Methyl methacrylate and respiratory sensitization: A Critical review

Methyl methacrylate (MMA) is a respiratory irritant and dermal sensitizer that has been associated with occupational asthma in a small number of case reports. Those reports have raised concern that it might be a respiratory sensitizer. To better understand that possibility, we reviewed the in silico, in chemico, in vitro, and in vivo toxicology literature, and also epidemiologic and occupational medicine reports related to the respiratory effects of MMA. Numerous in silico and in chemico studies indicate that MMA is unlikely to be a respiratory sensitizer. The few in vitro studies suggest that MMA has generally weak effects. In vivo studies have documented contact skin sensitization, nonspecific cytotoxicity, and weakly positive responses on local lymph node assay; guinea pig and mouse inhalation sensitization tests have not been performed. Cohort and cross-sectional worker studies reported irritation of eyes, nose, and upper respiratory tract associated with short-term peaks exposures, but little evidence for respiratory sensitization or asthma. Nineteen case reports described asthma, laryngitis, or hypersensitivity pneumonitis in MMA-exposed workers; however, exposures were either not well described or involved mixtures containing more reactive respiratory sensitizers and irritants.The weight of evidence, both experimental and observational, argues that MMA is not a respiratory sensitizer

Interaction between maternal and offspring diet to impair vascular function and oxidative balance in high fat fed male mice

Aims: to determine the impact of maternal and post-weaning consumption of a high fat diet on endothelium-dependent vasorelaxation and redox regulation in adult male mouse offspring.Methods: female C57BL6J mice were fed an obesogenic high fat diet (HF, 45% kcal fat) or standard chow (C, 21% kcal fat) pre-conception and throughout pregnancy and lactation. Post-weaning, male offspring were continued on the same diet as their mothers or placed on the alternative diet to give 4 dietary groups (C/C, HF/C, C/HF and HF/HF) which were studied at 15 or 30 weeks of age.Results: there were significant effects of maternal diet on offspring body weight (p<0.004), systolic blood pressure (p = 0.026) and endothelium-dependent relaxation to ACh (p = 0.004) and NO production (p = 0.005) measured in the femoral artery. With control for maternal diet there was also an effect of offspring post-weaning dietary fat to increase systolic blood pressure (p<0.0001) and reduce endothelium-dependent relaxation (p = 0.022) and ACh-mediated NO production (p = 0.007). There was also a significant impact of age (p<0.005). Redox balance was perturbed, with altered regulation of vascular enzymes involved in ROS/NO signalling.Conclusions: maternal consumption of a HF diet is associated with changes in vascular function and oxidative balance in the offspring of similar magnitude to those seen with consumption of a high fat diet post-weaning. Further, this disadvantageous vascular phenotype is exacerbated by age to influence the risk of developing obesity, raised blood pressure and endothelial dysfunction in adult lif