Low Dose Effects

see also Health/Nervous System Effects/ Parkinson Disease, and p.2, health/Endocrine Disruption,  Loss of Smell, glyphosate, glyphosate 2,  terrestrial invertebrates,  organochlorines,  organophosphates,  mixtures effects, microbiota changes  nervous system effects p2, 

Delayed Polyneuropathy in Farm Sprayers Due to Chronic Low Dose Pesticide Exposure Iran Red Crescent Med J. 2014 May 5;16(5):      In Iran, 60% of pesticides are organophosphate compounds that may lead to delayed polyneuropathy.  Tested Compound Muscle Action Potential (CMAP), amplitude and Distal Latency (DL) and Nerve Conduction Velocity (NCV) of sseveral nerves. The mean peroneal CMAP amplitude and NCV, sural PL, radial SNAP amplitude, PL and NCV in the case group were significantly different compared to control group. Mean exposure time to OPs in farm sprayers without neurological problem (40%) was 11.81 ± 5.84 years but in farm sprayers with neurological problems (60%) was 15.70 ± 9.08 years, which represents the effect of OPs exposure duration on neurologic problems.   Chronic low dose pesticide exposure could lead to delayed peripheral neuropathy as well as systemic (skin, eyes and lungs) complications. In farm sprayers electrodiagnostic indices were significantly abnormal as compared to control group. 

The Dose Disrupts the Pathway.:application of Paracelsus principle to mechanistic toxicology by Suvorov, Toxicological Science, 2024, 200(2), 228–234    Abstract:   Arguably the most famous principle of toxicology is “The dose makes the poison” formulated by Paracelsus in the 16th century. Application of the Paracelsus’s principle to mechanistic toxicology may be challenging as one compound may affect many molecular pathways at different doses with different and often nonlinear dose-response relationships. As a result, many mechanistic studies of environmental and occupational compounds use high doses of xenobiotics motivated by the need to see a clear signal indicating disruption of a particular molecular pathway. This approach ignores the possibility that the same xenobiotic may affect different molecular mechanism(s) at much lower doses relevant to human exposures. To amend mechanistic toxicology with a simple and concise guiding principle, I suggest recontextualization of Paracelsus’s following its letter and spirit: “The dose disrupts the pathway”. Justification of this statement includes observations that many environmental and occupational xenobiotics affect a broad range of molecular cascades, that most molecular pathways are sensitive to chemical exposures, and that different molecular pathways are sensitive to different doses of a chemical compound. I suggest that this statement may become a useful guidance and educational tool in a range of toxicological applications, including experimental design, comparative analysis of mechanistic hypotheses, evaluation of the quality of toxicological studies, and risk assessment.

Variability in Effect of Pesticides on Bumblebee Survival Tied to Gut Microbiome Health    (Beyond Pesticides, July 18, 2025) A study in Royal Society Open Science shows intraspecific differences (between individuals of a species) in wild bumblebees (Bombus vosnesenskii) exposed to an herbicide (glyphosate), a fungicide (tebuconazole), and an insecticide (imidacloprid), with gut microbiome health as a factor. 

Multitude of Studies Find Epigenetic Effects from PFAS and Other Endocrine Disrupting Pesticides     (Beyond Pesticides, January 16, 2025) In Ecotoxicology and Environmental Safety, researchers highlight a multitude of studies on endocrine disrupting chemicals (EDCs) and endocrine disrupting pesticides (EDPs) showing epigenetic effects from exposure.    In causing epigenetic modifications, the authors describe that EDCs can create changes “at the nuclear and mitochondrial DNA (nDNA and mtDNA) or RNA levels, without changing the underlying DNA sequence. These alterations modify the structure or conformation of DNA, influencing gene expression and, consequently, cellular function.” They continue, “The mechanisms of epigenetics include changes in DNA methylation, chromatin modifications and the involvement of certain noncoding RNAs.”     The researchers further explain: “Due to the distinct structural features of EDPs, the mode of their toxic action varies with different dosages, influencing the molecular mechanisms of hormone secretion, targets, and even the toxic pathways that affect various hormones in various ways indeed at extremely low concentrations. Nonetheless, the biological mechanisms underlying their effects remain incompletely understood.'      SNAP Comment: In other words, the basis of the North American pesticide regulatory system, 'the dose makes the poison" is grossly inadequate in evaluation of pesticide health effects. 

