"Journal of Toxicology and Environmental Health, Part B"

Holliman, Anna G.; Mackay, Laci; Biancardi, Vinicia C.; Tao, Ya-Xiong; Foradori, Chad D.

doi: 10.1080/10937404.2025.2468212pmid: 40016167

Atrazine is a chlorotriazine herbicide that is one of the most widely used herbicides in the USA and the world. For over 60 years atrazine has been used on major crops including corn, sorghum, and sugarcane to control broadleaf and grassy weed emergence and growth. Atrazine has exerted a major economic and environmental impact over that time, resulting in reduced production costs and increased conservation tillage practices. However, widespread use and a long half-life led to a high prevalence of atrazine in the environment. Indeed, atrazine is the most frequent herbicide contaminant detected in water sources in the USA. Due to its almost ubiquitous presence and questions regarding its safety, atrazine has been well-studied. First reported to affect reproduction with potential disruptive effects which were later linked to the immune system, cancer, stress response, neurological disorders, and cardiovascular ailments in experimental models. Atrazine impact on multiple interwoven systems broadens the significance of atrazine exposure. The endeavor to uncover the mechanisms underlying atrazine-induced dysfunction in mammals is ongoing, with new genetic and pharmacological targets being reported. This review aims to summarize the prominent effects of atrazine on mammalian physiology, primarily focusing on empirical studies conducted in lab animal models and establish correlations with epidemiological human studies when relevant. In addition, current common patterns of toxicity and potential underlying mechanisms of atrazine action will be examined.

Dorman, David C.; McGough, Doreen; Aschner, Michael; Levy, Len; Gross, Peggy

doi: 10.1080/10937404.2025.2476418pmid: 40289256

Specific Target Organ Toxicity – Repeated Exposure (STOT-RE) is a hazard class in both Globally Harmonized System and Classification, Labelling and Packaging (CLP) Regulation in the European Union (EU) legislation on hazard classification labeling and packaging of substances and mixtures. This legislation, used for the chemical safety assessment under the EU Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), evaluates long-term exposure of chemicals on human or animals and designates three categories of classification – STOT RE 1 (potential to produce significant toxicity to humans); STOT RE 2 (presumed to be toxic to humans), or not classified. Human epidemiologic studies identified neurologic effects as the most sensitive adverse health effect following repeated manganese (Mn) exposure. However, there are inadequate human studies to assess the neurotoxicity and STOT-RE classification of the chloride, sulfate, and nitrate forms of Mn. This review summarizes peer-reviewed studies with original data identified from searches of PubMed and OECD studies submitted as part of the REACH information requirement. This review included peer-reviewed studies that exhibited a duration of ≥21 days, including oral or inhalation exposure, and reported neurobehavioral, neurochemical or neuropathologic outcomes. A total of 75, 6, and 0 investigations met the inclusion criteria for this review for the chloride, sulfate, and nitrate forms of Mn, respectively. Based upon retrieved data or read-across principles a proposed classification of these Mn salts, following repeated oral or inhaled exposure, is STOT RE 2, target organ, the brain.