Diuron
J Liu, Oklahoma State University, Stillwater, OK, USA
Ó 2014 Elsevier Inc. All rights reserved.
l Name: Diuron
l Chemical Abstracts Service Registry Number: 330-54-1
l Trade Names: N0 -(3,4-Dichlorophenyl)-N,N-dimethylurea;
3-(3,4-Dichlorophenyl)-1,1-dimethylurea; DCMU; DMU;
Cekiuron; Crisuron; Dailon; Diater; Diurex; Duirol; Karmex
l Molecular Formula: C9H10Cl2N2O
l Chemical Structure:
O CH3
N hydroxylation and dealkylation with the urea moiety generally
Cl NH CH3
Cl
Background
Diuron (330-54-1) is used as an herbicide for weed control on
noncrop lands and agricultural crops such as asparagus, pine-
apple, cotton, and sugarcane. It is also used as a sterilant in soil,
a mildewcide in paints and stains, and an algicide in fish
production.
Uses
For decades, diuron has been one of the top 25 conven-
tional agricultural pesticides used in the United States, and it
is used extensively worldwide to control pre- and post-
emergence weeds. The annual usage of diuron in the US
agriculture has recently ranged from 2 to 6 million pounds
per year. It generally ranks in the top 5–7th pesticides in
usage in the United States for industrial and commercial
applications. Diuron is also used as biocide in antifouling
paints.
Environmental Fate and Behavior
Diuron is stable to hydrolysis (pH 5–9) and photolysis and is
therefore persistent in the environment. Diuron has generally
low adsorption to soils, but it is mobile, relatively persistent,
and capable of transport in surface runoff to groundwater.
Mobility of diuron in the soil is related to organic matter
content. It has the potential to leach into ground and to
contaminate ground and surface waters. Diuron, however, has
low water solubility (42 ppm). It has a low vapor pressure and
low probability of dispersal in air or volatilization from water
or soil.
Encyclopedia of Toxicology, Volume 2 http://dx.doi.org/10.1016/B978-0-12-386454-3.00140-8
Exposure and Exposure Monitoring
Dermal and inhalation routes are the primary exposure path-
ways in occupational settings. Ingestion usually occurs in acci-
dental exposure.
Toxicokinetics
Diuron is absorbed from the gastrointestinal and respiratory
tracts. There was no apparent tissue storage of diuron noted in
either rats or dogs after up to 2 months of feeding. It undergoes
unchanged.
In rats and dogs, the predominant metabolite was
N-(3,4-dichlorophenyl)-urea, accompanied by small amounts
of N-(3,4-dichlorophenyl)-N0 -methylurea, 3,4-dichloroaniline,
3,4-dichlorophenol, and unmetabolized diuron. In mouse liver
microsomes, eight metabolites were identified, with the
N-demethylated derivative being the major one, followed in
importance by three N-hydroxymethyl compounds. Metabo-
lites found in mammals are similar to those found in soil and
plants, wherein dealkylation and hydroxylation are also the
major metabolic pathways. The metabolites are mainly excreted
in urine and feces.
Mechanism of Toxicity
Diuron is a selective inhibitor of the Hill reaction in plant
photosynthesis. In some mammalian carcinogenic studies,
repeated high-dose exposure to diuron appeared to work as
a tumor promoter, and diuron may elicit tumor formation
by inducing cytotoxicity with subsequent sustained cell
proliferation.
Acute and Short-Term Toxicity
Animal
Diuron exhibits low acute toxicity. The oral LD50 in male rats
is >3 g kg1. Dietary protein levels have been reported to
influence the acute toxicity of diuron in albino juvenile rats.
A high acute dosage of diuron (at LD50s) in young rats caused
drowsiness and ataxia; animals that survived were irritable and
hyperexcitable. Diarrhea and clinical signs of renal dysfunction
were reported. Subacute exposure of diuron may cause growth
and developmental retardation in various organs and increase
erythropoiesis. No signs of skin irritation or sensitization were
found in guinea pigs. Diuron was able to induce multiple
hepatic microsomal enzymes in rats.
Human
Diuron produces little acute toxicity in humans except for irri-
tation of the skin, eyes, and nose.
215
216 Diuron
No clinical signs were reported in a surveillance program
covering 22 years of manufacturing activities.
