BACKGROUND: Deployment-related neurotoxicant exposures are implicated in the etiology of Gulf War illness (GWI), the multisymptom condition associated with military service in the 1990-1991 Gulf War (GW). A Q/R polymorphism at position 192 of the paraoxonase (PON)-1 enzyme produce PON1192 variants with different capacities for neutralizing specific chemicals, including certain acetylcholinesterase inhibitors.
METHODS: We evaluated PON1192 status and GW exposures in 295 GWI cases and 103 GW veteran controls. Multivariable logistic regression determined independent associations of GWI with GW exposures overall and in PON1192 subgroups. Exact logistic regression explored effects of exposure combinations in PON1192 subgroups.
RESULTS: Hearing chemical alarms (proxy for possible nerve agent exposure) was associated with GWI only among RR status veterans (OR = 8.60, p = 0.014). Deployment-related skin pesticide use was associated with GWI only among QQ (OR = 3.30, p = 0.010) and QR (OR = 4.22, p < 0.001) status veterans. Exploratory assessments indicated that chemical alarms were associated with GWI in the subgroup of RR status veterans who took pyridostigmine bromide (PB) (exact OR = 19.02, p = 0.009) but not RR veterans who did not take PB (exact OR = 0.97, p = 1.00). Similarly, skin pesticide use was associated with GWI among QQ status veterans who took PB (exact OR = 6.34, p = 0.001) but not QQ veterans who did not take PB (exact OR = 0.59, p = 0.782).
CONCLUSIONS: Study results suggest a complex pattern of PON1192 exposures and exposure-exposure interactions in the development of GWI.

Co-exposure soil studies of pollutants are necessary for an appropriate ecological risk assessment. Here, we examined the effects of two-component mixtures of metal oxide nanoparticles (ZnO NPs or goethite NPs) with the insecticide chlorpyrifos (CPF) under laboratory conditions in short-term artificial soil assays using Eisenia andrei earthworms. We characterized NPs and their mixtures by scanning electron microscopy, atomic force microscopy, dynamic light scattering and zeta potential, and evaluated effects on metal accumulation, oxidative stress enzymes, and neurotoxicity related biomarkers in single and combined toxicity assays. Exposure to ZnO NPs increased Zn levels compared to control in single and combined exposure (ZnO NPs + CPF) at 72 h and 7 days, respectively. In contrast, there was no indication of Fe increase in organisms exposed to goethite NPs. One of the most notable effects on oxidative stress biomarkers was produced by single exposure to goethite NPs, showing that the worms were more sensitive to goethite NPs than to ZnO NPs. Acetylcholinesterase and carboxylesterase activities indicated that ZnO NPs alone were not neurotoxic to earthworms, but similar degrees of inhibition were observed after single CPF and ZnO NPs + CPF exposure. Differences between single and combined exposure were found for catalase and superoxide dismutase (goethite NPs) and for glutathione S-transferase (ZnO NPs) activities, mostly at 72 h. These findings suggest a necessity to evaluate mixtures of NPs with co-existing contaminants in soil, and that the nature of metal oxide NPs and exposure time are relevant factors to be considered when assessing combined toxicity, as it may have an impact on ecotoxicological risk assessment.

BACKGROUND: Multiple sclerosis (MS) is a multifactorial disease of uncertain etiology damaging myelin sheaths around axons of the central nervous system. Myelin protects the axon from potentially harmful exogenous factors. The aetiological role of environmental exposure metals and organophosphates is unclear.
OBJECTIVE: Identify whether urinary levels of metals and organophosphates differed in MS patients and controls.
METHODS: We recruited MS patients from Ziv Medical Centre and healthy controls. MS patients were evaluated according to Expanded Disability Status Scale into mild and moderate-severe conditions. Each participant provided a urine sample and completed epidemiological questionnaires. The levels of six metal (Aluminum, Cadmium, Chromium, Lead, Mercury, Nickel) and one metalloid (Arsenic) and common organophosphates pesticide metabolites (6 dialkylphosphates, DAP) were measured in urine using inductively coupled plasma-mass spectrometry and gas-chromatography mass-spectrometry. We compared cases with controls in terms of urinary levels of these compounds using Mann-Whitney and Kruskall-Wallis tests.
RESULTS: Urinary cadmium and mercury levels were higher in the 49 MS patients than the 37 controls (p < 0.01). Cadmium levels were higher in moderate-severe MS patients (n = 24) than mild MS patients (n = 25) (p = 0.003).
CONCLUSIONS: Urinary cadmium and mercury levels were higher among MS patients than controls. Cadmium levels correlated with disease severity. Further studies are needed to explore potential causal pathways between these compounds and MS pathogenesis.

