Abstract  Includes "RCRA facility assessment, final report, Vulcan Materials Company, Wichita, Kansas" by John C. Parks at Ecology & Environment Inc., 1987.

Abstract  Background: Di-n-butyl phthalate (DBP) and di-iso-butyl phthalate (DiBP) are widely used in consumer products, enteric-coated tablets and as plasticizers for polymers. DnBP and DiBP are metabolized in humans to their monoesters mono-n-butyl phthalate (MnBP) and mono-iso-butyl phthalate (MiBP). These primary metabolites are currently used in human biomonitoring approaches to assess internal exposures. However, the simple monoesters are prone to external contamination and have rather short half-times of elimination. These shortcomings could be overcome using oxidized, secondary metabolites, when applicable. Methods: We investigated 160 spot urine samples (partly repeated from 110 volunteers) with no known occupational phthalate exposures for oxidised metabolites of both isomers with oxo-, hydroxy- and carboxy-functional groups. 3-carboxy-MPP (3cxMPP) was detected in 90% of the samples with a median concentration of 0.66 μg/L (95th percentile [95P]: 2.70 μg/L). 3-cxMPP is a metabolite of DnBP but also of other higher molecular weight phthalates, thus not specific to DnBP exposure. Results: 3cxMPP was comparably weakly correlated with MnBP (r = 0.56; P < 0.001) and weaker with MiBP (r = 0.30; P < 0.001). 3-hydroxy-MnBP (3OH-MnBP) was detected in 97% of the samples with a median of 1.73 μg/L (95P: 13.3 μg/L). 3OH-MnBP was highly correlated (r = 0.91; P < 0.001) with MnBP (median: 20.9 μg/L; 95P: 110.7) but excreted at about 10-fold lower concentrations. Regarding oxidised DiBP metabolites we detected OH-MiBP in all samples and at high concentrations (median: 10.5 μg/L; 95P: 119.4 μg/L). OH-MiBP was highly correlated with MiBP (r = 0.90; P < 0.001) and excreted at roughly half the concentration of MiBP (median: 27.3 μg/L; 95P: 193.0 μg/L). Thus, OH-MiBP is an excellent additional biomarker of DiBP exposure, supplementing MiBP. With limits of quantification of 0.1 μg/L for all metabolites, we detected no metabolites with a keto (oxo) functional group. Conclusion: Overall, our findings suggest that there are considerable differences in DiBP and DnBP metabolism which have to be taken account of when interpreting biomonitoring data.

Abstract  Phthalates are environmental contaminants used in the production of plastics, cosmetics and medical devices. Studies on the effects of phthalates on female reproductive health are particularly sparse and mostly restricted to high-dose exposure in rats. In the present study, pregnant rats were treated with 100mg/kg-d of di-eta-butyl-phthalate (DBP) or only the vehicle (control group), from GD 12 to GD 20 for evaluation of reproductive outcomes and fetal gonads analysis (F0), and from GD 12 to PND 21 to evaluate reproductive development and function on F1 female offspring. Results showed that all parameters were comparable between groups, although there was a significant increase in the fetal weight after DBP exposure. However, the body weight at birth was normal. Based on these data we can conclude that, in these experimental conditions, DBP did not disturb the reproductive development or function of female rats.

Abstract  Review human animal nitrosamines vinyl chloride polyvinyl chloride polycyclic aromatic hydrocarbons lead chrome diethylene glycol plastics neozone d angiosarcoma

Abstract  The focus of this review is to highlight the participation of members of the tumor necrosis factor (TNF) superfamily of proteins, particularly FasL and Fas, in triggering apoptosis of distinct testicular germ-cell subtypes after mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell injury. Despite the well-recognized expression of FasL and Fas in the testis, their functional role in this tissue and the cellular mechanisms that regulate germ-cell apoptosis in the testis remain poorly characterized. Over the last several years, evidence has been accumulating indicating the participation of the FasL/Fas signaling pathway in the testis as a key signaling event for triggering germ-cell apoptosis consequent to MEHP-induced Sertoli cell injury. It has also recently been revealed that the stability of the c-FLIP protein, a direct inhibitor of Fas signaling, in germ cells appears to be dependent on the activity of the p53 protein. Increased degradation of the c-FLIP protein is proposed to occur in distinct germ-cell subtypes as a secondary consequence to MEHP-induced Sertoli cell injury and may account for their sensitivity to undergo apoptosis. Taken together, these findings form the basis for our current hypothesis that MEHP-induced injury to Sertoli cells results in early increases in its expression of FasL and secondary changes in the regulation of Fas in germ cells as a result of p53 activation. An understanding of the primary cellular site of phthalate action in the Sertoli cell and of the extent of the resulting adverse outcomes that arise from this injury are required for an accurate appraisal of the risks of environmental phthalate exposure on human reproductive health during all phases of life.

