Estimating the risk of aflatoxin-induced liver cancer in Tanzania based on biomarker data.

Evidence about the magnitude of the aflatoxin menace can help policy makers appreciate the importance of the problem and strengthen policies to support aflatoxin mitigation measures. In this study, we estimated aflatoxin-induced liver cancer risk in 2016 for Tanzania and used the information to estimate the health burden due to the aflatoxin exposure in the country. The burden of aflatoxin-induced liver cancer was assessed based on available aflatoxin biomarker data from a previous epidemiology study, hepatitis B virus infection prevalence and population size of Tanzania in 2016. The health burden due to aflatoxin-induced liver cancer was estimated using disability adjusted life years (DALYs). The aflatoxin exposures ranged from 15.0-10,926.0 ng/kg bw/day (median, 105.5 ng/kg bw/day). We estimated that in 2016 there were about 1,480 (2.95 per 100,000 persons) new cases of aflatoxin-induced liver cancer in Tanzania and assumed all of them would die within a year. These morbidity and mortality rates led to a total loss of about 56,247.63 DALYs. These results show, quantitatively, the cases of liver cancer and related deaths that could be avoided, and the healthy life years that could be saved, annually, by strengthening measures to control aflatoxin contamination in Tanzania.

Estimating the health burden of aflatoxin attributable stunting among children in low income countries of Africa.

Numerous population-based studies have documented high prevalence of aflatoxin associated childhood stunting in low income countries. We provide an estimate of the disease burden of aflatoxin related stunting using data from the four African countries. For this empirical analysis, we obtained blood aflatoxin albumin adduct biomarker based exposure data as measured using ELISA technique and anthropometric measurement data from surveys done over a 12-year period from 2001 to 2012 in four low income countries in Africa. We used these data to calculate population attributable risk (PAR), life time disease burden for children under five by comparing two groups of stunted children using both prevalence and incidence-based approaches. We combined prevalence estimates with a disability weight, measuring childhood stunting and co-occurrence of stunting-underweight to produce years lived with disability. Using a previously reported mortality, years of life lost were estimated. We used probabilistic analysis to model these associations to estimate the disability-adjusted life-years (DALYs), and compared these with those given by the Institute for Health Metrics and Evaluation's Global Burden of Disease (GBD) 2016 study. The PAR increased from 3 to 36% for aflatoxin-related stunting and 14-50% for co-occurrence of stunting and underweight. Using prevalence-based approach, children with aflatoxin related stunting resulted in 48,965.20 (95% uncertainty interval (UI): 45,868.75-52,207.53) DALYs per 100,000 individuals. Children with co-occurrence of stunting and underweight due to exposure to aflatoxin resulted in 40,703.41 (95% UI: 38,041.57-43,517.89) DALYs per 100,000 individuals. Uncertainty analysis revealed that reducing aflatoxin exposure in high exposure areas upto non-detectable levels could save the stunting DALYs up to 50%. The burden of childhood all causes stunting is greater in countries with higher aflatoxin exposure such as Benin. In high exposure areas, these results might help guide research protocols and prioritisation efforts and focus aflatoxin exposure reduction. HEFCE Global Challenge Research Fund Aflatoxin project.

Prevalence and Exposure Assessment of Aflatoxins Through Black Tea Consumption in the Multan City of Pakistan and the Impact of Tea Making Process on Aflatoxins.

Aflatoxins are the highly toxic secondary metabolites of certain fungi, being mainly produced by Aspergillus flavus and Aspergillus parasiticus. Aflatoxins are classified as group 1 category carcinogens by the International Agency for Research on Cancer (IARC). A large number of food commodities are reported to be contaminated with aflatoxins. Tea is the world's second most consumed beverage and the consumption of tea is increasing day by day. Besides being a source of several health promoting substances, tea leaves are also reported to be contaminated with aflatoxins. However, not a single study is reported from Pakistan regarding the level of aflatoxins in commercially available black tea samples. The current study aimed to quantify the level of aflatoxins in commercially available branded and non-branded black tea samples. The estimated daily intake (EDI) of aflatoxins through branded and non-branded black tea consumption and the health risk assessment based on margin of exposure (MOE) approach was assessed. Furthermore, the impact of local tea making processes on the concentration of aflatoxins in tea beverage (filtrate) was also investigated.

Assessment of arsenic species in human hair, toenail and urine and their association with water and staple food.

Arsenic intake from household drinking/cooking water and food may represent a significant exposure pathway to induce cancer and non-cancer health effects. This study is based on the human biomonitoring of 395 volunteers from 223 households with private water sources located in rural Punjab, Pakistan. This work has shown the relative contribution of water and staple food to arsenic intake and accumulation by multiple biological matrix measurements of inorganic and organic arsenic species, while accounting for potential confounders such as age, gender, occupation, and exposure duration of the study population. Multi-variable linear regression showed a strong significant relationship between total arsenic (tAs) intake from water and concentrations of tAs, inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) in urine and toenail samples. tAs intake from staple food (rice and wheat) also showed a strong significant relationship with hair tAs and iAs. The sole impact of staple food intake on biomarkers was assessed and a significant correlation was found with all of the urinary arsenic metabolites. Toenail was found to be the most valuable biomarker of past exposure to inorganic and organic arsenic species of dietary and metabolic origin.

Risk assessment of deoxynivalenol in high-risk area of China by human biomonitoring using an improved high throughput UPLC-MS/MS method.

