adjusted for potential confounders and excluding subjects with undetectable phthalates, a 10-fold increase in semen DEHP was associated with a 23% increase in serum PRL, as well as a 26% increase in serum DBP and a 20% increase in serum DEHP. In logistic regression models all subjects demonstrated a dose-response relationship between above reference value PRL and semen DEHP (odds ratio per tertile adjusted for potential confounders = 1.0, 1.70, 3.50; P for trend = 0.01), and serum DBP (1.0, 1.10, 2.62; P for trend = 0.04), and serum DEHP (1.0, 1.46, 4.69; P for trend < 0.01). A positive correlation between serum estradiol and semen DEHP (linear regression), and an inverse correlation between semen DBP and serum testosterone and T:E(2) ratio (Spearman correlation) were also established.

CONCLUSIONSerum PRL is suggested to be positively associated with both DBP and DEHP exposure in adult men.

Adult ; Environmental Exposure ; Humans ; Logistic Models ; Male ; Phthalic Acids ; toxicity ; Prolactin ; blood

Cell Line, Tumor ; Cell Movement ; Diethylhexyl Phthalate/toxicity* ; Epithelial-Mesenchymal Transition ; Humans ; Neoplasm Invasiveness ; Phthalic Acids

Humans ; Nutrition Surveys ; Diabetes Mellitus, Type 2/chemically induced* ; Environmental Exposure/analysis* ; Environmental Monitoring ; Phthalic Acids/toxicity* ; Environmental Pollutants/toxicity*

OBJECTIVES: Maintaining the constant exposure to hydrophobic organic compouds in acute toxicity tests is one of the most difficult issues in the evaluation of their toxicity and corresponding risks. Passive dosing is an emerging tool to keep constant aqueous concentration because of the overwhelming mass loaded in the dosing phase. The primary objectives of this study were to develop the constant exposure condition for an acute mortality test and to compare the performance of the passive dosing method with the conventional spiking with co-solvent. METHODS: A custom cut polydimethylsiloxane (PDMS) tubing loaded with benzyl butyl phthalate (BBP) was placed in each well of a 24-well plate containing assay medium. The rate of the release of BBP from PDMS was evaluated by measuring the change in the concentration of BBP in the assay medium. The efficiency of maintaining constant exposure condition was also evaluated using a simple two-compartment mass transport model employing a film-diffusion theory. An acute mortality test using 10 C. elegans in each well was conducted for the evaluation of the validity of passive dosing and the comparative evaluation of the passive dosing method and the conventional spiking method. RESULTS: Free concentration in the assay medium reached 95% steady state value within 2.2 hours without test organisms, indicating that this passive dosing method is useful for an acute toxicity test in 24 hours. The measured concentration after the mortality test agreed well with the estimated values from partitioning between PDMS and the assay medium. However, the difference between the nominal and the free concentration became larger as the spiked concentration approached water solubility, indicating the instability of the conventional spiking with a co-solvent. CONCLUSIONS: The results in this study support that passive dosing provides a stable exposure condition for an acute toxicity test. Thus, it is likely that more reliable toxicity assessment can be made for hydrophobic chemicals using passive dosing.
Benzophenones ; Biological Availability ; Boronic Acids ; Caenorhabditis ; Caenorhabditis elegans ; Dibutyl Phthalate ; Dimethylpolysiloxanes ; Phthalic Acids ; Solubility ; Toxicity Tests, Acute

OBJECTIVETo observe the effects of dibutyl phthalate (DBP) and monobutyl phthalate (MBP) on the mRNA and protein expression of insulin-like factor 3 (INSL3) in the Leydig tumor cells (MA-10) of mice and the level of testosterone secreted from MA-10 cells.

METHODSThe MA-10 cells of mice, used as a cellular model, were exposed to DBP and MBP. The content of testosterone in the supernatant medium was measured by enzyme-linked immunosorbent assay; the mRNA and protein expression levels of INSL3 in MA-10 cells were measured by quantitative PCR and Western Blot.

