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Counter propagation artificial neural network categorical models for prediction of carcinogenicity for noncongeneric chemicals
One of the main goals of the new chemical regulation REACH (Registration, Evaluation and Authorisation of Chemicals) is to fill the gaps on the toxicological properties of chemicals that affect human health. Carcinogenicity is one of the endpoints under consideration. The information obtained from (quantitative) structure activity relationship ((Q)SAR) models is accepted as an alternative solution to avoid expensive and time-consuming animal tests. The reported results were obtained within the framework of the European project ‘Computer Assisted Evaluation of industrial chemical Substances According to Regulations (CAESAR)’. Intermediate results are demonstrated for counter propagation artificial neural network (CP ANN) models for the prediction category of the carcinogenic potency using two-dimensional (2D) descriptors from different software programs. A total of 805 non-congeneric chemicals were extracted from the Carcinogenic Potency Database (CPDBAS). The resulting models had prediction accuracies for internal (training) and external (test) sets as high as 91-93% and 68-70%, respectively. The sensitivity and specificity of the test set were 69-73 and 63-72% correspondingly. High specificity is critical in models for regulatory use that are aimed at ensuring public safety. Thus, the errors that give rise to false negatives are much more relevant. The authors discuss how they can increase the number of correctly predicted carcinogens using the correlation between the threshold and the values of the sensitivity and specificity.
Authors: Fjodorova, N.; Vracko, M.; Jezierska, A.; Novic, M.
Full Source: SAR and QSAR in Environmental Research 2010, 21(1-2), 57-75(English)
Occupational hazard evaluation of 11 IC manufacturing projects
In this study, the authors investigated the outbreak regularity and the distribution character of the occupational hazard risk factors which are raised during the manufacturing process of IC. In addition, scientific evidence for constituting measures of prevention and cure of the related occupational diseases was provided. Occupational hazard evaluation of 11 IC projects completed during 2003-2007 were collected and summarised, the outbreak regularity and the distribution character of the occupational hazard risk factors were analysed. The results showed that there were 14 kinds of chemical substances, which were all in line with national standards, except that values of arsine of individual monitoring points in air shop of ion implanter exceeded the national allowable limit; 8 kinds of physical factors accorded with national standards, except that intensity of noise exceeded national limit in production area. The authors concluded that based on the results from this study, IC manufacturing projects are all serious occupational hazard items. Management of occupational health should be strengthened, especially to formulate the emergency rescue preplans, fulfil the daily check, and enhance the staff training, which are the three most important measures to control the related occupational hazard efficiently.
Authors: Zhang, Jin-long; Qin, Hong
Full Source: Zhongguo Weisheng Gongchengxue 2010, 9(1), 36-37, 40 (Chinese)
Reproductive Toxicology and Teratology of Abused Toluene
Toluene is an organic solvent that is used widely by industry and is ubiquitous in our environment. As a result, exposure to solvents like toluene in work-related settings (i.e., relatively constant, low-level exposures) or through inhalant abuse (i.e., relatively intermittent, high-level exposures) is increasing for many women of reproductive age. The results from previous research suggests that the risk for pregnancy problems, as well as developmental delays and neurobehavioral difficulties, is higher for the children of women who have been exposed to high concentrations of organic solvents during pregnancy than for those who have not. These risks appear to be higher in cases of abuse exposure to solvents such as toluene, particularly in comparison to the risk for teratogenic outcomes with occupational solvent exposure. Despite this, the reproductive toxicology and teratology following abuse of toluene and other inhalants remains under-investigated. In this brief review, the current state of our understanding of the reproductive and teratogenic risk of gestational toluene abuse is explored. The data to date suggest that the high levels of toluene exposure typical with inhalant abuse are more detrimental to foetal development than typical occupational exposure, and preclinical paradigms can be beneficial for investigating the processes and risks of prenatal solvent exposure. The authors concluded that while substantial research has been done on the reproductive effects of occupational exposures to organic solvents, more research is needed on the outcomes and mechanisms of exposures typical of inhalant abuse.
Authors: Hannigan, John H.; Bowen, Scott E.
