Absorption, Distribution and Excretion
Diuron is readily absorbed through the gastrointestinal tract in rats and dogs. Tissue level of diuron were positively correlated with dosage. No apparent storage of diuron in tissues was noted ... Diuron is also partially excreted unchanged in feces and urine.
Root uptake of (14)C-Diuron from solution was studied. ... small amount of the monomethyl and demethylated derivatives were found in nutrient solution from ... soybeans, ... oat, and corn tops.
Diuron is most readily absorbed through the root system; less so through foliage & stems. Translocation is primarily upward in xylem.
Diuron was fed to five dairy cows at 0-550 ppm concentration levels. About 50% of the diuron was detected in the urine, 10% in the feces and 5% in the blood. Milk samples did not contain diuron. A positive correlation was noted between the concn of diuron products in urine and blood and a negative correlation between urine and feces. It is suggested that the remaining diuron is absorbed in the body or degraded into undetectable metabolites.

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Metabolism / Metabolites
Diuron is carcinogenic to the rat urinary bladder at high dietary levels. The proposed mode of action (MOA) for diuron is urothelial cytotoxicity and necrosis followed by regenerative urothelial hyperplasia. Diuron-induced urothelial cytotoxicity is not due to urinary solids. Diuron is extensively metabolized, and in rats, N-(3,4-dichlorophenyl)urea (DCPU) and 4,5-dichloro-2-hydroxyphenyl urea (2-OH-DCPU) were the predominant urinary metabolites; lesser metabolites included N-(3,4-dichlorophenyl)-3-methylurea (DCPMU) and trace levels of 3,4-dichloroaniline (DCA). In humans, DCPMU and DCPU have been found in the urine after a case of product abuse. To aid in elucidating the MOA of diuronand to evaluate the metabolites that are responsible for the diuron toxicity in the bladder epithelium, we investigated the urinary concentrations of metabolites in male Wistar rats treated with 2500 ppm of diuron, the urothelial cytotoxicity in vitro of the metabolites and their gene expression profiles. DCPU was found in rat urine at concentrations substantially greater than the in vitro IC50 and induced more gene expression alterations than the other metabolites tested. 2-OH-DCPU was present in urine at a concentration approximately half of the in vitro IC50, whereas DCPMU and DCA were present in urine at concentrations well below the IC50. For the diuron-induced MOA for the rat bladder, we suggest that DCPU is the primary metabolite responsible for the urothelial cytotoxicity with some contribution also by 2-OH-DCPU. This study supports a MOA for diuron-induced bladder effects in rats consisting of metabolism to DCPU (and 2-OH-DCPU to a lesser extent), concentration and excretion in urine, urothelial cytotoxicity, and regenerative proliferation.
This study was designed to investigate diuron biotransformation and disposition ... . The only metabolic pathway detected by liquid chromatography/mass spectometry in human liver homogenates and seven types of mammalian liver microsomes including human was demethylation at the terminal nitrogen atom. No other phase I or phase II metabolites were observed. The rank order of N-demethyldiuron formation in liver microsomes based on intrinsic clearance (V(max)/K(m)) was dog > monkey > rabbit > mouse > human > minipig > rat. All tested recombinant human cytochrome P450s (P450s) catalyzed diuron N-demethylation and the highest activities were possessed by CYP1A1, CYP1A2, CYP2C19, and CYP2D6. Relative contributions of human CYP1A2, CYP2C19, and CYP3A4 to hepatic diuron N-demethylation, based on average abundances of P450 enzymes in human liver microsomes, were approximately 60, 14, and 13%, respectively. Diuron inhibited relatively potently only CYP1A1/2 (IC(50) 4 uM)...
3,4-dichloroaniline (3,4-DCA) is a metabolite of diuron as well as two other pesticides, linuron and propanil. However, EPA's Metabolism Assessment Review Committee (MARC) concluded that residues of 3,4-DCA should not be aggregated for the diuron, linuron, and propanil risk assessments because 3,4-DCA is significant residue of concern for propanil, but is not a residue of concern per se for diuron or linuron. Although the analytical method for quantifying residues of concern from diuron converts all residues to 3,4-DCA as a convenience, 3,4-DCA was not a significant residue in any metabolism or hydrolysis study.
... In ... a woman poisoned with Diuron, 1-(3,4-dichlorophenyl)-3,3-dimethylurea, plus 3-amino-1,2,4-triazole, 1-(3,4-dichlorophenyl)-3-methylurea, and 1-(3,4-dichlorophenyl)urea were isolated from urine. The urine probably contained small amt of 3,4-dichloroaniline, but no unchanged herbicide.
For more Metabolism/Metabolites (Complete) data for Diuron (12 total), please visit the HSDB record page.
Diuron has known human metabolites that include N-demethyldiuron.

