Toxicologic Information About Insecticides
Used for Eradicating Mosquitoes
(West Nile Virus Control)
April 2005
Fenthion is an organophosphate used primarily as an insecticide and secondarily as an avicide and acaricide. It was used extensively preharvest on sugar cane, rice, field corn, beets, pome and stone fruit, citrus fruits, pistachio, cotton, olives, coffee, cocoa, vegetables, and vines. However, fenthion no longer has Food and Drug Administration approval because of an excess number of poisoningrelated deaths (TOXNET 1985). Used as a contact and stomach insecticide, it is highly persistent. The Environmental Protection Agency (EPA) classifies it as a Restricted Use Pesticide because of the special handling warranted by its toxicity. Fenthion is effective against fruit flies, leaf hoppers, cereal bugs, weaver birds, animal parasites, mites, aphids, and codling moths. Fenthion has been used in mosquito control (Thomson 1976), but it was voluntarily pulled from the market as a mosquitocide in 2004 (EPA 2005). Fenthion was used on cattle and swine and for mosquito (adulticide) control in Florida only (EPA 1999). Approximately 222,400–333,600 pounds of the active ingredient was used annually, of which 74,400–111,600 pounds are specifically used for mosquito control.
Fenthion is applied as ear tags and used in spot treatments and pour-on applications for livestock. Application to control mosquitoes is both aerial and ground. Fenthion is not recommended for residual indoor application because of its high mammalian toxicity (i.e., it is highly toxic to birds and moderately toxic to mammals). As a spray, it is extremely effective at controlling mosquitoes. However, it is hazardous to birds, honey bees, beneficial insects, and fish. Fenthion should not be applied for mosquito control in areas containing fish, shrimp, crabs, or crayfish.
Section 1. Environmental Factors
Use of fenthion as an insecticide releases the compound directly to the environment through applications in sprays, dusts, and other application mechanisms. If released to the atmosphere, fenthion degrades rapidly in the vapor phase by reacting with photochemically produced hydroxyl radicals (half-life of about 5 hours). Particulate-phase fenthion is subject to wet and dry deposition (HSDB 2003).
When released to soil or water, fenthion degrades through photodegradation and biodegradation; in the presence of sunlight, photodegradation is likely to dominate. Hydrolysis occurs, but it usually is too slow to be a significant route; hydrolysis half-lives of 101 days in distilled water and 69 days in saltwater have been reported. Additionally, volatilization is expected to be relatively slow. The reported persistence half-life of fenthion in water under field conditions ranges from 2.9 to 21.1 days for various ocean, river, swamp, lake, and canal waters (HSDB 2003). However, it may persist longer in some environments, such as salt marsh sediments (below several mm deep), where light and oxygen are limited. In plants, fenthion oxidizes to sulfoxide and sulfone, which are both highly insecticidal (Worthing 1987).
Fenthion adsorbs strongly to soil particles. This adsorption makes fenthion less likely to move or leach through the soil with water percolating through the ground (Witt et al. 1985). In soil, residues of fenthion persist for approximately 4–6 weeks (Harding 1979). Biodegradation and photo-oxidation are the significant routes in soil, with photo-oxidation dominant under sunlit conditions. The U.S. Department of Agriculture's Pesticide Properties Database lists the soil half-life of fenthion as 34 days (HSDB 2003). This insecticide is susceptible to biodegradation through anaerobic or nonphotolytic organisms (HSDB 2003).
The persistence time of fenthion and its residues from the last application to the time residue levels are low enough to allow harvest is 1 week for tomatoes and strawberries; 10 days for pears; 2 weeks for onions; 3 weeks for beans, citrus, citrus juice, and plums; and 4 weeks for potatoes and sweet potatoes (OHM/TADS 2003). The interval between application and harvest is 4½ weeks for rice and rice straw. Lactating cows given a dose of 9 mg/kg excreted approximately 50% of the fenthion and its residues in 1 month. The maximum excretion of fenthion residues occurred in the first 24 hours. The residues excreted were primarily hydrolysis products. About 2% of the applied fenthion from a lactating cow was later found in the milk.
A measured, mean bioconcentration factor of 16,600 in guppies, a measured bioconcentration factor of 62 in tadpoles, and estimated bioconcentration factors of 760 and 200 based upon a log Kow of 4.09 and a water solubility of 7.5 mg/L at 20 deg C, respectively, indicates that fenthion is likely to significantly bioconcentrate in aquatic organisms (HSDB 2003).
Section 2. Potential for Exposure
The general population is not likely to be exposed to large amounts of fenthion. Fenthion can be absorbed through dermal contact and by inhalation of dust particles. Occupational exposure to fenthion occurs through dermal contact and inhalation of dust and sprays, especially to workers applying the compound as an insecticide. Because fenthion has been detected in American foods, exposure to the general population can occur through consumption of foods containing fenthion residues. Ingestion is the important cause of severe poisoning with this compound (HSDB 2003).
