Arsenic exposure, urinary arsenic speciation, and peripheral vascular disease in blackfoot disease-hyperendemic villages in Taiwan

Long-term exposure to ingested inorganic arsenic is associated with peripheral vascular disease (PVD) in the blackfoot disease (BFD)-hyperendemic area in Taiwan. This study further examined the interaction between arsenic exposure and urinary arsenic speciation on the risk of PVD. A total of 479 (220 men and 259 women) adults residing in the BFD-hyperendemic area were studied. Doppler ultrasound was used to diagnose PVD. Arsenic exposure was estimated by an index of cumulative arsenic exposure (CAE). Urinary levels of total arsenic, inorganic arsenite (As(III)) and arsenate (As(V)), monomethylarsonic acid (MMA(V)), and dimethylarsinic acid (DMA(V)) were determined. Primary methylation index [PMI = MMA(V)/(As(III) + As(V))] and secondary methylation index (SMI = DMA(V)/MMA(V)) were calculated. The association between PVD and urinary arsenic parameters was evaluated with consideration of the interaction with CAE and the confounding effects of age, sex, body mass index, total cholesterol, triglycerides, cigarette smoking, and alcohol consumption. Results showed that aging was associated with a diminishing capacity to methylate inorganic arsenic and women possessed a more efficient arsenic methylation capacity than men did. PVD risk increased with a higher CAE and a lower capacity to methylate arsenic to DMA(V). The multivariate-adjusted odds ratios for CAE of 0, 0.1-15.4, and >15.4 mg/L x year were 1.00, 3.41 (0.74-15.78), and 4.62 (0.96-22.21), respectively (P < 0.05, trend test); and for PMI < or = 1.77 and SMI > 6.93, PMI > 1.77 and SMI > 6.93, PMI > 1.77 and SMI < or = 6.93, and PMI < or = 1.77 and SMI < or = 6.93 were 1.00, 2.93 (0.90-9.52), 2.85 (1.05-7.73), and 3.60 (1.12-11.56), respectively (P < 0.05, trend test). It was concluded that individuals with a higher arsenic exposure and a lower capacity to methylate inorganic arsenic to DMA(V) have a higher risk of developing PVD in the BFD-hyperendemic area in Taiwan.     

Arsenic exposure at low-to-moderate levels and skin lesions, arsenic metabolism, neurological functions, and biomarkers for respiratory and cardiovascular diseases: Review of recent findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh

The contamination of groundwater by arsenic in Bangladesh is a major public health concern affecting 35-75 million people. Although it is evident that high levels (> 300 μg/L) of arsenic exposure from drinking water are related to adverse health outcomes, health effects of arsenic exposure at low-to-moderate levels (10-300 μg/L) are not well understood. We established the Health Effects of Arsenic Longitudinal Study (HEALS) with more than 20,000 men and women in Araihazar, Bangladesh, to prospectively investigate the health effects of arsenic predominately at low-to-moderate levels (0.1 to 864 μg/L, mean 99 μg/L) of arsenic exposure. Findings to date suggest adverse effects of low-to-moderate levels of arsenic exposure on the risk of pre-malignant skin lesions, high blood pressure, neurological dysfunctions, and all-cause and chronic disease mortality. In addition, the data also indicate that the risk of skin lesion due to arsenic exposure is modifiable by nutritional factors, such as folate and selenium status, lifestyle factors, including cigarette smoking and body mass index, and genetic polymorphisms in genes related to arsenic metabolism. The analyses of biomarkers for respiratory and cardiovascular functions support that there may be adverse effects of arsenic on these outcomes and call for confirmation in large studies. A unique strength of the HEALS is the availability of outcome data collected prospectively and data on detailed individual-level arsenic exposure estimated using water, blood and repeated urine samples. Future prospective analyses of clinical endpoints and related host susceptibility will enhance our knowledge on the health effects of low-to-moderate levels of arsenic exposure, elucidate disease mechanisms, and give directions for prevention.     