Abstract  We developed a highly sensitive method for the quantitative detection of nine phthalate ester metabolites in human serum. This method requires denaturation of the serum enzymes immediately after blood collection to avoid the hydrolysis of the contaminant diester parent compounds introduced during blood collection and storage. Before analysis, the samples were subjected to an enzymatic deconjugation to hydrolyze the glucuronidated phthalate monoesters and a solid-phase extraction to isolate the monoesters from other serum components. The extracts were analyzed using reversed-phase high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. The limits of detection of all nine phthalate monoesters in serum were in the low nanogram-per-milliliter range (0.6-1.3 ng/mL). Stable isotope-labeled internal standards for all analytes were used to improve precision and for recovery corrections. This highly selective method permits the analysis of phthalate monoesters without interferences resulting from the hydrolysis of the ubiquitous contaminant phthalate diesters by serum enzymes. In addition, it allows the direct measurement of the active phthalate monoester metabolites reportedly responsible for the reproductive and developmental toxicity of certain phthalates.

Abstract  BACKGROUND: Anogenital distance (AGD), a sexually dimorphic measure of genital development, is a marker for endocrine disruption in animal studies and may be shorter in infant males with genital anomalies. Given the correlation between anogenital distance and genital development, we sought to determine if anogenital distance varied in fertile compared to infertile adult men.

METHODS: A cross sectional study of consecutive men being evaluated for infertility and men with proven fertility was recruited from an andrology clinic. Anogenital distance (the distance from the posterior aspect of the scrotum to the anal verge) and penile length (PL) were measured using digital calipers. ANOVA and linear regression were used to determine correlations between AGD, fatherhood status, and semen analysis parameters (sperm density, motility, and total motile sperm count).

FINDINGS: A total of 117 infertile men (mean age: 35.3±17.4) and 56 fertile men (mean age: 44.8±9.7) were recruited. The infertile men possessed significantly shorter mean AGD and PL compared to the fertile controls (AGD: 31.8 vs 44.6 mm, PL: 107.1 vs 119.5 mm, p<0.01). The difference in AGD persisted even after accounting for ethnic and anthropomorphic differences. In addition to fatherhood, on both unadjusted and adjusted linear regression, AGD was significantly correlated with sperm density and total motile sperm count. After adjusting for demographic and reproductive variables, for each 1 cm increase in a man's AGD, the sperm density increases by 4.3 million sperm per mL (95% CI 0.53, 8.09, p = 0.03) and the total motile sperm count increases by 6.0 million sperm (95% CI 1.34, 10.58, p = 0.01). On adjusted analyses, no correlation was seen between penile length and semen parameters.

CONCLUSION: A longer anogenital distance is associated with fatherhood and may predict normal male reproductive potential. Thus, AGD may provide a novel metric to assess reproductive potential in men.

Abstract  Phthalates are used as plasticizers and solvents in industrial, medical and consumer products; however, occupational exposure information is limited. We sought to obtain preliminary information on occupational exposures to diethyl phthalate (DEP), di-n-butyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP) by analyzing for their metabolites in urine samples collected from workers in a cross-section of industries. We also obtained data on metabolites of dimethyl phthalate (DMP), benzylbutyl phthalate (BzBP), di-isobutyl phthalate and di-isononyl phthalate. We recruited 156 workers in 2003-2005 from eight industry sectors. We assessed occupational contribution by comparing end-shift metabolite concentrations to the US general population. Evidence of occupational exposure to DEHP was strongest in polyvinyl chloride (PVC) film manufacturing, PVC compounding and rubber boot manufacturing where geometric mean (GM) end-shift concentrations of DEHP metabolites exceeded general population levels by 8-, 6- and 3-fold, respectively. Occupational exposure to DBP was most evident in rubber gasket, phthalate (raw material) and rubber hose manufacturing, with DBP metabolite concentrations exceeding general population levels by 26-, 25- and 10-fold, respectively, whereas DBP exposure in nail-only salons (manicurists) was only 2-fold higher than in the general population. Concentrations of DEP and DMP metabolites in phthalate manufacturing exceeded general population levels by 4- and >1000-fold, respectively. We also found instances where GM end-shift concentrations of some metabolites exceeded general population concentrations even when no workplace use was reported, e.g. BzBP in rubber hose and rubber boot manufacturing. In summary, using urinary metabolites, we successfully identified workplaces with likely occupational phthalate exposure. Additional work is needed to distinguish occupational from non-occupational sources in low-exposure workplaces.

