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

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In a later review of cancer epidemiology after exposure to atrazine for the United States EPA
(Blondell & Dellarco, 2003), four studies concerning prostate cancer were evaluated: a nested case–
control study among workers in a plant manufacturing triazine in Louisiana (Hessel et al., 2004), the
Agricultural Health Study which is a prospective cohort study of 55 332 male pesticide applicators
from Iowa and North Carolina (Alavanja et al., 2003), an ecological study conducted in California
(Mills, 1998), and a nested case–control study in Californian farm workers exposed to simazine
(a triazine derivative similar to atrazine) and several other pesticides (Mills & Yang, 2003).
In the studies in California, a borderline statistically significant correlation was found between
use of atrazine and prostate cancer in black males, but not among Hispanic, white, or Asian males
(Mills, 1998), and a borderline significant association was found between high use of simazine and
prostate cancer (Mills & Yang, 2003). However, both studies suffered from aggregation bias because
there was no or only a crude measure of exposure and the results should thus not be considered for
reaching conclusions about causation.
In the nested case–control study (Hessel et al., 2004), an elevated incidence of prostate cancer
was found in active employees who received intensive screening for prostate specific antigen (PSA),
but there was no increase in the incidence of advanced tumours or mortality, and proximity to atrazine-manufacturing
plants did not appear to be correlated with risk. Thus, the increase in incidence
of prostate cancer was probably attributable to increased detection because of the intensive screening
programme for PSA (MacLennan et al., 2002).
The largest and most reliable study (Alavanja et al., 2003) showed no association of atrazine
exposure with prostate cancer in cohort analysis of pesticide applicators. The overall conclusion of
the reviewers was that studies in manufacturing and farming populations do not support a finding that
atrazine is a likely cause of prostate cancer.
In a study of workers in a plant manufacturing triazine in Louisiana (MacLennan et al., 2003),
a borderline significant result was found for non-Hodgkin lymphoma on the basis of 4 observed
deaths vs 1.1 deaths expected. The study authors noted, however, that “one of the decedents whose
death certificate included a diagnosis of non-Hodgkin lymphoma had medical records including a
biopsy report that indicated a diagnosis of poorly differentiated nasopharyngeal cancer. This case
was not removed from our analysis.” This acknowledgment of bias on the basis of a misclassified
case means that the borderline statistically significant finding would no longer be significant if the
case were excluded. Therefore, the overall conclusion of the reviewers was that this evidence is not
sufficient to support a finding that atrazine is a likely cause of non-Hodgkin’s lymphoma.
Additional evaluations of the cancer incidences in the Agricultural Health Study did not find
any clear associations between exposure to atrazine and any cancer analysed (Rusiecki et al., 2004).
However, the authors pointed out that further studies were warranted for tumour types for which
there was a suggestion of trend (lung, bladder, non-Hodgkin lymphoma, and multiple myeloma). It
should be noted that the neuroendocrine mode of action of atrazine cannot account for the biological
plausibility of these tumours.
An evaluation of risk of breast cancer among farmers’ wives in the Agricultural Health Study
(30 454 participants with no history of breast cancer before cohort enrolment in 1993–1997) did
not find any association of increased incidence of breast cancer with the use of atrazine; however,
reduced risk of breast cancer among postmenopausal women were linked to their use of atrazine
(relative risk, RR, 0.4; 95% CI, 0.1–1.0) (Engel et al., 2005).
The incidence of cancer among pesticide applicators exposed to cyanazine (a triazine derivative
similar to atrazine) in the Agricultural Health Study has also been unremarkable (Lynch et al.,
2006).
Current evidence was not persuasive as to an association between ovarian cancer and exposure
to triazine. In a population-based case–control study of incident cases (n = 256) and control subjects
ATRAZINE 37–138 JMPR 2007