New experimental data on the human dermal absorption of Simazine and Carbendazim help to refine the assessment of human exposure.

Due to their widespread usage, people are exposed to pesticides on a daily basis. Although these compounds may have adverse effects on their health, there is a gap in the data and the methodology needed to reliably quantify the risks of non-occupational human dermal exposure to pesticides. We used Franz cells and human skin in order to measure the dermal absorption kinetics (steady-state flux, lag time and permeability coefficient) of Carbendazim and Simazine. These parameters were then used to refine the dermal exposure model and a probabilistic simulation was used to quantify risks resulting from exposure to pesticide-polluted waters. The experimentally derived permeability coefficient was 0.0034 cm h(-1) for Carbendazim and 0.0047 cm h(-1) for Simazine. Two scenarios (varying exposure duration and concentration, i.e. environmentally relevant and maximum solubility) were used to quantify the human health risks (hazard quotients) for Carbendazim and Simazine. While no risks were determined in the case of either scenario, the permeability coefficient, which is concentration independent and donor, formulation, compound and membrane specific, may be used in other scenarios and exposure models to quantify more precisely the dermally absorbed dose during exposure to polluted water. To the best of our knowledge, the dermal absorption kinetics parameters defined here are being published for the first time. The usage of experimental permeability parameters in combination with probabilistic risk assessment thus provides a new tool for quantifying the risks of human dermal exposure to pesticides.

Toxicity endpoint selections for a simazine risk assessment.

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.

Influence of soil properties on bioaccumulation of 14C-simazine in earthworms Eisenia foetida.

The toxicity of pesticides has been evaluated by several methods including tests with earthworms in both artificial and natural soils treated with the compounds. The ecological niches of earthworms make them good bioindicators of soil contamination. The bioaccumulation of 14C-simazine (6-chloro-N2-N4-diethyl- 1,3,5-triazine-2,4-diamine) was evaluated in earthworms (Eisenia foetida) maintained during three months in two substrates with different physical-chemical characteristics. The substrates were treated with 3.0 mg and 330 kBq of 14C-simazine kg(-1) substrate. Results indicated that worms did not influence simazine dissipation in both substrates as indicated by similar recoveries and with no statistical differences with and without earthworms. The radiocarbon recoveries were 86.8 and 95.3%, respectively in the substrates with lower and higher organic matter contents with earthworms, and 91.0 and 107.4% in the same substrates without worms. However, in earthworms the recoveries were statistically higher when they were maintained in the substrate with lower amount of organic matter (0.89%) than from the higher one (0.33%). Consequently, 14C-simazine bioconcentration factor (BCF) was also greater in the substrate with lower organic matter (6.89+/-1.55) than in the substrate with higher organic matter content (0.88+/-0.06). The results suggest that the higher soil organic matter content will cause lower probability of contamination of soil organisms with simazine.

Biodegradation of simazine in olive fields.

Simazine (2-chloro-4, bis ethylamino-1,3,5-triazine) is a herbicide of the s-triazine group used mainly to control broad-leaved weeds in different crops. Several papers report about simazine and other s-triazine derivates as being actual polluting agents. In fact, simazine has been detected in groundwater and soil. Since this herbicide has been extensively used in Andalusia (south of Spain), we are analyzing the levels of simazine residues found in the soil of olive fields. We are also simazine could be detected isolating live micro organisms able to degrade this compound, and are characterizing the metabolic pathways leading to this degradation and the fate of this compound in nature. With all these data in mind, we will try to develop a strategy for the bioremediation of contaminated soils. We have taken samples of soil from many olive orchards of Andalusia that have been treated with simazine. These samples were located with the help of a handheld GPS. The presence of simazine of these samples was detected by HPLC. In most of the samples taken no, and those where it could be, contained very low levels of this herbicide (lower than 0.5 ppm). Soil samples are being characterized to determine their physicochemical characteristics [pH, organic matter, texture, etc), and we are attempting to correlate all these parameters with the presence or absence of simazine. From some of the soils, we have isolated a group of micro organisms that can grow using simazine as the sole carbon and nitrogen sources. We are analyzing how the addition of carbon or nitrogen can influence the rate of the simazine degradation.

Influence of plant age and size on simazine toxicity and uptake.

