José L. Domingo

Metal‐induced developmental toxicity in mammals: A review

It is well established that certain metals are toxic to embryonic and fetal tissues and can induce teratogenicity in mammals. The main objective of this paper has been to summarize the toxic effects that excesses of certain metals may cause on mammalian development. The reviewed elements have been divided into four groups: (a) metals of greatest toxicological significance (arsenic, cadmium, lead, mercury, and uranium) that are wide-spread in the human environment, (b) essential trace metals (chromium, cobalt, manganese, selenium, and zinc), (c) other metals with evident biological interest (nickel and vanadium), and (d) metals of pharmacological interest (aluminum, gallium, and lithium). A summary of the therapeutic use of chelating agents in the prevention of metal-induced developmental toxicity has also been included. meso-2,3-Dimercaptosuccinic acid (DMSA) and sodium 2,3-dimercaptopropane-1-sulfonate (DMPS) have been reported to be effective in alleviating arsenic- and mercury-induced teratogenesis, whereas sodium 4,5-dihydroxybenzene-1,3-disulfonate (Tiron) would protect against vanadium- and uranium-induced developmental toxicity.

Reproductive and developmental toxicity of natural and depleted uranium: a review

Although the biokinetics, metabolism, and chemical toxicity of uranium are well known, until recently little attention was paid to the potential toxic effects of uranium on reproduction and development in mammals. In recent years, it has been shown that uranium is a developmental toxicant when given orally or subcutaneously (SC) to mice. Decreased fertility, embryo/fetal toxicity including teratogenicity, and reduced growth of the offspring have been observed following uranium exposure at different gestation periods. The reproductive toxicity, maternal toxicity, embryo/fetal toxicity, and postnatal effects of uranium, as well as the prevention by chelating agents of uranium-induced maternal and developmental toxicity are reviewed here. Data on the toxic effects of depleted uranium on reproduction and development are also reviewed.

Human exposure to perfluorinated chemicals through the diet: intake of perfluorinated compounds in foods from the Catalan (Spain) market.

The aim of this study was to determine the dietary intake of perfluorinated chemicals (PFCs) by the population of Tarragona County (Catalonia, Spain). PFC levels were determined in 36 composite samples of foodstuffs randomly purchased in various locations. Exposure to PFCs through the diet was estimated for various age/gender groups. Perfluorooctane sulfonate (PFOS), perfluorocarboxylate perfluorooctanoate (PFOA), and perfluoroheptanoic acid (PFHpA) were the only detected PFCs in foodstuffs. On average, for a standard adult man (70 kg of body weight), the dietary intake of PFOS was estimated to be 62.5 or 74.2 ng/day (assuming ND=0 or ND=1/2 LOD, respectively). Fish, followed by dairy products and meats, were the main contributors to PFOS intake. For an adult man, the intake of PFOS (1.07 ng/kg/day) and those of PFOA and PFHpA were lower than that recently reported for Canada (4.0 ng/kg/day), and considerably lower than that previously found in the United Kingdom, the only two countries where, to date, results concerning this issue have been reported. A correlation between dietary intake and blood levels of PFOS is suggested. However, the current results do not justify dietary intake as the main route of exposure governing blood concentrations of other PFCs.

Polycyclic Aromatic Hydrocarbons in Foods: Human Exposure through the Diet in Catalonia, Spain

The dietary intake of 16 polycyclic aromatic hydrocarbons (PAHs) (naphthalene, acenaphthylene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenz[a,h]anthracene, benzo[g,h,i]perylene, and indeno[1,2,3-c,d]pyrene) by the general population of Catalonia, Spain, was calculated. Concentrations of PAHs in food samples randomly acquired in seven cities of Catalonia from June to August 2000 were measured. Eleven food groups were included in the study. High-performance liquid chromatography was used to analyze PAHs. The dietary intakes of total and carcinogenic PAHs was calculated for five population groups: children, adolescents, male adults, female adults, and seniors. Among the analyzed PAHs, there was a predominance of phenanthrene (16.7 microg/kg) and pyrene (10.7 microg/kg). By food group, the highest levels of total PAHs were detected in cereals (14.5 microg/kg) and in meat and meat products (13.4 microg/kg). The mean estimated dietary intake of the sum of the 16 PAHs was as follows: male adults, 8.4 microg/day; adolescents, 8.2 microg/day; children, 7.4 microg/day; seniors, 6.3 microg/day; female adults, 6.3 microg/day. The calculated daily intake of PAHs would be associated with a 5/106 increase in the risk for the development of cancer in a male adult with a body weight of 70 kg.

