CONSIDERING DIMETHYL SULFOXIDE SOLVENT TOXICITY TO MAMMALIAN CELLS AND ITS BIOLOGICAL EFFECTS.

Dimethyl sulfoxide (DMSO) is a common solvent in biological and medical research for dissolving water-insoluble compounds and drugs. However, the impact of DMSO goes beyond its primary function. High-throughput and in vitro assays have uncovered various effects of DMSO in mammalian cells. The present article highlights the biological effects of DMSO on normal and cancerous mammalian cells.

Occupational exposure to organic solvents during pregnancy and child behavior from early childhood to adolescence.

BACKGROUND: Organic solvents are used in formulating an extensive range of products for professional use. Animal and human studies suggest that in utero solvent exposure may affect neurodevelopment. Our objective was to assess the association between occupational exposure to solvents during pregnancy and child behavior aged 2-12 years. METHODS: The French mother-child cohort PELAGIE (2002-2006) included 3,421 women recruited in early pregnancy. Occupational exposure to solvents was self-reported. For 459 children, parents used a questionnaire derived from the Child Behavior Checklist and the Preschool Social Behavior Questionnaire to assess their child's behavior, at age 2, and the Strengths and Difficulties Questionnaire at ages 6 and 12. A cross-lagged structural equation modeling approach was used to assess direct and indirect associations between exposure and child behavior. RESULTS: At age 2, an increased externalizing behavior score was suggested with prenatal exposure to solvents (mean change in standardized score (95%CI): 0.28 (-0.01, 0.57) for occasional exposure and 0.23 (-0.05, 0.51) for regular exposure). At ages 6 and 12, distinct sex-specific patterns were observed: among boys, no association with externalizing behavior was observed, while among girls, an association was seen for both occasional and regular exposure (total effect at age 12: 0.45 (0.06,0.83) and 0.40 (0.03, 0.76), respectively). For both sexes, occasional exposure may be associated with internalizing behavior at ages 6 and 12 (total effect at age 6: 0.37 (0.06, 0.68) and at age 12: 0.27 (-0.08, 0.62)). CONCLUSIONS: Occupational exposure to solvents during pregnancy may impact child behavior through either direct or cumulative effects during childhood; these associations may persist until early adolescence, especially among girls.

Bis-(2-Chloroisopropyl) ether.

Bis-(2-Chloroisopropyl) ether (BCIPE) was used as a solvent for fats, greases, paint, varnish removers, and in spotting and cleaning solutions. However, BCIPE has not been commercially manufactured or used for numerous years. In experimental animal studies, BCIPE is moderately toxic following acute oral, dermal, and inhalation routes of exposure. BCIPE is a severe eye irritant but not a dermal irritant or dermal sensitizer. BCIPE was not genotoxic or mutagenic in in vitro and in vivo assays; it was not toxic in a 3-generation reproductive dietary study in rats. Short-term, repeated inhalation and oral exposure in rats produced increased liver and kidney weights and congestion; dermal exposure in rabbits did not produce any observable adverse effects. BCIPE did not produce a statistically significant increase in tumors in two different 2-year dietary studies in mice and rats. In mice, technical grade BCIPE produced increased incidences of alveolar/bronchiolar adenomas in females, hepatocellular carcinomas in males, and a low incidence of forestomach hyperplasia (in both sexes at the high-dose). Further investigation with technical grade BCIPE concluded that these effects were species- and dose-specific with limited, if any, relevance to humans. The NOAEL of 400 ppm (15 mg/kg/day) from the 2-year dietary study in female rats was considered the point of departure for the health-based WEEL derivation. After adjustment for duration of exposure, interindividual variability, and intraindividual variability, an 8-h time-weighted average (TWA) WEEL value of 3 ppm (21 mg/m3) was derived. This exposure limit is expected to provide a significant margin of safety against any potential adverse health effects in workers.

Toxicological effects of solvent-extracted organic matter associated with PM2.5 on human bronchial epithelial cell line NL-20.

