The molecular mechanism of evaluating 17β-estradiol (E₂)-induced toxicity in female Daphnia magna has not been determined. In this study, the transcriptome of D. magna was analyzed after exposure to three different concentrations (0, 10, and 100 ng L⁻¹) of E₂ at 3, 6, and 12 h. The results showed 351–17,221 significantly up-regulated and 505–10,282 significantly down-regulated genes (P < 0.05). Overall, the selected largest 10,282 (10 ng L⁻¹vs control at 12 h) down-regulated and 17,221 (100 vs 10 ng L⁻¹) up-regulated genes were identified; following annotation, pathways in cancer and RNA transport were found to be enriched according to the interaction network. Among all completed comparisons, KEGG pathways related to the immune system, cancer, disease infection, and active compound metabolism were identified by short time series expression miner analysis. A different set of genes fluctuated in a “U”-shaped pattern over time and at different concentrations of E₂, whereas some genes associated with disintoxication showed a reverse “U”-shaped response as E₂ administration was increased. These results suggest that E₂ exposure caused transcriptional changes in the immune system, disintoxication, disease prevention, and the protein degradation pathway.

To assess hepatotoxicity and to determine the underlying mechanisms of carbamazepine (CBZ) toxicity in fish, histopathology and the liver proteome were examined after Chinese rare minnow (Gobiocypris rarus) were exposed to 1, 10, and 100 μg/L CBZ for 28 days. Histopathological changes included disruption of spatial structure, pyknotic nuclei, cellular vacuolization and deformation of cell nuclei, in addition to marked swelling of hepatocytes in all treatment groups. Protein analysis revealed that there were gender-specific responses in rare minnow following exposure, and there were 47 proteins in females and 22 proteins in males identified as differentially abundant following CBZ treatments. Pathway analysis revealed that cellular processes affected by CBZ included apoptosis, cell differentiation, cell proliferation, and the respiratory chain, indicating impaired energy homeostasis. Noteworthy was that 15 proteins identified as different in abundance were associated with carcinogenicity. Relative mRNA levels for select transcripts were consistent with the changes of proteins N-myc downstream regulated gene (NDRG), Tropomyosin 2-Beta (TPM2) and annexin A4 (ANXA4). Protein pyruvate kinase, liver and RBC (PKLR) were increased at 1 and 100 μg/L CBZ without significant difference in transcript levels. These findings characterize molecular responses and histological changes in the liver that generate new insights into CBZ hepatotoxicity in Chinese rare minnow.

This study investigated associations between long-term exposure to ambient volatile organic compounds (VOCs) and mortality. 58,760 Toronto residents (≥35 years of age) were selected from tax filings and followed from 1982 to 2004. Death information was extracted using record linkage to national mortality data. Land-use regression surfaces for benzene, n-hexane, and total hydrocarbons were generated from sampling campaigns in 2002 and 2004 and assigned to residential addresses in 1982. Cox regression was used to estimate relationships between each VOC and non-accidental, cardiovascular, and cancer mortality. Positive associations were observed for each VOC. In multi-pollutant models the benzene and total hydrocarbon signals were strongest for cancer. The hazard ratio for cancer that corresponded to an increase in the interquartile range of benzene (0.13 μg/m3) was 1.06 (95% CI = 1.02–1.11). Our findings suggest ambient concentrations of VOCs were associated with cancer mortality, and that these exposures did not confound our previously reported associations between NO2 and cardiovascular mortality.

