Chlorpyrifos (CPF) is an organophosphorus pesticide of concern because many in vivo animal studies have demonstrated developmental toxicity exerted by this substance; however, despite its widespread use, evidence from epidemiological studies is still limited. In this study, we have collected all the information generated in the twenty-first century on the developmental toxicity of CPF using new approach methodologies. We have critically evaluated and integrated information coming from 70 papers considering human, rodent, avian and fish models. The comparison of the collected evidence with available adverse outcome pathways allows us to conclude that adverse outcomes observed in animals, such as memory and learning impairments as well as reduction in cognitive function, could involve several mechanisms of action including inhibition of acetylcholinesterase, overactivation of glutamate receptors and activation of mitogen-activated protein kinase, extracellular signal-regulated kinase 1/2, followed by both disruption of neurotransmitter release and increase in oxidative stress and apoptosis.

Phosphorothionate insecticides such as parathion (O,O-diethyl O-p-nitrophenyl phosphorothioate) and chlorpyrifos (CPS; O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate; Dursban) are metabolically converted by oxidative desulfuration into paraoxon and chlorpyrifos-oxon (CPO). The insecticidal action of chlorpyrifos stems from inhibition of acetylcholinesterase (AChE) by CPO, resulting in severe cholinergic toxicity. Sensory peripheral neuropathy was observed in people exposed environmentally to chlorpyrifos sprayed in confined areas. We have examined the kinetics of inhibition of AChE and butyrylcholinesterase (BChE) by paraoxon and CPO. The bimolecular rate constants (ki) for inhibition by paraoxon of recombinant human (rH) AChE, recombinant mouse (rM) AChE, and fetal bovine serum (FBS) AChE were 7.0, 4.0, and 3.2 × 105 M−1 min−1. The ki values for the inhibition by CPO of rH AChE, fetal bovine serum AChE, human RBC AChE, Torpedo AChE, and recombinant mouse (rM) AChE were 9.3, 2.2, 3.8, 8.0, and 5.1 × 106 M−1 min−1, respectively. Inhibition of human serum BChE, rH BChE, and rM BChE by CPO yielded ki values of 1.65, 1.67, and 0.78 × 109 M−1 min−1, respectively. The ki values obtained for BChE from various species were 160- to 750-fold larger than those of AChE from parallel sources. Inhibition of the single-site mutant A328Y of rH BChE by CPO displayed a 21-fold lower rate than that of wild-type rH BChE (ki, 7.9 × 107 vs 1.67 × 109 M−1 min−1). The double mutant of acyl pocket residues of rH AChE, F295L/F297V, was inhibited by CPO with a 150-fold larger ki than wild type (1.5 × 109 vs 1.0 × 107 M−1 min−1). The increased rate obtained with the double mutant displaying characteristics of the BChE active center provides a rationale for higher efficacy of CPO scavenging by BChE, compared with AChE.

When assessing the air quality in textile and related industries, one of the most important issues to be considered is the exposure to chemicals substances, as it might represent a health concern in industry and is subject to different airborne chemical occupational limits. This chapter attempts to describe the factors which might have an impact in the air quality in textile and related industries, as well as including a characterisation of the exposure to substances and the analytical methodologies used for monitoring the exposure to chemicals in these occupational environments. The air quality at these types of industries is directly linked to the use, including in some cases manual application, of solvents containing different volatile organic compounds (VOCs). Several studies have observed in the last years a reformulation of the industrial solvents to reduce the exposure intensity to VOCs such as n -hexane in response to marketing criteria for less toxic products. Furthermore, the implementation of risk prevention techniques and other exposure control measures such as the use of local exhaust ventilation or other working practices has proven to be efficacious to improve the occupational safety in these industrial settings. Notwithstanding the aforementioned information, as an unsafe use of chemicals has been frequently monitored, further exposure reduction measures are required.

Ethyl acetate (CASRN: 141-78-6) is an organic solvent widely used for different applications in manufacturing, pharmaceutical, or food industry, mainly as a solvent for paints and lacquers. It has flammable properties. Population might be exposed to ethyl acetate mainly via inhalation route. It is an eye irritant and may cause dermatitis in medium-term and chronic exposures. There is no evidence that this substance is carcinogenic, mutagenic, or reprotoxic.

