Simazine

Description

While compounds exhibiting estrogen mimicry are structurally diverse, they share common properties such as retention in body fat deposits (highly lipophilic), ability to cross the placental barrier, transport in blood usually unbound to specialized serum proteins (e.g., steroid hormone binding globulin, SHBG/TeBG), and their affinity for the estrogenreceptor protein. If the environmental compound impersonates estrogen sufficiently, it associates with the estrogen-receptor protein and either disrupts the action of the native hormone or communicates activities similar to estrogen (i.e., antagonistic or agonistic activities). Association between a xenoestrogen and the estrogen receptor (ER), characterized by a wide range of affinities, is reversible and saturable. No metabolism of the ligand occurs when it is bound to the receptor protein. In addition to the phenotypic expression of gender, estrogens and their mimics may influence development and physiological processes in many organs of the body, particularly the reproductive tract, as well as the central nervous system and skeleton. It is obvious that fragile, biological events occurring during ovulation, pregnancy, fetal development, and lactation could easily be influenced by xenoestrogens with endocrine disruptor compound (EDC) activities, which mimic naturally occurring hormones.
With a variety of sensitive, rapid assays, xenoestrogens now may be detected and activities assessed by ER proteins. The range of techniques available includes both cell-free and whole-cell-based assays:
1. Rat uterine cytosol preparations containing ERs (a cell-free assay using radiolabeled ligand);
2. Recombinant human ER proteins produced by a bacteria, yeast, or baculovirus-infected insect cell system (cell-free assays using radiolabeled ligand);
3. A yeast cell system containing recombinant human ER and a reporter gene (yeast whole-cell assay);
4. The LUMI-CELL ER transcriptional activation assay (BG1Luc ER TA, a mammalian whole-cell assay); and 5. MCF7 cell proliferation assay (E-SCREEN assay) and modifications of this method (mammalian whole-cell assay).
Additionally, certain investigations are focused on differential recognition of EDCs by ER isoforms separated by highperformance liquid chromatography.

Chemical properties

Simazine is a combustible, white crystalline solid. Practically odorless.Its solubility in methanol is 400mg/L, its solubility in water is 5mg/L, its solubility in petroleum ether is 2mg/L and it is slightly soluble in chloroform. It has the advantages of stable chemical property, but it is easily hydrolyzed under the strong acid or alkali conditions and at higher temperatures to produce inactive hydroxyl derivatives. No corrosion. Original medicine m.p.224℃.

The Uses of Simazine

Simazine is a preemergence herbicide used to control broadleaf and grassy weeds. It is also used as a soil sterilant. Principal crops involved include maize, citrus, and deciduous fruit. Simazine is also used in aquatic weed control.

The Uses of Simazine

Selective preemergence systemic herbicide used to control many broad-leaved weeds and annual grasses in deep-rooted fruit and vegetable crops.

The Uses of Simazine

Xenoestrogens are used widely in a number of cosmetic products such as plasticizers, perfume fixatives, and solvents (e.g., dibutyl phthalate); and industrial chemicals and pollutants such as insecticides (e.g., methoxychlor, DDT, and DDE), epoxy resins, polycarbonate (e.g., bisphenol A), other plastics (e.g., butyl benzyl phthalate (BBP)), and herbicides (e.g., simazine). Compounds in this group exhibit a broad molecular and structural diversity, often mimicking the activities of naturally occurring hormones, since they are recognized by the hormone’s cognate receptor protein. Many compounds in this group of chemicals have been classified as environmental EDCs, defined by the US Environmental Protection Agency (EPA) as “an exogenous agent that interfere with synthesis, secretion, transport, metabolism, binding action, or elimination of natural blood-borne hormones that are present in the body and are responsible for homeostasis, reproduction and developmental processes.” However, not all EDCs are classified as xenoestrogens.
Although relative binding affinities (RBAs) of a number of compounds exhibiting xenoestrogenic activities, it should be noted that the values appearing here and in the reports listed under Further Reading are highly dependent on the type of ER-based assay used and the concentration of the compound tested. In addition, caution should be exercised in interpreting the results from assays performed in vitro compared to effects observed in vivo. Duration of exposure and dose in vivo, which are likely influenced by the lipophilic properties of many of the agents, should be considered in health risk assessment.
In summary, the body of experimental and epidemiological evidence suggesting that many substances in the environment may disrupt human health continues to expand to cover a wide range of exposures. Of greatest concern are the effects of transgenerational exposure to unrecognized agents, which may be present in foodstuffs, drinking water, and other consumables, including medications and cosmetics. Using hormone receptor-based technology and highly purified preparations of EDCs as standards, there is an opportunity to improve exposure and risk assessment for environmental estrogen mimics, as well as the quantitative analysis of their occurrence in the environment. However, discussions continue regarding the relationships between assessment in vitro of xenoestrogen activities and their effects in vivo resulting in a risk to health.

