Abstract A novel, simple and sensitive high-performance liquid chromatography with fluorescence detection method was developed and validated for the characterization of the preclinical pharmacokinetics of melatonin under pregnant conditions. Plasma samples (25 µL) were treated with 30 µL of ethanol absolute (containing the internal standard, IS). After a centrifugation process, aliquots of supernant (5 µL) were injected into the chromatographic system. Compounds were eluted on a Xbridge C18 (150 mm x 4.6 mm i.d., 5 µm particle size) maintained at 30°C. The mobile phase consisted in a mixture of aqueous solution of 0.4% phosphoric acid and acetonitrile (70:30 v/v). The wavelengths were set at 305 nm (excitation) and 408 nm (emission) and the total analysis time was 8 min/sample. All validation tests were obtained with accuracy and precision, according to FDA guidelines, over the concentration range of 0.005-20 µg/mL. Pharmacokinetic study showed that melatonin systemic exposure increased from day 14, with a significant difference at 19 days of gestation compared to the control group. Our findings suggest a decreased metabolism of melatonin as result of temporary physiological changes that occur throughout pregnancy. However, other maternal physiological changes cannot be ruled out. novel highperformance high performance conditions 25 (2 3 containing standard IS. IS . IS) process ( system C C1 150 (15 46 4 6 4. id i d i.d. size 30C 30°C 04 0 0.4 7030 70 (70:3 v/v. vv v/v v v/v) excitation (excitation 40 emission (emission minsample min sample min/sample precision guidelines 0.00520 000520 0.005 20 005 0.005-2 µgmL µg mL µg/mL 14 1 group pregnancy However out 2 15 (1 i.d 0. 703 7 (70: 00520 0.0052 00052 0005 0.00 00 0.005- (70 0052 000 0.0 (7

Abstract: Objective: To estimate de magnitude of Pb poisoning (≥5μg/dL blood) in 1-4 year old children and to identify the contribution of lead-glazed ceramics use (LGC) as a source of exposure in the 32 Mexican states. Materials and methods: Using the results from a sample of capillary blood lead (BPb) we estimated the prevalence of Pb poisoning, it’s association with LGC and national distribution. Results: The national prevalence of Pb poisoning was 17.4% representing 1.4 million children. The prevalence was 30.7% among LGC users and 11.8% in non-users. In 17 states the prevalence of Pb poisoning was ≥10%, in 11 states between 5-10%, and in 4 states <5%. Conclusions: There is a geographic differential distribution of the problem; confirming the association with LGC and estimating the contribution of other Pb exposure sources. This information offers a guide to implement prevention and control actions in Mexico.

Resumen: Objetivo: Estimar la magnitud de intoxicación por plomo (Pb) (≥5μg/dL en sangre) en niños de 1 a 4 años e identificar la contribución del uso de loza de barro vidriado con Pb (LBVPb) como fuente de exposición en los 32 estados de México. Material y métodos: Muestra de Pb en sangre (PbS) capilar de niños participantes en la Encuesta Nacional de Salud y Nutrición 2018-2019. Se estimó la prevalencia de intoxicación, su asociación con LBVPb y distribución nacional. Resultados: La prevalencia nacional de intoxicación fue 17.4%, lo cual representa 1.4 millones de niños. Esta prevalencia fue 30.7% entre usuarios de LBVPb y 11.8% entre no usuarios. En 17 estados la prevalencia de intoxicación es ≥10%; en 11 es ≥5-10% y en 4 es <5%. Conclusiones: Existe una distribución diferencial geográfica del problema; se confirma la asociación con LBVPb y se estima la contribución de otras fuentes de exposición. Esta información ofrece una guía para implementar acciones de prevención y control en México.

Abstract: Objective: To estimate the prevalence of elevated (≥5.0μg / dL) blood lead levels (BLL) and its association with the use of lead glazed ceramics (LGC). Materials and methods: In 2018, we measured capillary BLL in a representative sample of children 1 to 4 years old residing in Mexican localities under 100 000 inhabitants (Ensanut 100k). We inquired about use of LGC for food preparation and consumption. To estimate its association with BLL, multinomial logit models stratified by region were generated. Results: The prevalence of elevated BLL levels was 21.8%. For the North, Central and South regions, the prevalence were 9.8, 20.7 and 25.8%, respectively. The association with use and frequency of LGC was highly significant and differential by region. Conclusions: Lead exposure remains a public health problem in Mexico, particularly in the Central and South regions, and is strongly associated with the use of LGC.

Resumen: Objetivo: Estimar la prevalencia de niveles elevados (≥5.0μg/dL) de plomo en sangre (PbS) y su asociación con el uso de loza de barro vidriado con plomo (LBVPb). Material y métodos: En 2018 se midió PbS capilar en una muestra representativa de niños de 1 a 4 años de edad residentes en localidades de México menores de 100 000 habitantes (Ensanut 100k). Se indagó sobre uso de LBVPb para consumo de alimentos. Para estimar su asociación con PbS, se generaron modelos logit multinomial estratificados por región. Resultados: La prevalencia de niveles elevados de PbS fue de 21.8%. En las regiones Norte, Centro y Sur las prevalencias fueron 9.8, 20.7 y 25.8%, respectivamente. La asociación con uso y frecuencia de LBVPb fue altamente significativa y diferencial por región. Conclusiones: La exposición a plomo permanece como un problema de salud pública en México, particularmente en el Centro y Sur, y está fuertemente asociada con el uso de LBVPb.

Abstract: Objective: To estimate the prevalence of elevated (≥5.0μg / dL) blood lead levels (BLL) and its association with the use of lead glazed ceramics (LGC). Materials and methods: In 2018, we measured capillary BLL in a representative sample of children 1 to 4 years old residing in Mexican localities under 100 000 inhabitants (Ensanut 100k). We inquired about use of LGC for food preparation and consumption. To estimate its association with BLL, multinomial logit models stratified by region were generated. Results: The prevalence of elevated BLL levels was 21.8%. For the North, Central and South regions, the prevalence were 9.8, 20.7 and 25.8%, respectively. The association with use and frequency of LGC was highly significant and differential by region. Conclusions: Lead exposure remains a public health problem in Mexico, particularly in the Central and South regions, and is strongly associated with the use of LGC.

Resumen: Objetivo: Estimar la prevalencia de niveles elevados (≥5.0μg/dL) de plomo en sangre (PbS) y su asociación con el uso de loza de barro vidriado con plomo (LBVPb). Material y métodos: En 2018 se midió PbS capilar en una muestra representativa de niños de 1 a 4 años de edad residentes en localidades de México menores de 100 000 habitantes (Ensanut 100k). Se indagó sobre uso de LBVPb para consumo de alimentos. Para estimar su asociación con PbS, se generaron modelos logit multinomial estratificados por región. Resultados: La prevalencia de niveles elevados de PbS fue de 21.8%. En las regiones Norte, Centro y Sur las prevalencias fueron 9.8, 20.7 y 25.8%, respectivamente. La asociación con uso y frecuencia de LBVPb fue altamente significativa y diferencial por región. Conclusiones: La exposición a plomo permanece como un problema de salud pública en México, particularmente en el Centro y Sur, y está fuertemente asociada con el uso de LBVPb.