UNASSIGNED: The WHO 2021 data estimate that 2 million lives and 53 million disability-adjusted life-years were lost in 2019 due to exposures to selected chemicals. It is important to know the pattern and outcome of acute poisoning cases for proper planning, prevention and management. Knowing the pattern will also help in designing training modules for primary care physicians to make them aware about newer poisons and their management. Awareness regarding newer poisons consumed is necessary for early identification, initial management and timely referral to higher centres by primary care physicians. This study was performed to see the pattern and outcome of acute poisoning cases in North Indian population and various factors related to outcome.
UNASSIGNED: This study was conducted in department of medicine of a teaching institute in North India after approval by the Institutional Review Board. Patients admitted in the department during the study and fulfilling the inclusion criteria were enrolled in the study after obtaining consent.
UNASSIGNED: A total of 417 patients with poisoning were recruited in the study. Out of 417 patients, majority were males (59.5%). Maximum number of patients were in the age group of 21-30 years (33.8%), and rural population (79.9%) was found to be more affected. Most of the patients were students and private employees. Most common types of poisoning were snakebite (n = 109, 26.1%), organophosphate (n = 49, 11.8%) and aluminium phosphide (n = 39, 9.3%). Out of 417 patients, 349 (83.69%) improved, while 68 (16.3%) expired. Requirement of ventilatory support was most commonly associated with aluminium phosphide poisoning (30.12%) followed by organophosphate poisoning (24.1%).
UNASSIGNED: Poisoning was more common in young males and more prevalent in rural population. Pesticides and snakebite were major causes of poisoning. Among suicidal cases, family conflict (problem/altercation with family members/marital discord) was main reason for the consumption of poison. There is need for creation of poison information centre along with separate toxicological units in tertiary care hospitals.

Uncontrolled and unsafe use of pesticides can lead to acute and chronic toxicity in farmers, with neuropathy being one of the most common symptoms of chronic toxicity. However, the effects of this toxicity on farmers\' electroneuromyography (ENMG) are still unclear. To address this, we conducted a cross-sectional study from July to October 2017 in Ngablak District, Magelang, Central Java, Indonesia. Eligible farmers who were exposed to pesticides underwent electrophysiology examinations, as well as additional tests such as physical examination and laboratory testing. We collected general information such as age and work history by interview. In total, 64 farmers were included in this study. Out of these, 44 farmers were found to have polyneuropathy, with 41 of them having motor polyneuropathy and 19 of them having sensory polyneuropathy. Our findings showed that low blood cholinesterase was associated with distal latency prolongation (p-value: 0.014). The group exposed to organophosphate/carbamate pesticides was also significantly associated with prolonged distal latency (p-value: 0.012). However, motor polyneuropathy was significantly associated with chronic exposure to organophosphate/carbamate pesticides (p-value: 0.009) and not with low blood cholinesterase levels (p-value: 0.454). The study concludes that chronic exposure to organophosphate or carbamate pesticides could result in polyneuropathy disease, particularly in the motor system.

Organophosphorus insecticides (OPs), acting as serine phosphorylating agents in acetylcholinesterase (AChE), are highly effective neurotoxic insecticides. In our previous research, we found that six herbivorous pests and four ladybirds howed significantly higher AChE LC50 values than seven parasitoids and a predator (Epistrophe balteate), and that there was a significant correlation with the corresponding bimolecular rate constant (Ki) value. The Ki value of pests was much smaller than that of natural enemies and had a higher LC50 value.Then, we speculated that the low sensitivity of the pest AChE to OPs may be associated with its higher recovery and lower aging ability. In this work, the I50 and I90 were calculated, to determine the sensibility of AChE in ten representative species, including Plutella xylostella, Prodenia litura, Musca domestica, and Cavia porcellus, to paraoxon and malaoxon. The enzyme activities were measured at various time points, and kinetic calculations were used to obtain their spontaneous reactivation (Ks) and aging (Ka) constants, which were comprehensively compared. We conclude that the Ka and Ks of the AChE inhibited by OPs showed primarily species-specific correlations, and little correlation with the sensitivity to OPs. The differences in the AChE sensitivity to paraoxon among the ten species were much greater than in the sensitivity to malaoxon. Compared to paraoxon, malaoxon was more selective for Cavia porcellus. Coleoptera insects showed a stronger dephosphorylation ability than other insect groups. The recovery ability of phospho-AChE was stronger in mammals than in insects, which could be related to the low sensitivity of the AChE site of action to OPs. The Ka of the AChE inhibited by malaoxon was larger than that inhibited by paraoxon with the corresponding biomaterials, indicating that the OP type had a substantial relationship with the Ka of the AChE. We further discovered that, when insects were inhibited by OP, the tendency of AChE to undergo aging was greater than that of dephosphorylation. Overall, the study provides valuable information on the action mechanism of various OPs on AChE in several species, which could be used to further research into AChE and the potential dangers that organophosphates pose to animals.