Polybrominated diphenyl ethers in food and human dietary exposure: a review of the recent scientific literature

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants (BFRs) used to protect people from fires by reducing the flammability of combustible materials. In recent years, PBDEs have become widespread environmental pollutants, while body burden in the general population has been increasing. A number of studies have shown that, as for other persistent organic pollutants, dietary intake is one of the main routes of human exposure to PBDEs. The most recent scientific literature concerning the levels of PBDEs in foodstuffs and the human dietary exposure to these BFRs are here reviewed. It has been noted that the available information on human total daily intake through food consumption is basically limited to a number of European countries, USA, China, and Japan. In spite of the considerable methodological differences among studies, the results show notable coincidences such as the important contribution to the sum of total PBDEs of some congeners such as BDEs 47, 49, 99 and 209, the comparatively high contribution of fish and seafood, and dairy products, and the probably limited human health risks derived from dietary exposure to PBDEs. Various issues directly related to human exposure to PBDEs through the diet still need investigation.     

Urinary acrylamide metabolites as biomarkers for short-term dietary exposure to acrylamide.

It has previously been reported that heat-treated carbohydrate rich foods may contain high levels of acrylamide resulting in consumers being inadvertently exposed to acrylamide. Acrylamide is mainly excreted in the urine as mercapturic acid derivatives of acrylamide and glycidamide. In a clinical study comprising of 53 subjects, the urinary excretion of these metabolites was determined using solid-phase extraction and liquid chromatography with positive electrospray MS/MS detection. The median (range) total excretion of acrylamide in urine during 24 h was 16 (7-47) microg acrylamide for non-smokers and 74 (38-106) microg acrylamide for smokers, respectively. It was found that the median intake estimate in the study based on 24 h dietary recall was 21 (13-178) and 26 (12-67) for non-smokers and smokers, respectively. The median dietary exposure to acrylamide was estimated to be 0.47 (range 0.17-1.16) microg/kg body weight per day. In a multiple linear regression analysis, the urinary excretion of acrylamide metabolites correlated statistically significant with intake of aspartic acid, protein, starch and coffee. Consumption of citrus fruits correlated negatively with excretion of acrylamide metabolites.     

Differential sensitivity of blood, peripheral, and central cholinesterases in beagle dogs following dietary exposure to chlorpyrifos

Two studies were performed to find out whether exposure limits that protect brain acetylcholinesterase (AChE) will protect peripheral tissue AChE after exposure to chlorpyrifos (CPF), an organophosphate insecticide. In a methods-development study, male dogs (3/dose) were exposed to 0.0, 0.3, 0.6, or 1.2mg/kg/day CPF in their diets for 4 weeks. Mixed cholinesterase (mChE), AChE, and butyrylcholinesterase (BuChE) activities were measured in plasma, RBC, brain, left atrium and ventricle, diaphragm, quadriceps, and nodose ganglia. Plasma, brain and peripheral tissue BuChE was inhibited at all dose levels. While RBC AChE was inhibited at all doses, brain and peripheral AChE activities were unaffected. In the main study, dogs (4/sex/dose) were exposed to 0.0, 0.5, 1.0, or 2.0mg/kg/day CPF in their diets for six weeks and RBC AChE was significantly inhibited at all doses in both sexes. Diaphragm, quadriceps, and nodose ganglia AChE was unaffected by treatment. Brain AChE was decreased by approximately 6% compared to controls in high-dose groups, and this was considered a threshold effect. Left atrium AChE in high-dose dogs was 25.5% less (males) and 32.1% greater (females) than controls; these differences were attributed to chance. While peripheral tissue and brain AChE were not affected following exposure to 1.0mg/kg/day, RBC AChE was inhibited at all doses. These results show that RBC AChE is more sensitive than brain or peripheral tissue AChE to inhibition by CPF, and that protection of brain AChE would protect peripheral tissue AChE.     

The use of chemical occurrence data at European vs. national level in dietary exposure assessments: A methodological study

A typical EFSA approach to assess dietary exposure is to combine data from national consumption surveys with chemical occurrence data that have been pooled across the EU Member States (pooled approach). This approach was compared to the case where occurrence data were stratified by country and used for food categories where national data were abundant (semi-pooled approach), using cadmium as a case study. Some differences in estimated dietary exposure were observed between the pooled and semi-pooled approach. They were explained by differences, between the national and the European occurrence data, with respect to (1) contamination values and (2) sample proportions of food items classified in the food categories the assessment was based on. The latter aspect highlighted the sensitivity of the approach of directly aggregating monitoring data into food categories. Both the pooled and semi-pooled approach tended to be conservative relative to approaches used at national level. This appears to be attributed to differences in the way the available occurrence data is aggregated. Refinement of the studied methodologies would include a better separation of the food items with high concentration from those with low concentration.     