Because of fenthion’s use as a pesticide, EPA reviewed the likelihood of exposure to the public of unacceptable (i.e., high-risk) levels. In an extensive risk assessment, EPA (1999) identified the likelihood of such exposures in various scenarios, including dietary, residential, worker, drinking water, aggregate, and ecologic. For dietary risk assessments, the target exposure level above which risk is considered to be of concern is referred to as the populations-adjusted dose (PAD). An acute PAD (aPAD) and a chronic PAD (cPAD) are calculated by dividing the respective acute and chronic RfDs (aRfD and cRfD) by the Food Quality Protection Act Safety Factor. Because the Food Quality Protection Act Safety Factor was reduced to 1x for fenthion, the aPAD and cPAD are identical to the respective aRfD and cRfD. The margin of exposure (MOE) is defined as the ratio of the no-observedadverse- effect level (NOAEL) to the estimated exposure dose. Low MOEs indicate that human levels of exposure are close to the levels for the NOAEL in animals. Regulatory agencies have used MOEs <100 as flags for further evaluation.
The acute dietary risk exceeds EPA's level of concern for the general U.S. population and all population subgroups, including infants and children. At the 99.9th percentile, the risk for the most highly exposed subgroup (children aged 1–6 years) is 800% of the aPAD. The risk falls below EPA's level of concern (100% aPAD) between the 90th and 95th percentiles. The chronic dietary risk exceeds EPA’s level of concern for the general U.S. population and various population subgroups, excluding infants. The most highly exposed subgroup is children 1–6 years at 270% of the cPAD consumed. Beef fat and meat are the highest contributors to acute and chronic dietary risk for all population groups. Residue values for acute and chronic risk were extrapolated from data that do not represent the current label use pattern. Although these anticipated residues represent a best estimate by use of the limited data available, they are an overestimate.
Residential risk, of concern for toddlers, results from the use of fenthion as a wide-area mosquito adulticide. No risk concerns exist for exposure of adults associated with any treatment scenario. Risks exceed EPA's level of concern (i.e., MOE <100) for toddlers at the maximum aerial label rate until 8 days post-treatment and until 2 days post-treatment at the average application rate.
Worker risk is of concern because of the use of fenthion as a wide area mosquito adulticide. MOEs <100 for short-term exposure and <300 for intermediate-term exposure exceed EPA's level of concern. Short-term risks exceed the level of concern for mixing/loading and applying liquids aerially (MOEs <55), ground ultra-low volume (ULV) applicators (MOEs <55), aerial application of granulars (MOEs <85), and flaggers during aerial application (MOEs <35). These MOEs include the use of engineering controls where appropriate. Intermediate-term risks exceed the level of concern for mixing/loading and applying liquids aerially (MOEs <20), ground mixing/loading and applying liquids (MOEs <85), aerial application of granulars (MOEs <230), ground-based granular application (MOEs <20), and flagging during aerial application (MOEs <10).
Drinking water risk is low. Little concern exists for adults and children from exposure to fenthion in drinking water because (1) the estimated environmental concentrations used in these calculations were derived from conservative, screening-level models; (2) only minor exposure to surface water is possible because of the application rate and method; and (3) the targeted treatment areas are residential and not significant contributors to drinking water derived from surface water sources.
There is concern for acute aggregate risk and short-term and intermediate-term aggregate risk associated with the use of fenthion.
Ecologic risk is high from use of fenthion as a wide-area mosquito adulticide. EPA’s level of concern is exceeded for endangered bird species on an acute and chronic basis from the mosquito adulticide use. The level of concern is exceeded for endangered species of estuarine/marine invertebrates on an acute and chronic basis from the mosquito adulticide use.
Section 3. Health Effects/Toxicity
Health Effects in Humans
The principal toxicologic effect of fenthion and other
organophosphate insecticides is cholinesterase inhibition. The following health
effects can result:
- Common early signs or mild symptoms of acute cholinergic poisoning include miosis (pinpoint pupils), headache, nausea/vomiting, dizziness, muscle weakness, drowsiness, lethargy, agitation, and anxiety.
- Moderate or severe poisoning can result in chest tightness, difficulty breathing, bradycardia, tachycardia, hypertension, pallor, abdominal pain, incontinence, diarrhea, anorexia, tremor/ ataxia, fasciculation, lacrimation, heavy salivation, profuse sweating, blurred vision, poor concentration, confusion, and memory loss.
- Life-threatening or very severe signs and symptoms, such as coma, seizures, respiratory arrest, pulmonary edema, loss of reflexes, and flaccid paralysis, can occur at high doses, such as in attempted suicide.
