Environmental risk assessment of arsenic and fluoride in the Chaco Province, Argentina: research advances.

The arsenic (As) and fluoride (F⁻) concentration in groundwater and potential adverse human health risk was investigated in the Central-West Region of the Chaco Province, northern Argentina. The mean concentration of As in shallow groundwater was 95 µg/L, where 76% of samples exceeded the World Health Organization (WHO) guideline value of 10 µg/L, while in deep groundwater it was 90 µg/L, where 63% samples exceeded 10 µg/L. For As health risk assessment, the average daily dose, hazard quotient (HQ), and cancer risk were calculated. The values of HQ were found to be >1 in 77% of samples. This level of contamination is considered to constitute a high chronic risk compared with U.S. Environmental Protection Agency (EPA) guidelines. Further, a significant portion of the population has lifetime carcinogenic risk >10⁻4 and may suffer from cancer. A positive correlation was observed between As and F⁻ in groundwater. The Código Alimentario Argentino (CAA) suggested a limit of F⁻ in drinking water as low as 0.8 mg/L under tropical environmental conditions; however, in shallow (39%) and deep groundwater (32%), samples exceeded these values. Exposure to F⁻ was calculated and compared with the adequate intake of minimal safe level exposure dose of 0.05 mg/kg/d and it was noted that 42% of population may be at high risk of fluorosis. Chronic exposure to high As and F⁻ levels in this population represents a concern due to possible adverse health effects attributed to these elements.

Sustained systemic delivery of green tea polyphenols by polymeric implants significantly diminishes benzo[a]pyrene-induced DNA adducts.

The polyphenolics in green tea are believed to be the bioactive components. However, poor bioavailability following ingestion limits their efficacy in vivo. In this study, polyphenon E (poly E), a standardized green tea extract, was administered by sustained-release polycaprolactone implants (two, 2-cm implants; 20% drug load) grafted subcutaneously or via drinking water (0.8% w/v) to female S/D rats. Animals were treated with continuous low dose of benzo[a]pyrene (BP) via subcutaneous polymeric implants (2 cm; 10% load) and euthanized after 1 and 4 weeks. Analysis of lung DNA by (32)P-postlabeling resulted in a statistically significant reduction (50%; p = 0.023) of BP-induced DNA adducts in the implant group; however, only a modest (34%) but statistically insignificant reduction occurred in the drinking water group at 1 week. The implant delivery system also showed significant reduction (35%; p = 0.044) of the known BP diolepoxide-derived DNA adduct after 4 weeks. Notably, the total dose of poly E administered was >100-fold lower in the implant group than the drinking water group (15.7 versus 1,632 mg, respectively). Analysis of selected phase I, phase II, and nucleotide excision repair enzymes at both mRNA and protein levels showed no significant modulation by poly E, suggesting that the reduction in the BP-induced DNA adducts occurred presumably due to known scavenging of the antidiolepoxide of BP by the poly E catechins. In conclusion, our study demonstrated that sustained systemic delivery of poly E significantly reduced BP-induced DNA adducts in spite of its poor bioavailability following oral administration.

Benzothiazole toxicity assessment in support of synthetic turf field human health risk assessment.