Evolution of the dietary exposure to polycyclic aromatic hydrocarbons in Catalonia, Spain

The concentrations of 16 polycyclic aromatic hydrocarbons (PAHs) were determined in samples of foodstuffs widely consumed by the population of Catalonia, Spain. All samples were randomly acquired in 12 cities of Catalonia between March and June of 2006, and analyzed by gas chromatography-mass spectrometry. The dietary intake of total and carcinogenic PAHs was estimated for various age/gender groups of population. In order to determine the temporal trend on the dietary exposure to PAHs, the current results were compared with those of a previous survey (2000). The highest individual PAH levels corresponded to phenanthrene (29.66mug/kg), naphthalene (25.87mug/kg) and fluoroanthene (13.66mug/kg), while the lowest levels were benzo[a]pyrene (1.28mug/kg), benzo[k]fluoranthene (1.31mug/kg) and indeno[1,2,3-c,d]pyrene (1.44mug/kg). According to food groups, the highest levels of total PAHs were detected in meat and meat products (25.56mug/kg), oils and fats (23.48mug/kg), and cereals (20.44mug/kg). For an average male adult (70-kg body weight), the current dietary intake of the sum of PAHs was higher (12.0mug/day) than that found in our 2000 survey (8.4mug/day).     

Modelling framework for assessment of dietary exposure to added flavouring substances within the FACET (Flavours,Additives, and Food Contact Material Exposure Task) project

This paper provides a model to assess dietary exposure to flavouring substances intentionally added to food. The purpose is to describe the approaches currently available and their scientific basis. The proposed exposure model for flavouring substances envisages three different levels of refinement: basic, intermediate and refined. At the two first levels, the model may be applied to all 2543 substances actually in use in Europe, while the refined level has been applied to 41 target flavouring substances selected within the FACET project. The refined level entails the use of the probability of addition of the flavouring substance added to the food and of correction factors related to losses owing to the processing of a food.     

Human exposure to PBDEs through the diet in Catalonia, Spain: temporal trend. A review of recent literature on dietary PBDE intake

The mean concentrations of polybrominated diphenyl ethers (PBDEs) (sum tetra- to octaBDEs) were determined in samples of foodstuffs widely consumed by the population of Catalonia, Northeast Spain. The following six tetra-through heptabrominated congeners were also individually analyzed: PBDEs 47, 99, 100, 153, 154 and 183. Food samples were randomly acquired in 12 cities of Catalonia between March and June of 2006. The dietary intake of PBDEs was estimated for the population of this region. In order to determine the temporal trend on the exposure to PBDEs through the diet, the results were compared with those of a previous survey performed during 2000. The highest concentration of total PBDEs was found in fish and shellfish (563.9 ng/kg of wet weight), followed by oils and fats (359.3 ng/kg ww), and bakery products (98.8 ng/kg ww). Among six individually analyzed congeners, for most food groups BDE-47 and BDE-99 showed the highest levels. The dietary intake of PBDEs for a standard male adult of 70 kg body weight was 75.4 ng/day (or 1.1 ng/kg body weight/day, assuming ND = LOD/2). On a body weight basis, it means a decrease of 23% with respect to the daily intake of the 2000 survey (97.3 ng/day or 1.4 ng/kg/body weight/day). Finally, the current PBDE intake is compared with the results of recent studies on the dietary intake of PBDEs performed in various European, North American, and Asian countries.     

Can current dietary exposure models handle aggregated intake from different foods? A simulation study for the case of two foods

Current dietary exposure models provide estimates of long-term intake distributions using short-term food consumption survey data, by statistically modeling the aggregated intakes from different foods consumed on the same day for each participant of the survey. Food consumption behaviour in a population may, however, show all sorts of correlations which are not modelled in these exposure models. We developed a simulation model describing a hypothetical population of consumers, assuming various types of correlation between two foods. Using this simulation model we found that the impact of the correlations in many cases is limited, but in particular circumstances it can be substantial, depending on the properties of the marginal distributions. Further, we found that the usual approach of first aggregating the observed intakes over foods, and then applying the statistical exposure models to the total daily intakes may lead to deviating results, even when all correlations are assumed to be zero. The approach of analyzing the intakes from the separate foods, and then aggregating the results from the statistical model applied to each food performed much better. Our results illustrate that the simulation model can be used for validating dietary exposure models, and for indicating how exposure models may be improved.     