Abstract  The glass transition and structural relaxation dynamics of various binary glass-forming liquids are investigated with dielectric relaxation measurements across the entire composition range. Three categories of solutions with weak, intermediate, and strong mixing effects, namely methyl-m-toluate in methyl o-toluate, methyl m-toluate in di-n-butyl phthalate, and 1,2-propandiol in 2-hexylamine, are selected to address the mixing behaviors from near-ideal to nonideal cases. The glass transition temperatures, fragility indices, and stretching exponents of the solutions are determined and their composition dependence is the focus of this study. The experimental measurements show that mixing generally generates a negative deviation of fragility m relative to the composition average of the results of two neat components (ideal mixing law). This excess negative fragility proves to be a universal feature of binary systems, and the increase of the nonideal mixing degree results in a more pronounced negative deviation. In contrast, the composition dependence of the stretching exponents is more complex, and a transition from the negative to positive deviation is observed for substantial nonideal character. The study assists understanding the dynamics of multicomponent glass formers.

Abstract  Phthalate esters, including di(n-butyl) phthalate (DBP), are endocrine active compounds that can adversely affect male reproductive development at relatively high doses in the rat after in utero exposure. DBP effects include cryptorchidism, hypospadias, and reduced semen quality, which can be attributable in part to reduced testosterone biosynthesis in the fetal testis. In utero phthalate exposure of fetal testis on gestation days 12 ? 19 results in a reduction of key steroidogenic enzymes mRNA and protein levels including StAR, SR-B1, P450scc, and CYP17. However, the mechanism of this reduction is unknown. We hypothesize that phthalate exposure results in altered transcription factor binding in the promoter regions of affected genes. To examine this hypothesis, an in vivo footprinting method was employed to examine differences in transcription factor binding in steroidogenic gene promoters after phthalate treatment. In vivo footprinting employs ligation-mediated PCR to amplify single-sided DNA created by strand breaks after treatment with DNase I in the promoter sequence of the gene. Regions bound by transcription factors are protected from the DNase I and therefore not amplified. This method was adapted for use with an automated DNA sequencer to allow greater sensitivity and quantification. Results indicate that phthalate treatment induces a reduction in transcription factor binding between -35 and -70 bp upstream of the transcriptional start site in the proximal promoter region of StAR. Sequence analysis of this region reveals two highly consensus binding sites for GATA binding proteins as well as a half-site for Steroidogenic Factor-1 (SF-1). The disruption of activity of transcription factors known to be highly involved in activation of steroidogenic genes suggests a possible mechanism through which phthalates reduce testosterone production.

Abstract  A case study was conducted, using dibutyl phthalate (DBP), to explore an approach to using toxicogenomic data in risk assessment. The toxicity and toxicogenomic data sets relative to DBP-related male reproductive developmental outcomes were considered conjointly to derive information about mode and mechanism of action. In this manuscript, we describe the case study evaluation of the toxicological database for DBP, focusing on identifying the full spectrum of male reproductive developmental effects. The data were assessed to 1) evaluate low dose and low incidence findings and 2) identify male reproductive toxicity endpoints without well-established modes of action (MOAs). These efforts led to the characterization of data gaps and research needs for the toxicity and toxicogenomic studies in a risk assessment context. Further, the identification of endpoints with unexplained MOAs in the toxicity data set was useful in the subsequent evaluation of the mechanistic information that the toxicogenomic data set evaluation could provide. The extensive analysis of the toxicology data set within the MOA context provided a resource of information for DBP in attempts to hypothesize MOAs (for endpoints without a well-established MOA) and to phenotypically anchor toxicogenomic and other mechanistic data both to toxicity endpoints and to available toxicogenomic data. This case study serves as an example of the steps that can be taken to develop a toxicological data source for a risk assessment, both in general and especially for risk assessments that include toxicogenomic data.