RESULTSCompared with the control group, MA-10 cells showed increased synthesis of testosterone when exposed to low concentrations of DBP and MBP (10(-9) ∼ 10(-6) mol/L) and inhibited synthesis of testosterone when exposed to high concentrations of DBP and MBP (10(-3) mol/L), and the typical two-way effects became more significant as the time went one and the concentrations increased (P < 0.05). Compared with the control group, MA-10 cells showed significantly lower mRNA and protein expression levels of INSL3 when exposed to 10(-6) and 10(-4) mol/L DBP (P < 0.05); MA-10 cells showed increased protein expression of INSL3 when exposed to 10(-7) mol/L MBP, and the mRNA and protein expression levels of INSL3 decreased as the concentration of MBP increased.

CONCLUSIONDBP and MBP can inhibit the secretion of testosterone from MA-10 cells at high concentrations, but stimulate the secretion of testosterone at low concentrations. Both DBP and MBP have inhibitory effects on the mRNA and protein expression of INSL3 in MA-10 cells.

Animals ; Cell Line ; Dibutyl Phthalate ; toxicity ; Insulin ; metabolism ; Leydig Cells ; drug effects ; metabolism ; Male ; Mice ; Phthalic Acids ; toxicity ; Proteins ; metabolism ; Testosterone ; secretion

OBJECTIVETo study injury of liver and kidney among the workers exposed to terephthalic acid(TPA), ethylene glycol(EG) and(or) dowtherm A(DOW), and research for early biological monitoring indexes.

METHODSBy using the method of occupational epidemiology, an investigation of industrial hygiene in a chemical fibre corporation was carried out and the changes of the liver and kidney functions were analyzed among the workers who had been exposed to TPA, EG, DOW.

RESULTSThe values of serum gamma-glutamyl traspetidase(GGT) and total bile acid(TBA) in TPA + EG + DOW group men were (35.45 +/- 16.09) U/L, (10.29 +/- 6.76) mumol/L respectively and the values of serum alanine transaminase(ALT) and TBA in TPA + EG + DOW group women were(30.68 +/- 8.58) U/L, (9.53 +/- 6.63) mumol/L respectively, significantly higher than those in TPA, DOW and control groups(P < 0.05, P < 0.01). Compared with TPA, DOW and control groups, the values of urine N-acetyl-beta-D-glucosaminidase(NAG) and beta 2-2-microglobulim (beta 2-MG) in TPA + EG + DOW group of both men and women increased significantly(P < 0.05, P < 0.01), with(5.68 +/- 4.01) U/mmol Cr and (23.49 +/- 13.44) mg/mol Cr, and(6.68 +/- 4.68) U/mmol Cr and (22.80 +/- 13.00) mg/mol Cr, respectively. Analysis of regression indicated that both liver and renal injuries of the workers were evidently correlated with their exposure to TPA, EG and DOW after adjustment for the confounding factors such as sex, smoking, drinking, etc(P < 0.001).

CONCLUSIONBased on available knowledge, it is reasonable to assume that the joint actions should be considered on the injury of liver and kidney caused by TPA, EG and(or) DOW among the workers. Serum ALT, GGT, TBA, urine NAG and beta 2-MG should be suggested as biomarkers for liver and kidney damage.

Acetylglucosaminidase ; urine ; Alanine Transaminase ; blood ; Bile Acids and Salts ; blood ; Ethylene Glycol ; toxicity ; Female ; Humans ; Kidney ; drug effects ; Liver ; drug effects ; Male ; Occupational Exposure ; adverse effects ; Phenyl Ethers ; toxicity ; Phthalic Acids ; toxicity ; gamma-Glutamyltransferase ; blood

OBJECTIVETo provide more information for rational evaluation of potential risks of terephthalic acid (TPA), we studied the effects of TPA on rats' bladders in 90 days after TPA exposure.

METHODSSprague Dawley rats were subdivided into five groups, ingesting 0%, 0.04%, 0.2%, 1%, and 5% TPA respectively for a sub-chronic feeding study lasting for 90 days. Urine, serum and samples of brain, liver, lung, kidney, bladder, etc. were collected and analyzed.

