...In rats, > 97% of the (14)C/glyphosate/ in excreta, after a single oral dose, was shown to be unchanged compound. AMPA was the only metabolite, covering only 0.2-0.3% of the applied (14)C...
Following a single oral dose of 14C-glyphosate, amino methyl phosphonic acid (AMPA) was the only metabolite found in urine (0.2-0.3% of the administered dose) and feces (0.2-0.4% of the administered dose) /of male and female Sprague-Dawley rats/.
Studies of the metabolism of glyphosate in experimental animals (rats, rabbits, lactating goats, and chickens) indicate that it is not biotransformed, with essentially all the administered dose excreted as unchanged parent molecule.
Biotransformation of glyphosate occurs to a very low degree only. In rats it was shown that all of the carbon-14 in urine and feces, after a single oral application of (14)C-glyphosate, was present as unchanged parent compound. Also in rats, > 97% of the carbon-14 in excreta, after a single oral dose, was shown to be unchanged compound. AMPA was the only metabolite, covering only 0.2-0.3% of the applied carbon-14. In laying hens also, AMPA was the only metabolite, accounting for only a minor part of the applied amount.
IDENTIFICATION AND USE: Glyphosate is an odorless white solid. Glyphosate is a non-selective herbicide registered for use on many food and non-food field crops as well as non-crop areas where total vegetation control is desired. When applied at lower rates, glyphosate is also a plant growth regulator. HUMAN EXPOSURE AND TOXICITY: Glyphosate is an active ingredient of the most widely used herbicide and it is believed to be less toxic than other pesticides. However, several studies showed its potential adverse health effects to humans as it may be an endocrine disruptor. Concentrated solutions of glyphosate can also cause dermal irritation. Most intoxicated cases are from ingestion, inhalation, and skin exposure. Pulmonary edema, shock, and arrhythmia were the reported causes of mortality. Ingestion of glyphosate-surfactant herbicides can result in acute kidney injury, electrolyte abnormalities, acidosis, cardiovascular collapse, and death. In severe toxicity, the use of hemodialysis is reported, but largely unsupported by kinetic analysis. Commercial formulations were more cytotoxic than the active component alone, supporting the concept that additives in commercial formulations play a role in the toxicity attributed to glyphosate-based herbicides. Glyphosate was found nongenotoxic in human lymphocytes with or without metabolic activation. However it induced micronuclei formation and DNA damage in a buccal epithelial cell line (TR146). In addition, glyphosate was toxic to human placental JEG3 cells. ANIMAL STUDIES: Glyphosate did not produce dermal sensitization in guinea pigs. It produced moderate to severe eye irritation in rabbits. In a 13-week study with glyphosate administration, lesions of the salivary glands were found in rats and mice. A study in a 2-stage mouse skin carcinogenesis model and proteomic analysis suggested that glyphosate has tumor promoting potential in skin carcinogenesis. Studies in rats and rabbits indicated that technical glyphosate is not teratogenic. In the first /multigenerational/ study, the only effect noted was an increased incidence of unilateral renal tubular dilation in F3b male pups at 30 mg/kg body weight. Maternal exposure to glyphosate disturbed the masculinization process in the offsping and promoted behavioral changes and histological and endocrine problems in reproductive parameters. These changes associated with the hypersecretion of androgens increased gonadal activity and sperm production. The entire body of the developmental toxicity data reviewed fails to support a potential risk for increased cardiovascular defects as a result of glyphosate exposure during pregnancy. A broad array of in vitro and in vivo assays has consistently demonstrated that glyphosate and glyphosate-containing herbicide formulations are not genotoxic. Occasionally, however, related and contradictory data are reported, including findings of mouse liver and kidney DNA adducts and damage following intraperitoneal (ip) injection. ECOTOXICITY STUDIES: Gene expression data (mRNA levels) suggests that glyphosate-based herbicides have the potential to alter hormonal pathways during tadpole development. Roundup exposure had negative impact on the immune system of European sea bass. Roundup at environmentally relevant concentrations has lethal and genotoxic impact on the Indian skittering frog. Roundup also altered normal histology of the studied organs and caused a significant decrease in the number of copulations and mating success in male fish exposed to the herbicide in the neotropical native fish, Jenynsia multidentata.
Classification - D; not classifiable as to human carcinogenicity. Basis - Inadequate evidence for oncogenicity in animals. Glyphosate was originally classified as C, possible human carcinogen, on the basis of increased incidence of renal tumors in mice. Following independent review of the slides the classification was changed to D on the basis of a lack of statistical significance and uncertainty as to a treatment-related effect.