Toxicity Summary
IDENTIFICATION AND USE: Diuron is a solid. Diuron is a photosynthesis inhibitor that is used mainly for general weed control on noncrop areas. It has also been used in the selective control of germinating broadleaf and grass weeds in sugarcane, citrus, pineapples, cotton, asparagus, and temperate climate tree and bush fruits. It is also used as a soil sterilant. HUMAN STUDIES: It may irritate the skin, eyes, or nose. Diuron is cytotoxic in vitro in human cells and oxidative stress contributes to its toxicity. The victim of a suicide attempt did not show signs of intoxication after ingesting diuron and amitrole preparation. ANIMAL STUDIES: It caused irritation to eyes and mucous membranes of rabbits but a 50% water paste was not irritating to intact skin of guinea pigs. Diuron at high dietary levels (2500 ppm) induces rat urinary bladder hyperplasia after 20 weeks of exposure. It was also noted that genes related to the aryl hydrocarbon receptor signaling were upregulated in rats exposed to the diuron high dose (1250 and 2500 ppm). Diuron induced high incidences of urinary bladder carcinomas and low incidences of kidney pelvis papillomas and carcinomas in rats exposed to high doses (2500 ppm) in a 2-year bioassay. The proposed rat urothelial mode of action for this herbicide consists of metabolic activation to metabolites that are excreted and concentrated in the urine, leading to cytotoxicity, urothelial cell necrosis and exfoliation, regenerative hyperplasia, and eventually tumors. At 2500 ppm for 2 years, both rats and dogs showed growth retardation, slight anemia, presence of abnormal pigment, increased erythropoiesis, and splenic hemosiderosis. Some rats showed splenic enlargement, and dogs showed liver enlargement. Diuron at 750 ppm induced male offspring toxicity but these alterations were not permanent, as evidenced by absence of reproductive-system alterations in adult rats. A dietary concentration of 125 ppm did not adversely affect reproduction in a three-generation rat study. In rat developmental studies, reduction in mean fetal weight at 500 mg/kg was noted, and 250 mg/kg increased the number of anomalous fetuses. In zebrafish studies, changes in behavior, such as decrease in spontaneous coiling movements of embryos and reduction of thigmotaxis in larvae, were pronounced for diuron. Diuron was active in vitro when tested for endocrine disrupting potential. Diuron was tested in Salmonella strains TA1535, TA97, TA98, and TA100 with metabolic activation at 0, 10, 25, 50, 100, or 250 ug/plate and without activation at 0, 0.5, 1, 2.5, 5, or 10 ug/plate. No increase in reversion rate reported. Cytotoxicity with TA1535. ECOTOXICITY STUDIES: Diuron metabolites had estrogenic effects potentially mediated through enhanced estradiol biosynthesis and accelerated the ovarian development of Nile tilapia females. Further studies indicated that biotransformation of diuron to active metabolites alter signaling pathways of the CNS which may impact androgen and the stress response as well as behavior necessary for social dominance, growth, and reproduction in fish. Exposure to a concentration of diuron that is frequently encountered in the field during the oyster's gametogenesis stage can impact the next generation and may result in fitness disturbance. Negative effect of diuron on oyster reproduction potentiated by inducing both structural and functional modifications of the DNA. Further in oysters, parental diuron exposure has an impact on the DNA methylation pattern of its progeny. The effect of the herbicide diuron was evaluated using a recycling multi compartment algae, Daphnia magna, bacteria microecosystem. A concentration of 0.2 ppm diuron was lethal to the Daphnia magna population. Diuron had an effect on newly born animals, and therefore these did not mature. Diuron was correlated with severe and widespread dieback of the dominant mangrove, Avicennia marina (Forsk.) Vierh. var. eucalyptifolia (Val.) N.C. Duke (Avicenniaceae), its reduced canopy condition, and declines in seedling health within three neighbouring estuaries in the Mackay region of NE Australia. The likely consequences of such dieback included declines in coastal water quality with increased turbidity, nutrients and sediment deposition, as well as further dispersal of the toxic chemicals.
Diuron has been reported to bind to androgen receptors. This suggests that diuron may block the receptors and result in the toxicity on the reproductive system.