The present work aimed to assess the effects of two widespread metallic pollutants, copper and silver, along with environmentally-realistic temperature increases, on embryo-larval development of the Mediterranean mussel Mytilus galloprovincialis. First, mussel embryos upon fertilization were exposed for 48 h to increasing concentrations of Cu (0.5–500 μg/L) and Ag (0.1–100 μg/L) at different temperatures (18, 20, 22 or 24 °C) in order to characterize toxicity of each toxicant at the different tested temperatures. Increasing concentrations of a Cu-Ag mixture were then tested in order to assess the mixture effect at different temperatures (18, 20 or 22 °C). Embryotoxicity was measured after 48 h of exposure (D-larvae stage) considering both the percentage of abnormalities and developmental arrest in D-larvae. The results suggest that the optimum temperature for mussel larvae development is 18 °C (12.65± 1.6% malformations) and beyond 20 °C a steep increase of abnormal larvae was observed up to 100% at 24 °C. Ag was more toxic than Cu with a 50% effective concentration (EC50) at 18 °C of 6.58 μg/L and 17.6 μg/L, respectively. Temperature increased the toxicity of both metals as proved with the EC50 at 20 °C at 3.86 μg/L and 16.28 μg/L for Ag and Cu respectively. Toxic unit calculation suggests additive effects of Cu and Ag in mixture at 18 and 20 °C. These results highlight a possible impairment of M. galloprovincialis reproduction in the Mediterranean Sea in relation to increase of both pollutants and water temperature due to global warming.

Alternative assays are highly desirable to reduce the extensive experimental animal use in developmental toxicity testing. In the present study, we developed an improved test system for assessing neurodevelopmental toxicity using differentiating embryonic stem cells. We advanced previously established methods by merging, modifying and abbreviating the original 20-day protocol into a more efficient 13-day neural differentiation protocol. Using morphological observation, immunocytochemistry, gene expression and flow cytometry, it was shown predominantly multiple lineages of neuroectodermal cells were formed in our protocol and to a lower extent, endodermal and mesodermal differentiated cell types. This abbreviated protocol should lead to an advanced screening method using morphology in combination with selected differentiation markers aimed at predicting neurodevelopmental toxicity. Finally, the assay was shown to express differential sensitivity to a model developmental neurotoxicant, methyl mercury.

In this paper, we focus on the scheduling of preventive railway maintenance activities. The objective is to keep the railway infrastructure in good operating conditions at low costs, also taking into account the limited available resources in what concerns crew members. Equipments degrade with usage and age and a good preventive maintenance program can greatly reduce their unreliability in the sense that expectable failures can be anticipated. We propose a mixed integer programming formulation for the problem of scheduling preventive railway maintenance activities and a Variable Neighborhood Search (VNS) algorithm to solve large instances of the problem.

In the present study two new phages (phT4A and ECA2) were characterized and their efficacy was evaluated separately and in cocktail (phT4A/ECA2) to control Escherichia coli. The isolated phages, phT4A and ECA2, belonged to the Myoviridae and Podoviridae family, respectively and both are safe (no integrase and toxin codifying genes) to be used in bacterial control. In general, the increase of multiplicity of infection (MOI) from 1 to 100 promoted a significant increase in the efficiency of phage phT4A and phage cocktail phT4A/ECA2. Both phages were effective against E. coli, but phage phT4A (reduction of 5.8 log CFU/mL after 8 h treatment) was more effective than phage ECA2 phage (reduction of 4.7 log CFU/mL after 8 h treatment). The use of a cocktail phT4A/ECA2 was significantly more effective (reductions of 6.2 log CFU/mL after 6 h treatment) than the use single phage suspensions of phT4A and ECA2 (reductions 5.3 log CFU/mL and 4.9 log CFU/mL, respectively, after 6 h treatment). The rate of emergence of phage-resistant mutants was lower for phage phT4A when compared with phage ECA2 and phage cocktail phT4A/ECA2.The results indicate that in addition to the efficacy, the potential development of phage-resistant mutants must also be considered in the design of phage cocktails.