The heterogeneity and complexity of solvent-extracted organic matter associated with PM2.5 (SEOM-PM2.5) is well known; however, there is scarce information on its biological effects in human cells. This work aimed to evaluate the effect of SEOM-PM2.5 collected in northern Mexico City during the cold-dry season (November 2017) on NL-20 cells, a human bronchial epithelial cell line. The SEOM obtained accounted for 15.5% of the PM2.5 mass and contained 21 polycyclic aromatic hydrocarbons (PAHs). The cell viability decreased following exposure to SEOM-PM2.5, and there were noticeable morphological changes such as increased cell size and the presence of cytoplasmic vesicles in cells treated with 5-40 µg/mL SEOM-PM2.5. Exposure to 5 µg/mL SEOM-PM2.5 led to several alterations compared with the control cells, including the induction of double-stranded DNA breaks based (p < 0.001); nuclear fragmentation and an increased mitotic index (p < 0.05); 53BP1 staining, a marker of DNA repair by non-homologous end-joining (p < 0.001); increased BiP protein expression; and reduced ATF6, IRE1α, and PERK gene expression. Conversely, when exposed to 40 µg/mL SEOM-PM2.5, the cells showed an increase in reactive oxygen species formation (p < 0.001), BiP protein expression (p < 0.05), and PERK gene expression (p < 0.05), indicating endoplasmic reticulum stress. Our data suggest concentration-dependent toxicological effects of SEOM-PM2.5 on NL-20 cells, including genotoxicity, genomic instability, and endoplasmic reticulum stress.

Investigation of the in vitro toxic effects induced by real-time aerosol of electronic cigarette solvents using microfluidic chips.

The safety of propylene glycol (PG) and vegetable glycerin (VG) as solvents in electronic cigarette liquid has received increasing attention and discussion. However, the conclusions derived from toxicity assessments conducted through animal experiments and traditional in vitro methodologies have consistently been contentious. This study constructed an original real-time aerosol exposure system, centered around a self-designed microfluidic bionic-lung chip, to assess the biological effects following exposure to aerosols from different solvents (PG, PG/VG mixture alone and PG/VG mixture in combination with nicotine) on BEAS-2B cells. The study aimed to investigate the impact of aerosols from different solvents on gene expression profiles, intracellular biomarkers (i.e., reactive oxygen species content, nitric oxide content, and caspase-3/7 activity), and extracellular biomarkers (i.e., IL-6, IL-8, TNF-α, and malondialdehyde) of BEAS-2B cells on-chip. Transcriptome analyses suggest that ribosomal function could serve as a potential target for the impact of aerosols derived from various solvents on the biological responses of BEAS-2B cells on-chip. And the results showed that aerosols of PG/VG mixtures had significantly less effect on intracellular and extracellular biomarkers in BEAS-2B cells than aerosols of PG, whereas increasing nicotine levels might elevate these effects of aerosol from PG/VG mixture.

Experimental Ecotoxicology Procedures Interfere with Honey Bee Life History.

Apis mellifera was used as a model species for ecotoxicological testing. In the present study, we tested the effects of acetone (0.1% in feed), a solvent commonly used to dissolve pesticides, on bees exposed at different developmental stages (larval and/or adult). Moreover, we explored the potential effect of in vitro larval rearing, a commonly used technique for accurately monitoring worker exposure at the larval stage, by combining acetone exposure and treatment conditions (in vitro larval rearing vs. in vivo larval rearing). We then analyzed the life-history traits of the experimental bees using radio frequency identification technology over three sessions (May, June, and August) to assess the potential seasonal dependence of the solvent effects. Our results highlight the substantial influence of in vitro larval rearing on the life cycle of bees, with a 47.7% decrease in life span, a decrease of 0.9 days in the age at first exit, an increase of 57.3% in the loss rate at first exit, and a decrease of 40.6% in foraging tenure. We did not observe any effect of exposure to acetone at the larval stage on the capacities of bees reared in vitro. Conversely, acetone exposure at the adult stage reduced the bee life span by 21.8% to 60%, decreased the age at first exit by 1.12 to 4.34 days, and reduced the foraging tenure by 30% to 37.7%. Interestingly, we found a significant effect of season on acetone exposure, suggesting that interference with the life-history traits of honey bees is dependent on season. These findings suggest improved integration of long-term monitoring for assessing sublethal responses in bees following exposure to chemicals during both the larval and adult stages. Environ Toxicol Chem 2024;43:1320-1331. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

High-fat diet exacerbates 1-Bromopropane-induced loss of dopaminergic neurons in the substantia nigra of mice through mitochondrial damage associated necroptotic pathway.

