ABSTRACT
BACKGROUND@#Traditional toxicological studies focus on individual compounds. However, this single-compound approach neglects the fact that the mixture exposed to human may act additively or synergistically to induce greater toxicity than the single compounds exposure due to their similarities in the mode of action and targets. Mixture effects can occur even when all mixture components are present at levels that individually do not produce observable effects. So the individual chemical effect thresholds do not necessarily protect against combination effects, an understanding of the rules governing the interactive effects in mixtures is needed. The aim of the study was to test and analyze the individual and combined estrogenic effects of a mixture of three endocrine disrupting chemicals (EDCs), bisphenol A (BPA), nonylphenol (NP) and diethylstilbestrol (DES) in immature rats with mathematical models.@*METHOD@#In the present study, the data of individual estrogenic effects of BPA, NP and DES were obtained in uterotrophic bioassay respectively, the reference points for BPA, NP and DES were derived from the dose-response ralationship by using the traditional no observed adverse effect (NOAEL) or lowest observed adverse effect level (LOAEL) methods, and the benchmark dose (BMD) method. Then LOAEL values and the benchmark dose lower confidence limit (BMDL) of single EDCs as the dose design basis for the study of the combined action pattern. Mixed prediction models, the 3 × 2 factorial design model and the concentration addition (CA) model, were employed to analyze the combined estrogenic effect of the three EDCs.@*RESULTS@#From the dose-response relationship of estrogenic effects of BPA, NP and DES in the model of the prepuberty rats, the BMDL(NOAEL) of the estrogenic effects of BPA, NP and DES were 90(120) mg/kg body weight, 6 mg/kg body weight and 0.10(0.25) μg/kg body weight, and the LOAEL of the the estrogenic effects of three EDCs were 240 mg/kg body weight, 15 mg/kg body weight and 0.50 μg/kg body weight, respectively. At BMDL doses based on the CA concept and the factorial analysis, the mode of combined effects of the three EDCs were dose addition. Mixtures in LOAEL doses, NP and DES combined effects on rat uterine/body weight ratio indicates antagonistic based on the CA concept but additive based on the factorial analysis. Combined effects of other mixtures are all additive by using the two models.@*CONCLUSION@#Our results showed that CA model provide more accurate results than the factorial analysis, the mode of combined effects of the three EDCs were dose addition, except mixtures in LOAEL doses, NP and DES combined effects indicates antagonistic effects based on the CA model but additive based on the factorial analysis. In particular, BPA and NP produced combination effects that are larger than the effect of each mixture component applied separately at BMDL doses, which show that additivity is important in the assessment of chemicals with estrogenic effects. The use of BMDL as point of departure in risk assessment may lead to underestimation of risk, and a more balanced approach should be considered in risk assessment.
Subject(s)
Animals , Rats , Benzhydryl Compounds , Toxicity , Diethylstilbestrol , Toxicity , Dose-Response Relationship, Drug , Drug Interactions , Endocrine Disruptors , Toxicity , Estrogens , Toxicity , Models, Theoretical , Phenols , Toxicity , Rats, Sprague-Dawley , Risk AssessmentABSTRACT
<p><b>OBJECTIVE</b>To assess dietary exposure of diethylhexyl phthalate(DEHP) among Chinese population, including general population, children aged 2-6 years, adolescent aged 7-12, young people aged 13-17, adults aged 18-59 years old as well as older people aged 60 and above and its health risk.</p><p><b>METHODS</b>A total of 6 650 food samples were collected during 2011 to 2013 from 140 local markets of 14 provinces in China, which covered major foods in China. Samples were detected by GC-MS and categorized into 22 food groups. Food consumption data were taken from China National Nutrition and Health Survey performed in 2002 including 68 959 subjects. Mean concentrations of DEHP in food were combined with individual food consumption data to estimate dietary exposure, and food contributors to dietary DEHP intake were also calculated. Then, the exposure was compared with the tolerable daily intake (TDI, 50 µg·kg(-1)-d(-1)) of DEHP.</p><p><b>RESULTS</b>DEHP level in foods (n = 6 650) was in the range of not detected to 43.80 mg/kg. Mean dietary intakes of DEHP in general population was 2.07 (95% CI: 0.06-4.09) µg·kg(-1)·d(-1), accounting for 4.14 percent of TDI (50 µg·kg(-1)·d(-1)). Mean dietary intake for population aged 2-6, 7-12, 13-17, 18-59 as well as elderly aged 60 and above were 3.92 (95% CI: 0.83-7.01), 3.02 (95% CI: 0.69-5.36), 2.17 (95% CI: 0.54-3.81), 1.83 (95% CI: 0.46-3.21) and 1.66 (95% CI: 0.38-2.94) µg·kg(-1)·d(-1) respectively. The 97.5 percentile intakes in the general populations was 4.73 µg·kg(-1)·d(-1), accounting for 9.46% of TDI. Main food sources of DEHP were rice (28.4% (0.59/2.07)), melon solanaceous vegetables (14.7% (0.30/2.07)) and flour (13.2% (0.27/2.07)) for the general population.</p><p><b>CONCLUSION</b>The results suggested that dietary exposure to DEHP among Chinese population was lower than tolerable daily intake of DEHP and there were no health concerns based on generally accepted exposure limits. Rice, melon solanaceous vegetables and flour were main food contributors of DEHP dietary intake for Chinese populations.</p>
Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Humans , Middle Aged , Asian People , China , Diet , Diet Surveys , Diethylhexyl Phthalate , Flour , Food , Food Contamination , Gas Chromatography-Mass Spectrometry , Oryza , Risk Assessment , VegetablesABSTRACT
Objective To investigate the pollution status of algae and microcystin(MC)in Dianshan Lake,Shanghai City and Poyang Lake,Jiangxi Province.Methods Water samples were collected from different sites of the above lakes,as the pretreatment of intracellular and extracellular microcystins was finished,MC-LR concentration was detected by ELISA.Results The proportion of Cyanobacteria in Dianshan Lake was 38.8% and 68.2% respectively,the mean content of MC was 281.78 and 1 145.77 pg/ml respectively.In Poyang Lake,the proportion of Cyanobacteria was 48.9% and 73.7% respectively,the mean content of MC was 80.53 and 405.65 pg/ml respectively.In the same water-blooming lake,MC content was significantly lower in July than that in October(P
ABSTRACT
Objective To explore the regulatory effect of apigenin on the blood pressure of the spontaneous hypertension rat(SHR) rats and the possible mechanism.Methods The case groups of rats were fed with different dosage of apigenin(0.03,0.05,0.11 g/kg) by gavage for 4 consecutive weeks,while the control groups were treated with equal cubage of oil.The body weight,heart rate,blood pressure were measured every week.Results After 4 weeks of treatment with apigenin,the blood pressure of SHR in all doses groups decreased significantly;besides,apigenin could reduce the content of ET-1 and AngII,however,it didn't change NOS activity.Conclusion Apigenin has a regulatory effect on blood pressure,its lowest effective dose is 0.03 g/kg bw and it may decrease the blood pressure through reducing the content of ET-1 and AngII,not through the NO/NOS pathway.