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Growth impairment is a major public health issue for children in Tanzania. The question remains as to whether dietary mycotoxins play a role in compromising children's growth. We examined children's exposures to dietary aflatoxin and fumonisin and potential impacts on growth in 114 children under 36 months of age in Haydom, Tanzania. Plasma samples collected from the children at 24 months of age (N = 60) were analyzed for aflatoxin B1-lysine (AFB1-lys) adducts, and urine samples collected between 24 and 36 months of age (N = 94) were analyzed for urinary fumonisin B1 (UFB1). Anthropometric, socioeconomic, and nutritional parameters were measured and growth parameter z-scores were calculated for each child. Seventy-two percent of the children had detectable levels of AFB1-lys, with a mean level of 5.1 (95% CI: 3.5, 6.6) pg/mg albumin; and 80% had detectable levels of UFB1, with a mean of 1.3 (95% CI: 0.8, 1.8) ng/ml. This cohort had a 75% stunting rate [height-for-age z-scores (HAZ) < −2] for children at 36 months. No associations were found between aflatoxin exposures and growth impairment as measured by stunting, underweight [weight-for-age z-scores (WAZ) < −2], or wasting [weight-for-height z-scores (WHZ) < −2]. However, fumonisin exposure was negatively associated with underweight (with non-detectable samples included, p = 0.0285; non-detectable samples excluded, p = 0.005) in this cohort of children. Relatively low aflatoxin exposure at 24 months was not linked with growth impairment, while fumonisin exposure at 24–36 months based on the UFB1 biomarkers may contribute to the high growth impairment rate among children of Haydom, Tanzania; which may be associated with their breast feeding and weaning practices.

In Jutiapa, agroecological conditions favored FB production. UFB1 mirrored the estimated FB intake. UFB1 > 0.1 ng/mL resulted in a dose-dependent increase in the risk of exceeding FB intake of 2 μg/kg b.w./day compared to women with no detectable UFB1 . More than 50% exceeded 2 μg/kg b.w./day when UFB1 was >0.5 ng/mL. UFB2 and UFB3 were rarely detected confirming that FB1 is either absorbed better or preferentially excreted in urine.

Fumonisins (FB) are mycotoxins found in maize. The purpose of this study was to 1) determine the relationship between FB1, FB2 and FB3 intake and urinary excretion in humans, 2) validate a method to isolate urinary FB on C18-SPE cartridges for international shipment, and 3) test the method using samples from Guatemala. Volunteers (n=10) consumed 206 grams/day of tortillas and biscuits prepared from masa flour and a product containing maize flour. Volunteers estimated their daily urine output and samples were analyzed for FB1, FB2 and FB3 and hydrolyzed FB1. Only FB1 was detected in urine suggesting lower absorption of FB2 and FB3. Excretion was highly variable peaking soon after consumption began and decreasing rapidly after consumption stopped. Within five days after consumption ended FB1 was not detected in urine. In a study with eight volunteers, the average total urinary FB1 was 0.5% of the intake. FB1 was detected in 61% (107/177) of the samples collected in Guatemala. The results support the use of urinary FB1 to assess ongoing exposure in population based studies. However, relating the FB1 concentration in urine to dietary intake of FB by individual subjects will be complicated due to inter-individual variability and the rapidity of clearance.