In recent years, accumulating evidence supports that occupational exposure to solvents is associated with an increased incidence of Parkinson's disease (PD) among workers. The neurotoxic effects of 1-bromopropane (1-BP), a widely used new-type solvent, are well-established, yet data on its relationship with the etiology of PD remain limited. Simultaneously, high-fat consumption in modern society is recognized as a significant risk factor for PD. However, whether there is a synergistic effect between a high-fat diet and 1-BP exposure remains unclear. In this study, adult C57BL/6 mice were fed either a chow or a high-fat diet for 18 weeks prior to 12-week 1-BP treatment. Subsequent neurobehavioral and neuropathological examinations were conducted to assess the effects of 1-BP exposure on parkinsonian pathology. The results demonstrated that 1-BP exposure produced obvious neurobehavioral abnormalities and dopaminergic degeneration in the nigral region of mice. Importantly, a high-fat diet further exacerbated the impact of 1-BP on motor and cognitive abnormalities in mice. Mechanistic investigation revealed that mitochondrial damage and mtDNA release induced by 1-BP and high-fat diet activate NLRP3 and cGAS-STING pathway- mediated neuroinflammatory response, and ultimately lead to necroptosis of dopaminergic neurons. In summary, our study unveils a potential link between chronic 1-BP exposure and PD-like pathology with motor and no-motor defects in experimental animals, and long-term high-fat diet can further promote 1-BP neurotoxicity, which underscores the pivotal role of environmental factors in the etiology of PD.

Toxicity of organic solvents and surfactants to the sea urchin embryos.

A comparative toxicity of widely applied organic solvents (methanol, ethanol, n-propanol, i-propanol, n-butanol, 2-butanol, i-butanol, t-butanol, 3-methoxy-3-methylbutanol-1 (MMB), ethylene glycol, diethylene glycol, 2-methoxyethanol, 2-ethoxyethanol, glycerol, ethyl acetate, acetonitrile, benzene, dioxane, dimethylformamide, dimethylacetamide, dimethylsulfoxide, 2-pyrrolidone, and N-methyl-2-pyrrolidone) and surfactants (PEG 300, PEG 6000, Tween 20, Tween 80, miramistin, and Cremophor EL) was studied using a sea urchin embryo model. Sea urchin embryo morphological alterations caused by the tested chemicals were described. The tested molecules affected P. lividus embryo development in a concentration-dependent manner. The observed phenotypic anomalies ranged from developmental delay and retardation of plutei growth to formation of aberrant blastules and gastrules, cleavage alteration/arrest, and embryo mortality. Discernible morphological defects were found after embryo exposure with common pharmaceutical ingredients, such as glycerol, Tween 80, and Cremophor EL. In general, solvents were less toxic than surfactants. PEG 6000 PEG 300, DMSO, ethanol, and methanol were identified as the most tolerable compounds with minimum effective concentration (MEC) values of 3.0-7.92 mg/mL. Previously reported MEC value of Pluronic F127 (4.0 mg/mL) fell within the same concentration range. Toxic effects of methanol, ethanol, DMSO, 2-methoxyethanol, 2-ethoxyethanol, Tween 20, and Tween 80 on P. lividus embryos correlated well with their toxicity obtained using other cell and animal models. The sea urchin embryos could be considered as an appropriate test system for toxicity assessment of solvents and surfactants for their further application as solubilizers of hydrophobic molecules in conventional in vitro cell-based assays and in vivo mammalian models. Nevertheless, to avoid adverse effect of a solubilizing agent in ecotoxicological and biological experiments, the preliminary assessment of its toxicity on a chosen test model would be beneficial.

Successful prevention of organic solvent induced disorders: history and lessons.

In this discussion paper, we describe the history of the science and societal action resulting in the mitigation of neurotoxic disorders from exposure to organic solvents at the workplaces in Sweden. When alkyd paints were introduced in large scale in construction painting in the 1960s and 1970s, Scandinavian unions voiced increasing concern as members reported symptoms like headache and vertigo, supported by participatory studies and case studies. Although acute and chronic neurotoxic effects were established for some specific solvents such as carbon disulphide, this was not the case for those used in the new paints. Union advocacy promoted formal epidemiological studies, providing increasing evidence for chronic neurotoxicity at levels far below current occupational exposure levels. The results were widely disseminated and accepted and led to concerted action with preventive measures, most importantly substitution of the organic solvents in paints for indoor use, but also drastic reductions in occupational exposure limits. The findings also resulted in funding of further research on solvent toxicity and the establishment of expert groups to advice authorities on occupational standards for exposure to chemicals. The substitution strategy was subsequently adopted in many other countries and occupational exposure limits were lowered, although several years or even decades later. While the societal context in Sweden was unique in many ways, we conclude that there are lessons to be learned from this preventive success when addressing current challenges.