Fenthion has been used widely in many parts of the world to control household pests and mosquitoes. Twenty-seven of 28 workers who sprayed fenthion as residual indoor application for 15 days in a malaria-control operational trial without taking adequate precautions demonstrated various degrees of poisoning. These degrees included headaches, vertigo, blurred vision, muscle and abdominal pains, cramps, diarrhea, and prolonged vomiting. Severe reduction of whole-blood cholinesterase activity was observed and remained reduced a month after the end of spraying. However, in a second smaller spraying operation when precautions were more stringent, only one of 12 men showed mild symptoms (IPCS 2003).
In mosquito larviciding operations, dermal exposure averaged 3.6 mg/h with both power and hard sprayers and 12.3 mg/h with a granular formulation dispersed by hand. Some workers showed some plasma cholinesterase depression, but in no case was erythrocyte cholinesterase depressed (IPCS 2003).
A woman who attempted suicide with fenthion at approximately 4 months’ gestation survived the cholinergic crisis but remained unconscious for 96 hours. She eventually completely recovered and delivered a healthy baby at term (Karalliedde et al. 1988).
In a subchronic toxicity study, groups of four men given oral doses of 0.02 or 0.07 mg/kg/day for 4 weeks had no symptoms. No hematologic or clinical chemistry changes were seen, although at 0.07 mg/kg, significant plasma cholinesterase depression was noted (EPA 1998). Plasma cholinesterase was considered to be inhibited relative to group pretest values. In less than 24 hours after the initial dose, the level was depressed 8%, and levels reached 30% inhibition after 3 weeks. The group dosed with 0.02 mg/kg/day reached levels of 5%–12% inhibition starting 1 week after exposure. Inhibition in the control group was actually increased relative to pretest. The dose of 0.02 mg/kg/day is considered a threshold for inhibition because at least some statistical tests reported by the study author were significant compared with the control group. The threshold NOEL/LOEL is 0.02 mg/kg/day, and a NOEL is not considered definitely established for inhibition of plasma cholinesterase.
Health Effects in Laboratory Animals
Studies in laboratory animals exposed to fenthion dermally,
orally, or by inhalation are summarized in Table 1, with NOAELs and
lowest-observed-adverse-effect level (LOAELs) indicated.
A dermal LD50 value of 330 mg/kg was reported for rats and oral LD50 values in rats range from 190 to 615 mg/kg (Worthing 1983). No effects were observed in rats exposed by inhalation to 1197 mg/m3 for 1 hour (ACGIH 1991). Monkeys given fenthion by stomach tube for 2 years had inhibition of plasma and erythrocyte cholinesterase as early the first week at a dose of 0.2 mg/kg/day (EPA 1998). In rabbits exposed dermally to 5–400 mg/kg/day for 21 days, severe signs of cholinesterase inhibition were evident, and death occurred at 200 and 400 mg/kg/day. Clinical signs were seen at 150 mg/kg/day, but signs of neurotoxicity were seen at 100 mg/kg/day. Local dermal irritation occurred at >50 mg/kg/day but not at 5 mg/kg/day (EPA 1998).
Several studies of animals treated orally with fenthion are available. Plasma cholinesterase was inhibited in beagles given fenthion in the diet for 1 year at 0.262 mg/kg/day and higher. No cholinesterase inhibition was seen at 0.056 mg/kg/day, whereas brain cholinesterase was inhibited at 1.228 mg/kg/day (EPA 1998). In monkeys dosed by stomach tube with fenthion for 2 years, plasma cholinesterase was frequently inhibited at the lowest dose tested of >0.02 mg/kg/day, and erythrocyte cholinesterase was frequently inhibited at >0.07 mg/kg/day (EPA 1998). Brain cholinesterase was not inhibited at any dose up to 0.2 mg/kg/day. In rats given fenthion in the diet for 2 years, plasma, erythrocyte, and brain cholinesterase was inhibited at the lowest doses (0.2 mg/kg/day for males and 0.3 mg/kg/day for females). No indication of systemic toxicity was found in this group, but the 0.8 mg/kg/day group had epididymal pathology (vacuolation), vacuolation of the nasolacrimal duct, pneumonia, lung weight change, skin lesions, ocular effects, and clinical signs (EPA 1998). Plasma cholinesterase was inhibited in mice given fenthion in the diet for 2 years at the lowest dose of 0.014 mg/kg/day and higher, whereas erythrocyte cholinesterase was inhibited at >0.71 mg/kg/day (EPA 1998).