Pesticides are widely employed in rice crops since the ecosystem and surroundings of paddy promote insects, weeds, and fungal and bacterial pathogens. Each commonly utilised pesticide possesses different uses. For instance, fungicides control fungal issues, herbicides curb weed growth, and insecticides destroy and repel insects. Although several ways to categorise them exist, pesticides are typically classified according to their chemical compositions. Rice production remains one of the most dominant crops grown in most Southeast Asian countries as it is a staple food. Nonetheless, the crop is highly dependent on pesticides, leading to growing concerns over the potential adverse effects of pesticides on the environment and human health. Despite the availability of numerous studies on the subject, a comprehensive understanding of the specific effects of pesticides on paddy fields in Southeast Asia is still lacking. Consequently, reviewing existing knowledge is necessary for synthesising and identifying research gaps to better inform policymakers, farmers, and other stakeholders in the agricultural sector. The objectives of the present review paper were to review the interactions between pesticides and the environment by understanding the physical and chemical properties of the chemicals, compare pesticide transportation modes in air, water, and soil and how they affect the environment, and evaluate and discuss the effects of pesticides on non-targeted organisms. This study assessed pesticide innovation reported between 1945 and 2021 for a better understanding of the utilisation of the chemicals over time. The pesticides assessed in this study were classified based on their chemical compounds, such as organochlorines, organophosphates, carbamates, and pyrethroid. This review could provide a comprehensive understanding of the interactions between pesticides and the environment and their impacts on non-targeted organisms.

There are limited literatures studying the pancreatic involvement in organophosphate (OP) poisoning using biochemical means. This study focused on assessing the type of OP poisoning and determining the association of serum amylase levels with the patient\'s presentation and outcome.
UNASSIGNED: A cross-sectional study was carried out in the Maharajgunj Medical Campus, Tribhuwan University Teaching Hospital, Kathmandu, Nepal, after ethical approval [Ref: IRB/308 (6-11-E)]. We collected data from 172 participants with OP poisoning over the period of 2 years using nonprobability purposive sampling method. All patients with age group 16-75 years having a history of OP poisoning within the previous 24 h with clinical features and physical evidence of poisoning were included in the study. Those participants with indications of exposure to an entirely different poisons, poisoning with multiple poisons, OP poisoning along with alcohol, chronic alcoholics, comorbid conditions, taking drugs that could affect serum amylase levels (azathioprine, thiazides, furosemide, etc.), and/or treated in other hospitals after poisoning were excluded from the study. Appropriate statistical calculations were made using the statistical package for social sciences (SPSS), version 21. The P-value of less than 0.05 was considered statistically significant.
UNASSIGNED: Metacid (53.5%, 92) was the most common OP poison. There were significantly higher mean values of serum amylase levels either within 12 h of exposure (468.60 vs. 135.4 IU/ml, P<0.001) or after 12 h of exposure (152.0 vs. 58.9 IU/ml, P<0.001) in dead participants than alive ones. The participants with initial and after 12 h of exposure-serum amylase level 100 or more IU/ml had more than two-fold and 18-fold higher odds of severe/life-threatening severity (odds ratio=2.40, 95% CI: 1.28-4.52, P=0.007 and odds ratio=18.67, 95% CI: 8.02-43.47, P<0.001) respectively than those with less than 100 IU/ml.
UNASSIGNED: The clinical severity of OP poisoning is directly related to serum amylase levels. Importantly, higher mean values of serum amylase levels were depicted in those participants with OP poisoning culminating to death. Thus, serum amylase level could be one of the easy measurable prognostic marker of OP poisonings.

