Pesticide profiles : Toxicity, environmental impact and fate - Chapter 9 pptx

Whether these ences are due to variation in reporting the symptoms or due to differences in theway the compounds act in the organisms is currently unknown 14.Teratogenic effects Some mem

chapter nine Ureas

9.1 Class overview and general description

Background

Substituted urea compounds (compounds in which different functional groupsare substituted for one or more of the hydrogens in the urea molecule) are widelyused as herbicidal agents, and to a lesser degree as insecticides (1,2) The generalstructure of the substituted urea molecule is shown in Figure 9.1 The compound’sidentity, structure, and activity are defined by the substituents and their arrangement

on the molecule (1,2) The substituted urea herbicides include the phenylurea bicides (Figure 9.1A) and the sulfonylurea herbicides (Figure 9.1B), which are thetwo major groups of substituted urea herbicides (2) The benzoylphenylureas (Figure9.1C) are the major class of ureas used for insect control (1) Examples of these threetypes of substituted urea compounds are listed in Table 9.1

her-Ureas usage

Phenyl- and sulfonylureasThe phenylurea compounds include some of the most commercially importantherbicides: fenuron and diuron (2) There are at least 20 different compounds withinthis subgroup They are principally used for the control of annual and perennialgrasses and are applied pre-emergence, i.e., before target plants have emerged (2,4).The sulfonylurea compound group is a relatively new class of herbicides firstintroduced in 1982, and has fewer members than the phenylurea class (2) Sulfonylureas are also used for control of broadleaf weed species in addition to annual andperennial grasses (2,4) They may be applied pre- or post-emergence (4) Thesulfonyl urea herbicides are nearly 100 times more toxic to target plants than theolder compounds (2) In addition, they are applied at relatively low applicationrates and have a low toxicity to humans and other animals Thus, this class ofcompound is expected to see continuing research and development activity in thecoming years (3)

BenzoylphenylureasBenzoylphenylurea compounds are very useful in controlling a wide variety ofinsect pests, both within and outside of Integrated Pest Management systems (1).The potential for their use as insecticidal agents was first recognized in the early

1970s by researchers in the Netherlands (1) A number of benzoylphenylurea pounds have been developed for this use, and have a number of advantages overbroad-spectrum organochlorine or organophosphate insecticides (1) Chief amongthese are their specificity for larval and juvenile stages, very low toxicity to verte-brates, and consistent performance in the field (1) Benzoylphenyl compounds aregenerally expected to show low environmental persistence and relatively low ortemporary impacts on most non-target invertebrate species, especially beneficialspecies (e.g., pollinators) (1,5,6) A notable exception to this rule are aquatic inver-tebrates, which may be severely affected by exposure (5,6).

com-Mechanism of action and toxicology: phenylureas

Mechanism of actionPhenylurea herbicides are generally well-absorbed through the roots (but notfoliage) and moved through xylem to the leaves where they disrupt photosynthesis(2,4) One exception is siduron, which does not affect photosynthesis but rather rootgrowth (2) Disruption of photosynthesis occurs by binding of the herbicide to acritical site in the Photosystem II region of the chloroplasts, shutting down CO2

fixation and energy production (4) Indirect production of reactive lipid peroxidescontributes to a loss of membrane integrity and organelle function within the cell(4) Outward signs of these processes include yellowing or blanching of the leaves(foliar chlorosis) and browning (necrosis) due to changes in the chlorophyll and celldeath (4)

Acute toxicityPhenylureas exhibit a range of acute oral toxicities, ranging from moderately topractically nontoxic; reported acute oral rodent LD50 values range from a low of 644

mg/kg (in the case of tebuthiuron) to greater than 5000 mg/kg (in the case offluometuron) (4,7–13) Via the dermal route, they are generally slightly toxic, with

C Figure 9.1 Generic structures for phenylurea (A), sulfonylurea (B), and benzoylphenyl- urea (C) compounds.