Occurrence and exposure assessment of aflatoxins in Zhejiang province,China

The purpose of this study was to assess the risk of aflatoxins due to multiple food consumption among the Zhejiang population. Ultra-high-performance liquid chromatography coupled with tandem mass spectrometry method was used to determine aflatoxins in 792 samples. Aflatoxins were detected in 27.1% of the samples at levels between 0.07 and 262.63 μg kg⁻¹, and aflatoxins B₁ was the most frequently detected among different types of samples. 0.8% of peanut oil, 3.39% of nut products as well as 1.1% of condiments contaminated with aflatoxins B₁ exceeded China national tolerance limits. Peanut oil had the highest incidence of aflatoxin, with a range from 0.17 to 22.50 μg kg⁻¹. Using bags conferred limited advantages in reducing aflatoxin contents. Moreover, peanut and rice were the main contributors to dietary exposure to aflatoxins among Zhejiang residents. Finally, the margin of exposure values obtained by rice consumption were far from the safe margin of 10,000, indicating a potential risk to public health. The results pointed out the need for further prioritization of aflatoxins B₁ risk-management actions in Zhejiang.     

Considerations when using longitudinal cohort studies to assess dietary exposure to inorganic arsenic and chronic health outcomes

Dietary arsenic exposure and chronic health outcomes are of interest, due in part to increased awareness and data available on inorganic arsenic levels in some foods. Recent concerns regarding levels of inorganic arsenic, the primary form of arsenic of human health concern, in foods are based on extrapolation from adverse health effects observed at high levels of inorganic arsenic exposure; the potential for the occurrence of these health effects from lower levels of dietary inorganic arsenic exposure has not been established. In this review, longitudinal cohort studies are evaluated for their utility in estimating dietary inorganic arsenic exposure and quantifying statistically reliable associations with health outcomes. The primary limiting factor in longitudinal studies is incomplete data on inorganic arsenic levels in foods combined with the aggregation of consumption of foods with varying arsenic levels into a single category, resulting in exposure misclassification. Longitudinal cohort studies could provide some evidence to evaluate associations of dietary patterns related to inorganic arsenic exposure with risk of arsenic-related diseases. However, currently available data from longitudinal cohort studies limit causal analyses regarding the association between inorganic arsenic exposure and health outcomes. Any conclusions should therefore be viewed with knowledge of the analytical and methodological limitations.     

Determination of arsenic levels in lake water,sediment, and foodstuff from selected area of Sindh,Pakistan: Estimation of daily dietary intake

The aim of present study was to develop a database of arsenic (As) in lake water, ground water, sediment, soil, vegetables, grain crops and fish to evaluate the potential human health risks posed by higher level of As, in south east part of Sindh, Pakistan during 2005–2007. The total concentration of As in various samples under study was determined by electrothermal atomic absorption spectrophotometry (ETAAS). The reliability and accuracy of technique was checked by different certified reference materials. The concentration of As in lake and ground water samples exceeded the WHO guideline values. The concentration of As in lake sediment and agricultural soil samples ranged between 11.3–55.8 and 8.7–46.2 mg/kg while acid soluble As (acetic acid 0.11 mol/L) was observed in the range of 1.48–3.54 and 0.34–3.78 mg/kg, respectively. It was observed that the leafy vegetables (spinach, coriander and peppermint) contain higher As levels (0.90–1.20 mg/kg) as compared to ground vegetables (0.048–0.25) and grain crops (0.248–0.367 mg/kg) on dried weight basis. The estimated daily intake of total As in the diet was 9.7–12.2 μg/kg body weight/day.     