Developmental toxicity in rats and rabbits and reproductive toxicity in rats also has been evaluated for fenthion (EPA 1998). In rats given 0, 1, 4.2, or 18 mg/kg/day by gavage on gestation days 6–16, the high-dose group displayed clinical signs that included tremors, lacrimation, exophthalmos, hypoactivity, urine-stained ventral surface and salivation, and decreases in body weight gain. The rate of resorptions (in excess of the historical control) also was slightly higher in the high-dose group. Plasma, erythrocyte, and brain cholinesterase were inhibited at 1.0 mg/kg/day and higher. Fetal brain cholinesterase also was inhibited in the high-dose group at day 20. Rabbits were treated with fenthion by gavage at doses of 0, 1, 2.75, or 7.5 mg/kg/day on gestation days 6–18. Dams had soft stools and brain cholinesterase inhibition at >2.75 mg/kg/day and decreased body weight at 7.5 mg/kg/day. Resorptions and unossified metacarpals in the high-dose group increased slightly. In a twogeneration study, rats were fed fenthion in the diet at concentrations equivalent to 0, 0.05, 0.10, 0.70, or 5 mg/kg/day (EPA 1998). At 0.7 mg/kg/day, cytoplasmic vacuolization of the epithelial ductal cells of the epididymis, and inhibition of plasma and erythrocyte cholinesterase occurred. Decreased epididymal weight, decreased fertility, increased maternal weight during premating, decreased weight gain during gestation, decreased pup weight gain during lactation, and inhibition of brain cholinesterase were observed at 5 mg/kg/day.
Carcinogenicity
One carcinogenicity test on fenthion indicated that this
insecticide may be a carcinogen in male mice (NCI 1979). However, no
carcinogenic effects were observed in other 2-year feeding studies
of rats and mice (EPA 1998). The National Cancer Institute assessed
the carcinogenicity of fenthion in Fischer 344 rats fed doses of 0,
10, or 20 ppm (equivalent to 0, 0.5, or 1 mg/kg/day). This study
raised the question of possible compound-related increases in C-cell
adenomas of the thyroid and interstitial-cell tumors of the testes.
Evidence was not found of increases in these same tumor types in the
more recent study at higher dose levels. Thus, fenthion is not
considered carcinogenic in the rats in this study (EPA 1998).
Fenthion did not demonstrate carcinogenicity in the 2-year feeding
study in mice (EPA 1998). Data are insufficient to permit
conclusions about the carcinogenicity of fenthion to humans.
Genotoxicity
Fenthion was not mutagenic when tested in a yeast assay (Simmon
1976). Tests on mice also did not show mutagenic effects from
fenthion (ACGIH 1986). Fenthion was mutagenic in unscheduled DNA
synthesis and mouse micronucleus assays. However, it did not result
in postimplantation lethal effects in mice dosed with single doses
of either 10 or 25 mg/kg in a previously run dominant lethal study.
This study is considered very old, with associated uncertainties,
and a new one is needed that follows current guidelines for dominant
lethal testing (EPA 1998).
Table 1. Health Effect Levels of Fenthion in Humans and
Laboratory Animals (PDF Version 62k)
In animals, fenthion absorbs quickly into the bloodstream through the digestive tract, lungs, and skin and is systemically distributed (Gallo et al. 1991). It is eliminated through the urine and the feces (Thomson 1976). A single dose of the insecticide has prolonged action, suggesting that much of it is stored in body fat and later released for metabolism (HSDB 2003). Fenthion and its metabolites were found in the fat of steers slaughtered 3 days after dermal application of fenthion (Gallo et al. 1991). When 9 mg fenthion per kilogram was applied dermally to cows, 45%–55% of the dose was excreted in urine, 2.0%–2.5% was excreted in feces, and 1.5%–2.0% was recovered in milk (Gallo et al. 1991).
In rats, 86% of an oral dose is eliminated in 7 days (45% in urine and 40% in feces). Metabolites include the sulfone and disulfoxide of both the parent compound and its oxygen analogue (IPCS 2003). The toxicity of fenthion could be altered by interactions with chemicals that interfere with its detoxication, chemicals that have the same mechanism of action, or chemicals that induce hepatic microsomal enzymes.
Section 5. Standards and Guidelines for Protecting Human Health
Regulatory standards and guidance values are summarized in Table 2.
| Table 2. Regulatory Standards and Guidance Values | ||
| Standard/Guidance | Value | Reference |
| Acute Reference Dose (aRfD) | 0.0007 mg/kg/day* | EPA 1999 |
| Chronic Reference Dose (cRfD) | 0.00007 mg/kg/day* | EPA 1999 |
| Voluntary Cancellation in 2004 | None | EPA 2005 |
| Occupational Standards: Occupational Safety and Health Administration, American Conference of Governmental Industrial Hygienists: Threshold Limit Value (TLV) 8-hour time-weighted average, skin | 0.2 mg/m³ | ACGIH 1994 |
| World Health Organization Acceptable Daily Intakes | 0.001 mg/kg/day | Lu et al. 1995 |
| *From EPA 1999 Revised Risk Assessment. | ||
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