reported dermal LD50 values above 5000 mg/kg in rabbits (4,7–12) Tebuthiuron againstands out, with a reported dermal LD50 of greater than 200 mg/kg in rabbits,indicating moderate toxicity via this route (4) Via the inhalation route, the phenyl-ureas are generally slightly toxic, with reported 4-hour inhalation LC50 values ofgreater than 2 mg/L in rats (4,7–13) Most of them do not cause skin sensitization

in guinea pigs or skin irritation in rabbits, but most do cause slight to mild eyeirritation in rabbits (4,7–12)

Linuron has shown the capacity to cause skin sensitization in guinea pigs, andtebuthiuron caused slight skin irritation in rabbits (4)

The symptoms that accompany acuteexposure to phenylurea compounds varywidely For instance, acute exposure of rats to tebuthiuron by ingestion caused a loss

of appetite, a lack of energy, and muscle incoordination (13), while similar exposure

of rats to fluometuron caused muscle weakness, watery eyes, extreme exhaustion,and collapse (11) Fluometuron also has caused cholinesterase depression in guineapigs exposed to 0.6 mg/L over a 2-hour period (11) Signs of diuron exposure in rats

Table 9.1 Examples of Substituted Urea Compounds

Phenylureas Benzthiazuron Chlorbromuron Chlorotoluron Chloroxuron Daimuron Difenoxuron Dimefuron Diuron*

Ethidimuron Fenuron Flufenoxuron Fluometuron*

Forchlorfenuron Isouron

Linuron*

Monuron Neburon Siduron Tebuthiuron*

Sulfonylureas Bensulfuron Chlorimuron Chlorsulfuron Primisulfuron-methyl*

Sulfometuron-methyl*

Triasulfuron Benzoylphenylureas Chlorfluazuron Diflubenzuron*

Penfluron Trilumuron

Note: * indicates that a profile of this compound is included in this chapter.

included depression of central nervous system activity (10) Whether these ences are due to variation in reporting the symptoms or due to differences in theway the compounds act in the organisms is currently unknown (14).

Teratogenic effects

Some members of the phenylurea class have shown the capacity to cause opmental effects in animal tests Diuron has caused irregularities in skeletal forma-tion in rats at doses above 125 mg/kg/day over days 6 to 15 of gestation, and hasalso caused developmental effects in offspring of rabbits given 2000 mg/kg/dayduring gestation (4,8) Flurometuron also caused some secondary effects in rats andrabbits receiving 100 mg/kg/day during gestation (4,8)

devel-Both linuron and tebuthiuron have not shown adverse effects on fetal ment at relevant doses Linuron was negative for teratogenicity at doses (adminis-tered during gestation) of 25 mg/kg/day in rabbits or approximately 6 mg/kg/day

develop-in rats (4,14) Tebuthiuron did not show any teratogenic capacity at 56 mg/kg/day

in rats over three generations, at 180 mg/kg/day in rats during gestation, nor at 25mg/kg/day in rabbits (4,8)

Mutagenic effects

The vast majority of mutagenicityassays and tests for genotoxicity performedusing diuron, fluometuron, linuron, and tebuthiuron have not shown them to havethe potential to cause these effects (4,17,18) They have included the Ames mutage-nicity assay, tests for chromosomal aberration with Chinese hamster ovary cell cul-tures and mouse micronuclei, and tests for DNA repair inhibition in rat liver celllines (4,17,18)

Carcinogenic effects

Some members of the class have been linked to increased tumor production inanimal systems Fluometuron has shown mixed results, causing increased livertumors and leukemia at doses of 87 mg/kg/day in mice over 2 years, but not in rats

at any dose tested (4,17) Diuron has not caused cancer in rats at low levels ofexposure (10), nor has tebuthiuron at the highest doses tested in rats and mice (4).Linuron has shown the capacity to produce increased tumors of the liver in mice at

180 mg/kg/day, and of the testes in rats at doses of 72.5 mg/kg/day (4,10,14)

Organ toxicity

Animal studies have shown the blood-forming system, liver, pancreas, spleen,and kidneys to be potentially affected by exposure to phenylurea compounds