Although animal data have suggested the carcinogenic activity of trihalomethanes (THMs), there is inconsistent evidence supporting the link between THM exposure and cancers in humans.We investigated the association between specific and total blood THM levels with the risk of total cancer mortality in adults.We analyzed data from the 1999–2004 Third National Health and Nutrition Examination Survey and the Linked Mortality File of the United States. A total of 933 adults (20–59 years of age) with available blood THM levels and no missing data for other variables were included. Four different THM species (chloroform, bromodichloromethane (BDCM), dibromochloromethane (DBCM) and bromoform) were included, and the codes associated with cancer (malignant neoplasm) were C00 through C97, based on the underlying causes of death listed in the International Classification of Disease 10the Revision.Compared with adults in the lowest DBCM, bromoform, and total brominated THM tertiles, those in the highest DBCM, bromoform, and total brominated THM tertiles exhibited adjusted hazard ratios (HR) of total cancer mortality of 4.97 (95% confidence interval (CI) = 1.59–15.50), 4.94 (95% CI = 1.56–15.61), and 3.42 (95% CI = 1.21–15.43) respectively. The risk of total cancer mortality was not associated with increases in blood chloroform and total THM levels.We found that the baseline blood THM species, particularly brominated THMs, were significantly associated with total cancer mortality in adults. Although this study should be confirm by other studies, our findings suggest a possible link between THM exposures and cancer.

Long-term exposure to PM₂.₅ has been linked to lung cancer incidence and mortality, but limited evidence existed for other cancers. This study aimed to assess the association between PM₂.₅ on cancer specific mortality. An ecological study based on the cancer mortality data collected from 5,565 Brazilian cities during 2010–2018 using a difference-in-differences approach with quasi-Poisson regression, was applied to examine PM₂.₅-cancer mortality associations. Globally gridded annual average surface PM₂.₅ concentration was extracted and linked with the residential municipality of participants in this study. Sex, age stratified and exposure-response estimations were also conducted. Totalling 1,768,668 adult cancer deaths records of about 208 million population living across 5,565 municipalities were included in this study. The average PM₂.₅ concentration was 7.63 μg/m³ (standard deviation 3.32) with range from 2.95 μg/m³ to 28.5 μg/m³. With each 10 μg/m³ increase in three-year-average (current year and previous two years) concentrations of PM₂.₅, the relative risks (RR) of cancer mortality were 1.16 (95% confidence interval [CI]: 1.11–1.20) for all-site cancers. The PM₂.₅ exposure was significantly associated with several cancer-specific mortalities including oral, nasopharynx, oesophagus, and stomach, colon rectum, liver, gallbladder, larynx, lung, bone, skin, female breast, cervix, prostate, brain and leukaemia. No safe level of PM₂.₅ exposure was observed in the exposure-response curve for all types of cancer. In conclusion, with nationwide cancer death records in Brazil, we found that long-term exposure to ambient PM₂.₅ increased risks of mortality for many cancer types. Even low level PM₂.₅ concentrations had significant impacts on cancer mortality.

Thousands of chemicals exist in hydraulic-fracturing (HF) fluids and wastewater from unconventional oil gas development. The carcinogenicity of these chemicals in HF fluids and wastewater has never been systematically evaluated.In this study, we assessed the carcinogenicity of 1,173 HF-related chemicals in the HF chemical data from the US Environmental Protection Agency (EPA).We linked the HF chemical data with the agent classification data from the International Agency for Research on Cancer (IARC) at the World Health Organization (WHO) (N = 998 chemicals) to evaluate human carcinogenic risk of the chemicals and with the Carcinogenic Potency Database (CPDB) from Toxnet (N = 1,534 chemicals) to evaluate potential carcinogenicity of the chemicals.The Chemical Abstract Service Registry Numbers (CASRNs) for chemicals were used for data linkage. Among 1,173 chemicals, 1,039 were identified only in HF fluids, 97 only in wastewater, and 37 in both. Compared with IARC, we found information of 104 chemicals, and 48 of them may have potentially carcinogenic risk to human, among which 14 are definitely carcinogenic, 7 probably carcinogenic, and 27 possibly carcinogenic. Using the CPDB data, it suggests that 66 chemicals are potentially carcinogenic based on rats and mouse models.Conclusions Our evaluation suggests that exposure to some chemicals in HF fluids and wastewater may increase cancer risk, and the identified chemicals could be selected as the priority list for drinking water exposure assessment or cancer-related health studies.