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Interactions
Diuron and antimycin A act between both cytochromes b and cl of the respiratory chain, the rate of inhibition versus concentration of diuron yields hyperbolic kinetics whereas antimycin A shows a sigmoidal inhibition curve. Combined effects of antimycin A and diuron on yeast mitochondrial state 4 respiration as well as the apparent ki of diuron is significantly decreased in the presence of antimycin A. The interaction coefficient between antimycin A and diuron was 0.4, suggesting that antimycin A induced conformational change in the b-cl segment of the respiratory chain allows diuron to bind more tightly to its site of action.

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Non-Human Toxicity Values
LD50 Rat (male) oral 3400 mg/kg
LD50 Rat oral 1017 mg/kg

Diuron can cause cancer according to The Environmental Protection Agency (EPA).
Diuron is a white crystalline solid. It is a wettable powder. The primary hazard is the threat to the environment. Immediate steps should be taken to limit its spread to the environment. It can cause illness by inhalation, skin absorption and/or ingestion. It is used as a herbicide.
Diuron is a member of the class of 3-(3,4-substituted-phenyl)-1,1-dimethylureas that is urea in which both of the hydrogens attached to one nitrogen are substituted by methyl groups, and one of the hydrogens attached to the other nitrogen is substituted by a 3,4-dichlorophenyl group. It has a role as a photosystem-II inhibitor, a xenobiotic, an environmental contaminant, a mitochondrial respiratory-chain inhibitor and a urea herbicide. It is a dichlorobenzene and a 3-(3,4-substituted-phenyl)-1,1-dimethylurea.
Diuron, also known as DCMU (3-(3,4-dichlorophenyl)-1,1-dimethylurea), is an herbicide in the urea chemical family that inhibits photosynthesis. It was introduced by Bayer in 1954 under the trade name of Diuron. DCMU is a very specific and sensitive inhibitor of photosynthesis, the process by which plants use light, water, and carbon di-oxide from the atmosphere to form plant sugars and cellulose. Diuron blocks electron transport at a critical point in this process. It blocks the plastoquinone binding site of photosystem II, disallowing the electron flow from where it is generated, in photosystem II, to plastoquinone. This interrupts the photosynthetic electron transport chain in photosynthesis and thus reduces the ability of the plant to turn light energy into chemical energy (ATP and reductant potential).
A pre-emergent herbicide.

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Mechanism of Action
/Chlorophyll/ fluorescence measurements indicated significant electron transport inhibition in /intact soybean/ leaves 1 hr after treatment with 40 mM solutions of ... diuron.
The potent inhibitory effect of substituted ureas on the photosynthetic mechanism of ... plants ... /is exerted through inhibition of/ Hill reaction, ie, evolution of oxygen in presence of living chloroplasts & suitable hydrogen acceptor. /Substituted ureas/

C9H10CL2N2O

233.09

232.017

330-54-1

Diuron-d6;1007536-67-5

3120

White, crystalline solid
Colorless crystals
White powder

1.3±0.1 g/cm3

362.3±52.0 °C at 760 mmHg

158-159°C

172.9±30.7 °C

0.0±0.9 mmHg at 25°C

1.565

2.88

1

1

1

14

211

0

CN(C(NC1=CC(Cl)=C(Cl)C=C1)=O)C

XMTQQYYKAHVGBJ-UHFFFAOYSA-N

InChI=1S/C9H10Cl2N2O/c1-13(2)9(14)12-6-3-4-7(10)8(11)5-6/h3-5H,1-2H3,(H,12,14)

3-(3,4-dichlorophenyl)-1,1-dimethylurea

HW 920; Dirurol; Diuron

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

DMSO : ~250 mg/mL (~1072.55 mM)

Solubility in Formulation 1: ≥ 6.25 mg/mL (26.81 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 6.25 mg/mL (26.81 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 6.25 mg/mL (26.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly.

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