Glyphosate is a broad-spectrum, extremely effective, low-toxic herbicide. The environment frequently contains cyanide chemicals, which are residues left over from glyphosate herbicides. Exposure to glyphosate may disrupt oocyte maturation by causing the generation of early cells and oxidants. In mouse oocytes, glyphosate triggers early cell staining and autophagy [2].

Absorption, Distribution and Excretion
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.
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.
For more Absorption, Distribution and Excretion (Complete) data for GLYPHOSATE (11 total), please visit the HSDB record page.

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Metabolism / Metabolites
...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.

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Biological Half-Life
Male and female Sprague-Dawley rats received single intraperitoneal injections of radiolabeled (14)C glyphosate. The dose level of glyphosate used for male and female rats was 1150 mg/kg. Blood samples were collected 0.25, 0.50, 1, 2, 4, 6 and 10 hours after injection. ... Assuming first order kinetics, the decrease in radioactivity in bone marrow occurred with a half-life of 7.6 and 4.2 hours for males and females, respectively. Similarly, the half-lives of the radioactivity in plasma were approximately 1 hour for both sexes.
The kinetics of whole body elimination were estimated using the radioactivity (14)C measured in urine and feces after a single oral dose of (14)C-glyphosate (10 or 1000 mg/kg body weight). Because of the lack of biotransformation of glyphosate it is valid to base kinetics on total radioactivity. The elimination appeared to be biphasic. The half-life of the alpha elimination phase at 10 mg/kg body weight was 5.87 hr (males) or 6.22 hr (females); at 1000 mg/kg body weight this was 5.26 hr (males)or 6.44 hr (females). The half-life of the beta phase at 10 mg/kg body weight was 79 hr (males) or 106 hr (females); at 1000 mg/kg body weight this was 181 hr (males) or 337 hr (females).
The toxicokinetics of glyphosate after single 100 mg/kg intravenous (i.v.) and 400 mg/kg oral doses were studied in rats. ... 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.

[1]. Evaluation of carcinogenic potential of the herbicide glyphosate, drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies. Crit Rev Toxicol. 2015;45(3):185-208.

[2]. Zhang JW, et al The toxic effects and possible mechanisms of glyphosate on mouse oocytes. Chemosphere. 2019 Dec;237:124435.

[3]. Toxic Effects of Glyphosate on the Nervous System: A Systematic Review. Int J Mol Sci. 2022 Apr 21;23(9):4605.

Glyphosate is the active ingredient in weed killer products such as RoundUp™. Glyphosate products are one of the most widely used weed killers worldwide in farms and in home gardens and lawns. These products typically contain glyphosate in combination with other ingredients that help improve the absorption of the glyphosate into the plant. Glyphosate-based formulations (GBFs) are easily bought in most stores. These products can have different combinations of other ingredients or different concentrations of glyphosate.
Glyphosate can cause cancer according to California Labor Code and the World Health Organization's International Agency for Research on Cancer (IARC).
Glyphosate is an odorless white powder. Decomposition begins at approximately 419 °F (darkens). pH (1% solution in water) 2.5. (NTP, 1992)
Glyphosate is a phosphonic acid resulting from the formal oxidative coupling of the methyl group of methylphosphonic acid with the amino group of glycine. It is one of the most commonly used herbicides worldwide, and the only one to target the enzyme 5-enolpyruvyl-3-shikimate phosphate synthase (EPSPS). It has a role as an agrochemical, an EC 2.5.1.19 (3-phosphoshikimate 1-carboxyvinyltransferase) inhibitor and a herbicide. It is a phosphonic acid and a glycine derivative. It is a conjugate acid of a glyphosate(2-) and a glyphosate(1-).
Glyphosate has been reported in Glycine max and Phaseolus vulgaris with data available.
Glyphosate is a synthetic organophosphate compound that blocks the activity of enolpyruvylshikimate-3-phosphate (EPSP) synthase and is used as a broad-spectrum pesticide. It is characterized as a volatile, moderately toxic, colorless, odorless crystalline solid or powder, and exposure occurs by inhalation, ingestion, or contact.
Active compound in herbicidal formulations that inhibits 3-PHOSPHOSHIKIMATE 1-CARBOXYVINYLTRANSFERASE.
See also: ... View More ...

