Health risk assessment from exposure to particles during packing in working environments

Packing of raw materials in work environments is a known source of potential health impacts (respiratory, cardiovascular) due to exposure to airborne particles. This activity was selected to test different exposure and risk assessment tools, aiming to understand the effectiveness of source enclosure as a strategy to mitigate particle release. Worker exposure to particle mass and number concentrations was monitored during packing of 7 ceramic materials in 3 packing lines in different settings, with low (L), medium (M) and high (H) degrees of source enclosure. Results showed that packing lines L and M significantly increased exposure concentrations (119-609 μg m-3 respirable, 1150-4705 μg m-3 inhalable, 24755-51645 cm-3 particle number), while nonsignificant increases were detected in line H. These results evidence the effectiveness of source enclosure as a mitigation strategy, in the case of packing of ceramic materials. Total deposited particle surface area during packing ranged between 5.4-11.8x105 μm2 min-1, with particles depositing mainly in the alveoli (51-64%) followed by head airways (27-41%) and trachea bronchi (7-10%). The comparison between the results from different risk assessment tools (Stoffenmanager, ART, NanoSafer) and the actual measured exposure concentrations evidenced that all of the tools overestimated exposure concentrations, by factors of 1.5-8. Further research is necessary to bridge the current gap between measured and modelled health risk assessments

Characterization of a Novel Splicing Variant in Acylglycerol Kinase (AGK) Associated with Fatal Sengers Syndrome

Mitochondrial functional integrity depends on protein and lipid homeostasis in the mitochondrial membranes and disturbances in their accumulation can cause disease. AGK, a mitochondrial acylglycerol kinase, is not only involved in lipid signaling but is also a component of the TIM22 complex in the inner mitochondrial membrane, which mediates the import of a subset of membrane proteins. AGK mutations can alter both phospholipid metabolism and mitochondrial protein biogenesis, contributing to the pathogenesis of Sengers syndrome. We describe the case of an infant carrying a novel homozygous AGK variant, c.518+1G>A, who was born with congenital cataracts, pielic ectasia, critical congenital dilated myocardiopathy, and hyperlactacidemia and died 20 h after birth. Using the patient’s DNA, we performed targeted sequencing of 314 nuclear genes encoding respiratory chain complex subunits and proteins implicated in mitochondrial oxidative phosphorylation (OXPHOS). A decrease of 96-bp in the length of the AGK cDNA sequence was detected. Decreases in the oxygen consumption rate (OCR) and the OCR:ECAR (extracellular acidification rate) ratio in the patient’s fibroblasts indicated reduced electron flow through the respiratory chain, and spectrophotometry revealed decreased activity of OXPHOS complexes I and V. We demonstrate a clear defect in mitochondrial function in the patient’s fibroblasts and describe the possible molecular mechanism underlying the pathogenicity of this novel AGK variant. Experimental validation using in vitro analysis allowed an accurate characterization of the disease-causing variant