Fate in humans and animals

Some members of the phenylurea class (e.g., linuron and tebuthiuron) are fairlyreadily absorbed through the gastrointestinal tract, whereas others are rather poorlyabsorbed (4,7,17) Those that are not readily absorbed are excreted via fecesunchanged (4,17) Those which may be absorbed and distributed systemically typi-cally undergo rapid transformation and elimination via urine, typically within a fewdays (4,8) Overall, most class members possess a low potential for bioaccumulation

in food animals or humans

Ecological effects

Effects on birds

Phenylurea compounds are typically slightly to practically nontoxic to birds,with reported acuteoral LD50 values above 2000 mg/kg for bobwhite quail in mostcases (4,8) The reported acute oral LD50 for diuron is 1730 mg/kg in bobwhite quail(4) The reported subchronic dietary LC50 values in pheasants, mallards, and Japanesequail are above 5000 ppm for most members of this chemical class (4,8)

Effects on aquatic organisms

Phenylurea compounds are slightly to moderately toxic to freshwater fish, and

in most cases only slightly toxic to freshwater invertebrates Reported 48- and/or96-hour LC50 values for most members of the class range from 4 to greater than 40

mg/L in such species as rainbow trout, bluegill sunfish, carp, and catfish (4,8) Diuron

is more toxic to aquatic invertebrates than most members of this class, with a reported48-hour LC50 of 1 to 2.5 mg/L in Daphnia (4,8)

Effects on other organisms (non-target species)

Phenylurea compounds are generally nontoxic to bees (4,8) Some of them (e.g.,tebuthiruon) may be less selective, and may impact non-target plant species (4).Environmental fate

Breakdown in soil and groundwater

All of the phenylureas will remain active in the soil from a few months up to ayear in some cases and are broken down by the action of soil microorganisms (2).The measured field half-lives for many members of the class range from 25 to over

360 days (19) They are generally poorly bound to most soils, with reported Koc values

of 80 to 500, indicating a moderate to high potential for migration (19) Phenylureacompounds show little tendency to evaporate from soil, and soil pH does not appear

to significantly affect their adsorption (20) Many phenylurea compounds have beendetected in groundwater (20)

Breakdown in water

Phenylureas are generally stable and long-lived in aqueous systems, and willnot easily undergo hydrolysis except with extreme acidic or basic conditions (3,4,20).One example is fluometuron, which has been reported to have a half-life in aqueoussystems of over 100 weeks, and is stable over the pH range of 1 to 13 (11) Theprimary means of breakdown in aquatic systems is via microbial systems, althoughthey may also undergo photolysis (2,8) Conditions that limit the availability ofoxygen for microbial aerobic breakdown of the phenylureas will increase their lon-gevity in the water environment

Breakdown in vegetation

Phenylureas are readily absorbed from roots and translocated to foliage throughxylem; they are not readily absorbed through the foliage (4) In tolerant plants, theyare rapidly metabolized by loss of methyl groups (N-demethylation) and addition

of hydroxyl groups in their place (hydroxylation), thus forming compounds that donot adversely affect the plant like the unmetabolized herbicide (4) Plants incapable

of detoxifying the phenylureas, or which process them only slowly, will suffer theadverse effects the herbicides cause (4)

Mechanism of action and toxicology: sulfonylureas

Mechanism of action

Sulfonylurea herbicides are also well-absorbed and translocated through theroots, as well as through the foliage (4) Some members of the class (e.g., sulfometu-ron-methyl) may show lesser translocation (4) These compounds inhibit a key

enzyme in the biosynthesis of necessary branched-chain amino acids (e.g., leucine,isoleucine, and valine), and thereby limit the plant’s ability to construct the proteinsnecessary to build more cells (4) Deprived of the ability to manufacture necessaryproteins, growth (meristematic) regions suffer inhibited growth and survival

