01 Feb Sleep apnoea and pesticide exposure
Pesticide misuse, and subsequent overexposure has gone unchecked in recent decades, despite efforts by organisations to try and protect both human health and the environment.
Carbofuran Usage in Australia
One of these pesticides is called Carbofuran, this is an insecticide and nematicide that is registered for use only in certain states of Australia. Recently the Carbofuran has been nominated for review because of human health concerns[1]. Carbofuran has very limited current use in Australia. While there are carbofuran maximum residue limits (MRLs) in place for rice, sugarcane and some cereal crops, there has been no use of carbofuran products in those industries for quite some time. Use in the tobacco industry ceased in late 2006 with the closure of the industry in Australia.
The interest in this topic arose because one group of researchers in USA have developed one investigation about the associations between pesticide exposure and sleep apnoea among pesticide applicators from a US farming population[2].
Abstract
Introduction: Carbamate and organophosphate pesticides inhibit acetylcholinesterase, and poisoning leads to respiratory depression. Thus, involvement in sleep apnea is plausible, but no data exist at lower levels of exposure. Other pesticides could impact sleep apnea by different mechanisms but have not been studied. Our study examines the associations between pesticide exposure and sleep apnea among pesticide applicators from a US farming population.
Participants and methods: We analyzed data from 1569 male pesticide applicators, mostly farmers, from an asthma case-control study nested within the prospective Agricultural Health Study. On questionnaires, participants reported use of specific pesticides and physician diagnosis plus prescribed treatments for sleep apnea. We used multivariable logistic regression to estimate associations between ever use of 63 pesticides and sleep apnea (234 cases, 1335 noncases).
Results: The most notable association was for carbofuran, a carbamate (100 exposed cases, odds ratio 1.83, 95% confidence interval 1.34-2.51, P = .0002). Carbofuran use began before reported onset of sleep apnea in all cases.
Discussion: This study adds to the known adverse health outcomes of exposure to carbofuran, a pesticide canceled in the United States in 2009 for most agricultural purposes but persists in the environment and remains in use in some other countries.
Conclusions: We conducted the first epidemiological study investigating the association of pesticide exposure and sleep apnea. Our results in a male agricultural population suggests that exposure to carbofuran is positively associated with sleep apnea.
As the abstract says the positive relationship was observed for carbofuran, which all 96 (of 100) sleep apnea cases with available timing data reported first exposure before onset of sleep apnea; use began a median of 26.5 years before (interquartile range = 19.5-32.5). We had data on lifetime days of use for carbofuran (Table 3). The positive association with carbofuran did not attenuate at higher exposures (Ptrend = .003).
Mechanism of Action
The primary mode of action of carbofuran, like other carbamates and organophosphates, is via inhibition of the enzyme acetylcholinesterase. Organophosphates are regarded as irreversible inhibitors of acetylcholinesterase, whereas carbamates, including carbofuran, are slowly reversible inhibitors. With either, acetylcholine accumulates at nerve junctions, leading to overstimulation of acetylcholine receptors with later toxicity and potential perturbation of the sympathetic, parasympathetic, and peripheral nervous systems. Acetylcholinesterase acts on cholinergic neurons involved in control of breathing in the sleep-wake cycle. Poisoning by any pesticides with this mechanism of action could result in respiratory depression. Thus, carbamates could play a role in the onset and/or progression of central sleep apnea.
Carbofuran can influence neurologic function via mechanisms other than acetylcholinesterase inhibition. In fish, carbofuran impacts levels of other neurotransmitters including dopamine, norepinephrine, and serotonin. The degree and direction of these changes vary by brain region. Behavioral changes observed in fish after carbofuran exposure may be more sensitive indicators of neurotoxicity than altered brain catecholamine levels. Carbofuran increased various oxidative stress parameters in the rat brain and produced motor and cognitive deficits; administration of the antioxidant N-acetylcysteine reduced these effects. Of note, recently, a computational approach has shown that carbofuran mimics melatonin, a critical hormone in the sleep-wake cycle, and can bind to its receptor. The increasing data implicating melatonin, a hormone crucial in the regulation of the sleep-wake cycle, in the sleep apnea or its severity together with the ability of carbofuran to mimic melatonin provide an alternative or complementary mechanism for an impact of carbofuran exposure on sleep apnea.
Limitations
One limitation of this study was how sleep apnoea was measured (apnoea was self-reported instead of being evaluated by polysomnography). It may be a good article that can help the physicians to identify another population that might have a risk factor for developing sleep apnoea.
References
Brittney O. Baumert, Megan Ulmer Carnes, Jane A. Hoppin, Chandra L. Jackson, Dale P. Sandler, Laura Beane Freeman, Paul K. Henneberger, David M. Umbach, Srishti Shrestha, Stuart Long, Stephanie J. London. Sleep apnea and pesticide exposure in a study of US farmers. Sleep Health, ISSN: 2352-7218, Vol: 4, Issue: 1, Page: 20-26. 2018. https://www.sciencedirect.com/science/article/pii/S2352721817301742
Carbofuran Chemical Review. Australian Pesticides and Veterinary Medicines Authority. Available online: https://apvma.gov.au/node/12426