Introduction: With the increasing clinical use of titanium dioxide nanoparticles (nano-TiO2), a better understanding of their safety in the human use is critical. The present study aims to review the potential application of nano-TiO2 as targeted cancer therapy based on their toxicity risk which highly dependent on their physio-chemical properties. Methods: This review was performed based on PRISMA-P protocol that begin with literature searching on the selected databases; PubMed, Springer Link, Science Direct and general search engine; Google Scholar from 2013 to 2018. Studies retrieved by the pre-determined keywords (titanium dioxide nanoparticles, toxicity, genotoxicity, cytotoxicity, targeted cancer therapy) that assessed toxicity risk of nano-TiO2 in cancer therapeutics were included. Results: The search retrieved 252 articles. Assessment of eligibility by application of inclusion criteria yielded 14 articles. Nano-TiO2 induced cytotoxicity and genotoxicity in dose and time-dependent manner killing the cancerous cells. All studies used primary particles size < 100 nm with mean of 39.38 and standard deviation of 30.47 which is lower than the mean denoting diameter distribution from selected studies are concentrated from the mean. Conclusion: This review suggest that TiO2 nanoparticles can be considered as an ideal candidate for drug-delivery vehicle for targeted cancer therapy by specifically tailored their physio-chemical properties of this nanoparticles according to desired target site and functions to ensure its optimal efficacy.
Toxicity risk

The ex vivo biosensor assay is developed to assess the health effects and toxicological mechanism of environmental pollutants with internal environment homeostasis changes by integrating the in vivo exposure evaluation, in vitro outcomes analysis, and systematic environment component screening. This toxicology testing model combines the real-world exposure of people in the field and the study of molecular mechanism exploration in lab experiments to overcome the shortcomings of a single toxicology method. It provides a new technique and perspective for toxicity testing and risk assessment in mesoscale between macroscopic population study and microscopic mechanism exploration.
Biosensing Techniques ; Environmental Pollutants/toxicity* ; Humans ; Risk Assessment ; Toxicity Tests

Introduction: Aluminium exposure and toxicity are uncommon in humans. However it may occur in patients on long term haemodialysis (HD) due to water exposure during treatment. We retrospectively assessed the extent of aluminium exposure in our HD and peritoneal dialysis (PD) patients from 2002 to 2008. Materials and Methods: The study population included 43 HD patients and 77 PD patients whose blood samples were collected at four monthly intervals. In addition, HD patients were also interviewed on lifestyle factors (aluminium cookware, diet, aluminium-containing medications and tap water consumption) that may impact on serum aluminium levels. Reverse osmosis (RO) water aluminium levels were also collected during this timeframe. Results: More patients on HD had readings above the accepted range (>0.01mg/L) than peritoneal dialysis (36.9% vs. 23.8%). The mean aluminium values for HD and PD patients were 63.35 ± 34.69μg/L and 38.34 ± 17.02μg/L respectively (p<0.05). Use of aluminium cookware was identified as a risk factor for high aluminium readings in HD patients. The trend of serum aluminium correlated with that of RO water aluminium during the studied period. There was no evidence of clinical toxicity in our patients during follow up. Conclusion: The study showed that HD patients are at a higher risk of aluminium toxicity compared to PD patients. Treated RO water aluminium should be analysed on a regular basis to prevent aluminium toxicity in HD patients. Lifestyle factors may have an impact on aluminium levels in patients with renal disease.
Complications ; Dialysis ; Heavy Metal Toxicity ; Risk Factors

OBJECTIVETo establish the threshold of toxicological concern(TTC) approach and to apply it in the risk assessment of metabolites, degradation and reaction products of pirimicarb.

METHODSTTC decision tree approach based on Cramer classification was established and Lazar software was used to predict the genotoxicity of the seven transformation products of pirimicarb, namely, R34836, R34885, R35140, R31805, R34865, R16210 and R16192. Dietary exposure in general population as well as in six age population groups was estimated by using data from the Chinese National Nutrition and Health Survey and pirimicarb residue data from national chemical surveillance data in 2011. TTC decision tree approach was used for risk assessment and the exposure was compared with the corresponding TTC values.

RESULTSOf the seven transformations of pirimicarb active substance, namely, R34836, R34885, R35140, R31805, R34865, R16210 and R16192, the maximum dietary exposure of mean and large portion(P 97.5) were all belong to 2-6 age group. The mean exposures of the seven transformation products for 2-6 age group,were 0.0290, 0.0207, 0.0015, 0.0320, 0.0005, 0.6918 and 0.1274 µg/kg,respectively, and the corresponding P 97.5 exposures were 0.0817,0.0581,0.0042,0.0900,0.0014, 1.9459 and 0.3585 µg/kg. Besides, the mean and P 97.5 exposure of R16210 for 2-6 age group was the largest,which were 0.6918 and 1.9459 µg/kg, accounting for 46.12% and 129.73% of the TTC threshold,respectively.

