A Global Assessment of Gold, Titanium, Strontium and Barium Pollution Using Sperm Whales (Physeter Macrocephalus) As an Indicator Species

This study provides a global baseline for barium, gold, titanium and strontium as marine pollutants using the sperm whale (Physeter macrocephalus) as an indicator species. Barium, gold, titanium and strontium are metals that are little studied in marine environments. However, their recent emergence as nanomaterials will likely increase their presence in the marine environment. Moreover, nanosized particles are likely to exhibit toxic outcomes not seen in macrosized particles. Biopsies from free ranging sperm whales were collected from around the globe. Total barium levels were measured in 275 of 298 sperm whales tested for barium and collected from 16 regions around the globe. The global mean for barium was 0.93 +/- 0.2ug/g with a detectable range from 0.1 to 27.9ug. Total strontium levels were measurable in all 298 sperm whales producing a global mean level of 2.2 +/- 0.1ug/g and a range from 0.2 to 11.5ug/g. Total titanium levels were also measured in all 298 sperm whales producing a global mean level of 4.5 +/- 0.25ug/g with a range from 0.1 to 29.8ug/g. Total gold levels were detected in 50 of the 194 sperm whales collected from 16 regions around the globe. Detectable levels ranged from 0.1 to 2.3ug/g tissue with a global mean level equal to 0.2 +/- 0.02ug/g. Previous reports of these metals were much lower than the mean levels reported here. The likely explanation is location differences and consistent with this explanation, we found statistically significant variation among regions. These data provide an important global baseline for barium, gold, titanium and strontium pollution and will allow for important comparisons to be made over time to assess the impact of nanomaterials on whales and the marine environment

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

One Environmental Health: an emerging perspective in toxicology [version 1; referees: 2 approved]

The One Environmental Health research approach, a subspecialty of the One Health initiative, focuses on toxic chemicals. Distinct disciplines work together to give a holistic perspective of a health concern through discrete disciplines, including, but not limited to, public health and the medical and veterinary sciences. In this article, we illustrate the concept of One Environmental Health with two case studies. One case study focuses on alligators and contributions to the field of endocrine disruption. The other case study focuses on whales and contributions to understanding carcinogenic metals. Both studies illustrate how the health of sentinel organisms has the potential to inform about the health of humans and the ecosystem

Polycyclic Aromatic Hydrocarbon-DNA Adducts in Gulf of Mexico Sperm Whale Skin Biopsies Collected in 2012

The northern Gulf of Mexico has a long history of polycyclic aromatic hydrocarbon (PAH) contamination from anthropogenic activities, natural oil seepages, and the 2010 Deepwater Horizon explosion and oil spill. The continental shelf of the same area is a known breeding ground for sperm whales (Physeter macrocephalus). To evaluate PAH-DNA damage, a biomarker for potential cancer risk, we compared skin biopsies collected from Gulf of Mexico sperm whales in 2012 with skin biopsies collected from sperm whales in areas of the Pacific Ocean in 1999-2001. All samples were obtained by cross-bow and comprised both epidermis and subcutaneous blubber. To evaluate exposure, 7 carcinogenic PAHs were analyzed in lipids extracted from Pacific Ocean sperm whale blubber, pooled by sex and location. To evaluate PAH-DNA damage, portions of all tissue samples were formalin fixed, paraffin embedded, sectioned, and examined for PAH-DNA adducts by immunohistochemistry (IHC) using an antiserum elicited against benzo[a]pyrene-modified DNA, which cross-reacts with several high molecular weight (HMW) carcinogenic PAHs bound to DNA. The IHC showed widespread epidermal nuclear localization of PAH-DNA adducts in the Gulf of Mexico whales (n=15) but not in the Pacific Ocean whales (n=4). A standard semi-quantitative scoring system revealed significantly higher PAH-DNA adducts in the Gulf of Mexico whales compared to the whales from the Pacific Ocean study (p=0.0002)

Protein tyrosine phosphatase (PTP) inhibition enhances chromosomal stability after genotoxic stress: decreased chromosomal instability (CIN) at the expense of enhanced genomic instability (GIN)?