Improper pesticide management can lead to environmental problems such as water quality degradation and ecological stress. Recent research in our laboratory has focused on development of constructed wetlands to assimilate pesticide-contaminated water. For improved aesthetics, these wetlands have been established with ornamental plant species. The effectiveness of a plant species for phytoremediation depends in part on its tolerance for the contaminant. Plant tolerance for pesticides may vary depending on plant age and size. This study examined the influence of plant age and size on the uptake, distribution, and toxicity of the herbicide simazine [2-chloro-4,6-bis(ethylamino)-1,3,5-triazine] in two ornamental wetland plants: parrot feather [Myriophyllum aquaticum (Vell.) Verdc.] and canna (Canna x hybrida L. 'Yellow King Humbert'). Plants of different ages and sizes were exposed to simazine in 10% Hoagland's nutrient solution. Toxicity was characterized using plant growth, water uptake, and photosynthetic yield during exposure and postexposure periods. In addition, other plants were exposed to [14C] simazine in nutrient medium to characterize pesticide uptake and translocation. Four-week-old parrot feather and canna were more tolerant of simazine than two-week-old plants. The two-week-old plant tissues of both species had higher tissue burdens of simazine than four-week-old plants. Simazine was primarily accumulated in the leaves of both parrot feather and canna. These results suggest that plants in a constructed wetland designed for simazine assimilation would be more vulnerable to simazine toxicity shortly after emergence.

Metalaxyl and simazine toxicity to and uptake by Typha latifolia.

This research focused on the potential use of common cattails (Typha latifolia) for removing metalaxyl and simazine residues from contaminated water. Specifically, it established toxicity thresholds to the herbicide simazine and characterized the uptake and distribution of simazine and metalaxyl by the plants. Simazine tolerance levels were determined by exposing plants to a series of six concentrations (0-3.0 mg L(-1)) in aqueous nutrient media for 7 days. Metalaxyl toxicity was not evaluated because other studies indicated it was relatively nontoxic to plants. Toxicity endpoints measured included fresh mass production after 7 days of exposure and 7 days postexposure. Pesticide uptake and distribution were determined by growing plants in nutrient media amended with (14)C-ring-labeled metalaxyl (0.909 mg L(-1)) or simazine (0.242 mg L(-1)) for 1, 3, 5, or 7 days. Plants were dissected, and tissues were combusted and analyzed by liquid scintillation spectroscopy. Cattail fresh mass production was reduced 84 and 117% at 1.0 and 3.0 mg L(-1) simazine, respectively, after 7 days of exposure. Metalaxyl and simazine activity in solution was reduced 34 and 65%, respectively, after 7 days. By day 7, activity from both pesticides was detected predominantly in the leaves. Uptake of each pesticide was correlated with water uptake throughout the 7 days. These results suggest that the common cattail may be a good candidate for incorporation into a phytoremediation scheme for metalaxyl and simazine.

In vitro metabolism of simazine, atrazine and propazine by hepatic cytochrome P450 enzymes of rat, mouse and guinea pig, and oestrogenic activity of chlorotriazines and their main metabolites.

1. The in vitro metabolism of chlorotriazines, simazine (SIZ), atrazine (ATZ) and propazine (PRZ) in liver microsomes from rat, mouse and guinea pig and the oestrogenic activity of chlorotriazines and their main metabolites have been studied. 2. The formation rates of products in chlorotriazine metabolism were determined by HPLC. The principal reactions catalysed by the cytochrome P450 (P450) system were N-monodealkylation and isopropylhydroxylation in all liver microsomes. As a result, 2-chloro-4-ethylamino-6-amino-1,3,5-triazine (M1) (SIZ-M1 for SIZ and ATZ-M1 for ATZ) and 2-chloro-4-amino-6-isopropylamino-1,3,5-triazine (M2) (ATZ-M2 for ATZ and PRZ-M2 for PRZ), and 2-chloro-4-ethylamino-6-(1-hydroxyisopropylamino)-1,3,5-triazine (M3) (ATZ-M3 for ATZ) and 2-chloro-4-isopropylamino-6-(1-hydroxyisopropylamino)-1,3,5-triazi ne (M4) (PRZ-M4 for PRZ) were detected as the metabolites. N-bidealkylation was not found in this system. 3. The formation rates of N-deethylated metabolites (SIZ-M1 and ATZ-M2) were generally higher in mouse than in rat and guinea pig. The formation rates of N-deisopropylated metabolites (ATZ-M1 and PRZ-M2) in guinea pig were the lowest among the three animal species. The formation rates of isopropylhydroxylated metabolites (ATZ-M3 and PRZ-M4) were remarkably low in mouse compared with rat and guinea pig. 4. The enzyme kinetics of chlorotriazine metabolism were examined by Eadie-Hofstee analyses. Some species differences in Michaelis-Menten parameters for each metabolite were observed, and the ranking orders were varied among the metabolites. 5. The binding affinity of chlorotriazines (SIZ, ATZ and PRZ) and their metabolites (M1-4) for recombinant human oestrogen receptor-alpha was assayed using the fluorescence polarization method. The binding affinity of M2 was significantly higher than those of parent compounds and other metabolites, although the oestrogenic activity was remarkably low compared with that of 17beta-oestradiol (E2). 6. These results suggest that the pattern of metabolism of SIZ, ATZ and PRZ by the P450 system differs extensively among rat, mouse and guinea pig, and that M2 may be an activated metabolite of chlorotriazines.