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Mechanism of Action
Previous studies demonstrate that glyphosate exposure is associated with oxidative damage and neurotoxicity. Therefore, the mechanism of glyphosate-induced neurotoxic effects needs to be determined. The aim of this study was to investigate whether Roundup (a glyphosate-based herbicide) leads to neurotoxicity in hippocampus of immature rats following acute (30min) and chronic (pregnancy and lactation) pesticide exposure. Maternal exposure to pesticide was undertaken by treating dams orally with 1% Roundup (0.38% glyphosate) during pregnancy and lactation (till 15-day-old). Hippocampal slices from 15 day old rats were acutely exposed to Roundup (0.00005-0.1%) during 30min and experiments were carried out to determine whether glyphosate affects (45)Ca(2+) influx and cell viability. Moreover, /this study/ investigated the pesticide effects on oxidative stress parameters, (14)C-alpha-methyl-amino-isobutyric acid ((14)C-MeAIB) accumulation, as well as glutamate uptake, release and metabolism. Results showed that acute exposure to Roundup (30min) increases (45)Ca(2+) influx by activating NMDA receptors and voltage-dependent Ca(2+) channels, leading to oxidative stress and neural cell death. The mechanisms underlying Roundup-induced neurotoxicity also involve the activation of CaMKII and ERK. Moreover, acute exposure to Roundup increased (3)H-glutamate released into the synaptic cleft, decreased GSH content and increased the lipoperoxidation, characterizing excitotoxicity and oxidative damage. /This study/ also observed that both acute and chronic exposure to Roundup decreased (3)H-glutamate uptake and metabolism, while induced (45)Ca(2+) uptake and (14)C-MeAIB accumulation in immature rat hippocampus. Taken together, these results demonstrated that Roundup might lead to excessive extracellular glutamate levels and consequently to glutamate excitotoxicity and oxidative stress in rat hippocampus.
Glyphosate is the primary active constituent of the commercial pesticide Roundup. The present results show that acute Roundup exposure at low doses (36 ppm, 0.036 g/L) for 30 min induces oxidative stress and activates multiple stress-response pathways leading to Sertoli cell death in prepubertal rat testis. The pesticide increased intracellular Ca(2+) concentration by opening L-type voltage-dependent Ca(2+) channels as well as endoplasmic reticulum IP3 and ryanodine receptors, leading to Ca(2+) overload within the cells, which set off oxidative stress and necrotic cell death. Similarly, 30 min incubation of testis with glyphosate alone (36 ppm) also increased (45)Ca(2+) uptake. These events were prevented by the antioxidants Trolox and ascorbic acid. Activated protein kinase C, phosphatidylinositol 3-kinase, and the mitogen-activated protein kinases such as ERK1/2 and p38MAPK play a role in eliciting Ca(2+) influx and cell death. Roundup decreased the levels of reduced glutathione (GSH) and increased the amounts of thiobarbituric acid-reactive species (TBARS) and protein carbonyls. Also, exposure to glyphosate-Roundup stimulated the activity of glutathione peroxidase, glutathione reductase, glutathione S-transferase, gamma-glutamyltransferase, catalase, superoxide dismutase, and glucose-6-phosphate dehydrogenase, supporting downregulated GSH levels. Glyphosate has been described as an endocrine disruptor affecting the male reproductive system; however, the molecular basis of its toxicity remains to be clarified. We propose that Roundup toxicity, implicated in Ca(2+) overload, cell signaling misregulation, stress response of the endoplasmic reticulum, and/or depleted antioxidant defenses, could contribute to Sertoli cell disruption in spermatogenesis that could have an impact on male fertility.
A deregulation of programmed cell death mechanisms in human epidermis leads to skin pathologies. We previously showed that glyphosate, an extensively used herbicide, provoked cytotoxic effects on cultured human keratinocytes, affecting their antioxidant capacities and impairing morphological and functional cell characteristics. The aim of the present study, carried out on the human epidermal cell line HaCaT, was to examine the part of apoptosis plays in the cytotoxic effects of glyphosate and the intracellular mechanisms involved in the apoptotic events. /This study/ conducted different incubation periods to reveal the specific events in glyphosate-induced cell death. /It/ observed an increase in the number of early apoptotic cells at a low cytotoxicity level (15%), and then, a decrease, in favor of late apoptotic and necrotic cell rates for more severe cytotoxicity conditions. At the same time, /the study/ showed that the glyphosate-induced mitochondrial membrane potential disruption could be a cause of apoptosis in keratinocyte cultures.
Herbicides have been recognized as the main environmental factor associated with human neurodegenerative disorders such as Parkinson's disease(PD). Previous studies indicated that the exposure to glyphosate, a widely used herbicide, is possibly linked to Parkinsonism, however the underlying mechanism remains unclear. We investigated the neurotoxic effects of glyphosate in differentiated PC12 /rat/ cells and discovered that it inhibited viability of differentiated PC12 cells in dose-and time-dependent manners. Furthermore, the results showed that glyphosate induced cell death via autophagy pathways in addition to activating apoptotic pathways. Interestingly, deactivation of Beclin-1 gene attenuated both apoptosis and autophagy in glyphosate treated differentiated PC12 cells, suggesting that Beclin-1 gene is involved in the crosstalk between the two mechanisms.
For more Mechanism of Action (Complete) data for GLYPHOSATE (7 total), please visit the HSDB record page.

C3H8NO5P

169.07

169.014

1071-83-6

Glyphosate-d2;2733532-11-9;Glyphosate-13C2,15N;1185107-63-4;Glyphosate-d2-1

3496

White to off-white solid powder

1.7±0.1 g/cm3

465.8±55.0 °C at 760 mmHg

230 °C (dec.)(lit.)

235.5±31.5 °C

0.0±2.5 mmHg at 25°C

1.529

-2.36

4

6

4

10

162

0

XDDAORKBJWWYJS-UHFFFAOYSA-N

InChI=1S/C3H8NO5P/c5-3(6)1-4-2-10(7,8)9/h4H,1-2H2,(H,5,6)(H2,7,8,9)

2-(phosphonomethylamino)acetic acid

Glyphosate Folusen Atila Lancer

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~13.89 mg/mL (~82.16 mM)

Solubility in Formulation 1: 6.67 mg/mL (39.45 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).

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 (Please use freshly prepared in vivo formulations for optimal results.)