Prevalent occupational exposures and risk of lung cancer among women: Results from the application of the Canadian Job-Exposure Matrix (CANJEM) to a combined set of ten case-control studies.

BACKGROUND: Worldwide, lung cancer is the second leading cause of cancer death in women. The present study explored associations between occupational exposures that are prevalent among women, and lung cancer. METHODS: Data from 10 case-control studies of lung cancer from Europe, Canada, and New Zealand conducted between 1988 and 2008 were combined. Lifetime occupational history and information on nonoccupational factors including smoking were available for 3040 incident lung cancer cases and 4187 controls. We linked each reported job to the Canadian Job-Exposure Matrix (CANJEM), which provided estimates of probability, intensity, and frequency of exposure to each selected agent in each job. For this analysis, we selected 15 agents (cleaning agents, biocides, cotton dust, synthetic fibers, formaldehyde, cooking fumes, organic solvents, cellulose, polycyclic aromatic hydrocarbons from petroleum, ammonia, metallic dust, alkanes C18+, iron compounds, isopropanol, and calcium carbonate) that had lifetime exposure prevalence of at least 5% in the combined study population. For each agent, we estimated lung cancer risk in each study center for ever-exposure, by duration of exposure, and by cumulative exposure, using separate logistic regression models adjusted for smoking and other covariates. We then estimated the meta-odds ratios using random-effects meta-analysis. RESULTS AND CONCLUSIONS: None of the agents assessed showed consistent and compelling associations with lung cancer among women. The following agents showed elevated odds ratio in some analyses: metallic dust, iron compounds, isopropanol, and organic solvents. Future research into occupational lung cancer risk factors among women should prioritize these agents.

Toxicity test profile for deep eutectic solvents: A detailed review and future prospects.

Deep eutectic solvents (DESs) are preferable in terms of starting materials, storage and synthesis, simplicity, and component material affordability. In several industries ranging from chemical, electrochemical, biological, biotechnology, material science, etc., DES has demonstrated remarkable potential. Despite all these accomplishments, the safety issue with DES must be adequately addressed. Different DES interacts with the cellular membranes differently. It is not possible to classify all DES as easily biodegradable. By expanding the current understanding of the toxicity and biodegradation of DES, interactions between organisms and cellular membranes can be linked. The DES toxicity profile varies according to their concentration, the nature of the individual components, and how they interact with living things. Therefore, the results of this review can serve as a baseline for DES development in the future.

Modeling the impact of heat stress on the toxicokinetics of toluene and acetone.

Many workers can be exposed simultaneously to heat and volatile chemicals. In a controlled human exposure study, it was observed that an increase in ambient temperature was associated with increased blood concentrations for acetone and toluene. Based on the expected changes in physiological parameters that occur with an increase in ambient temperature, we aimed to develop a PBPK model for acetone and toluene that could account for the impact of temperature on the kinetics of these solvents. Changes in temperature-dependent physiological parameters (i.e. blood flows, cardiac output, alveolar ventilation) based on recent measurements in volunteers were introduced in the PBPK models to simulate observed blood concentrations for different temperature exposure conditions. Because initial simulations did not adequately predict solvent kinetics at any temperature, the most sensitive parameter (alveolar ventilation; Qp) was, therefore, optimized on experimental acetone blood concentrations to obtain a relationship with temperature. The new temperature-dependent Qp relationship gave Qp values consistent with the literature and estimated a mean increase of 19% at 30 °C (wet bulb globe temperature) compared to 21 °C. The integration of a new temperature-dependent Qp relationship in the PBPK toluene model yielded adequate simulations of the experimental data for toluene in blood, exhaled air and urine. With further validation with other solvents, the temperature-dependant PBPK model could be a useful tool to better assess the risks of simultaneous exposure to volatile chemicals and heat stress and interpret biomonitoring data in workers as well as in the general population. TRN: NCT02659410, Registration date: January 15, 2016.

Occupational exposures and cancer risk in commercial laundry and dry cleaning industries: a scoping review.

