Disturbed relaxin signaling pathway and testicular dysfunction in mouse offspring upon maternal exposure to simazine.

Simazine is a triazine herbicide that is being widely applied worldwide and commonly detected in surface and groundwater. Despite its popular use in controlling weeds and algae, very limited information is available regarding its toxicity. In the present study, pregnant mice were orally exposed to low doses (0, 5, 50, or 500 µg/kg body weight per day) of simazine during gestation and lactation, during which no overt maternal toxic response was detected, and their offspring was assessed. Simazine-exposed male offspring showed decreased body, testicular, and epididymis weight, increased testicular apoptosis, and decreased sperm concentrations. Differentially-expressed genes in the testes of male offspring exposed to simazine were identified by DNA microarray, revealing 775 upregulated and 791 downregulated genes; among these, the relaxin-family peptide receptor 1 (Rxfp1), which is the receptor for relaxin hormone, was significantly downregulated. In addition, the expression of target genes in the relaxin pathway, including nitric oxide synthase 2 (Nos2) and Nos3, was significantly decreased in simazine-exposed F1 testes. Moreover, simazine inhibited NO release, and knockdown of Rxfp1 blocked the inhibitory action of simazine on NO production in testicular Leydig cells. Therefore, the present study provides a better understanding of the toxicities associated with the widely used herbicide simazine at environmentally relevant doses by demonstrating that maternal exposure interferes with the pleotropic relaxin-NO signaling pathway, impairing normal development and reproductive activity of male offspring.

Sister chromatid exchanges and micronuclei analysis in lymphocytes of men exposed to simazine through drinking water.

In some cities of the autonomous community of Extremadura (south-west of Spain), levels of simazine from 10 to 30 ppm were detected in tap water. To analyse the possible effect of this herbicide, two biomarkers, sister chromatid exchanges (SCE) and micronuclei (MN), were used in peripheral blood lymphocytes from males exposed to simazine through drinking water. SCE and MN analysis failed to detect any statistically significant increase in the people exposed to simazine when compared with the controls. With respect to high frequency cells (HFC), a statistically significant difference was detected between exposed and control groups.

The role of herbicides in the erosion of salt marshes in eastern England.

Laboratory studies and field trials were conducted to investigate the role of herbicides on saltmarsh vegetation, and their possible significance to saltmarsh erosion. Herbicide concentrations within the ranges present in the aquatic environment were found to reduce the photosynthetic efficiency and growth of both epipelic diatoms and higher saltmarsh plants in the laboratory and in situ. The addition of sublethal concentrations of herbicides resulted in decreased growth rates and photosynthetic efficiency of diatoms and photosynthetic efficiency of higher plants. Sediment stability also decreased due to a reduction in diatom EPS production. There was qualitative evidence that diatoms migrated deeper into the sediment when the surface was exposed to simazine, reducing surface sediment stability by the absence of a cohesive biofilm. Sediment loads on leaves severely reduced photosynthesis in Limonium vulgare. This, coupled with reduced carbon assimilation from the effects of herbicides, could have large negative consequences for plant productivity and over winter survival of saltmarsh plants. The data support the hypothesis that sublethal herbicide concentrations could be playing a role in the increased erosion of salt marshes that has occurred over the past 40 years.

Field effects of simazine at lower trophic levels--a review.

Simazine is a triazine herbicide used in agriculture, pot-plant and tree production. The total concentrations (dissolved + adsorbed) in soil depend on the application rate, for example an application rate of 1500 g simazine/ha will result in approximately 4 mg simazine/kg in the top 1 cm. It may be spread to adjacent areas due to drift, runoff or evaporation. In fresh water concentrations approximately 4 microg simazine/l has been recorded. In aerial fallout--rain--concentrations of 0.680 microg simazine/l has been recorded. In both soil and water, degradation studies have in most cases shown DT50 times that vary between a few days and 150 days, indicating that total or near total disappearance time may be at least three times longer. Low temperatures and drought may prolong the dissipation time by a factor of two or more. Laboratory studies indicate that the primary site of decomposition in the aquatic environment is the sediment. Field studies showed deleterious effects of simazine on terrestrial invertebrates at application rates below 2 kg simazine/ha. The direct toxicity was not confirmed by laboratory results, however, these were sparse and did not cover a broad range of soil organisms. No field studies were found dealing with invertebrates, but laboratory studies have shown deleterious effects of simazine on aquatic invertebrates at concentrations above 20 microg simazine/l. Simazine is phytotoxic to many non-target species at rates below the recommended rate. At least under some environmental conditions, simazine can remain for a long time in the active layer and still be toxic to sensitive plants 1 year after application. Despite its phytotoxicity many plant species become more and more tolerant in cases of repeated use for many years and some have become resistant. Simazine is not highly toxic to soil microflora and algae, although some species definitely are affected both in an inhibitory and a stimulatory way. Most investigations predict no long-term consequences to soil and aquatic microflora in association with recommended and appropriate use giving rise to maximum expected environmental concentrations of 5 mg simazine/kg in soil and 4 microg simazine/l in water.