Full Source: Systems Biology in Reproductive Medicine 2010, 56(2), 184-200 (English)
Adverse Effects of Low Level Heavy Metal Exposure on Male Reproductive Function
Lead, cadmium, mercury, and arsenic are often referred to as “heavy metals”, which are toxic for wildlife, experimental animals, and humans. While experimental animal and human occupational studies with high exposure levels generally support an adverse role for these metals in human reproductive outcomes, information on the effects of low, environmentally-realistic exposure levels of these metals on male reproductive outcomes is limited. In this study, the authors review the literature on effects of exposure to low levels of these metals on measures of male fertility (semen quality and reproductive hormone levels) and provide supporting evidence from experimental and occupational studies. In addition, potentially modifying effects of genetic polymorphisms on these associations are discussed. A brief review of the literature on the effects of three trace metals, copper, manganese, and molybdenum, that are required for human health, yet may also cause adverse reproductive effects, follows. Overall, there were few studies examining the effects of exposure to low levels of these metals on male reproductive health. For all metals, there were several well-designed studies with sufficient populations appropriately adjusted for potential confounders and many of these reported harmful effects. However, many studies lacked sufficient numbers of participants to be able to detect differences in outcomes between exposed and non-exposed individuals, did not clearly identify the source and characteristics of the participants, and did not control for other exposures that could alter or contribute to the outcomes. The evidence for the effects of low exposure was strongest for cadmium, lead, and mercury and less certain for arsenic. The potential modifying effects of genetic polymorphisms has not been fully explored. The authors concluded that further studies on the reproductive effects of these toxic ubiquitous metals on male reproduction are required to expand the knowledge base and to resolve inconsistencies.
Authors: Wirth, Julia J.; Mijal, Renee S.
Full Source: Systems Biology in Reproductive Medicine 2010, 56(2), 147-167 (English)
Blue-Light Hazard from CO2 Arc Welding of Mild Steel
This study quantified the blue-light hazard from CO2 arc welding of mild steel. The spectral radiance of arcs in CO2 arc welding of mild steel was measured for solid and flux-cored wires at welding currents of 120-480 A. Effective blue-light radiance and the maximum acceptable exposure duration were calculated from the spectral radiance using their definitions in American Conference of Governmental Industrial Hygienists guidelines. The results demonstrated that the effective blue-light radiance ranged from 22.9 to 213.1 Wcm-2sr-1. The corresponding maximum acceptable exposure duration was only 0.47-4.36 s, meaning that the total daily exposure to the welding arc without eye protection should not exceed this duration. The authors concluded that the results indicated that it is very hazardous to view the arcs in CO2 arc welding of mild steel. Welders and their helpers should use appropriate eye protectors in these arc welding operations. Furthermore, they should avoid direct light exposure when starting an arc-welding operation.
Authors: Okuno, T.; Ojima, J.; Saito, H.
Full Source: Annals of Occupational Hygiene 2010, 54(3), 293-298 (English)
Exposure to beryllium and occurrence of lung cancer: findings from a cox Proportional hazards analysis of data from a retrospective Cohort Mortality study
In the present study, the authors assessed highly confounded patterns in a standardised mortality ratio (SMR) analysis of lung cancer in beryllium worker cohorts. Cox proportional hazards single and multivariate models were used to assess confounding and the SMR patterns. The findings confirmed the lack of association of lung cancer with time worked. The original study’s finding of lung cancer highly associated with earlier plants and or with workers hired in the 1940s compared to the 1950s could not be confirmed. The pattern of higher rates of lung cancer with increasing latency was attenuated when covariates were added to the model. Lower SMR and hazard ratios could not be confirmed for workers hired in the 1960s. This may be related to assumed lower beryllium exposures. The patterns observed provide little support for an association of lung cancer with beryllium work factors. The authors concluded that these results are likely due to the absence in the original study of a significant overall excess of lung cancer after smoking adjustment.
Authors: Levy, Paul S.; Roth, H. Daniel; Deubner, David C.
Full Source: Journal of Occupational and Environmental Medicine 2009, 51(4), 480-486 (Eng)
Determination and Characterisation of Hydroxylated Polychlorinated Biphenyls (OH-PCBs) in Serum and Adipose Tissue of Japanese Women Diagnosed with Breast Cancer
During this study, the authors detected polychlorinated biphenyls (PCB) and hydroxylated-PCB concentrations in blood serum and breast adipose tissue. In addition, the total TH (3,5,5’-triiodothyronine [tT3], total L-thyroxine [tT4]) concentrations were detected in blood serum of Japanese women diagnosed with breast cancer (n ) 51) to assess how PCB affect thyroid hormone homeostasis. Results demonstrated that ª90OH-PCB concentrations in serum and adipose tissue were 630 pg/g serum wet weight and 140 pg/g lipid weight, respectively; OH-PCBs concentrations in adipose tissue were 4-5 times lower than in serum. tT3 and tT4 serum concentrations (n ) 20) were 1.3 ng/g serum wet weight and 62 ng/g serum wet weight, respectively. Among all OH-PCB, 4’-OH-CB101/120, 4-OH-CB107/4’-OH-CB108, 3’-OH-CB138, 4-OH-CB146, 3-OHCB153, 4’-OH-CB172, and 4-OH-CB187 were the dominant serum congeners. No significant correlation between TH and OH-PCB concentrations in serum was observed (p >0.05). the authors concluded that the findings from this study indicate the relationship between OH-PCB concentrations and thyroid hormone markers was rare. By analysing 2 types of human biological samples, it was estimated OH-PCB have little effect on thyroid hormone homeostasis.