The herbicide glyphosate and the insecticides malathion and diazinon were classified as probably carcinogenic to humans (Group 2A). For the herbicide glyphosate, there was limited evidence of carcinogenicity in humans for non-Hodgkin lymphoma. The evidence in humans is from studies of exposures, mostly agricultural, in the USA, Canada, and Sweden published since 2001. In addition, there is convincing evidence that glyphosate also can cause cancer in laboratory animals. On the basis of tumours in mice, the United States Environmental Protection Agency (US EPA) originally classified glyphosate as possibly carcinogenic to humans (Group C) in 1985. After a re-evaluation of that mouse study, the US EPA changed its classification to evidence of non-carcinogenicity in humans (Group E) in 1991. The US EPA Scientific Advisory Panel noted that the re-evaluated glyphosate results were still significant using two statistical tests recommended in the IARC Preamble. The IARC Working Group that conducted the evaluation considered the significant findings from the US EPA report and several more recent positive results in concluding that there is sufficient evidence of carcinogenicity in experimental animals. Glyphosate also caused DNA and chromosomal damage in human cells, although it gave negative results in tests using bacteria. One study in community residents reported increases in blood markers of chromosomal damage (micronuclei) after glyphosate formulations were sprayed nearby.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
国际癌症研究机构:草甘膦
IARC Carcinogenic Agent:Glyphosate
来源:International Agency for Research on Cancer (IARC)
毒理性
致癌物分类
国际癌症研究机构(IARC)致癌物分类:2A组:可能对人类致癌
IARC Carcinogenic Classes:Group 2A: Probably carcinogenic to humans
来源:International Agency for Research on Cancer (IARC)
The toxicokinetics of glyphosate after single 100 mg/kg intravenous (i.v.) and 400 mg/kg oral doses were studied in rats. Serial blood samples were obtained after i.v. and oral administration. Plasma concentrations of glyphosate and its metabolite aminomethyl phosphonic acid (AMPA) were determined by HPLC method. After i.v. and oral administration, plasma concentration-time curves were best described by a two-compartment open model. For glyphosate, the elimination half-lives (T(1/2beta)) from plasma were 9.99 hr after i.v. and 14.38 hr after oral administration. The total plasma clearance was not influenced by dose concentration or route and reached a value of 0.995 L/hr/kg. After i.v. administration, the apparent volume of distribution in the second compartment (V(2)) and volume of distribution at steady state (V(ss)) were 2.39 and 2.99 L/kg, respectively, suggesting a considerable diffusion of the herbicide into tissues. After oral administration, glyphosate was partially and slowly absorbed with a T(max) of 5.16 hr. The oral bioavailability of glyphosate was found to be 23.21%. Glyphosate was converted to AMPA. The metabolite AMPA represented 6.49% of the parent drug plasma concentrations. The maximum plasma concentrations of glyphosate and AMPA were 4.62 and 0.416 microg/mL, respectively. The maximum plasma concentration of AMPA was achieved at 2.42 hr. For AMPA, the elimination half-life (T(1/2beta)) was 15.08 hr after oral administration of glyphosate parent compound.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
草甘膦在老鼠体内的分布情况进行了研究。雄性F344/N老鼠通过灌胃方式摄入了5.6或56毫克/千克的放射性标记草甘膦。在72小时内,每隔24小时收集一次尿液和粪便,并分析其活性。在给药后3到96小时,选定的老鼠被处死,以确定放射性在组织中的分布。在大约72小时内,大约20到30%的剂量通过尿液排出,70到80%通过粪便排出。只有大约1%的剂量残留在组织中,主要在肝脏和 small intestine(小肠)。
The disposition of glyphosate was studied in rats. Male F344/N rats were gavaged with 5.6 or 56 mg/kg radiolabeled glyphosate. Urine and feces were collected at 24 hour intervals for 72 hr and analyzed for activity. Selected rats were killed 3 to 96 hr post dosing to determine the tissue distribution of radioactivity. Approximately 20 to 30% of either dose was eliminated in the urine and 70 to 80% in the feces over 72 hr. Only about 1% of the dose remained in the tissues, mostly in the liver and small intestine.
... There is rapid elimination, no biotransformation, and minimal tissue retention of glyphosate in various species, including mammals, birds, and fish.
Greater than 90% of an orally administered dose of glyphosate is rapidly eliminated in 72 hr /by laboratory animals/. ... Typically, approximately 70% of the administered dose is eliminated in the feces, with the remainder eliminated in the urine. In all cases, less than 0.5% of the administered dose is found in the tissue and organs, demonstrating that glyphosate does not bioaccumulate in edible tissues.
1.周国泰,化学危险品安全技术全书,化学工业出版社,1997 2.国家环保局有毒化学品管理办公室、北京化工研究院合编,化学品毒性法规环境数据手册,中国环境科学出版社.1992 3.Canadian Centre for Occupational Health and Safety,CHEMINFO Database.1998 4.Canadian Centre for Occupational Health and Safety, RTECS Database, 1989
Synthesis and Anti-HIV Activity of Novel N-1 Side Chain-Modified Analogs of 1-[(2-Hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT)
作者:Renée Pontikis、Rachid Benhida、Anne-Marie Aubertin、David S. Grierson、Claude Monneret
DOI:10.1021/jm960765a
日期:1997.6.1
1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (1, HEPT) were synthesized and evaluated for their anti-HIV-1 activity. In particular, the influence of substitution of the terminal hydroxy group of the acyclic structure of HEPT and the structural rigidity of this side chain were investigated. Halo (7, 8), azido (9), and amino (10-15) derivatives were synthesized from HEPT via the p-tosylate derivative 6. Acylation
N-Substituted carboxy-N-phosphonomethylglycines and the salts thereof as
申请人:Monsanto Company
公开号:US04312662A1
公开(公告)日:1982-01-26
This disclosure relates to novel N-substituted carboxy-N-phosphonomethylglycines and the salts thereof which are useful as herbicides. This disclosure further relates to herbicidal compositions containing such N-substituted carboxy-N-phosphonomethylglycines and the salts thereof and to herbicidal methods employing such compounds and compositions.
Process for preparing N-phosphonomethylglycine and derivatives
申请人:Monsanto Company
公开号:US04650613A1
公开(公告)日:1987-03-17
There is disclosed a process for the preparation of N-phosphonomethylglycine by dealkylation of N-alkyl-N-phosphonomethylglycine. The N-alkyl moiety contains an electron withdrawing group in the 2-position. Certain novel N-alkyl-N-phosphonomethylglycines are disclosed.