What are the applications of Application

Simazine is a selective pre-emergence herbicide

Definition

ChEBI: A diamino-1,3,5-triazine that is N,N'-diethyl-1,3,5-triazine-2,4-diamine substituted by a chloro group at position 6.

Production Methods

Simazine is prepared by reacting two equivalents of ethylamine in the presence of an acid acceptor. It is stable in neutral and slightly basic or acidic media, but is hydrolyzed by stronger acids and bases especially at higher temperatures. Primary exposures occur during application, not during production, and include both inhalation and dermal components.

General Description

White to off-white crystalline powder.

Air & Water Reactions

Insoluble in water.

Reactivity Profile

Simazine is hydrolyzed by strong acids and alkalis .

Health Hazard

Inconsistent data in the literature; oral LD50values in rats reported as 970 and 5000 mg/L,showing a wide difference; toxicity is of loworder.

Fire Hazard

Literature sources indicate that Simazine is nonflammable.

Agricultural Uses

Pre-emergence herbicide, Algaecide: and ornamental crops, turf grass, orchards, and vineyards. At higher rates, it is used for non-selective weed control in industrial areas. Before 1992, simazine was used to control submerged weeds and algae in large aquariums, farm ponds, fish hatcheries, swimming pools, ornamental ponds, and cooling towers. Simazine is available in wettable powder, waterdispersible granule, liquid, and granular formulations. It may be soil-applied. Not approved for use in EU countries. A U.S. EPA restricted Use Pesticide (RUP) for all land uses because of its potential to contaminate ground water

Trade name

AKTINIT S®; ALCO® Simizine; AQUAZINE®; ATLAS SIMAZINE®; BATAZINA®; BITEMOL®; CALIBER®; CDT®; CEKUSAN®; CEKUZINA-S®; FRAMED®; G 27692®; GEIGY 27692®; GESARAN®; GESATOP®; GESATOP-50®; H 1803®; HARLEQUIN®; HERBAZIN® 500 BR; HERBAZIN® 50; HERBEX®; HERBOXY®; HUNGAZIN DT®; OXON ITALIA SIM-TROL®; PREMAZINE®; PRIMATEL S®; PRIMATOL S®; PRINCEP®; PRINCEP® 80W; SIMADEX®; SIMANEX®; SIMAZINE® 80W; SIMAZAT®; SIM-TROL®; TAFAZINE®; TAFAZINE® 50-W; TANZINE®; TAPHAZINE®; TOTAZINE®; TRIAZINE A 384®; W 6658®; WEEDEX®; ZEAPUR®

Potential Exposure

A potential danger to those involved in the manufacture, formulation, and application of this preemergence herbicide. Pesticide not in use; TRI and/or IUR indicates importers or manufacturers are unlikely. Banned for use in the EU.

Carcinogenicity

No tumorigenic response was seen in mice treated orally at doses ranging from 75 to 215mg/kg. In a 2-year feeding study in rats, 100 ppm produced mammary tumors. Sarcomas at the injection sitewere produced in another study ofboth rats and mice. Simazinewas fedtoratsatdoselevelsequivalent to 0,0.5,5,and 50mg/kg for 2 years.Bodyweight and hematological changes were seen primarily at the highest dose. After 24 months at 50mg/kg, an increase in ovarian atrophy and Sertoli cell hyperplasia were seen. Increases in mammary gland tumors were seen in females at 50mg/kg.