Authors: Nomiyama, Kei; Yonehara, Tomonori; Yonemura, Saori; Yamamoto, Megumi; Koriyama, Chihaya; Akiba, Suminori; Shinohara, Ryota; Koga, Minoru
Full Source: Environmental Science & Technology 2010, 44(8), 2890-2896 (Eng)
Distribution of PCBs, Their Hydroxylated Metabolites, and Other Phenolic Contaminants in Human Serum from Two European Countries
Human exposure to polychlorinated biphenyl (PCB) mixtures may result in the formation of different hydroxylated PCB (HO-PCB) profiles due to different exposures or dissimilar metabolism of parent compounds. This study investigated the PCB and HO-PCB levels and profiles in human serum samples collected in 2 European countries with different degrees of pollution. There was no significant difference between levels of sum PCB measured in each sample set; median concentration was 3100 pg/mL for Romanian (n ) 53) and 3380 pg/mL for Belgian samples (n ) 22). However, median concentrations recorded for sum HO-PCB were almost double in Belgian (310 pg/mL) versus Romanian (175 pg/mL) samples. HO-PCB detection frequency in Belgian samples was significantly higher than Romanian samples. Main contributors to sum HO-PCB in Belgian samples were 4HO-CB107 > 4HO-CB146 > 4HO-CB187 (76% from sum HO-PCB) and 4HO-CB187 > 4HO-CB146 > 3’HO-CB138 (66% from sum of HO-PCB) in Romanian samples. The HO-PCB profile showed higher chlorinated HO-PCB had a higher contribution in Romanian versus Belgian samples. This suggested differences in PCB profiles between populations can lead to formation of different HOPCB metabolite profiles, presenting different risks for populations. No clear preferential mechanism of HO-PCB metabolite formation (HO-direct insertion vs. 1,2 Cl atom shift) could be highlighted for studied samples. The main chlorinated phenolic compound in Belgian samples was pentachlorophenol (PCB) which accounted for e85% of total quantified phenolics; in Romanian samples, PCP accounted for only 35% of chlorinated phenolic compounds.
Authors: Dirtu, Alin C.; Jaspers, Veerle L. B.; Cernat, Roberta; Neels, Hugo; Covaci, Adrian
Full Source: Environmental Science & Technology 2010, 44(8), 2876-2883 (Eng)
Exposure to hydroxylated polychlorinated biphenyls (OH-PCBs) in the prenatal period and subsequent neurodevelopment in Eastern Slovakia
Hydroxylated polychlorinated biphenyls (OH-PCBs), unlike PCBs, are in general readily excreted yet are still detected in humans and animals. Active transport of OH-PCBs across the placenta and hydroxylation of PCBs by the foetus suggest the potential for greater impact on the foetus compared with the parent PCB compounds. However, little is known about their health effects, particularly in humans. This study evaluated the associations between prenatal OH-PCB exposure and neurodevelopment in children at 16 months of age in eastern Slovakia. A birth cohort (n ) 1,134) was enrolled during 2002-2004. Six OH-PCB metabolites (4-OH-CB-107, 3-OH-CB-153, 4-OHCB-146, 3’-OH-CB-138, 4-OH-CB-187, and 4’-OH-CB-172) were measured in a subset of the cohort. The Bayley Scales of Infant Development were administered to the children at the 16-month follow-up visit. Multiple linear regression models were developed to predict standardised scores for the Mental Development Index (MDI) and Psychomotor Development Index (PDI) from maternal (n ) 147) and cord (n ) 80) serum OH-PCB concentrations, adjusting for sex of child, district, HOME (Home Observation for Measurement of the Environment) score, and maternal score on Raven’s Progressive Matrixes. The results showed that cord 4-OH-CB-107 was significantly associated with lower MDI (â ) -2.27; p ) 0.01) and PDI (â ) -4.50; p ) 0.004). Also, maternal 4-OHCB- 107 was significantly associated with lower MDI (â ) -1.76; p ) 0.03) but not PDI. No other OH-PCB metabolites were associated with decreased PDI or MDI. The authors concluded that the results from this study showed a significant association of 4-OH-CB-107 with decreased MDI, which can possibly be mediated by endocrine disruption, altered neurotransmitter functions, or reduced thyroid hormone concentrations in the brain.
Authors: Park, Hye-Youn; Park, June-Soo; Sovcikova, Eva; Kocan, Anton; Linderholm, Linda; Bergman, Ake; Trnovec, Tomas; Hertz-Picciotto, Irva
Full Source: Environmental Health Perspectives 2009, 117(10), 1600-1606 (Eng)