Scope Fumonisin (FB) occurs in maize and is an inhibitor of ceramide synthase (CerS). We determined the urinary FB1 (UFB1) and sphingoid base 1-phosphate levels in blood from women consuming maize in high and low FB exposure communities in Guatemala. Methods and results FB1 intake was estimated using the UFB1. Sphinganine 1-phosphate (Sa 1-P), sphingosine 1-phosphate (So 1-P), and the Sa 1-P/So 1-P ratio were determined in blood spots collected on absorbent paper at the same time as urine collection. In the first study, blood spots and urine were collected every three months (March 2011 to February 2012) from women living in low (Chimaltenango and Escuintla) and high (Jutiapa) FB exposure communities (1240 total recruits). The UFB1, Sa 1-P/So 1-P ratio, and Sa 1-P/ml in blood spots were significantly higher in the high FB1 intake community compared to the low FB1 intake communities. The results were confirmed in a follow-up study (February 2013) involving 299 women living in low (Sacatepéquez) and high (Santa Rosa and Chiquimula) FB exposure communities. Conclusions High levels of FB1 intake are correlated with changes in Sa 1-P and the Sa 1-P/So 1-P ratio in human blood in a manner consistent with FB1 inhibition of CerS.

No abstract

Fumonisins (FB) are mycotoxins found in maize. They are hypothesised risk factors for neural tube defects (NTDs) in humans living where maize is a dietary staple. In LM/Bc mice, FB1-treatment of pregnant dams induces NTDs and results in increased levels of sphingoid base 1-phosphates in blood and tissues. The increased level of sphingoid base 1-phosphates in blood is a putative biomarker for FB1 inhibition of ceramide synthase in humans. Collection of blood spots on paper from finger sticks is a relatively non-invasive way to obtain blood for biomarker analysis. The objective of this study was to develop and validate in an animal model, and ultimately in humans, a method to estimate the volume of blood collected as blood spots on absorbent paper so as to allow quantification of the molar concentration of sphingoid base 1-phosphates in blood. To accomplish this objective, blood was collected from unexposed male LM/Bc and FB1-exposed pregnant LM/Bc mice and humans and applied to two types of absorbent paper. The sphingoid base 1-phosphates, absorbance at 270 nm (A270), and total protein content (Bradford) were determined in the acetonitrile:water 5% formic acid extracts from the dried blood spots. The results show that in both mouse and human the A270, total protein, and blood volume were closely correlated and the volume of blood spotted was accurately estimated using only the A270 of the extracts. In mouse blood spots, as in tissues and embryos, the FB1-induced changes in sphingolipids were correlated with urinary FB1. The half-life of FB1 in the urine was short (<24 h) and the elevation in sphingoid base 1-phosphates in blood was also short, although more persistent than the urinary FB1.

Co-occurrence of fumonisin B1 (FB1) and aflatoxin B1 (AFB1) in maize has been demonstrated in many surveys. Combined-exposure to FB1 and AFB1 was of concern to the Joint FAO/WHO Expert Committee on Food Additives because of the known genotoxicity of AFB1 and the ability of FB1 to induce regenerative proliferation in target tissues. Humans living where maize is a dietary staple are at high risk for exposure to both mycotoxins. Our work has focused on Guatemala, a country in Central America where maize is consumed in large amounts every day and where intake of FB1 has been shown to be potentially quite high using biomarker-based studies. In 2012 a survey was conducted which analysed maize samples for FB1 and AFB1 from all 22 departments of Guatemala. The results show that the levels of AFB1 exposure are also potentially quite high in Guatemala, and likely throughout Central America and Mexico. The implications of co-exposure for human health are numerous, but one area of particular concern is the potential of FB1 to modulate AFB1 hepatoxicity and/or hepatocarcinogenicity. Both the mechanism of action of FB1 and its ability to promote liver carcinogenicity in rats and rainbow trout is consistent with this concern. In farm and laboratory animals FB1 inhibits ceramide synthases, key enzymes in de novo ceramide biosynthesis. The inhibition of sphingolipid signalling pathways mediating programmed cell death and activation of pathways stimulating cell proliferation in livers of individuals exposed to AFB1 could contribute to the tumorigenicity of AFB1. Studies investigating the health effects of either toxin should consider the potential for co-exposure to both toxins. Also, in countries where maize-based food are prepared by alkaline treatment of the maize kernels, the effect of traditional processing on AFB1 levels and toxicity needs to be determined, especially for maize highly contaminated with AFB1.