Inappropriate survival signaling after DNA damage may facilitate clonal expansion of genetically compromised cells, and it is known that protein tyrosine phosphatase (PTP) inhibitors activate key survival pathways. In this study we employed the genotoxicant, hexavalent chromium [Cr(VI)], which is a well-documented carcinogen of occupational and environmental concern. Cr(VI) induces a complex array of DNA damage, including DNA double strand breaks (DSBs). We recently reported that PTP inhibition bypassed cell cycle arrest and abrogated Cr(VI)-induced clonogenic lethality. Notably, PTP inhibition resulted in an increase in forward mutations at the HPRT locus, supporting the hypothesis that PTP inhibition in the presence of DNA damage may lead to genomic instability (GIN), via cell cycle checkpoint bypass. The aim of the present study was to determine the effect of PTP inhibition on DNA DSB formation and chromosomal integrity after Cr(VI) exposure. Diploid human lung fibroblasts were treated with Cr(VI) in the presence or absence of the PTP inhibitor, sodium orthovanadate, for up to 24. h, and cells were analyzed for DNA DSBs and chromosomal damage. Cr(VI) treatment induced a rapid increase in DNA DSBs, and a significant increase in total chromosomal damage (chromatid breaks and gaps) after 24. h. In sharp contrast, PTP inhibition abrogated both DNA DSBs and chromosomal damage after Cr(VI) treatment. In summary, PTP inhibition in the face of Cr(VI) genotoxic stress decreases chromosomal instability (CIN) but increases mutagenesis, which we postulate to be a result of error-prone DNA repair. © 2012 Elsevier B.V

A Global Assessment of Chromium Pollution Using Sperm Whales (Physeter macrocephalus) as an Indicator Species

Chromium (Cr) is a well-known human carcinogen and a potential reproductive toxicant, but its contribution to ocean pollution is poorly understood. The aim of this study was to provide a global baseline for Cr as a marine pollutant using the sperm whale (Physeter macrocephalus) as an indicator species. Biopsies were collected from free-ranging whales around the globe during the voyage of the research vessel The Odyssey. Total Cr levels were measured in 361 sperm whales collected from 16 regions around the globe detectable levels ranged from 0.9 to 122.6 μg Cr g tissue−1 with a global mean of 8.8 ± 0.9 μg g−1. Two whales had undetectable levels. The highest levels were found in sperm whales sampled in the waters near the Islands of Kiribati in the Pacific (mean = 44.3 ± 14.4) and the Seychelles in the Indian Ocean (mean = 19.5 ± 5.4 μg g−1). The lowest mean levels were found in whales near the Canary Islands (mean = 3.7 ± 0.8 μg g−1) and off of the coast of Sri Lanka (mean = 3.3 ± 0.4 μg g−1). The global mean Cr level in whale skin was 28-times higher than mean Cr skin levels in humans without occupational exposure. The whale levels were more similar to levels only observed previously in human lung tissue from workers who died of Cr-induced lung cancer. We conclude that Cr pollution in the marine environment is significant and that further study is urgently needed

Global Mercury and Selenium Concentrations in Skin From Free-Ranging Sperm Whales (Physeter Macrocephalus)

Pollution of the ocean by mercury (Hg) is a global concern. Hg persists, bioaccumulates and is toxic putting high trophic consumers at risk. The sperm whale (Physeter macrocephalus), is a sentinel of ocean health due to its wide distribution, longevity and high trophic level. Our aim was to survey Hg concentrations worldwide in the skin of free-ranging sperm whales considering region, gender and age. Samples were collected from 343 whales in 17 regions during the voyage of the research vessel, Odyssey, between 1999 and 2005. Skin was analyzed for total Hg and detected in all but three samples with a global mean of 2.5±0.1 μg g(-1) ranging from 0.1 to 16.0 μg g(-1). The Mediterranean Sea had the highest regional mean with 6.1 μg g(-1) followed by Australia with 3.5 μg g(-1). Considering gender, females and males did not have significantly different global Hg concentrations. The variation among regions for females was significantly different with highest levels in the Mediterranean and lowest in Sri Lanka; however, males were not significantly different among regions. Considering age in males, adults and subadults did not have significantly different Hg concentrations, and were not significantly different among regions. The toxic effects of these Hg concentrations are uncertain. Selenium (Se), an essential element, antagonizes Hg at equimolar amounts. We measured total Se concentrations and found detectable levels in all samples with a global mean of 33.1±1.1 μg g(-1) ranging from 2.5 to 179 μg g(-1). Se concentrations were found to be several fold higher than Hg concentrations with the average Se:Hg molar ratio being 59:1 and no correlation between the two elements. It is possible Hg is being detoxified in the skin by another mechanism. These data provide the first global analysis of Hg and Se concentrations in a free-ranging cetacean