{"title":"整合支持草甘膦可能的发育性神经毒性(DNT)的不同证据流","authors":"A.F. Hernández","doi":"10.1016/j.toxlet.2025.07.064","DOIUrl":null,"url":null,"abstract":"<div><div>Glyphosate, the active ingredient in glyphosate-based herbicides (GBHs), is extensively used for weed control, with recent concerns emerging over its potential developmental neurotoxicity (DNT). Regulatory assessments in the EU have identified a critical data gap regarding DNT studies on glyphosate acid. This presentation synthesises evidence from epidemiological, <em>in vivo</em>, and new approach methodologies (NAMs) to assess its neurodevelopmental effects. Epidemiological studies yielded inconsistent findings. Some reported associations between prenatal glyphosate exposure and autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and developmental delays, while others find no significant links. These inconsistencies can be attributed to variations in exposure assessment and study design. Animal studies provide more consistent evidence supporting neurodevelopmental effects. Rodent models indicate that glyphosate exposure disrupts neurotransmitter systems, induces oxidative stress, alters endocrine signalling, and promotes neuroinflammation, leading to cognitive impairments, anxiety-like behaviours, and deficits in social interaction. However, these effects are primarily observed with GBHs rather than glyphosate alone. Regulatory guideline studies remain limited, with a single DNT study on glyphosate trimesium reporting positive effects, though this form is not representative of glyphosate acid's toxicological profile. Zebrafish studies further corroborate glyphosate's neurotoxic potential. <em>In vitro</em> research shows that glyphosate induces apoptosis, disrupts neuronal differentiation, and activates glial cells, while <em>in silico</em> modelling predicts interactions with neurotransmitter receptors and endocrine pathways. Remarkably, GBHs appear more neurotoxic than glyphosate alone, likely due to surfactant components enhancing toxicity. A weight-of-evidence approach suggests that while GBHs may pose neurodevelopmental risks, no definitive DNT liabilities for glyphosate acid have been established. Addressing the identified data gap through further research is essential to refine its neurotoxicological profile.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Page S20"},"PeriodicalIF":2.9000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"S07-01 Integration of different streams of evidence supporting possible developmental neurotoxicity (DNT) of glyphosate\",\"authors\":\"A.F. Hernández\",\"doi\":\"10.1016/j.toxlet.2025.07.064\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Glyphosate, the active ingredient in glyphosate-based herbicides (GBHs), is extensively used for weed control, with recent concerns emerging over its potential developmental neurotoxicity (DNT). Regulatory assessments in the EU have identified a critical data gap regarding DNT studies on glyphosate acid. This presentation synthesises evidence from epidemiological, <em>in vivo</em>, and new approach methodologies (NAMs) to assess its neurodevelopmental effects. Epidemiological studies yielded inconsistent findings. Some reported associations between prenatal glyphosate exposure and autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and developmental delays, while others find no significant links. These inconsistencies can be attributed to variations in exposure assessment and study design. Animal studies provide more consistent evidence supporting neurodevelopmental effects. Rodent models indicate that glyphosate exposure disrupts neurotransmitter systems, induces oxidative stress, alters endocrine signalling, and promotes neuroinflammation, leading to cognitive impairments, anxiety-like behaviours, and deficits in social interaction. However, these effects are primarily observed with GBHs rather than glyphosate alone. Regulatory guideline studies remain limited, with a single DNT study on glyphosate trimesium reporting positive effects, though this form is not representative of glyphosate acid's toxicological profile. Zebrafish studies further corroborate glyphosate's neurotoxic potential. <em>In vitro</em> research shows that glyphosate induces apoptosis, disrupts neuronal differentiation, and activates glial cells, while <em>in silico</em> modelling predicts interactions with neurotransmitter receptors and endocrine pathways. Remarkably, GBHs appear more neurotoxic than glyphosate alone, likely due to surfactant components enhancing toxicity. A weight-of-evidence approach suggests that while GBHs may pose neurodevelopmental risks, no definitive DNT liabilities for glyphosate acid have been established. Addressing the identified data gap through further research is essential to refine its neurotoxicological profile.</div></div>\",\"PeriodicalId\":23206,\"journal\":{\"name\":\"Toxicology letters\",\"volume\":\"411 \",\"pages\":\"Page S20\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Toxicology letters\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0378427425016479\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0378427425016479","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"TOXICOLOGY","Score":null,"Total":0}
S07-01 Integration of different streams of evidence supporting possible developmental neurotoxicity (DNT) of glyphosate
Glyphosate, the active ingredient in glyphosate-based herbicides (GBHs), is extensively used for weed control, with recent concerns emerging over its potential developmental neurotoxicity (DNT). Regulatory assessments in the EU have identified a critical data gap regarding DNT studies on glyphosate acid. This presentation synthesises evidence from epidemiological, in vivo, and new approach methodologies (NAMs) to assess its neurodevelopmental effects. Epidemiological studies yielded inconsistent findings. Some reported associations between prenatal glyphosate exposure and autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and developmental delays, while others find no significant links. These inconsistencies can be attributed to variations in exposure assessment and study design. Animal studies provide more consistent evidence supporting neurodevelopmental effects. Rodent models indicate that glyphosate exposure disrupts neurotransmitter systems, induces oxidative stress, alters endocrine signalling, and promotes neuroinflammation, leading to cognitive impairments, anxiety-like behaviours, and deficits in social interaction. However, these effects are primarily observed with GBHs rather than glyphosate alone. Regulatory guideline studies remain limited, with a single DNT study on glyphosate trimesium reporting positive effects, though this form is not representative of glyphosate acid's toxicological profile. Zebrafish studies further corroborate glyphosate's neurotoxic potential. In vitro research shows that glyphosate induces apoptosis, disrupts neuronal differentiation, and activates glial cells, while in silico modelling predicts interactions with neurotransmitter receptors and endocrine pathways. Remarkably, GBHs appear more neurotoxic than glyphosate alone, likely due to surfactant components enhancing toxicity. A weight-of-evidence approach suggests that while GBHs may pose neurodevelopmental risks, no definitive DNT liabilities for glyphosate acid have been established. Addressing the identified data gap through further research is essential to refine its neurotoxicological profile.