Levels of ochratoxin A in blood from Norwegian and Swedish blood donors and their possible correlation with food consumption

Blood levels of ochratoxin A were determined in 406 Scandinavian blood donors (206 from Oslo, Norway, and 200 from Visby on the island of Gotland, Sweden), using an HPLC method. In connection with the blood collection, the subjects were asked to fill in a food questionnaire to obtain individual dietary information relevant to ochratoxin A exposure. The mean plasma level of ochratoxin A was 0.18 ng/ml in Oslo and slightly higher, 0.21 ng/ml (P=0.046) in Visby. There was no correlation between plasma levels of ochratoxin A and the estimated total dietary intake of ochratoxin A based on consumption data and levels in food (retrieved from the literature), neither was the plasma level of ochratoxin A correlated with the total amount of food consumed. However, consumption of several foods, including cereal products, wine, beer and pork, were to some minor degree related to high plasma levels of ochratoxin A. The strongest correlations (correlation coefficient r>0.4; P<0.001) were observed for women in relation to the consumption of beer or medium brown bread. Correlation analysis of combinations of two or more food categories did not result in any statistically significant correlation.     

Human dietary exposure to polycyclic aromatic hydrocarbons: A review of the scientific literature

Polycyclic aromatic hydrocarbons (PAHs) are a group of over 200 different organic compounds that are mainly formed as the result of pyrolytic processes. For the general population, a number of studies have shown that, as for other environmental organic contaminants, the major route of exposure to PAHs is through food consumption. In this paper, the scientific literature concerning the concentrations of PAHs in food and the human dietary intake of these compounds, is reviewed. Unexpectedly, we have detected a considerable lack of scientific papers for countries such as Australia, Canada, Germany, or Japan, among many others, which seems rather unusual given the important scientific and social interest on the knowledge of the health risks of human exposure to environmental pollutants. The data from countries for which the human dietary intake of PAHs is available, show important differences among them, which would be explained by a number of factors, being probably the most important, the different methodologies used in the respective surveys. Regarding the influence of cooking on the levels of PAHs in foodstuffs, and the consequent intake, we conclude that it depends, not only on the particular cooking process, but even more on the specific characteristics of the respective food items.     

Integrating variability in half-lives and dietary intakes to predict mercury concentration in hair

Methylmercury (MeHg) is a bioaccumulative environmental toxin that exerts its effect on fetal and infant neurodevelopment. Mercury concentration in hair is a good biomarker of MeHg accumulation in the body, with seafood being the main source of MeHg in humans. Therefore, modeling the link between food intake and mercury concentration in hair is a key step in assessing the risk of MeHg exposure. Using repeated measurements of diet and mercury concentration in hair, we studied 125 French pregnant women who consumed seafood (e.g., fish, mollusks and crustaceans) and compared their individual estimated dietary MeHg intakes with their hair mercury concentrations. We used a one-compartment toxicokinetic model for these comparisons. We integrated and estimated the between-person variability in MeHg half-life into the model. In a second model, we took into account an intra-individual MeHg intake variability to improve the performance of the toxicokinetic model.     

Lack of maternal dietary exposure effects of bisphenol A and nonylphenol during the critical period for brain sexual differentiation on the reproductive/endocrine systems in later life

Two potential endocrine-disrupting chemicals, bisphenol A (BPA) and nonylphenol (NP), were assessed for their long-lasting effects on endocrine/reproductive systems following transplacental and lactational exposure to rat offspring during a time-window that included the critical period for brain sexual differentiation. Each chemical was mixed with diet at concentrations of 60, 600 and 3000 ppm and was provided to maternal Sprague-Dawley rats from gestational day (GD) 15 to postnatal day (PND) 10. Ethinylestradiol (EE) at 0.5 ppm was used as an estrogenic reference drug. During pregnancy and lactation, including the exposure period, a soy-free rodent diet was provided to eliminate possible modification of the study results by plant-derived phytoestrogens. Effects on endocrine/reproductive systems were evaluated by examining the anogenital distance, organ weights before puberty, onset of puberty, estrous cyclicity, and organ weights and histopathology of adult endocrine organs (at 11 weeks of age), as well as the volume of the sexually dimorphic nucleus of preoptic area. Both NP and BPA, at high doses, caused decreases in maternal body weights and retardation of offspring growth, but neither affected any of the endocrine/reproductive endpoints of offspring, whereas EE induced irreversible changes in estrous cyclicity and histopathology of ovaries and uterus of adult females. The results indicated that maternal dietary exposure to NP or BPA at concentrations up to 3000 ppm from GD 15 through PND 10 do not exert any apparent adverse effects on the endocrine/reproductive systems of offspring.     