Abstract  The tannery effluents at Kanpur (India) have been in use for irrigation since last many years, polluting soil directly while ground water and food crops indirectly. Gas chromatography-mass spectrometric analysis of the test samples revealed the presence of organic compounds including diisooctyl phthalate, phenyl N-methylcarbamate, dibutyl phthalate, bis 2-methoxyethyl phthalate, and higher alkanes. Tannery effluent extracts were prepared using XAD-4/8 resins, dichloromethane, chloroform, and hexane and tested with Ames Salmonella test and DNA repair-defective Escherichia coli K-12 mutants. In the presence of XAD-concentrated tannery effluent, TA98 found to be the most sensitive strain in terms of mutagenic index followed by TA97a whereas in terms of mutagenic potential TA102 was most responsive. The extracts were also found genotoxic as determined in terms of survival of E. coli K-12 mutants, suggesting the presence of DNA damaging compounds in the tannery effluents. In the light of results, precautious use of tannery effluents for irrigation is suggested.

Abstract  A gram negative isolate designated JDC-41 was obtained from river sludge using mixtures of phthalate esters as the sole source and energy. The isolate was identified as Ochrobactrum sp. based on its 16S rRNA gene sequence. Over 87% of supplied di-n-butyl phthalate (DBP) was degraded by JDC-41 in a pH neutral mineral salts medium at 30 degrees C within 48 h. Increased DBP (50-500 mg/L) in the culture correspondingly increased degradation half-life from 3.83 to 18.12 h. DBP induced cells more rapidly degraded DBP.

Abstract  An analysis method is reported for dibutyl phthalate and related compounds with high selectivity and sensitivity by using the selective molecularly imprinted solid-phase extraction (MISPE) technique. In this report, dibutyl phthalate (DBP) is employed as the template molecule, and the molecularly imprinted polymers (MIPs) are synthesized through the bulk polymerization of methacrylic acid (MAA). The Scatchard plot suggests that the template-polymer system has two-site binding behavior with the dissociation constants of 0.5187 and 0.01898 mmol L(-1), respectively. The rebinding test, based on the MISPE column technique, shows the recoveries of soybean milk samples spiked with 5 phthalates are in the range of 75.8-107.5% with the relative standard deviations of 1.80-10.08%, indicating the feasibility of the prepared MIPs for phthalates extraction. Finally, the method is used to analyze the trace level of phthalates in commercial soybean milk.

Abstract  The construction and electrochemical response characteristics of two new polyvinyl chloride (PVC) membrane sensors for the determination of sibutramine hydrochloride were described. The sensors are based on the ion association complexes of sibutramine with sodium tetraphenylborate (NaTPB) or phosphotungstic acid (PTA) using dibutyl phthalate as plasticizing solvent. The sensors display a fast, stable response over the concentration range 3.84 x 10(-5)-1.00 x 10(-2) M sibutramine hydrochloride monohydrate (SibuCl), with cationic slopes of 57.7 +/- 0.57 and 59.7 +/- 1.79 mV concentration decade(-1) and detection limits of 8.91 x 10(-6) and 1.47 x 10(-5) M in case of sibutramine-tetraphenylborate (Sibu-TPB) and sibutramine-phosphotungstate ((Sibu)(3)-PT), respectively. The proposed sensors have been successfully applied for the determination of sibutramine hydrochloride in Regitrim capsules in batch and flow injection (FI) conditions.

Abstract  OBJECTIVE: To investigate the inhibitory mechanisms of testosterone (T) biosynthesis in rats exposed to dibutyl phthalate (DBP).

METHODS: Male Wistar rats were randomly divided into five groups by weight, including 0.25, 0.50, 1.00, 2.00 g/kg DBP groups and corn oil control group, with 16 rats in each group. DBP was administered by gavage once a day. After 30 days exposure, eight rats in each group were killed and the others were killed after 15 days without DBP administration. The levels of T and glucocorticoid (GC) in serum were determined by radioimmunoassay. The expression levels of 11 beta-dedroxysteriod dehydrogenase (11 beta-HSD) mRNA and steroidogenesis acute regulatory protein (StAR) mRNA were determined by RT-PCR. The protein expression level of glucocorticoid receptor (GR) was investigated by Western blotting.

