Pesticide residues in food — 2007: Toxicological ... - ipcs inchem

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Appendix 1 Application of the IPCS Conceptual Framework for Cancer
Risk Assessment (IPCS Framework for Analysing the Relevance of a
Cancer Mode of Action for Humans): consideration of mammary gland
tumours in female Sprague-Dawley rats exposed to atrazine .......................... 118
Mammary gland tumours associated with atrazine exposure in female
Sprague-Dawley rats ........................................................................................ 118
References ....................................................................................................... 124
Explanation
Atrazine, 6-chloro-N 2 -ethyl-N 4 -isopropyl-1,3,5-triazine-2,4-diamine (International Union
of Pure and Applied Chemistry, IUPAC) (Chemical Abstracts Service, CAS No. 1912-24-9), is a
selective systemic herbicide of the chlorotriazine class, which is used for the control of annual broadleaf
and grassy weeds. It acts as a photosynthetic electron transport inhibitor at the photosystem
II receptor site. Atrazine and its chloro-s-triazine metabolites deethyl-atrazine (DEA), deisopropylatrazine
(DIA) and diaminochlorotriazine (DACT) have been found in surface and groundwater as
a result of the use of atrazine as a pre-emergent or early post-emergent herbicide. Hydroxyatrazine
is more commonly detected in groundwater than in surface water. The relative order of concentrations
of these substances measured in rural wells in the USA was generally as follows: atrazine ~
DEA ~DACT > DIA > hydroxyatrazine. However, concentrations of DEA that are severalfold those
of the parent compound have been reported.
Atrazine was evaluated previously by WHO, a tolerable daily intake (TDI) of 0.0005 mg/kg bw
being established in the 1993 Guidelines for Drinking-water Quality on the basis of a no-observedadverse-effect
level (NOAEL) of 0.5 mg/kg bw per day in a study of carcinogenicity in rats and
using a safety factor of 1000 (100 for inter- and intraspecies variation and 10 to reflect potential
carcinogenic risk to humans).
Atrazine has not been previously evaluated by JMPR, and no acceptable daily intake (ADI) had
been established. For that reason, the WHO Drinking-water Guidelines Programme recommended
that atrazine should be evaluated toxicologically by JMPR.
The database on atrazine was extensive, consisting of a comprehensive set of studies with
atrazine and its four key metabolites, which complied with good laboratory practice (GLP), as well
as a large number of published studies. The present Meeting did not aim to perform a review of
the database de novo, but to summarize the key studies, focusing on the issues of carcinogenicity,
endocrine disruption (especially neuroendocrine mode of action) and immunotoxicity. Reference
was made to a number of reviews made by national and international agencies and organizations in
recent years.
Summary data were provided on the occurrence of atrazine residues in water, abstracted from
monitoring data collected in areas where atrazide is widely used. Globally, atrazine is most commonly
used as a pre-emergent or early post-emergent herbicide in corn in the USA and Brazil. Much
smaller amounts are used in sorghum (Australia and the USA), sugar-cane (Brazil and the USA),
oilseed crops (Australia) and tree plantations (Australia). The non-agricultural uses of atrazine (e.g.
railways, road embankments, turf, home garden) have largely been removed from atrazine labels in
recent years.
Because atrazine is somewhat persistent in the environment and is reasonably mobile in soils,
a number of studies have monitored the concentrations of atrazine in groundwater and surface water
over the last two decades. Recent monitoring data show declining levels and incidences of detections
of atrazine and its chloro-s-metabolites (DIA; DEA and DACT) compared with data collected
ATRAZINE 37–138 JMPR 2007