title: Toxicity endpoint selections for a simazine risk assessment.
abstract: BACKGROUND
  California uses simazine at one of the highest levels for states in the United States (approximately 2.5 million lbs 2006-2010). Simazine causes neuroendocrine disruption and mammary cancer in test animals. A risk assessment was prioritized by the California Department of Pesticide Regulation because of the nondietary concern for simazine exposure to occupational/nonoccupational simazine users, resident nonusers, and bystanders (especially children and children exhibiting pica) at greatest risk.
  
  
  METHODS
  No observed effect levels (NOELs) from animal studies as well as human exposure data were used to determine nondietary values for the above populations. Registrant-submitted and open literature studies focusing on oral (major human route) effects for simazine and the major metabolites desisopropyl-s-atrazine and diaminochlorotriazine were reviewed as part of the hazard identification process.
  
  
  RESULTS
  Developmental, reproduction, and chronic studies provided the lowest NOELs for the acute (5 mg/kg/day), subchronic (0.56 mg/kg/day), and chronic (0.52 mg/kg/day) exposure durations, respectively. A benchmark dose (95th percentile) was calculated for mammary tumorigenesis, assuming a threshold mechanism in rats (benchmark dose lower limit [95th percentile; BMDL05 ]: 2.9 mg/kg/day). Margins of exposure and uncertainty factors (100-300×, depending on exposure scenario) were used to characterize risk for designated population subgroups.
  
  
  CONCLUSIONS
  Fetal developmental delays, endocrine disruption, and mammary tumors resulted from simazine treatment. Systemic and maternal/fetal effects determined the critical NOELs used in risk assessment. Margins of exposures for most scenarios were below acceptable levels, especially for children who may be bystanders where simazine is applied and children who exhibit pica. This risk characterization raises a concern for long-term effects in humans.
authors: Medical Toxicology Branch, Department of Pesticide Regulation, California Environmental Protection Agency, Sacramento, California.
authors: Marilyn
authors: M
authors: Silva
authors: Poorni
authors: P
authors: Iyer
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004781:Environmental Exposure; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D006540:Herbicides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity*; D006801:Humans; D061986:MCF-7 Cells; D011817:Rabbits; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism; D012098:Reproduction / Q000187:drug effects*; D018570:Risk Assessment; D012839:Simazine / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity*
chemical_list: D006540:Herbicides; D011960:Receptors, Estrogen; D012839:Simazine
keywords: developmental; endocrine effects; mammary tumors; reproductive toxicity; risk assessment; simazine; uncertainty factors