RESULTS: During exposure period, in 1.00 and 2.00 g/kg DBP groups, the levels of T were (0.260 +/- 0.218) ng/ml and (0.260 +/- 0.342) ng/ml, the levels of GC were (13.470 +/- 5.661) ng/ml and (13.740 +/- 3.977) ng/ml, the levels of T and GC in control group were (1.045 +/- 1.222) ng/ml and (9.224 +/- 3.496) ng/ml. There were statistic differences between 1.00 and 2.00 g/kg DBP groups and control group (t(T) values were -2.295 and -2.295, t(GC) values were 2.159 and 2.296, respectively, P < 0.05). The expression level of StAR mRNA was significantly down-regulated in 1.00 and 2.00 g/kg DBP groups, while StAR/beta-Actin values were 0.657 +/- 0.060 and 0.407 +/- 0.033, and compared to control group (0.871 +/- 0.081), there was statistic difference (t values were -3.707 and -8.037, P < 0.05). In 1.00 and 2.00 g/kg DBP groups, the expression of 11 beta-HSD mRNA and the expression of GR protein were increased in DBP dose-dependent manner, while 11 beta-HSD/beta-Actin values were 0.538 +/- 0.138 and 0.988 +/- 0.133, and GR/beta-Actin were 0.785 +/- 0.106 and 0.956 +/- 0.076, respectively. There were statistic difference, as compared to the controls (0.285 +/- 0.106 and 0.275 +/- 0.035) (t(11 beta-HSD/beta-Actin) values were 2.829 and 7.860, t(GR/beta-Actin) values were 8.064 and 10.77, respectively, P < 0.05).Linear correlation and regression revealed that there were positive correlation between DBP dose and the expression levels of 11 beta-HSD mRNA and GR protein, with r values of 0.766 and 0.790, respectively. In post-exposure period, there were no statistic differences of all above index among DBP groups and control group.

CONCLUSION: DBP might inhibit T production in rats through GR mediation.

Abstract  Polar and non-polar secondary metabolites as well as phenolic compounds of Aspergillus parasiticus grown on hazelnut were analyzed by high-resolution high performance liquid chromatography-mass spectroscopy and fourier transform infrared spectroscopy. Several novel and beneficial compounds such as dibutyl phthalate, pyrogallol, fumagillol, italicic acid and sorbicillin were identified from A. parasiticus for the first time. Some of these compounds have the potential to be used in pharmaceutical industry.

Abstract  A marine sulfate-reducing bacterium SRB-22 was isolated by means of the agar shake dilution method and identified as Desulfovibrio desulfuricans by morphological, physiological and biochemical characteristics and 16S rDNA analysis. In the bioassay, its extract showed broad-spectrum antimicrobial activity using the paper disc agar diffusion method. This isolate showed a different antimicrobial profile than either ampicillin or nystatin and was found to produce at least eight antimicrobial components by bioautography. Suitable fermentation conditions for production of the active constituents were determined to be 28 day cultivation at 25 degrees C to 30 degrees C with a 10% inoculation ratio. Under these conditions, the SRB-22 was fermented, extracted and chemically investigated. So far an antimicrobial compound, mono-n-butyl phthalate, and an inactive compound, thymine, have been isolated and characterized.

Abstract  Recently air pollutants and irritants have been labelled as possible exogenous risk factors for allergic disorders. Although the underlying causes of allergic disorders such as atopic dermatitis and asthma remain unclear, the T helper type 2 (Th2) cell-mediated allergic inflammatory cascade may contribute to their pathogenesis. In the last decade, it has been documented that one of the candidates for triggering Th2 commitment is thymic stromal lymphopoietin (TSLP), the expression of which is up-regulated in the lesions of allergic patients. Here, we describe TSLP function in a fluorescein isothiocyanate (FITC) -induced contact hypersensitivity (CHS) model. A cytokine profile indicated that the model was dominantly mediated by the Th2 milieu. Interestingly, TSLP was increased in the skin during the sensitization phase when stimulated by a solvent, dibutyl phthalate (DBP), but not by FITC hapten or another solvent, acetone. Ear swelling in FITC-induced CHS was totally abrogated by removing DBP from the sensitization or elicitation phase, and was restored by complementary injection of TSLP. Inversely, the ear swelling was suppressed by injection of small interfering RNA against TSLP during the sensitization phase, which was concomitant with decreasing expression of interleukin-4 at the swollen skin site. Taken together, DBP-induced TSLP during the sensitization phase plays a role in establishing FITC-induced CHS and may be one of the causes of Th2 commitment in the model, suggesting that certain environmental toxins, such as DBP, may endow pro-allergic and atopic predisposition in humans or animals.