Acute toxicity

Sulfonylurea compounds are, in general, practically nontoxic via the oral route,with reported rodent LD50 values of greater than 5000 mg/kg for most of the com-pounds (4,7,8) Via the dermal route, they are generally slightly toxic, with reporteddermal LD50 values of greater than 2000 mg/kg in rabbits (8,15) They are, in general,slightly toxic via the inhalation route in rodents, with reported 4-hour inhalation

LC50 values of greater than 5 mg/L (4,8,15) They generally test negative for skin

sensitization in guinea pigs, although sulfometuron can cause slight skin irritation

in rabbits, and both primisulfuron and sulfometuron can cause slight to mild eyeirritation in rabbits (4,15)

Chronic toxicity

Much like the phenylureas, sulfonylurea compounds have caused decreasedbody weight gain, increased liver weights, and anemia-like conditions in test animals,but at generally higher dose levels These effects were caused by primisulfuron-methyl in dogs at doses levels of 125 mg/kg/day over 1 year, and by sulfometuron-methyl at 25 mg/kg/day in the same animals for the same length of time (15,21) Inrats, these effects occurred at much higher dose levels, 180 and 375 mg/kg/day,

respectively, over 90 days (15,21) Studies of primisulfuron in rats and mice over 18months showed disorders of the teeth and bones (4).

Reproductive effects

No reproductive effects due to sulfometuron-methyl were seen in rats or rabbits

at 300 mg/kg/day in separate studies (4), but 300 mg/kg/day did cause decreased

fecundity (litter size) in rats in another study (4) Primisulfuron-methyl has causedeffects on the testes of males rats exposed to 250 mg/kg/day over two generations(15) These effects were also observed in other chronic studies in rats It is not clearwhat the overall trend for this chemical class might be

Teratogenic effects

Sulfometuron was not observed to cause teratogenic effects in rats or rabbits at

doses of 300 mg/kg/day (21), but primisulfuron-methyl did cause delayed skeletaldevelopment and/or lack of bone formation in offspring of rats given doses of 100mg/kg/day in two separate studies (15)

of 180 mg/kg/day produced increased liver tumors in mice over 18 months in onestudy, but not in another (4,15)

Organ toxicity

Animal studies have shown the liver, kidneys, spleen, and blood-forming system

to be potentially affected by exposure to sulfonylurea compounds

Fate in humans and animals

Primisulfuron is not readily absorbed via the intestines, and is generally nated unchanged via the feces (15) Sulfometuron is readily absorbed through theintestine, but rapidly metabolized and eliminated within 28 to 40 hours, depending

elimi-on the dose (22) Neither compound is expected to bioaccumulate in animal systems.Ecological effects

Effects on birds

Sulfonylurea compounds are practically nontoxic to wildfowl, with reported

subchronic dietary LC50 values greater than 2000 ppm in bobwhite quail and mallardducks (4)

Effects on aquatic organisms

Sulfonylurea compounds are only slightly toxic to freshwater fish, with reported96-hour LC50 values of greater than 10 mg/L in rainbow trout and bluegill sunfish(15,23) They are practically nontoxic to Daphnia, with 96-hour LC50 values reportedlygreater than 100 mg/L (15,23) Sulfometuron has been implicated in some instances

of mass fish kills, but it is not clear what its actual role might have been in thosecases (24).

Effects on other organisms (non-target species)

Sulfonylurea compounds are not considered toxic to bees (4)

Environmental fate

Breakdown in soil and groundwater

Sulfonylurea compounds are of low to moderate persistence in the soil ment, with reported field half-lives of 4 to 60 days (19,25) They are readily brokendown by soil microbes, and more rapidly under well-oxygenated (aerobic) conditions(4,15,24) Degradation by sunlight may play a greater role in the breakdown of sulfo-meturon-methyl than primisulfuron-methyl (15,24) Ground cover, pH, and soil typehave all been shown to influence the rate of disappearance of sulfometuron-methyl inseveral field studies (24,26,27) Since photodegradation is of lesser importance forprimisulfuron, ground cover may not show very much effect on its loss from soils.The sulfonylurea compounds are poorly bound to most soils, and may be mobile(19,25), depending on pH and water solubility (4) At pH 7, solubility ranges from

environ-70 mg/L for primisulfuron to 27.9 mg/L for chlorsulfuron If the water has a pH of