Organophosphate poisoning occurs frequently, and despite treatment, increased severity and intensive care unit (ICU) admissions have been observed. We hypothesized that early hemoperfusion/hemadsorption (HA) therapy would change the clinical course of the disease.
We performed a prospective, open, randomized controlled study at an academic ICU. Adult patients referred for an acute cholinergic toxidrome were screened. Patients meeting inclusion and exclusion criteria were randomized to standard of care (SoC) or HA therapy plus SoC, which included 2 6-h cycles of HA 12 h apart beginning within the first 24 h of ICU admission. The primary outcome was a comparison of ICU length of stay (LOS).
There were no significant baseline differences between the groups. The median ICU LOS was 6.5 days (IQR 4.5-10) in the HA group compared to 8 days (IQR 3.5-17) for the control group, p = 0.58. Among patients with an excess ICU LOS ≥7 days, the median ICU LOS was significantly shorter for the HA group, 10 days (IQR 8-12) compared to 17 days (IQR 14-22) for the control group, p = 0.001, resulting in a cost saving of EUR 7308 per patient. Duration (8 days vs. 13.5 days) and cumulative dosage (316 mg vs. 887 mg) of atropine among patients with excess ICU LOS were significantly lower in the HA group compared to the SoC group, respectively. A similar reduction in the duration of mechanical ventilation (HA = 6 days vs. SoC = 15 days, p = 0.001) was found. The combination of day 28 mortality and severe complications was lower in the HA group (10%, n = 2/20) compared to the SoC group (42%, 14/33) p = 0.01.
HA therapy resulted in significant cost savings driven by a reduced LOS among patients with excess ICU LOS ≥7 days. This therapy was also associated with a significant reduction in the combination of day 28 mortality and severe complications including cardiac arrest, organ dysfunction, reintubation, and tracheostomy.

Organophosphate (OP) insecticides, including chlorpyrifos, have been linked with numerous harmful health effects on maternal and child health. Limited data are available on the biological mechanisms and endogenous pathways underlying the toxicity of chlorpyrifos exposures on pregnancy and birth outcomes. In this study, we measured a urinary chlorpyrifos metabolite and used high-resolution metabolomics (HRM) to identify biological perturbations associated with chlorpyrifos exposure among pregnant women in Thailand, who are disparately exposed to high levels of OP insecticides.
This study included 50 participants from the Study of Asian Women and their Offspring\'s Development and Environmental Exposures (SAWASDEE). We used liquid chromatography-high resolution mass spectrometry to conduct metabolic profiling on first trimester serum samples collected from participants to evaluate metabolic perturbations in relation to chlorpyrifos exposures. We measured 3,5,6-trichloro-2-pyridinol (TCPy), a specific metabolite of chlorpyrifos and chlorpyrifos-methyl, in first trimester urine samples to assess the levels of exposures. Following an untargeted metabolome-wide association study workflow, we used generalized linear models, pathway enrichment analyses, and chemical annotation to identify significant metabolites and pathways associated with urinary TCPy levels.
In the 50 SAWASDEE participants, the median urinary TCPy level was 4.36 μg TCPy/g creatinine. In total, 691 unique metabolic features were found significantly associated with TCPy levels (p < 0.05) after controlling for confounding factors. Pathway analysis of metabolic features associated with TCPy indicated perturbations in 24 metabolic pathways, most closely linked to the production of reactive oxygen species and cellular damage. These pathways include tryptophan metabolism, fatty acid oxidation and peroxisome metabolism, cytochromes P450 metabolism, glutathione metabolism, and vitamin B3 metabolism. We confirmed the chemical identities of 25 metabolites associated with TCPy levels, including glutathione, cystine, arachidic acid, itaconate, and nicotinamide adenine dinucleotide.
The metabolic perturbations associated with TCPy levels were related to oxidative stress, cellular damage and repair, and systemic inflammation, which could ultimately contribute to health outcomes, including neurodevelopmental deficits in the child. These findings support the future development of sensitive biomarkers to investigate the metabolic underpinnings related to pesticide exposure during pregnancy and to understand its link to adverse outcomes in children.