Vanadium and tungsten derivatives as antidiabetic agents

Tungstate is an oxyanion that has biological similarities to vanadate. In recent years, a number of studies have shown the antidiabetic effects of oral tungstate in animal models of diabetes. However, because of the tissue accumulation and potential toxicity derived from chronic administration of vanadium and tungsten compounds, the pharmacological use of vanadate or tungstate in the treatment of diabetes is not necessarily exempt from concern. In the context of a potential use in the treatment of human diabetes mellitus, the most relevant toxic effects of vanadium derivatives are reviewed and compared with those reported for tungsten. Hematological and biochemical alterations, loss of body weight, nephrotoxicity, immunotoxicity, reproductive and developmental toxicity, and behavioral toxicity have been reported to occur following exposure to vanadium compounds. Moreover, vanadium also has a mitogenic activity affecting the distribution of chromosomes during mitosis and inducing aneuploidyrelated end points. In contrast to vanadate, studies about the toxic effects of tungstate are very scant. Early investigations in cats, rabbits, dogs, mice, and rats showed that tungstate was less toxic than vanadate when given intravenously. Although in vitro investigations showed a direct effect of tungstate on the embryo and fetus of mice at concentrations similar to those causing effects in vivo, information on the potential cellular toxicity of tungstate is particularly scarce. Taking into account the recent interest of tungstate as a new potential oral antidiabetic agent, an exhaustive evaluation of its toxicity in mammals is clearly necessary.

Polycyclic aromatic hydrocarbons (PAH) in foods and estimated PAH intake by the population of Catalonia, Spain: Temporal trend

The concentrations of 16 polycyclic aromatic hydrocarbons (PAH) were determined in various foodstuffs randomly purchased in Catalonia (Spain) during November and December of 2008. Dietary intake of PAH was subsequently estimated according to age and sex for the general population of Catalonia. The current results were compared with those of previous studies performed in 2000 and 2006. The highest PAH levels corresponded to phenanthrene (18.18 microg/kg), naphthalene (13.31 microg/kg), and pyrene (8.46 microg/kg), whereas the lowest concentrations were those of dibenzo[a,h]anthracene (0.89 microg/kg), indeno[1,2,3-c,d]pyrene (0.94 microg/kg), and benzo[k]fluoranthene (1.00 microg/kg). With respect to the contribution of total carcinogenic PAH, benzo[a]pyrene contributed 47.77% or 48.22%, depending on the TEF value used. By food groups, the current highest levels of total PAH were detected in meat and meat products (38.99 microg/kg), followed by oils and fats (18.75 microg/kg), and dairy products (7.57 microg/kg). The highest contribution to PAH dietary intake corresponded to the group of meat and meat products (4.75 microg/day). The estimated mean dietary intake for a standard male adult (70-kg body weight) was 6.72 microg/day, a lower value than those found in our 2000 (8.42 microg/day), and 2006 surveys (12.04 microg/day). With regard to the results of other recent studies, the current PAH concentrations were comparatively lower.