BACKGROUND: The laundry and dry cleaning industries are critical for maintaining cleanliness and hygiene in our daily lives. However, they have also been identified as sources of hazardous chemical exposure for workers, leading to potentially severe health implications. Despite mounting evidence that solvents like perchloroethylene and trichloroethylene are carcinogenic, they remain commonly used in the industry. Additionally, while alternative solvents are increasingly being utilized in response to indications of adverse health and environmental effects, there remains a significant gap in our understanding of the potential risks associated with exposure to these new agents. METHODS: This study aims to identify gaps in the literature concerning worker exposure to contemporary toxic chemicals in the laundry and dry cleaning industry and their associated carcinogenic risks. A scoping review of peer-reviewed publications from 2012 to 2022 was conducted to achieve this objective, focusing on studies that detailed chemical exposures, sampling methods, and workers within the laundry and dry cleaning sector. RESULTS: In this scoping review, 12 relevant papers were assessed. A majority (66%) examined perchloroethylene exposure, with one notable finding revealing that biomarkers from dry cleaners had significant micronuclei frequency and DNA damage, even when exposed to PCE at levels below occupational exposure limits. Similarly, another study supported these results, finding an increase in early DNA damage among exposed workers. Separate studies on TCE and benzene presented varied exposure levels and health risks, raising concern due to their IARC Group 1 carcinogen classification. Information on alternative solvents was limited, highlighting gaps in health outcome data, exposure guidelines, and carcinogenic classifications. CONCLUSION: Research on health outcomes, specifically carcinogenicity from solvent exposure in dry cleaning, is limited, with 66% of studies not monitoring health implications, particularly for emerging solvents. Further, findings indicated potential DNA damage from perchloroethylene, even below set occupational limits, emphasizing the need to reevaluate safety limits. As alternative solvents like butylal and high-flashpoint hydrocarbons become more prevalent, investigations into the effects of their exposure are necessary to safeguard workers' health. This scoping review is registered with the Open Science Framework, registration DOI: https://doi.org/10.17605/OSF.IO/Q8FR3 .

Repeated toluene and cyclohexane inhalation produces differential effects on HPA and HPT axes in adolescent male rats.

Misused volatile solvents typically contain toluene (TOL) as the main psychoactive ingredient. Cyclohexane (CHX) can also be present and is considered a safer alternative. Solvent misuse often occurs at early stages of life, leading to permanent neurobehavioral impairment and growth retardation. However, a comprehensive examination of the effects of TOL and CHX on stress regulation and energy balance is lacking. Here, we compared the effect of a binge-pattern exposure to TOL or CHX (4,000 or 8,000 ppm) on body weight, food intake, the hypothalamus-pituitary-adrenal (HPA) and hypothalamus-pituitary-thyroid (HPT) axes in male adolescent Wistar rats. At 8,000 ppm, TOL decreased body weight gain without affecting food intake. In addition, TOL and CHX altered the HPA and HPT axes' function in a solvent- and concentration-dependent manner. The highest TOL concentration produced HPA axis hyperactivation in animals not subjected to stress, which was evidenced by increased corticotropin-releasing-factor (CRF) release from the median eminence (ME), elevated adrenocorticotropin hormone (ACTH) and corticosterone serum levels, and decreased CRF mRNA levels in the hypothalamic paraventricular nucleus (PVN). TOL (8,000 ppm) also increased triiodothyronine (T3) serum levels, decreased pro-thyrotropin-releasing-hormone (pro-TRH) mRNA transcription in the PVN, pro-TRH content in the ME, and serum thyroid stimulating hormone (TSH) levels. CHX did not affect the HPA axis. We propose that the increased HPT axis activity induced by TOL can be related to the impaired body weight gain associated with inhalant misuse. These findings may contribute to a better understanding of the effects of the misused solvents TOL and CHX.

In vitro screening of imidazolium and pyrrolidinium based ionic liquids toxicity on subcellular fractions of the Mediterranean mussel Mytilus galloprovincialis.

Ionic liquids (ILs) have been considered eco-friendly alternatives to conventional organic solvents. However, several studies have reported that ILs exert toxicity towards aquatic invertebrates. Applying in vitro methodology, the aim of the present study was to evaluate the potential effect of three ILs on the biochemical performance of exposed Mytilus galloprovincialis digestive gland and gills cellular fractions. Carboxylesterase might be involved in the derived toxicity mechanism of ILs as activity levels increased significantly in digestive gland exposed fractions. This group of ILs did not seem to induce genotoxicity, except in gills cellular fractions exposed to 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide. In the literature, in vitro methodology has been suggested as an important complement to animal testing and in silico studies. The present research underlines its efficacy as a quick pre-screening before in vivo testing, particularly with heterogenic groups of substances with high variability in composition, such as ILs and deep eutectic solvents.

