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Evaluation of Health Hazards by exposure to Triazines and Degradation Products
3 Human toxicity
3.1 Single dose toxicity
No data were found.
3.2 Skin irritation
A case-report exist of a male farmer who was diagnosed with acute contact dermatitis on his hands and forearms on the same day as he had been exposed dermally to atrazine and
cyanazine (Schlicher and Beat 1972 – quoted from ATSDR 2001).
A total of 124 cases of contact dermatitis were noted in the former USSR among workers manufacturing simazine and propazine. Serious cases lasting 7-10 days involved erythema,
oedema, and a vesiculopapular reaction that sometimes progressed to the formation of bullae. (Elizarov 1972 - quoted from IARC 1999b, WHO 1996b).
3.3 Sensitisation
A 0.5% suspension of an atrazine or simazine formulation did not cause skin sensitisation on repeated application to 50 humans (Shelanski and Gittes 1965 - quoted from EC 1996a,b).
3.4 Repeated dose toxicity
No data were found.
3.5 Toxicity to reproduction
The use of a number of pesticides and chemicals, including atrazine, in the three-month period preceding a pregnancy was assessed from a questionnaire completed by 1898 couples on
farms in Ontario, Canada. The use of atrazine itself was not associated with increased odds ratios for miscarriage, pre-term delivery, or babies who were small for gestational age. In
some instances, combined exposure to a variety of chemicals including atrazine generated odds ratios of 2 or greater. (Savitz et al. 1997 – quoted from ATSDR 2001, IARC 1999a).
Atrazine was not associated with any decrease in fecundity in a survey (in which a number of confounders were controlled for) of 1048 couples on farms in Ontario, Canada. Pesticide
exposure was defined as pesticide use on the farm during the month of trying to conceive or at any time during the prior 2 months. (Curtis et al. 1999 – quoted from ATSDR 2001).
An ecological study in Iowa, USA, that examined the association of triazines in the 856 municipal drinking water supplies with intrauterine growth retardation, prematurity, and low birth
weight found a greater risk of intrauterine growth retardation in live births by women in 13 communities served by a water system containing elevated levels of triazines. Multiple linear
regression analysis showed that the levels of atrazine, cyanazine, and metalachlor were each significant predictors of community intrauterine growth retardation rates in the exposed
communities. No definite causal relationship between any single water contaminant and risk of intrauterine growth retardation could be determined due to lack of individual exposure
data and the limited ability to control for confounding factors. (Munger et al. 1997 – quoted from ATSDR 2001).
3.6 Mutagenic and genotoxic effects
No statistically significant increase in micronucleus formation and sister chromatid exchange of peripheral blood lymphocytes was found in 34 males from Spain exposed to simazine in
the drinking water at levels of 10 to 30 ppm compared to controls drinking water with no detectable level of simazine. A statistically significant increase was found in high frequency cells,
HFC (the percent of lymphocytes with more than 11 sister chromatid exchanges). The HFC sample could contain a subpopulation of more sensitive cells or a subpopulation of
long-living lymphocytes that accumulated DNA-lesions in vivo. The authors conclude that their findings indicate the lack of potential cytogenetic hazard due to simazine exposure.
(Suárez et al. 2003).
3.7 Carcinogenic effects
A combined analysis of the results of two cohort studies of agricultural chemical production workers (4917 male persons) in the USA showed decreased mortality from cancers at all
sites combined among the subset of workers (55%) who had definite or probable exposure to triazines. Site-specific cancer analysis in this subset of workers yielded no significant
findings. A non-significant increase in the number of deaths from non-Hodgkin lymphoma was seen, but was based on only 3 observed cases. Two of these three men had had less than
one year of employment involving exposure to triazines. Exposure to pesticides other than triazine herbicides was not controlled for in the analysis. (Sathiakumar et al 1996 – quoted
from IARC 1999a).
In a cohort study of American workers (2213 persons) at a plant that mainly made atrazine and other triazines, decreased mortality was observed. The total number of deaths from
cancer was not significantly different from controls. A significant increase (standardized mortality ratio (SMR): 372, 95% confidence interval (CI): 101-952) in the number of deaths
from non-Hodgkin lymphoma was seen, but the 4 observed cases were not concentrated in the subgroup with long duration of employment and many years since hire. The study was
limited by its small size, by the relative young age and short follow-up of the workers, and by the lack of exposure data. In a companion study of cancer incidence in the same group of
workers, a 1.8-fold increase in prostate cancer incidence was found. Bias could not be ruled out as a reason for this increase because the excess of prostate cancer occurred primarily in
company employees, who had been screened annually with prostate-specific antigen tests. (MacLennan et al. 2003).