5, the solubility of sulfometuron-methyl decreases to 8 mg/L The half-lives of most

of the sulfonylurea compounds in soil are 1 or 2 months (4,8) Though the lurea compounds are potentially mobile within the soil, field studies show thatneither primisulfuron-methyl nor sulfometuron-methyl were significantly mobilebeyond a depth of 3 inches (8,20,26,27)

sulfony-Breakdown in surface water

Sulfometuron is relatively short-lived in the water environment, with reportedfield half-lives of several days to 1 or 2 months; primisulfuron may be more persistent(15,24) Both compounds undergo aerobic breakdown, and anaerobic conditions maylengthen their residence time in water (15,24)

Breakdown in vegetation

Primisulfuron-methyl is readily absorbed by both the roots and foliage of plants,and quickly translocated to all parts of the plant (4) In resistant plants, it is rapidlymetabolized, mainly by hydroxylation of the phenyl and pyrimidinyl ring structures,and subsequent linkage to glucose and elimination (4) The metabolism of sulfometu-ron-methyl is not well-understood (4)

Mechanism of action and toxicology: benzoylphenylureas

Mechanism of action

Benzoylphenylurea compounds inhibit the ability of insects to synthesize anintegral component of their exoskeleton cuticles, chitin (1,6) These protein and chitinshells are secreted by insect epidermal cells at regulated intervals within the insectlifespan, with most chitin production occurring during early and juvenile stages ofdevelopment (6) Depending on the insect species and dose rates, benzoylphenylureainhibition of chitin synthesis results in the inability of fertilized eggs to hatch prop-erly, the ability of hatched larvae to secrete chitin, or the ability of juvenile stages to

molt properly and advance to the next life stage (6) There are several schools ofthought as to how the benzoylphenylureas may act to inhibit chitin synthesis andexoskeleton formation (6) It is thought by some researchers that the most plausiblemechanism is that benzoylphenylureas inhibit chitin synthetase, the enzyme respon-sible for stringing together the N-acetylglucosamine (amino-substituted glucosesugar molecules) building blocks into the polymer to form chitin (6).

Relatively less is known about the toxicology and environmental fate of themembers of this class other than diflubenzuron (1) Insofar as the structure of achemical compound determines its activity in biological and environmental systems,diflubenzuron can be considered representative of the toxicological and environmen-tal properties of other members of the benzoylphenylurea chemical class Typically,the generic chemical structure may yield reliable predictive information about mem-bers of a general chemical class, but until actual data are gathered and analyzed for

a specific compound, such predictions must be considered tentative in nature

9.2 Individual profiles

9.2.1 Diflubenzuron

Trade or other names

Diflubenzuron is sold under the trade name Dimilin Other trade names includeDU112307, ENT-29054, Micromite, and OMS-1804

Regulatory status

Some formulations of diflubenzuron may be classified as Restricted Use cides (RUPs) in the U.S RUPs may be purchased and used only by certified appli-cators Diflubenzuron is classified as toxicity class III — slightly toxic Productscontaining it bear the Signal Word CAUTION

Pesti-Introduction

Diflubenzuron is a benzoylphenylurea used on forest and field crops to tively control insects and parasites Principal target insect species are the gypsy moth,forest tent caterpiller, several evergreen-eating moths, and the boll weevil It is alsoused as a larvae control chemical in mushroom operations and animal houses.Diflubenzuron is a stomach and contact poison It acts by inhibiting the production

selec-of chitin, a compound that makes the outer covering selec-of the insect hard and thusinterferes with the formation of the insect’s cuticle or shell It is available as asuspension concentrate, wettable powder, or granules

Figure 9.2 Diflubenzuron.