Synthetic turf fields cushioned with crumb rubber may be a source of chemical exposure to those playing on the fields. Benzothiazole (BZT) may volatilize from crumb rubber and result in inhalation exposure. Benzothiazole has been the primary rubber-related chemical found in synthetic turf studies. However, risks associated with BZT have not been thoroughly assessed, primarily because of gaps in the database. This assessment provides toxicity information for a human health risk assessment involving BZT detected at five fields in Connecticut. BZT exerts acute toxicity and is a respiratory irritant and dermal sensitizer. In a genetic toxicity assay BZT was positive in Salmonella in the presence of metabolic activation. BZT metabolism involves ring-opening and formation of aromatic hydroxylamines, metabolites with mutagenic and carcinogenic potential. A structural analogue 2-mercaptobenzothiazole (2-MBZT) was more widely tested and so is used as a surrogate for some endpoints. 2-MBZT is a rodent carcinogen with rubber industry data supporting an association with human bladder cancer. The following BZT toxicity values were derived: (1) acute air target of 110 µg/m(3) based upon a BZT RD(50) study in mice relative to results for formaldehyde; (2) a chronic noncancer target of 18 µg/m(3) based upon the no-observed-adverse-effect level (NOAEL) in a subchronic dietary study in rats, dose route extrapolation, and uncertainty factors that combine to 1000; (3) a cancer unit risk of 1.8E-07/µg-m(3) based upon a published oral slope factor for 2-MBZT and dose-route extrapolation. While there are numerous uncertainties in the BZT toxicology database, this assessment enables BZT to be quantitatively assessed in risk assessments involving synthetic turf fields. However, this is only a screening-level assessment, and research that better defines BZT potency is needed.

Human health risk assessment of synthetic turf fields based upon investigation of five fields in Connecticut.

Questions have been raised regarding possible exposures when playing sports on synthetic turf fields cushioned with crumb rubber. Rubber is a complex mixture with some components possessing toxic and carcinogenic properties. Exposure is possible via inhalation, given that chemicals emitted from rubber might end up in the breathing zone of players and these players have high ventilation rates. Previous studies provide useful data but are limited with respect to the variety of fields and scenarios evaluated. The State of Connecticut investigated emissions associated with four outdoor and one indoor synthetic turf field under summer conditions. On-field and background locations were sampled using a variety of stationary and personal samplers. More than 20 chemicals of potential concern (COPC) were found to be above background and possibly field-related on both indoor and outdoor fields. These COPC were entered into separate risk assessments (1) for outdoor and indoor fields and (2) for children and adults. Exposure concentrations were prorated for time spent away from the fields and inhalation rates were adjusted for play activity and for children's greater ventilation than adults. Cancer and noncancer risk levels were at or below de minimis levels of concern. The scenario with the highest exposure was children playing on the indoor field. The acute hazard index (HI) for this scenario approached unity, suggesting a potential concern, although there was great uncertainty with this estimate. The main contributor was benzothiazole, a rubber-related semivolatile organic chemical (SVOC) that was 14-fold higher indoors than outdoors. Based upon these findings, outdoor and indoor synthetic turf fields are not associated with elevated adverse health risks. However, it would be prudent for building operators to provide adequate ventilation to prevent a buildup of rubber-related volatile organic chemicals (VOC) and SVOC at indoor fields. The current results are generally consistent with the findings from studies conducted by New York City, New York State, the U.S. Environmental Protection Agency (EPA), and Norway, which tested different kinds of fields and under a variety of weather conditions.

Synthetic Turf Fields, Crumb Rubber, and Alleged Cancer Risk.

Most synthetic turf fields have crumb rubber interspersed among the simulated grass fibers to reduce athletic injuries by allowing users to turn and slide more readily as they play sports or exercise on the fields. Recently, the crumbs have been implicated in causing cancer in adolescents and young adults who use the fields, particularly lymphoma and primarily in soccer goalkeepers. This concern has led to the initiation of large-scale studies by local and federal governments that are expected to take years to complete. Meanwhile, should the existing synthetic turf fields with crumb rubber be avoided? What should parents, players, coaches, school administrators, and playground developers do? What should sports medicine specialists and other health professionals recommend? Use grass fields when weather and field conditions permit? Exercise indoors? Three basic premises regarding the nature of the reported cancers, the latency of exposure to environmental causes of cancer to the development of clinically detectable cancer, and the rarity of environmental causation of cancer in children, adolescents, and young adults suggest otherwise.

Assessment of the mutagenic potential of Cr(VI) in the oral mucosa of Big Blue® transgenic F344 rats.