Chronic Toxicity
Animal
A 14 month feeding study in female rats (0.5–1 g kg1)
caused hemolytic anemia and methemoglobinemia. At high
subchronic dosages, male rats exhibited changes in spleen,
bone marrow, and blood chemistry; increased mortality; and
growth retardation. In a 24 month dog study, higher dosages
(1250 ppm) led to hemolytic anemia and hemosiderin
deposition. When adverse effects were found, most long-
term exposure studies reported effects primarily on body
weight.
Human
Little is known regarding effects of long-term exposure to
diuron in humans.
Immunotoxicity
There is very little information available regarding the
immunotoxic potential of diuron. It was reported that splenic
white pulp was depleted and the hemosiderin deposition in
the red pulp was increased in rats after 28 days of feeding
with 1250 or 2500 ppm of diuron. A decrease in CD4þ cells
was also noted in these rats. Diuron was also shown to exert
immunosuppressant effects on the ascidian Botryllus
hemocytes.
Reproductive Toxicity
In pregnant female rats exposed to diuron (250 mg kg1 day1)
during gestation days 6–15, birth defects such as wavy ribs,
extra ribs, and delayed ossification were reported in offspring.
Diuron showed no teratogenic activity in mice, however. There
were no changes in the male rat reproductive system following
gestational to peripubertal exposure.
Genotoxicity
Diuron lacked mutagenic potential in a number of bacterial and
mammalian cell assays.
Carcinogenicity
Diuron is considered as a ‘known/likely’ human carcinogen by
all routes. Administration of diuron in the diet (2500 ppm)
caused mammary gland adenocarcinomas in female NMRI
mice, urinary bladder carcinomas in both sexes of Wistar rats,
and kidney carcinoma in the male rats.
Clinical Management
Treatment is symptomatic.
Ecotoxicology
The acute LD50 of diuron in mallard ducks was >2 g kg1. In
bobwhite quail, the LC50 (8 day) was 1730 ppm. Diuron is
moderately toxic to fish and aquatic invertebrates. In bluegill,
sheepshead minnow, and Daphnia, LC50 concentrations were
around 5–8 ppm. The LD50 in honeybees was about 0.15 mg
per bee.
Exposure Standards and Guidelines
The US Environmental Protection Agency chronic oral reference
dose is 3 mg kg1 day1, and the European acceptable daily
intake is 7 mg kg1 day1. The American Conference of
Governmental Industrial Hygienists threshold limit value time-
weighted average is 10 mg m3.
See also: Pesticides; Pollution, Water.
Further Reading
da Rocha, M.S., Nascimento, M.G., Cardoso, A.P., de Lima, P.L., Zelandi, E.A., de
Camargo, J.L., de Oliveira, M.L., 2010. Cytotoxicity and regenerative proliferation
as the mode of action for diuron-induced urothelial carcinogenesis in the rat.
Toxicol. Sci. 113, 37–44.
de Moura, N.A., Grassi, T.F., Rodrigues, M.A., Barbisan, L.F., 2010. Potential effects of
the herbicide diuron in mammary and urinary bladder two-stage carcinogenesis in
a female Swiss mouse model. Arch. Toxicol. 84, 165–173.
Domingues, A., Barbisan, L.F., Camargo, J.L.V., Spinardi-Barbisan, A.L.T., 2007.
Effects of the herbicide diuron on general parameters of toxicity, lymphohemato-
poietic organs and lymphocytes subpopulations. J. Venom. Anim. Toxins Incl. Trop.
Dis. 13 (4), 981.
Giacomazzi, S., Cochet, N., 2004. Environmental impact of diuron transformation:
a review. Chemosphere 56, 1021–1032.
Menin, A., Ballarin, L., Bragadin, M., Cima, F., 2008. Immunotoxicity in ascidians:
antifouling compounds alternative to organotins – II. The case of diuron and TCMS
pyridine. J. Environ. Sci. Health Part B 43, 644–654.
Relevant Websites
http://www.apvma.gov.au/products/review/docs/diuron_prf_summary.pdf – Australian
Pesticides & Veterinary Medicines Authority: The Reconsideration of Approvals of
the Active Constituent Diuron, Registrations of Products containing Diuron and their
Associated Labels.
http://www.epa.gov/oppsrrd1/REDs/diuron_red.pdf – US Environmental Protection Agency.
http://www.epa.gov/pesticides – US EPA Pesticides: Search for Diuron.