Reproductive effects

Day-old ducks and turkeys fed moderate amounts of the pesticide in their dietsfor 90 days had decreased testosterone levels after 42 days, but this did not occur inchickens and pheasants in the same study Combs and wattles, which reflect hormone

activity, showed some abnormalities Some were underdeveloped and others moredeveloped compared to controls A short-term decrease in testosterone levels wasshown in the sexually immature rats, but no clear-cut change was shown in youngbull calves (16)

A three-generation study on rats at low doses showed no effect on matingperformance It does not appear that diflubenzuron has a significant effect on repro-duction (16,28)

Teratogenic effects

Diflubenzuron does not appear to be teratogenic Newborn rats and rabbits didnot develop any birth defects after their mothers were exposed to low levels ofdiflubenzuron (1 to 4 mg/kg/day)on days 6 to 18 of gestation (16,28)

Organ toxicity

Animal studies have shown the liver and spleen to be target organs

Fate in humans and animals

Intestinal absorption in mammals decreases with increasing dose levels (28) For

example, in rats, the total excretion in urine and bile decreased from about 50% of

the dose at 4 mg/kg to only 4% at 900 mg/kg Mice showed similar results

A cow given 10 mg/kg orally, eliminated almost all of the product over a 4-day

period There were only minute amounts of the pesticide in the milk The chemical

is not degraded in the digestive tract, but that which is absorbed by the gut is

completely broken down before excretion (16) Rabbits’ skin absorbed only very

small amounts, all of which was recovered in the urine

Chickens excreted almost all of an oral dose in 13 days Their eggs had low levels

of pesticide residues (0.3 to 0.6 mg/kg) from day 9 to the end of the 9-week study

Body tissues (non-fatty) do not retain diflubenzuron (16)

Ecological effects

Effects on birds

Diflubenzuron is practically nontoxic to wild birds Bobwhite quail and mallard

ducks both have an 8-day dietary LC50of greater than 4640 ppm (4,7,8)

Effects on aquatic organisms

Diflubenzuron is practically nontoxic to fish and aquatic invertebrates The LC50

values (96-hour) for diflubenzuron in various fish are: bluegill sunfish, 660 mg/L;

rainbow trout, 240 mg/L; saltwater minnow, 255 mg/L; and channel catfish, 180

mg/L In oyster larvae and juveniles EC50 values were 130 and 250 mg/L,

respec-tively (4,7,8) Arthropods are most susceptible in the premolting stage For instance,

fiddler crabs, exposed for as little as 1 week at levels up to 0.05 mg/L exhibited limb

regeneration effects (29) Fish tissue can show some traces of the metabolites when

water is contaminated with diflubenzuron; however, tissue concentrations decline

steadily with time in clean water

Effects on other organisms ( non-target species )

The compound is nontoxic to bees (4)

Environmental fate

Breakdown in soil and groundwater

Diflubenzuron has a low persistence in soil The rate of degradation in soil is

strongly dependent on the particle size of the diflubenzuron (12) It is rapidly

degraded by microbial processes The half-life in soil is 3 to 4 days (19) Under field

conditions, diflubenzuron has very low mobility (8,19)

Breakdown in water

In sterilized water (no microbes), there appears to be little degradation under

neutral or acidic conditions However, under field conditions, it is degraded rapidly

Residues could not be detected in field water 72 hours after an application of 110

g/ha Other studies suggest a half-life of 1 to 3 weeks (4,7,8)

Breakdown in vegetation

Very little diflubenzuron is absorbed, metabolized, or translocated in plants

Residues on crops such as apples have a half-life of 5 to 10 weeks The half-life in

oak leaf litter is 6 to 9 months (4,7,8)

Physical properties

Diflubenzuron is a white crystalline solid (7)

Chemical name: 1-(4-chlorophenyl)-3-(2,6-difluorobenzoyl)urea (7)

CAS#: 35367-38-5

Molecular weight: 310.7 (7)

Solubility in water: 0.14 mg/L @ 20°C, insoluble (7)

Solubility in other solvents: DMSO s.; acetone s.s.; methanol s

Melting point: 210–230°C (technical with decomposition) (7)

Vapor pressure:<0.033 mPa @ 50°C (7)

Partition coefficient (octanol/water): Not available

Trade or other names

Trade names for products containing diuron include Crisuron, Diater, Di-on,

Direx, Karmex, and Unidron It is often used in combination with other pesticides

such as bromacil and hexazinone

Figure 9.3 Diuron.