Effects of chloro-s-triazine herbicides and metabolites on aromatase activity in various human cell lines and on vitellogenin production in male carp hepatocytes.

We investigated a potential mechanism for the estrogenic properties of three chloro-s-triazine herbicides and six metabolites in vitro in several cell systems. We determined effects on human aromatase (CYP19), the enzyme that converts androgens to estrogens, in H295R (adrenocortical carcinoma), JEG-3 (placental choriocarcinoma), and MCF-7 (breast cancer) cells; we determined effects on estrogen receptor-mediated induction of vitellogenin in primary hepatocyte cultures of adult male carp (Cyprinus carpio). In addition to atrazine, simazine, and propazine, two metabolites--atrazine-desethyl and atrazine-desisopropyl--induced aromatase activity in H295R cells concentration-dependently (0.3-30 microM) and with potencies similar to those of the parent triazines. After a 24-hr exposure to 30 microM of the triazines, an apparent maximum induction of about 2- to 2.5-fold was achieved. The induction responses were confirmed by similar increases in CYP19 mRNA levels, determined by reverse-transcriptase polymerase chain reaction. In JEG-3 cells, where basal aromatase expression is about 15-fold greater than in H295R cells, the induction responses were similar but less pronounced; aromatase expression in MCF-7 cells was neither detectable nor inducible under our culture conditions. The fully dealkylated metabolite atrazine-desethyl-desisopropyl and the three hydroxylated metabolites (2-OH-atrazine-desethyl, -desisopropyl, and -desethyl-desisopropyl) did not induce aromatase activity. None of the triazine herbicides nor their metabolites induced vitellogenin production in male carp hepatocytes; nor did they antagonize the induction of vitellogenin by 100 nM (EC(50) 17beta-estradiol. These findings together with other reports indicate that the estrogenic effects associated with the triazine herbicides in vivo are not estrogen receptor-mediated, but may be explained partly by their ability to induce aromatase in vitro.

Simazine toxicosis in sheep.

A case of simazine toxicosis in sheep was investigated. Affected animals exhibited generalized muscle tremors which progressed to mild tetany followed by collapse of the hind legs. Other signs included a short prancing gait with head tucked in a similar manner to that of a show pony. Death occurred within 2 to 3 d of the appearance of clinical signs. Mild to acute myocardial degeneration was evident; the livers had mild to acute hepatic fatty change. The levels of simazine found in livers varied from less than 0.2 mg/kg to almost 2 mg/kg in the worst affected animals.

[Biological value of Mironovskaya-808 winter wheat grown using the herbicide simazine]. / Biologicheskaia tsennost' ozimoi pshenitsy Mironovskaia-808, vyrashchennoi s primeneniem gerbitsida simazina.

The biological value of spring wheat Mironovskaya-808 grown with the use of simazine which was introduced into soil prior to appearance of shoots at doses of 0.5 and 1.0 kg/ha has been studied. The organoleptic parameters evaluated by the method of closed testing and physicochemical parameters characterizing the corn quality (protein fat, gluten and ash content, moisture, acidity) of experimental samples did not differ from those of the reference sample. Relative biological value of wheat grown with the use of simazine at a dose of 1.0 kg/ha evaluated by the test-object Tetrahymena pyriformis was slightly higher as compared to the control. The effect of test wheat samples on some parameters of protein metabolism was also studied in male rats (the content of protein and its fractions in blood serum, liver and brain as well as activity of enzymes participating in protein metabolism regulation: aminotransferases of blood serum and liver, catepsins, histidase and tryptophan oxygenase of the liver). According to the data obtained no adverse effect of spring wheat Mironovskaya-808 grown with the use of simazine on the above parameters of protein metabolism was recorded in test animals.