Significant decreasing trend in human dietary exposure to PCDD/PCDFs and PCBs in Catalonia, Spain

The concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDFs), and 18 polychlorinated biphenyls (PCBs) were determined in samples of foodstuffs widely consumed by the population of Catalonia, Spain. The dietary intake of PCDD/PCDFs and dioxin-like (DL)-PCBs was subsequently estimated for the population of this Spanish region. These results were compared with those of a previous survey performed during 2000. For PCDD/PCDFs, the highest WHO-TEQ values corresponded to oils and fats (0.223 ng/kg), followed by fish and seafood (0.131 ng/kg) and dairy products (0.057 ng/kg), while the lowest levels were found in fruits (0.003 ng/kg), as well as in vegetables and milk (0.009 ng/kg). For DL-PCBs the highest WHO-TEQ values corresponded to the groups of fish and seafood (0.761 ng/kg) followed by oils and fats (0.169 ng/kg), and dairy products (0.039 ng/kg), while the lowest values were observed in fruits (0.004 ng/kg), and vegetables (0.005 ng/kg) and tubers (0.006 ng/kg). The current dietary intakes of PCDD/PCDFs, DL-PCBs, and PCDD/PCDFs plus DL-PCBs were estimated to be 25.7, 52.4, and 78.1 pg WHO-TEQ/day vs. 95.4, 150.1, and 245.5 pg WHO-TEQ/day found in our previous survey. It means reductions of 73%, 65%, and 68%, for PCDD/PCDFs, DL-PCBs, and PCDD/PCDFs plus DL-PCBs, respectively. The current estimated intake for an adult male, 1.12 pg WHO-TEQ/kg body weight per day, is lower than most intakes recently reported in a number of countries over the world.     

The effect of various dietary fibres on tissue concentration and chemical form of mercury after methylmercury exposure in mice

The whole-body retention of mercury after exposure of BALB/c mice to methylmercury was measured in animals fed fibre-free, 5% pectin, 5% cellulose or 5, 15 or 30% wheat bran diets. The rate of elimination of mercury was dependent on the diet fed, with dietary bran increasing the rate of elimination. The incorporation of 15 or 30% bran in the diet of the mice decreased the total mercury concentration in the brain, blood and small intestine, although the effects were significant only in those animals on 30% bran diet. The fibres had little effect on mercury levels in other tissues. The proportion of mercury found in the mercuric form was significantly greater in liver, kidneys and gut of mice fed bran. The results suggest that dietary bran may reduce the levels of mercury in the brain after methylmercury exposure and may therefore reduce the neurotoxic effects of the organomercurial. We suggest that wheat bran exerts its effects on mercury retention and brain level via a modification of the metabolic activity of the gut microflora.     

Arsenic induced apoptosis in rat liver following repeated 60 days exposure

BACKGROUND: Accumulation of the wide spread environmental toxin arsenic in liver results in hepatotoxcity. Exposure to arsenite and other arsenicals has been previously shown to induce apoptosis in certain tumor cell lines at low (1-3 microM) concentration. AIM: The present study was focused to elucidate the role of free radicals in arsenic toxicity and to investigate the nature of in vivo sodium arsenite induced cell death in liver. METHODS: Male wistar rats were exposed to arsenite at three different doses of 0.05, 2.5 and 5mg/l for 60 days. Oxidative stress in liver was measured by estimating pro-oxidant and antioxidant activity in liver. Histopathological examination of liver was carried out by light and transmission electron microscopy. Analysis of DNA fragmentation by gel electrophoresis was used to identify apoptosis after the exposure. Terminal deoxy-nucleotidyl transferase mediated dUTP Nick end-labeling (TUNEL) assay was used to qualify and quantify apoptosis. RESULTS: A significant increase in cytochrome-P450 and lipid peroxidation accompanied with a significant alteration in the activity of many of the antioxidants was observed, all suggestive of arsenic induced oxidative stress. Histopathological examination under light and transmission electron microscope suggested a combination of ongoing necrosis and apoptosis. DNA-TUNEL showed an increase in apoptotic cells in liver. Agarose gel electrophoresis of DNA of hepatocytes resulted in a characteristic ladder pattern. CONCLUSION: Chronic arsenic administration induces a specific pattern of apoptosis called post-mitotic apoptosis.