Exposure to high concentrations of hexavalent chromium [Cr(VI)] in drinking water was associated with an increased incidence of oral tumors in F344 rats in a 2-year cancer bioassay conducted by the National Toxicology Program. These tumors primarily occurred at 180 ppm Cr(VI) and appeared to originate from the gingival mucosa surrounding the upper molar teeth. To investigate whether these tumors could have resulted from a mutagenic mode of action (MOA), a transgenic mutation assay based on OECD Test Guideline 488 was conducted in Big Blue(®) TgF344 rats. The mutagenic oral carcinogen 4-nitroquinoline-1-oxide (4-NQO) served as a positive control. Mutant frequency was measured in the inner gingiva with adjacent palate, and outer gingiva with adjacent buccal tissue. Exposure to 10 ppm 4-NQO in drinking water for 28 days increased mutant frequency in the cII transgene significantly, from 39.1 ± 7.5 × 10(-6) to 688 ± 250 × 10(-6) in the gingival/buccal region, and from 49.8 ± 17.8 × 10(-6) to 1818 ± 362 × 10(-6) in the gingival/palate region. Exposure to 180 ppm Cr(VI) in drinking water for 28 days did not significantly increase the mutant frequency in the gingival/buccal (44.4 ± 25.4 × 10(-6)) or the gingival/palate (57.8 ± 9.1 × 10(-6)) regions relative to controls. These data indicate that high (∼180,000 times expected human exposure), tumorigenic concentrations of Cr(VI) did not significantly increase mutations in the gingival epithelium, and suggest that Cr(VI) does not act by a mutagenic MOA in the rat oral cavity.

Mechanisms, proof, and unmet needs: the perspective of a cancer activist.

Cancer activists who participate with cancer researchers in shaping public health policy provide a different perspective on the question of breast cancer etiology. We place a higher priority on reducing women's exposure to suspected breast carcinogens than in debating the specific biochemical mechanisms by which these agents may operate. As the fruits of AIDS activism and antismoking campaigns illustrate, answers to mechanistic questions have not been and should not be the driving force behind public health policy. As such, cancer activists embrace a form of conservatism that advocates prudence in the face of exposure to estrogenic and other endocrine-disrupting chemicals. This perspective stands in contrast to scientific conservatism, which directs its caution toward the issue of proof. Unmet needs for cancer activists refer not so much to data gaps as to the failure to eliminate ongoing cancer hazards. For this author and activist, unmet needs include ending women's continued exposure to such common estrogenic compounds as detergents, triazine herbicides, plastics, and polychlorinated biphenyls.

Biological monitoring of occupational exposure to electrophilic compound during rubber industry.

Electrophilic compounds are widely used in industry. Rubber processing is the famous example of sites where workers are exposed to electrophilic compounds. Besides their immediate effect on different body systems, electrophilic compounds include most mutagenic and carcinogenic substances. The present study was carried out to elucidate the possibility of using non selective assays in the biological monitoring of occupational exposure to electrophilic compounds. The study included a total number of 40 workers exposed to chemicals during rubber industry (n=25 exposed) and comparison group (n=15). The biochemical tests carried out on each subject included: (1) Estimation of thioether levels in urine as a biological indices of electrophilic compounds. (2) Non selective assays as urinary RNase and alpha esterase, glutathione-S-transferase and aryl sulphatase. Their determination is recommended in the biological monitoring of workers exposed to such agents beside the medical surveillance of workers exposed to such chemicals. The study finding showed significant increase in the levels of thioether and all the non-selective assays among exposed workers rather than the comparison group.

High cortisol and cortisone levels are associated with breast milk dioxin concentrations in Vietnamese women.