A pooled analysis of the results of three population-based case-control studies of men in Kansas, eastern Nebraska and Iowa-Minnesota, USA, (933 cases, 2918 controls) in which the
risk for non-Hodgkin lymphoma in relation to atrazine and other herbicides on farms were evaluated, showed a significant age and state adjusted association (odds ratio: 1.4, CI:
1.1-1.8).The association was weaker (odds ratio: 1.2, CI: 0.9-1.7) when adjustment was made for reported use of phenoxyacetic acid herbicides or organophosphate insecticides. A
sub-analysis of results for farmers in Nebraska, the state in which the most detailed information on atrazine use was available, showed no excess risk for non-Hodgkin lymphoma among
farmers who had used atrazine for at least 15 years after adjustment for use of other pesticides. In a case-control study of non-Hodgkin lymphoma among women (134 cases, 707
controls) in eastern Nebraska, a slight, non-significant increase in risk (odds ratio: 1.2, CI: 0.6-2.6) was seen among women who had ever used triazines on farms. The odds ratio was
not adjusted for use of other types of pesticides. (Zahm et al. 1993a,b - quoted from ATSDR 2001, IARC 1999a).
A small but statistically significant association (odds ratio: 1.7, CI: 1.0-2.8) was found between atrazine exposure and the non-Hodgkin lymphoma subtype defined by t(14;18)
chromosomal translocation in a case-control study of a subgroup of the men from Iowa-Minnesota mentioned in the previous study. (Schroeder et al. 2001).
Case-control studies of Hodgkin's lymphoma, soft-tissue sarcoma, and colon cancer in Kansas, leukaemia in Iowa-Minnesota, and multiple myeloma in Iowa showed no significant
excess risk among persons handling triazine herbicides. (Hoar et al. 1985,1986, Brown et al. 1990,1993 – quoted from IARC 1999a).
In a case-control study in Italy (65 cases, 126 controls), the odds ratios for primary malignant epithelial tumours of the ovary, adjusted for age, number of live births, and use of
contraceptives were 2.7 (90% CI: 1.0-6.9) for definitely exposed and 1.8 (90% CI: 0.9-3.5) for possibly exposed. The odds ratios were slightly higher among women with at least 10
years of occupational contact with triazines when compared with those with fewer than 10 years of contact. The odds ratios were not adjusted for exposure to other types of pesticides.
(Donna et al. 1989 - quoted from IARC 1999a, WHO 1996a,b).
In a nested case-control study (222 cases, 1110 controls) in California, USA, within a cohort of a predominantly Hispanic labour union, an elevated risk of prostate cancer was found in
farm workers with relative high exposure to simazine compared to workers with lower levels of exposure. Increased risk was also experienced with other specific pesticides. (Mills and
Yang 2003).
An ecological study that assessed the correlation of the amount of pesticides used in California counties to the incidence rates of each of several cancer types (non-Hodgkin's lymphoma,
leukaemia, soft-tissue sarcoma, brain cancer, prostate cancer, and testicular cancer) found a correlation between atrazine use and brain and testis cancers and leukaemia in Hispanic
males, and prostate cancer in black males. These segments of the population had traditionally been employed as farm workers and had had the greatest potential for exposure to
pesticides. No individual exposure data were available. (Mills 1998 – quoted from ATSDR 2001).
An ecological study in Kentucky, USA, that examined the association of atrazine exposure indices with breast and ovarian cancer incidence rates found an inverse association (with
increasing exposure linked to decreasing incidence rates) between atrazine levels and ovarian cancer and no association between atrazine levels and breast cancer. Exposure indices to
atrazine were derived based on public water measurements, acres of corn planted, and pounds of atrazine sold. No individual exposure data were available. (Hopenhayn et al. 2002).
An ecological study in Ontario, Canada, that examined the association of atrazine in the drinking water supply with cancer incidence rates found a positive association between atrazine
levels and stomach cancer but a negative association between atrazine levels and colon cancer. The average atrazine contamination level was 163 ng/l. No individual exposure data were
available. Potential confounding variables were considered. (Van Leewen et al. 1999 – quoted from ATSDR 2001).
IARC have concluded that there is inadequate evidence in humans for the carcinogenicity of atrazine and simazine (IARC 1999a,b).
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Version 1.0 October 2004, © Danish Environmental Protection Agency
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