Abstract  This study shows that the androgen receptor agonistic potency is clearly concealed by the effects of androgen receptor antagonists in a total sediment extract, demonstrating that toxicity screening of total extracts is not enough to evaluate the full in vitro endocrine disrupting potential of a complex chemical mixture, as encountered in the environment. The anti-androgenic compounds were masking the activity of androgenic compounds in the extract with relatively high anti-androgenic potency, equivalent to 200 nmol flutamide equivalents/g dry weight. A two-step serial liquid chromatography fractionation of the extract successfully separated anti-androgenic compounds from androgenic compounds, resulting in a total androgenic potency of 3,820 pmol dihydrotestosterone equivalents/g dry weight. The fractionation simplified the chemical identification analysis of the original complex sample matrix. Seventeen chemical structures were tentatively identified. Polyaromatic hydrocarbons, a technical mixture of nonylphenol and dibutyl phthalate were identified to contribute to the anti-androgenic potency observed in the river sediment sample. With the GC/MS screening method applied here, no compounds with AR agonistic disrupting potencies could be identified. Seventy-one unidentified peaks, which represent potentially new endocrine disrupters, have been added to a database for future investigation.

Abstract  New clobutinol (Clob) ion-selective polyvinyl chloride (PVC) membrane electrodes, based on the ion-associates of Clob with phosphotungstic acid or phosphomolybdic acid were prepared using dibutyl phthalate as plasticizing solvent. The electrodes were characterized in terms of membrane composition, temperature and pH. The sensors showed a near-Nernstian response over the concentration ranges (6.31 x 10(-6))-(1.00 x 10(-2)) and (5.01 x 10(-5))-(1.00 x 10(-2))M in the case of clobutinol-phosphotungstate ((Clob)(3)-PT) applying batch and flow injection (FI) analysis, respectively, and (1.58 x 10(-5))-(1.00 x 10(-2)) and (5.01 x 10(-5))-(1.00 x 10(-2))M in case of clobutinol-phosphomolybdate ((Clob)(3)-PM) for batch and FI analysis systems, respectively. The electrodes were successfully applied for the potentiometric determination of ClobCl in pharmaceutical preparation and urine in steady state and flow injection conditions. The electrodes exhibit good selectivity for Clob with respect to a large number of inorganic cations, sugars and amino acids.

Abstract  The internal solid contact sensor for the determination of doxycycline hydrochloride (DC) was developed based on a conducting polypyrrole (PPy) film immobilized on a glassy carbon electrode surface casted by a plasticized polyvinyl chloride (PVC) membrane containing an ion-pair compound of DC with tetraphenylborate (TPB) and dibutylphthalate (DBP) as plasticizer. Effects of various factors for the electropolymerization of pyrrole or aniline, including monomer concentration, acidity or inorganic salt and thickness of polymer film were investigated experimentally. It was found that the slope and the linear range of SCSs changed with both the different concentration of monomer and of KCl in electrolyte solution and with the different substrate material and a marked influence of the change of solution pH on the potential response of sensor occurred when sample solution pH>3.5. Under the condition of pH 2.8, the sensor showed a near-Nernstian response over the range of DC concentration of 1.0x10(-2)-1.0x10(-5) mol l(-1) with the slope (at 25 degrees C) of 54.4 mV per decade. The detection limit obtained was 4.0x10(-6) mol l(-1).The sensor was successfully applied to determination of DC in pharmaceutical formulation.

Abstract  OBJECTIVE: To identify and analyze the differential expression of ubiquitin C-terminal hydrolase L-1 (UCHL1) in the testis of rat offspring after maternal exposure to di-n-butyl phthalate (DBP).

METHODS: Forty pregnant rats were randomly divided into two groups and given DBP by gastric intubation at the dose of 800 mg/(kg x d) or none from the 14-18th day of pregnancy. Testes were harvested from the fetal and neonatal rats of the normal and exposed groups respectively at GD19 and PND22. The expression of UCHL1 was detected and analyzed by Western blot and immunohistochemistry.

RESULTS: The UCHL1 expression was 50% lower in the DBP-exposed group than in the normal controls on GD19 (P < 0.01), but showed no significant difference between the two groups on PND22 (P > 0.05). UCHL1 was mainly located in the cytoplasm and nuclei of spermatogonia, primary spermatocytes and sub-primary spermatocytes in the developmental phase of the testis.

CONCLUSION: Exposure in utero to DBP affects the UCHL1 expression in testicular spermatogenic cells, disturbs the balance of the ubiquitin-proteasome system and consequently causes maldevelopment of the testis with thinner seminiferous tubules and reduced count of spermatogenic cells.