Regulatory status

Diuron is a General Use Pesticide (GUP) The U.S EPA classifies it as toxicity

class III — slightly toxic However, products containing diuron bear the Signal Word

WARNING because it can irritate the eyes and throat

Introduction

Diuron is a substituted urea herbicide used to control a wide variety of annual

and perennial broadleaf and grassy weeds as well as mosses It is used on non-crop

areas and many agricultural crops such as fruit, cotton, sugarcane, alfalfa, and wheat

Diuron works by inhibiting photosynthesis It may be found in formulations as

wettable powders and suspension concentrates

Toxicological effects

Acute toxicity

Diuron is slightly toxic to mammals The oralLD50 in rats is 3400 mg/kg The

dermal LD50 is greater than 2000 mg/kg (4,8) Some signs of central nervous system

depression have been noted at high levels of diuron exposure For humans, the only

reported case of acute, oral exposure to the herbicide produced no significant

symp-toms or toxicity (4,8,10)

Chronic toxicity

Male rats given extremely high doses of diuron over a 2-week period showed

changes in their spleen and bone marrow Other chronic effects attributed to moderate

to high doses of the pesticide over time included changes in blood chemistry, increased

mortality, growth retardation, abnormal blood pigment, and anemia When fed small

amounts of diuron in food for 2 years, animal species showed no adverse effects (4,8)

Reproductive effects

Daily low doses of diuron fed to female rats through three successive generations

caused significantly decreased body weight of offspring in the second and third

litters The fertility rate remained unaffected (8) It is unlikely that diuron will cause

reproductive effects in humans at expected levels of exposure

Teratogenic effects

Diuron is teratogenic at high doses Administered to pregnant rats on days 6

through 15 of gestation, it produced no birth defects in the offspring at doses of up

to 125 mg/kg/day However, doses of 250 mg/kg/day caused wavy ribs, extra ribs,

and delayed bone formation There were also weight decreases in offspring at 500

mg/kg/day There was no increase in the severity of the rib deformation at this

higher dose (4,8) Pregnant mice given very high doses of diuron (nearly 2000

mg/kg/day) exhibited reproductive and embryotoxic effects Developmental effects

were found in their offspring (4,8)

Mutagenic effects

Diuron does not appear to be mutagenic The majority of tests have shown that

diuron does not produce mutations in animal cells or in bacterial cells (4,8)

Fate in humans and animals

Diuron is excreted in the feces and urine of test animals Breakdown of thecompound is similar in animals, plants, and soil Cows fed very low doses of diuron

in their diets had small amounts of residues in whole milk Cattle fed small amountsaccumulated low levels of diuron in fat and muscle, liver, and kidney (4,8)

Ecological effects

Effects on birds

Diuron is slightly toxic to birds In bobwhite quail, the dietary LC50 is 1730 ppm

In Japanese quail and ring-necked pheasant, it is greater than 5000 ppm The LC50

is approximately 5000 ppm in mallard ducks (4,8)

Effects on aquatic organisms

The LC50 (48-hour) values for diuron range from 4.3 to 42 mg/L in fish, and from

1 to 2.5 mg/L for aquatic invertebrates The LC50 (96-hour) is 3.5 mg/L for rainbowtrout (4,8) Thus, diuron is moderately toxic to fish and highly toxic to aquatic

invertebrates

Effects on other organisms ( non-target species )

Diuron is nontoxic to bees (4)