A risk assessment of deoxynivalenol (DON) was recently conducted for the residents in Henan province, China, where wheat as the staple food are highly consumed. A high-throughput sensitive UPLC-MS/MS method following 96-well µElution solid-phase extraction (SPE) were developed and validated for the determination of DON biomarkers in human urine. Isotope labelled internal standard, 13C-DON, was used for accurate quantification. Urinary samples collected from 151 healthy Chinese aged 2-78 years were processed with and without enzyme hydrolysis to determine total and free biomarkers, respectively. DON, and de-epoxy-deoxynivalenol (DOM-1) to a lesser extent, can be frequently detected in these samples both with and without enzyme hydrolysis. Free DOM-1 was detected at low level in human urine for the first time. Total DON was detected in all samples with a mean concentration at 47.6 ng mL-1. The mean and median probable daily intakes (PDI) for the whole participants, estimated to be 1.61 µg/kg bw and 1.10 µg/kg bw, both exceeded the PMTDI (1 µg/kg bw/day), indicating a potential risk for the residents in this area, especially for children and adolescents.

Toxicological effects of regulated mycotoxins and persistent organochloride pesticides: In vitro cytotoxic assessment of single and defined mixtures on MA-10 murine Leydig cell line.

Epidemiological studies show that there is global decline in male fertility primarily as a result of poor sperm quality and this is attributed to exposure to endocrine disrupting chemicals (EDCs) in the environment, food and pharmaceutical products, including mycotoxins and pesticides. The Leydig cells in the male testes are responsible for producing androgens, hormones that play major roles in male development and reproductive function. Therefore, any toxin that affects the function and morphology of the Leydig cells may result in sub-fertility or infertility. The cytotoxic effects of single and binary mixtures of aflatoxin B1 (AFB1), ochratoxin A (OTA), deoxynivalenol (DON), zearalenone (ZEN), alpha-zearalenol (α-ZOL), beta-zearalenol (ß-ZOL), 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane (p,p'-DDT) and 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE) on a model cell line, the MA-10 Leydig cells, were evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5-dipenyltetrazolium bromide (MTT) assay after 48h of exposure. With single toxin treatment at doses between 0.1µM and 64µM for 48h, DON was the most cytotoxic to MA-10 cells with a half maximal inhibitory concentration (IC50) value of 12.3µM followed by α-ZOL (IC50: 28µM) and OTA (IC50: 30µM) while the IC50 of AFB1, p,p'-DDT and p,p'-DDE were above the highest concentration tested (64µM). Co-exposure with p,p'-DDT or p,p'-DDE enhanced the toxicity of DON, OTA and ZEN to MA-10 Leydig cells, particularly at higher concentrations. This highlights the possible adverse effects on male reproductive health following co-exposure to these toxins.

Human exposure assessment of different arsenic species in household water sources in a high risk arsenic area.

Understanding arsenic speciation in water is important for managing the potential health risks associated with chronic arsenic exposure. Most arsenic monitoring studies to date have only measured total arsenic, with few looking at arsenic species. This study assessed 228 ground water sources in six unstudied villages in Pakistan for total, inorganic and organic arsenic species using ion chromatography inductively coupled plasma collision reaction cell mass spectrometry. The concentration levels approached 3090µgL-1 (95% CI, 130.31, 253.06) for total arsenic with a median of 57.55µgL-1, 3430µgL-1 (median=52) for arsenate (As+5) and 100µgL-1 (median=0.37) for arsenite (As+3). Exceedance of the WHO provisional guideline value for arsenic in drinking water (10µgL-1) occurred in 89% of water sources. Arsenic was present mainly as arsenate (As+5). Average daily intake of total arsenic for 398 residents living in the sampled houses was found up to 236.51µgkg-1day-1. This exposure estimate has indicated that 63% of rural residents exceeded the World Health Organization's provisional tolerable daily intake (PTDI) of 2.1µgkg-1day-1 body weight. Average daily intake of As+5 was found to be 15.63µgkg-1day-1 (95% CI, 5.53, 25.73) for children ≤16 and 15.07µgkg-1day-1 (95% CI, 10.33, 18.02) for adults. A mean daily intake of 0.09µgkg-1day-1 was determined for As+3 for children and 0.26µgkg-1day-1 for adults. Organic arsenic species such as monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and Arsenobetaine (AsB) were found to be below their method detection limits (MDLs).

Deoxynivalenol exposure assessment in young children in Tanzania.

SCOPE: This study assessed deoxynivalenol (DON) exposure in children from three geographic locations within Tanzania, over three time points in 1 year, using a urinary biomarker of exposure. METHODS AND RESULTS: A total of 166 children aged 6-14 months were studied at a maize harvest and followed up twice at 6-month intervals. On two consecutive days, morning urine was collected from each child and urinary DON was measured using an LC-MS method, with and without ß-glucuronidase hydrolysis in order to assess free DON (fDON) and glucuronide DON. Overall, urinary DON increased significantly along with the three visits (geometric mean 1.1, 2.3, and 5.7 ng/mL, at visits 1, 2, and 3, respectively, p < 0.01). fDON was 22% of urinary total DON. Urinary DON excretion rate was 74% in village Kikelelwa based on food DON level and food consumption. Assuming 360 mL of urine excreted per day, 10, 19, and 29% of children at visits 1, 2, and 3, respectively, exceeded the provisional maximum tolerable daily intake of 1000 ng/kg b.w./day. CONCLUSION: Young children in Tanzania are chronically exposed to DON due to eating contaminated maize, although exposure levels varied markedly by region and season.