Organic solvents and Multiple Sclerosis: the doubled risk dilemma.

BACKGROUND: Compensation for industrial disease in the UK may be obtained in two ways. A State scheme includes a list of accepted associations between occupations and diseases with evidence of a causative association. Epidemiological evidence of a doubled risk in the occupation concerned is usually required. This takes no account of variation of exposures within occupations, excluding many occupations where risk is less than doubled. In such cases, compensation for a perceived industrial illness may be obtained in Civil Courts, where excessive exposures can be considered. AIMS: To show that in the Civil Courts evidence of excessive exposure may lead to compensation for diseases which are not yet compensable as Industrial Injuries in the UK and to draw attention to the association of multiple sclerosis (MS) with solvent exposure. METHODS: We report the case of an industrial spray painter, who claimed his MS had been caused by high-level exposure to organic solvents, and our examination of the epidemiological evidence submitted. RESULTS: The painter received compensation by an out-of-court settlement, despite the overall epidemiological risk in relation to solvent exposure having been shown to be less than doubled. The evidence hinged on individual risk in relation to high exposure, genetic susceptibility and demonstration of a plausible mechanism. CONCLUSIONS: High organic solvent exposure may lead to the development of MS. Those giving evidence in Court need to be able to discuss the epidemiological and toxicological issues in relation to exposure in the individual case.

The acute vapour inhalation toxicity of 2-butoxyethanol. Points considered when designing and conducting a study in Guinea pigs and evaluating existing inhalation toxicity data on low volatility solvents.

This publication reports the outcome of an acute inhalation toxicity study with guinea pigs by nose-only exposure to the substance 2-butoxyethanol at exposures close to the maximum attainable saturation vapour concentration. We describe the methods used to ensure exposure only to saturation vapour at a level as high as could be practically achieved whilst avoiding aerosol formation. We consider the practical difficulties and implications of testing substances at or close to their saturation vapour concentration and the criteria that should be used to critically assess such studies, especially with reference to the GHS (Globally Harmonised System) for classification and labelling, where a clear differentiation between gases, vapours and dust and mists applies. Guinea pigs showed no adverse effects when exposed for 4 h to the maximum attainable concentration of pure 2-butoxyethanol vapour. If guinea pigs are regarded as the most appropriate species to assess short term toxicity to humans from exposure to 2-butoxyethanol, because they are like humans not sensitive to haemolysis of red blood cells caused by exposure to the substance, then the data from this study shows that 2-butoxyethanol presents a low acute inhalation toxicity hazard.

The impact of solvents on the toxicity of the banned parathion insecticide.

The aerial crop dusting and spraying of fields with the phosphorothioate insecticide parathion in the late 1900s, significantly improved crop yields but resulted in high levels of occupational toxicity in handlers and agricultural workers, as well as cases of intentional self-harm poisoning, culminating in its banning in many western countries by early 2000s. However because of the low solubility and volatility of parathion, most available products were formulated using organic solvents e.g. xylene, to increase the efficacy of the aerosols and dusts. In the present study, the toxicity of parathion was assessed when formulated in an aqueous solvents (ethanol/PBS (1:9)), and delivered to macaques as an aerosol. Doses of 780 µg/kg and 1.56 mg/kg were delivered one day apart, using a modified nebulizer calculated to result in lung deposition of ∼480 µg/kg with a similar or larger amount being swallowed; these doses being similar to the estimated lethal oral dose 286ug/kg - 1.43 mg/kg of formulated parathion in humans. Surprisingly, this dose (a combined amount of ∼14 mg) caused only low AChE inhibition and moderate BChE inhibition with no clinical symptoms, indicating that the use of organic solvents may have previously played a critical role in the severity of parathion toxicity following inhalation exposure. In addition, unlike constitutively toxic OPs, which are highly toxic when inhaled, these results are consistent with the idea that phosphorothioate insecticides appear to be more intoxicating following oral than inhalation exposure. However, this still remains uncertain because the presence of organic solvents in the ingested parathion studies was not always known.

Solvent exposure strongly linked to Parkinson's.

Military recruits exposed to TCE decades ago have increased risk of the brain disease.