RESULTSTPA ingesting decreased the value of urinary pH, and increased the contents of Ca2+, Zn2+, Mg2+, Na+, K+ in urine. The volume of 24 h urine was significantly increased in male rats in the 1% and 5% TPA groups. Urinary white sediment was found in both sexes, and its formation in male rats seemed more susceptible than that in female rats. Alpha 2u-globulin (AUG) in serum and urine of male rats was markedly increased in a dose-dependent manner. Fifteen cases of hyperplasia (simple or atypical) were determined in the 5% TPA ingesting group, 14/52 in male rats and 1/23 in female rats. Among them 3 male rats had no stone or calculus. Those with either bladder stones or hyperplasia were accompanied with urinary white sediments.

CONCLUSIONWhite sediment accompanied with elevated urine AUG is the basis of TPA induced urolith formation, and is also associated with TPA induced bladder epithelial cell proliferation. It can act as an early biomarker for the potential toxic effect of TPA.

Alpha-Globulins ; urine ; Animals ; Biomarkers ; urine ; Female ; Hyperplasia ; chemically induced ; Male ; Phthalic Acids ; toxicity ; Rats ; Rats, Sprague-Dawley ; Urinary Bladder ; drug effects ; pathology ; Urinary Bladder Calculi ; chemically induced

Air Pollutants ; analysis ; Animals ; Child ; Esters ; toxicity ; Humans ; Liver ; drug effects ; Phthalic Acids ; analysis ; metabolism ; toxicity ; Reproduction ; drug effects ; Soil Pollutants ; analysis ; Thyroid Gland ; drug effects ; Water Pollutants, Chemical ; analysis

OBJECTIVETo study the effects of butyl benzyl phthalate on neurobehavioral development of rats.

METHODSLevels of 0 (control), 0.05%, 0.25%, and 0.75% butyl benzyl phthalate (BBP) was given in the diet from 4 weeks of age of female F0 generation to 6 weeks of age of F1 generation in Wistar rats, including the period of the female F0 generation's mating, gestation and lactation and the F1 generation's growth and development. Selected parameters of neurobehavioral development were observed in F1 generation.

RESULTS(1)For the male F(1) generation, surface righting at postnatal (PND) 4 th day was significantly delayed in the low-dose group (P < 0.05) (scoring: 56 vs 61), cliff avoidance at PND 7 was significantly depressed in the high-dose group (P < 0.05) (scoring: 41), air righting at PND 14 was significantly depressed in all treatment groups (P < 0.05). In open field test, low- and high-dose groups moved more than control group (P < 0.05). In Morris water maze test, the escape latency was significantly delayed in the low-dose group at the 5th day of the 5 days' place navigation task (P < 0.05). (2) For the female F1 generation, there were no differences among groups in any parameter in the experiment (P > 0.05).

CONCLUSIONBBP may affect the neurobehavioral development only in male rats in the F1 generation.

Animals ; Behavior, Animal ; drug effects ; Dose-Response Relationship, Drug ; Female ; Growth and Development ; drug effects ; Male ; Maze Learning ; drug effects ; Motor Activity ; drug effects ; Phthalic Acids ; toxicity ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Wistar

Recent epidemiological evidence demonstrates that boys born to women exposed to phthalates during pregnancy have an increased incidence of cryptorchidism, hypospadias, testicular cancer and spermatogenic dysfunction, which are collectively referred to as testicular dysgenesis syndrome (TDS). TDS may be attributed to the dysfunction of Leydig cells and Sertoli cells during their differentiation after exposure to phthalates in utero. Fox example, Leydig cell functions are significantly affected by phthalates, leading to the decrease of two Leydig cell products--insulin-like growth factor 3 (INSL3) and testosterone, which are critical factors for testis descent. The disorientation of Leydig cells and Sertoli cells in the adult testis may be the cause of spermatogenic dysfunction.
Adult ; Cryptorchidism ; epidemiology ; Female ; Fetus ; drug effects ; Gonadal Dysgenesis ; chemically induced ; Humans ; Infant, Newborn ; Infertility, Male ; epidemiology ; Leydig Cells ; drug effects ; Male ; Maternal Exposure ; adverse effects ; Phthalic Acids ; toxicity ; Pregnancy ; Syndrome ; Testicular Diseases ; epidemiology ; Testis ; cytology