CONCLUSIONTTC decision tree approach is a useful tool for prior screening and primary risk assessment of the transformation products of pesticide active substance.

Carbamates ; toxicity ; Food Contamination ; Humans ; Maximum Allowable Concentration ; Pesticide Residues ; toxicity ; Pesticides ; toxicity ; Pyrimidines ; toxicity ; Risk Assessment

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.
Animals ; Benzhydryl Compounds ; toxicity ; Diethylstilbestrol ; toxicity ; Dose-Response Relationship, Drug ; Drug Interactions ; Endocrine Disruptors ; toxicity ; Estrogens ; toxicity ; Models, Theoretical ; Phenols ; toxicity ; Rats ; Rats, Sprague-Dawley ; Risk Assessment

Recently, the International Agency for Research on Cancer (IARC) has classified outdoor air pollution and the particulate matter component of outdoor air pollution as class I carcinogen. Air pollution is consistently associated with lung cancer in epidemiologic and experimental studies. The IARC assessment is specifically designed as hazard identification, and it does not quantify the magnitude of the cancer risk. This article addresses the magnitude of the lung cancer risk in the population due to ambient air pollution exposure.
Air Pollutants ; toxicity ; Air Pollution ; adverse effects ; Carcinogens, Environmental ; toxicity ; Humans ; Lung Neoplasms ; etiology ; Particulate Matter ; toxicity ; Risk Factors

Risk Factors ; Tars ; toxicity ; Tobacco Products ; standards ; toxicity ; Tobacco Use Disorder ; etiology ; prevention & control

This study aims to establish the occupational exposure limit (OEL) in the air for workplace of warfarin based on the available toxicological studies and field investigations by using questionnaire and air monitoring. The clinical therapeutic dose was used as lowest observed effect level (LOEL), and no observed effect level (NOEL) was achieved by using a safety factor. The highest concentration of warfarin monitored in the worksite of centrifuge washing, drying and packing were 0.029 mg/m3, 0.051 mg/m3 respectively, which did not exceed the OEL 0.1 mg/m3 recommended by NIOSH and ACGIH. Considering its feasibility for enforcement and protection for workers, we recommend OEL 0.1 mg/m3 of warfarin in China.
Anticoagulants ; toxicity ; China ; Humans ; Occupational Exposure ; standards ; Risk Factors ; Warfarin ; toxicity

In this study, the content of five heavy metals(Pb, Cd, As, Hg, and Cu) in 59 batches of Lonicerae Japonicae Flos(LJF) medicinal materials and pieces were determined by inductively coupled plasma mass spectrometry(ICP-MS). The health risk assessment was processed using the maximum estimated daily intake(EDI), target hazard quotients(THQ), and carcinogenic risks(CR) assessment models. With reference to the limit standard for heavy metal content in LJF specified in 2020 edition of Chinese Pharmacopoeia, five batches produced in Hebei were found to contain excessive Pb, and the remaining 54 batches met the specifications, with the unqualified rate of 8.47%. Comparative analysis of heavy metal content in LJF samples from three different producing areas, namely Shandong, Henan, and Hebei showed that the levels of Pb, As, and Hg in LJF from Hebei were significantly higher than those from Henan and Shandong. The samples produced in Shandong contained the highest content of Cd. The samples from Hebei contained the highest content of Cu while those from Shandong had the lowest content of Cu. As demonstrated by health risk assessment based on the EDI, THQ and CR models, these 59 batches of LJF samples did not cause significant health hazards for the exposed population, and there was no potential non-carcinogenic or carcinogenic risk. In conclusion, a few of LJF samples contained excessive heavy metals, so some measures, including controlling production environment, cultivating management mode, and optimizing processing methods, should be taken for ensuring the medication safety of LJF.
Drugs, Chinese Herbal ; Environmental Pollution/analysis* ; Mercury/toxicity* ; Metals, Heavy/toxicity* ; Risk Assessment

Perfluoroalkyl substances (PFASs) have been distributed in environment and human body worldwide. Due to their bioaccumulative and multiple organ toxic, these compounds have raised more and more attention in recent years. The precursors of PFASs can be metabolized to PFASs both in environment and human body, which makes an important contribution to human body burdens. Apart from transformation into PFASs, some of these precursors themselves or their metabolic intermediates also have toxicity effects, such as estrogen-like properties, protein binding, cytotoxicity and so on, and there might be a potential harmful impact on human health. In this paper, the toxicity and biotransformation of PFASs and their precursors were introduced briefly.
Environment ; Environmental Pollution ; Fluorocarbons ; toxicity ; Health ; Humans ; Risk