ATRAZINE AND ITS METABOLITES

Atrazine is a selective systemic herbicide of the chlorotriazine class, used for the control of annual broadleaf and grassy w eeds. Atrazine and its chloro- s -triazine metabolites— deethyl-atrazine (DEA), deisopropyl-atrazine (DIA) and diaminochlorotriazine (DACT)—have been found in su rface water and groundwater as a result of the use of atrazine as a pre-emergent or early post-emergent herbicide. The metabolite hydroxyatrazine is more comm only detected in groundwater than in surface water.

0.1 mg/l for atrazine and its chloro- s -triazine metabolites Guideline values 0.2 mg/l for hydroxyatrazine

Occurrence Concentrations rarely exceed 2 μg/l and are commonly well below 0.1 μg/l Group ADI for atrazine and its
chloro- s -triazine metabolites 0–0.02 mg/kg body weight based on the NOAEL for atrazine of 1.8 mg/kg body weight per day identified on the basis of luteinizing hormone surge suppression and subsequent disruption of the estrous cycle seen at 3.6 mg/kg body weight per day in a 6-month study in rats, using a safety factor of 100 ADI for hydroxyatrazine 0–0.04 mg/kg body weight based on the NOAEL of 1.0 mg/kg body weight per day identified on the basis of kidney toxicity at 7.8 mg/kg body weight per day in a 24-month study in rats, and using a safety factor of 25, based on kinetic considerations Limit of detection Atrazine : 1 ng/l, isotope dilution MS with solid-phase extraction; 10 ng/l, GC/MS with solid-phase extraction; 50 ng/l, LC/MS with solid-phase extraction; 0.1 μg/l, GC with nitrogen–phosphorus
detection
Metabolites : 5 ng/l, capillary GC with nitrogen thermionic specific detection and HPLC with photodiode array absorption detection following extraction with styrene-divinylbenzene sorbents and elution
with acetone Treatment performance 0.1 μg/l can be achieved using GAC or PAC; also effective are
bankside filtration and nanofiltration

Guideline derivation

• allocation to water

• body weight

• consumption 20% of ADI 60 kg adult 2 litres/day

Additional comments • JMPR considered that the NOAEL for atrazi ne is protective for the consequences of neuroendocrine and other adverse effects caused by prolonged exposure to atrazine and its chloro- s -triazine
metabolites.

• 20% allocation will be very conservative in most countries, as it is expected that exposure of the public will be primarily through drinking-water.

Assessment date This assessment was conducted in 2009. Principal references FAO/WHO (2007) Atrazine. In: Pesticide residues in food—2007. Joint FAO/WHO Meeting on Pesticide Residues. Rome, Food and Agriculture Organization of the United Nations (FAO Plant Production and Protection Paper 191; http://www.fao.org/ag/AGP/AGPP/Pesticid/JMPR/DOWNLOAD/200 7_rep/report2007jmpr.pdf).

FAO/WHO (2009) Atrazine. In: Pesticide residues in food—2007
evaluations. Part II. Toxicological . Geneva, World HealthOrganization (http://whqlibdoc.who.int/publications/2009/9789241665230_eng.pdf).

WHO (2009) Atrazine and its metabolites in drinking-water. Background document for development of WHO Guidelines for Drinking-water Quality. Geneva, World Health Organization (WHO/HSE/WSH/09.01/11).

JMPR agreed that it is unlikely that atrazine is genotoxic and concluded that atrazine is not likely to pose a carcinog enic risk to humans, as the mode of carcin ogenic action in certain susceptible rat strains is not relevant for human risk assessment. The weight of
evidence from the epidemiological studies also did not support a causal association between exposure to atrazine and the occurrence of cancer in humans. In special studies of reproduc tive toxicity, exposure of rats during ea rly pregnancy (i.e. the LH-dependent period) caused increased pre-implantation or post-implantation losses, including full-litter re sorptions. Attenuation of th e LH surge and subsequent disruption of the estrous cycle (characterized by an increase in da ys in estrus) were observed at and above 3.65 mg/ kg body weight per day, with a NOAEL of 1.8 mg/kg body weight per day. The effects on the LH surge and disruption of the estrous cycle were further supported by a number of s hort-term mechanistic studies. Additional experiments suggested that the effects of atrazine on LH and pr olactin secretion are mediated via a hypothalamic site of acti on. JMPR concluded that atrazine was not teratogenic. Studies using a variety of te st systems in vitro and in vivo indicated th at modulation of the immune system occurs after exposure to atrazine. However, effects suggestive of impaired function of the immune system were observed only at doses greater than those
shown to affect neur oendocrine function, lead ing to disruption of the estrous cycle or developmental effects. The toxicity profile s and mode of acti on of the chloro- s -triazine metabolites are similar to those of atrazine; the potency of these metabolites w ith regard to their neuroendocrine-disruptin g properties appeared to be si milar to that of the parent compound. The metabolite hydrox yatrazine does not have the same mode of action or toxicity profile as atrazine a nd its chlorometabolites. The main effect of hydr oxyatrazine was kidney toxicity (owing to its low solubility in water, resulting in crystal formation and a subsequent inflammatory response), and ther e was no evidence that hydroxyatrazine has neuroendocrine-disrupt ing properties. There was no ev idence of carci nogenicity, and hydroxyatrazine did not show ge notoxicity in an adequate rang e of tests in vitro and in
vivo.