Environmental fate

Breakdown in soil and groundwater

Diuron is moderately to highly persistent in soils Residue half-lives are from 1month to 1 year (19) Some pineapple fields contained residues 3 years after the lastapplication Mobility in the soil is related to organic matter and to the type of residue.The metabolites are less mobile than the parent compound (20)

In California, diuron has been found in groundwater in the 2- to 3-ppb range

It has also been found in Ontario groundwater where it has been linked with landapplications (20)

Physical properties

Diuron is a colorless crystalline compound in its pure form (7)

Chemical name: N-(3,4-dichlophenyl)-N,N-dimethyl urea (7)

Vapor pressure: 0.41 mPa @ 50°C (7)

Partition coefficient (octanol/water): Not available

DuPont Agricultural Products

Walker’s Mill, Barley Mill Plaza

Trade or other names

Trade names include C-2059, Ciba-2059, Cotoran, Cotorex, Cottonex, Flo-Met,Higalcoton, Lanex, and Pakhtaran

Regulatory status

Fluometuron is a practically nontoxic compound in EPAtoxicity class II due toits potential to cause skin sensitization Labels of fluometuron products must bearthe Signal Word WARNING Fluometuron is a General Use Pesticide (GUP)

Figure 9.4 Fluometuron.

Fluometuron is a selective herbicide that acts on susceptible plants by inhibitingphotosynthesis Fluometuron is registered by the EPA exclusively for use on cottonand sugarcane It can be applied pre-emergence, for weed control before planting,

or post-emergence, after target crops and weeds come up, and may have residualactivity for several months Fluometuron is available in liquid, dry flowable, andwettable powder formulations

Toxicological effects

Acute toxicity

Fluometuron is practically nontoxic by ingestion, with a reported oralLD50 of

6416 to 8900 mg/kg in rats (4,8) Via the dermal route, it is also practically nontoxic;the dermal LD50 is greater than 2000 mg/kg in rats, and greater than 10,000 mg/kg

in rabbits (4,7) Fluometuron is a mild skin irritant and causes skin sensitization inguinea pigs It may cause corneal opacity in test animals (33) It is irritating to themucous membrane lining the skin, gastrointestinal tract, and respiratory system The

inhalation LC50 in rats is greater than 2 mg/L, indicating moderate to low toxicity

by this route (4)

While there have been no reports of cases of fluometuron poisoning in humans,this herbicide is considered a mild inhibitor of cholinesterase Cholinesterase inhi-bition was observed in guinea pigs exposed by inhalation to about 0.6 mg/L for 2hours (33) Examination of rats used for LD50 testing revealed increased brain weight(17) Other symptoms of fluometuron poisoning in rats include muscular weakness,tearing or watery eyes, extreme exhaustion, and collapse (17)

Chronic toxicity

Rats were fed 7.5, 75, or 750 mg/kg/day for 90 days At the highest dose,decreased body weight and congestion in the spleen, adrenals, liver, and kidneys,

as well as abnormalities in red blood cells were evident (8,17) When doses of 1.5,

15, or 150 mg/kg/day were fed to puppies for 90 days, congestion of the liver,kidneys, and spleen occurred at the highest dose No effects were seen at 15mg/kg/day (8,17) Prolonged or repeated exposure to fluometuron may cause con-junctivitis or skin sensitization (4,8)

Reproductive effects

There were no reproductive effects due to fluometuron seen in pregnant ratsgiven doses as high as 50 mg/kg/day during gestation, even though toxic effects inthe mother were observed (4,8) Pregnant rabbits were given doses of 50, 500, or 1000mg/kg/day by stomach tube during days 6 through 19 of gestation An increase inthe number of resorbed fetuses was found at all treatment doses Reduction inmaternal body weight and food consumption occurred at doses of 500 and 1000mg/kg/day (17) The evidence indicates that fluometuron will not cause reproduc-tive effects in humans at expected levels of exposure

Teratogenic effects

Some secondary developmental effects were seen in the progeny of rats andrabbits receiving 100 mg/kg/day during gestation (4,8) These higher dose dataindicate that teratogenic effects are not likely in humans at expected exposure levels