Environmental Fate

Soil. The reported half-life in soil is 75 days (Alva and Singh, 1991). Under laboratory conditions, the half-lives of simazine in a Hatzenbühl soil (pH 4.8) and Neuhofen soil (pH 6.5) at 22°C were 45 and 100 days, respectively (Burkhard and Guth, 1981).
The half-lives for simazine in soil incubated in the laboratory under aerobic conditions ranged from 27 to 231 days (Zimdahl et al., 1970; Beynon et al., 1972; Walker, 1976, 1976a). In field soils, the disappearance half-lives were lower and ranged from 11 to 91 days (Roadhouse and Birk, 1961; Clay, 1973; Joshi and Datta, 1975; Marriage et al., 1975).
Groundwater. According to the U.S. EPA (1986) simazine has a high potential to leach to groundwater.
Plant. Simazine is metabolized by plants to the herbicidally inactive 6-hydroxysimazine which is further degraded via dealkylation of the side chains and hydrolysis of the amino group releasing carbon dioxide (Castelfranco et al., 1961; Humburg et al., 1989).
Photolytic. Pelizzetti et al. (1990) studied the aqueous photocatalytic degradation of simazine and other s-triazines (ppb level) using simulated sunlight (λ >340 nm) and titanium dioxide as a photocatalyst. Simazine rapidly degraded forming cyanuric acid, nitrates and other intermediate compounds similar to those found for atrazine. Mineralization of cyanuric acid to carbon dioxide was not observed (Pelizzetti et al., 1990). In aqueous solutions, simazine is converted exclusively to hydroxysimazine by UV light (λ = 253.7 nm). The UV irradiation of methanolic solutions of simazine afforded simetone (2-methoxy-4,6-bis(ethylamino-s-triazine). Photodegradation of simazine in methyl alcohol did not occur when irradiated at wavelengths >300 nm (Pape and Zabik, 1970).
Chemical/Physical. Emits toxic fumes of nitrogen oxides and chlorine when heated to decomposition (Sax and Lewis, 1987). In the presence of hydroxy or perhydroxy radicals generated from Fenton’s reagent, simazine undergoes dealkylation to give 2-chloro-4,6- diamino-s-triazine as the major product (Kaufman and Kearney, 1970).

Shipping

UN3077 Environmentally hazardous substances, solid, n.o.s., Hazard class: 9; Labels: 9-Miscellaneous hazardous material, Technical Name Required. UN2763 Triazine pesticides, solid, toxic, Hazard Class: 6.1; Labels: 6.1-Poisonous materials.

Toxicity evaluation

With regard to estrogen-associated toxicity, the primary mechanism appears to be via association with the estrogen receptor proteins (ERa and ERb) and subsequent alteration in the signal transduction pathway. While largely acting as estrogen antagonists, some xenoestrogens (e.g., diethylstilbestrol (DES)) may act as agonists at low doses and antagonists at elevated doses. Furthermore, compounds such as DES are classified as an EDC since it may promote transgenerational effects, including development of clear cell adenocarcinoma of the vagina in daughters of mothers administered DES as a therapeutic.
Many studies of toxicokinetics suggest the difficulty in extrapolating quantitative structure–activity relationships (QSARs) of particular compounds with their influence on biological responses (e.g., reproduction, neuroendocrine behavior). Several compounds classified as xenoestrogens (BPA and BBP) are reported to have estrogenic activity, although the concentrations required in vitro for the effects and those doses given in vivo to animal models are significantly higher than the estimated doses observed in human exposure. The variety of ERbased tests for assessing QSARs of diverse xenoestrogens cannot address the effects of long-term exposure to low doses of these compounds. In addition, factors such as age at exposure and mixtures of compounds influence latent effects of chronic exposure. However, QSAR models using results from ER-based tests are used for chemical risk management and development of regulatory practices.

Incompatibilities

Powder may form explosive mixture with air. Incompatible with strong oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides.

Waste Disposal

Strong acid or alkaline hydrolysis leads to complete degradation of simazine. However,large quantities of simazine should be incinerated in a unit operating @ 850℃ equipped with off-gas scrubbing equipment. In accordance with 40CFR165, follow recommendations for the disposal of pesticides and pesticide containers. Must be disposed properly by following package label directions or by contacting your local or federal environmental control agency, or by contacting your regional EPA office.