Glyphosate Mixtures Show Lethal and Sublethal Effects to Embryos, Highlights Regulatory Deficiencies   (Beyond Pesticides, November 13, 2024) A study in Chemosphere, conducted by researchers from the Institute of Biochemistry and Molecular Biology in Germany, reveals the varied lethal and sublethal effects of different glyphosate mixtures through tests on the South African clawed frog, Xenopus laevis (X. laevis). After exposing embryos to four glyphosate formulations, mortality, morphological defects, altered heartbeat rate, and impaired heart-specific gene expression are observed.    The formulations consist of varying concentrations of the active ingredient glyphosate, as well as other active and inert ingredients. such as 10–20% d-glucopyranose,  1–5% N–N-dimethyl-C12-C14-(even numbered)-alkyl-1-amines, 1–10% isopropylamine, 1–3% lauryl dimethyl betaine, 0.25–1% dodecyl dimethylamine. Kyleo only lists the active ingredients glyphosate (27.9%) and 2,4-D (32%).”      All solutions were prepared with glyphosate concentrations of 0.01, 0.1, 1, 10, and 100 mg/L. “The exposure of embryos to 0.01–10 mg/L glyphosate reflects environmentally relevant concentrations already measured in different countries, with 100 mg/L glyphosate representing ‘worst-case’ scenarios (e.g., incorrect handling or improper disposal), but already measured in water bodies in Argentina,” the researchers state.'   The high glyphosate levels caused high mortality. Exposure to 0.1 mg/L glyphosate altered gene exoression in various ways depending on the formulation. 'The different formulations selected for exposure experiments showed varying degrees of lethal effects at the same concentrations of the active ingredient glyphosate,” the researchers summarize. With the varied results, the authors hypothesize that the other ingredients play a role in toxicity.'

Study of Chemical Mixtures at Low Concentrations Again Finds Adverse Health Effects   (Beyond Pesticides, April 10, 2024) Researchers in a 2024 Chemosphere study find synergistic relationships in certain chemical mixtures, particularly heptachlor and triallate and trifluralin and lindane at lower concentrations, respectively.... “According to a Centers for Disease Control (CDC) assessment, more than 50 pesticides are detected in blood or urine samples from the US population,” Researchers point to a cause for concern.... Researchers “used the exposure data from a complex operating site with legacy pesticide pollution.... “Only volatile COPCs... in soil and groundwater were included in this study (triallate, trifluralin, lindane, heptachlor, dieldrin, and aldrin,” the researchers indicate in the Methods section. Quantitative risk assessment for pesticide exposure was rooted on oral exposure... which demands a higher dose to induce an identifiable adverse effect relative to inhalation exposure. In other words, using an oral reference dose may underestimate the potential risk....  Researchers did find values suggesting “significant health concerns” to toddlers, infants, teenagers, and adults in “commercial and industrial land use.”... “Nine of the 15 tested binary mixtures of pesticides synergistically reduced cell viability. Seven mixtures (Trifluralin/Heptachlor, Trifluralin/Aldrin, Lindane/Heptachlor, Lindane/Aldrin, Heptachlor/Dieldrin, Heptachlor/Aldrin and Dieldrin/Aldrin) were synergistic at higher concentrations. However, two mixtures of herbicides and OCPs (organochlorine pesticides) (Trifluralin/Lindane and Triallate/Heptachlor) interacted synergistically at lower concentrations'.    SNAP Comment: All the pesticides listed were historically registered in Canada except dieldrin and two still are:trifluralin and triallate. 'There are 23,078 federal sites listed in the FCSI maintained by the Treasury Board of Canada Secretariat, including 5,337 active contaminated sites and 2,355 suspected sites. 15,386 are listed as closed because remediation is complete or because no action was necessary following assessment.' Inventory of federal contaminated sites.    'Research shows adverse health effects most likely occur within a 1.8 mile boundary around a Superfund site.' Millions of Americans Live Near Toxic Waste Sites. How Does This Affect Their Health?(February 16, 2022)

Study first to link weed killer Roundup to convulsions in animals   (Florida Atlantic University, 23 August, 2022)      'Results, published in Scientific Reports, showed that glyphosate and Roundup increased seizure-like behavior in soil-dwelling roundworms and provides significant evidence that glyphosate targets GABA-A receptors. These communication points are essential for locomotion and are heavily involved in regulating sleep and mood in humans. What truly sets this research apart is that it was done at significantly less levels than recommended by the EPA and those used in past studies.     "The concentration listed for best results on the Roundup Super Concentrate label is 0.98 percent glyphosate, which is about 5 tablespoons of Roundup in 1 gallon of water," said Naraine. "A significant finding from our study reveals that just 0.002 percent glyphosate, a difference of about 300 times less herbicide than the lowest concentration recommended for consumer use, had concerning effects on the nervous system."     "As of now, there is no information for how exposure to glyphosate and Roundup may affect humans diagnosed with epilepsy or other seizure disorders," said Dawson-Scully. "Our study indicates that there is significant disruption in locomotion and should prompt further vertebrate studies."'  see also New Evidence Shows Roundup Damages the Nervous System  (Beyond Pesticides, August 30, 2022) 

Implications for Human Health: Chronic Inhalation of Paraquat in Low-Doses Disrupts Sense of Smell   SNAP Comment: As of 9 March 3021, the PMRA still lists 3  paraquat labels as being registered in Canada. The commercial product is Gramoxone 200 SL.   (Beyond Pesticides, February 18, 2021) 'New research published in the journal Toxicological Sciences finds extended inhalation of the common herbicide paraquat causes male mice to lose some sense of smell, even at low doses. This study highlights the significance of understanding how specific chemical exposure routes can influence disease development. Olfactory (relating to the sense of smell) impairment is a precursory feature of Parkinson’s disease (PD), and studies connect paraquat poisoning to PD risk.'