OBJECTIVE: Dioxin (polychlorinated dibenzodioxins+polychlorinated dibenzofurans) is one of the most toxic chemical substances known. Although it is suspected to cause endocrine disruption, very few epidemiological studies have been carried out on its effects on human steroid hormones. The aim of this study was to elucidate the association of dioxin exposure with steroid hormone levels in the saliva and serum of Vietnamese women. STUDY DESIGN: Two areas, namely Phu Cat (hot spot) and Kim Bang (nonexposed area), were selected for the study. The study subjects consisted of 51 and 58 women respectively. Saliva, blood, and breast milk samples were collected from the subjects in both the areas. METHODS: Cortisol, cortisone, DHEA, androstenedione, estrone, and estradiol levels in serum and saliva were determined by liquid chromatography-tandem mass spectrometry; dioxin concentrations in breast milk were measured by gas chromatography-mass spectrometry. RESULTS: Dioxin concentrations in the breast milk of women from the dioxin hot spot were three to four times higher than those in the breast milk of women from the nonexposed area. Good correlations were found between the levels of six steroid hormones in saliva and those in serum respectively. Salivary and serum cortisol and cortisone levels in women from the dioxin hot spot were significantly higher than those in women from the nonexposed area (P<0.001) and those in all the subjects were positively associated with dioxin concentrations in Vietnamese women (P<0.01). CONCLUSION: These results suggest that dioxin influences steroidogenesis in humans. Saliva samples can be used for hormone analysis and are therefore excellent specimens in epidemiological studies.

Dephenylation of the rubber chemical N-phenyl-2-naphthylamine to carcinogenic 2-naphthylamine: a classical problem revisited.

N-phenyl-2-naphthylamine (PBNA) represents an example of a suspected carcinogen that is found negative in mutagenicity and clastogenicity testing as well as in long-term animal carcinogenicity bioassays in several species, but for which a carcinogenic risk cannot be excluded because of its metabolic conversion to the known human carcinogen 2-naphthylamine. Also, epidemiologic studies failed to indicate an elevated bladder cancer risk in humans occupationally exposed to PBNA. The amounts of 2-naphthylamine found in the urine of different species including humans after exposure to PBNA indicate unequivocally that PBNA is dephenylated to some extent. These are not explained by the 2-naphthylamine impurities in technical-grade PBNA. To explain the metabolic dephenylation process, it has been suggested that PBNA is metabolized by cytochrome P-450 (CYP) enzymes to the phenolic derivative 4'-hydroxy-N-phenyl-2-naphthylamine, followed by its further oxidation to the quinone imine, which subsequently hydrolyses to form the dephenylation product 2-naphthylamine. Phenolic metabolites from the initial CYP-mediated activation step are rapidly conjugated. Quantitatively, dephenylation of PBNA to 2-naphthylamine is a minor pathway. The dog represents an animal model that appears to approximate the human metabolism and biological activation of PBNA. Based on published data, a worst-case scenario indicates that about 1% of total PBNA taken up is transferred into 2-naphthylamine. However, in vitro as well as in vivo findings with PBNA may point to a significantly smaller conversion rate, as metabolites anticipated from the metabolism of 2-naphthylamine were not detected so far. The assumption, which may well be an overestimation, is compatible with findings in animal experiments, and explains the lack of direct evidence of carcinogenicity of PBNA in both experimental and epidemiological studies.

A review of world literature finds iron oxides noncarcinogenic.

Iron oxide appeared in the first list of 154 Threshold Limit Values adopted by the American Conference of Governmental Industrial Hygienists at its April 1949 annual meeting. It was set to control dust and fume at the recommended value of 15 mg/M3, at the time, the limit for an inert or "nuisance" dust, and was based on studies of welders made earlier by the U.S. Dept. of Labor and by Drinker and Nelson. By 1964, the TLV was tentatively reduced to 10 mg/M3 after a considerable body of literature had accumulated not only on the health experience of welders, but of other occupations involving iron oxides as well. As a group, these studies indicated that 15 mg/M3 permitted too great accumulations of iron pigmentation in the lung whose chronic retention effects were not known with certainty. Also, an occasional report of cancer of the lungs appeared particularly among British hematite miners, although these findings were immediately questioned on statistical grounds. In seeming confirmation of these early reports of cancer, an alarming number of reports of cancer of the lung and respiratory tract among welders and foundrymen began to appear by 1970, reaching a crescendo by the end of that decade. As past chairman of the TLV Committee, I decided to examine the bases of these findings. This review is the result of this examination.