Vanadium: A review of the reproductive and developmental toxicity

While the essentiality of vanadium for living organisms has yet to be established with certainty, vanadium has become an increasingly important environmental metal. Moreover, in recent years pharmacological interest in vanadium has also increased because of the hypothetical utilization of oral vanadium as an alternative therapy to parenteral insulin in diabetic patients. Adverse effects of vanadium depend on the circulating levels of this element. Among those effects, it is now well established that vanadate (V+5) and vanadyl (V+4) may be reproductive and developmental toxicants in mammals. Decreased fertility, embryolethality, fetotoxicity, and teratogenicity have been reported to occur in rats, mice, and hamsters following vanadium exposure. The reproductive vanadium toxicity, the maternal and embryo/fetal toxicity of this trace element, the perinatal and postnatal effects of vanadium, as well as the prevention by chelating agents of vanadium-induced developmental toxicity are reviewed here. The developmental effects of vanadium in pregnant diabetic rats are also summarized.

Health risks of dietary exposure to perfluorinated compounds

Perfluorinated compounds (PFCs) form a diverse group of chemicals with surface-active properties manufactured for over 50 years. In recent years, a number of studies have reported the ubiquitous distribution of PFCs in human tissues and wildlife. Although the relative importance of the routes of human exposure to these compounds is not well established yet, it has been suggested that food intake and packaging, water, house dust, and airborne are all potentially significant sources. However, dietary intake is probably the main route of exposure to these compounds, including perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), the most extensively investigated PFCs. This paper reviews the state of the science regarding the concentrations of PFCs in foodstuffs, human dietary exposure to these compounds and their health risks. The influence of processing, cooking and packaging on the PFCs levels in food is also discussed. Because of the rather limited information about human dietary exposure, studies to determine exposure to PFCs through the diet for the general population of a number of countries are clearly necessary. The correlation of PFCs body burdens and dietary intake of PFCs should be also established.

Concentrations of polybrominated diphenyl ethers, hexachlorobenzene and polycyclic aromatic hydrocarbons in various foodstuffs before and after cooking

The cooking-induced changes in the levels of polybrominated diphenyl ethers (PBDEs), hexachlorobenzene (HCB), and 16 polycyclic aromatic hydrocarbons (PAHs) in various foodstuffs were investigated. Foods included fish (sardine, hake and tuna), meat (veal steak, loin of pork, breast and thigh of chicken, and steak and rib of lamb), string bean, potato, rice, and olive oil. For each food item, raw and cooked (fried, grilled, roasted, boiled) samples were analyzed. There were some variations in the concentrations of PBDEs before and after cooking. However, they depended not only on the cooking process, but mainly on the specific food item. The highest HCB concentrations were found in sardine, being lower in cooked samples. All cooking processes enhanced HCB levels in hake, while very scarce differences could be noted in tuna (raw and cooked). In general terms, the highest PAH concentrations were found after frying by being the values especially notable in fish, excepting hake, where the highest total PAH levels corresponded to roasted samples. The results of this study show that, in general, cooking processes are only of a limited value as a means of reducing PBDE, HCB and PAH concentrations in food.

Human exposure to dioxins through the diet in Catalonia, Spain: carcinogenic and non-carcinogenic risk

The main objectives of this study were to estimate the dietary intake of dioxins by the population of Catalonia, Spain, to determine which food groups showed the greatest contribution to this intake, and to assess the health risks potentially associated with the dietary dioxin intake. From June to August 2000, food samples were randomly acquired in seven cities of Catalonia. Dioxin concentrations were determined in 108 samples belonging to the following groups: vegetables, fruits, pulses, cereals, fish and shellfish, meats and meat products, eggs, milk and dairy products, and oils and fats. Estimates of average daily food consumption were obtained from recent studies. Total dietary intake of dioxins for the general population of Catalonia was estimated to be 95.4 pg WHO-TEQ/day (78.4 pg I-TEQ/day), with fish and shellfish (31%), diary products (25%), cereals (14%) and meat (13%) showing the greatest percentages of contribution to dioxin intake. The contribution of all the rest of food groups to the total dietary intake was under 20%. The non-carcinogenic risk index of dioxin intake through the diet was in the range 0.34-1.36, while the carcinogenic risk level was 1,360 excess cancer over a lifetime of 70 years. Our results corroborate the decreasing tendency in dietary intake of dioxins found in recent studies (2000-2001) from various countries.