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Folpet

Publication Date: 9/95

TRADE OR OTHER NAMES

Some trade names for products containing folpet include Cosan T, Faltan, Folnit, Folpel, Ftalan, Fungitrol 11, Intercide TMP, Orthoraltan 50, Orthophaltan, Phthaltan, Sanfol, Spolacid, Trifol, Folpet, Folpan, Folpex, Phaltan, Vinicoil, and Thiophal (1, 3, 10). Mixed formulations include (folpet +) aluminum phosethyl, captafol, cymoxanil, dinocap, mancozeb, and metalaxyl (1). Formulation types include wettable powders and dusts.

REGULATORY STATUS

Folpet is no longer sold in the United States (3).

INTRODUCTION

Folpet is a protective leaf-fungicide. Its mode of action inhibits normal cell division of a broad spectrum of microorganisms. It is used to control cherry leaf spot, rose mildew, rose black spot, and apple scab. Used on berries, flowers, ornamentals, fruits and vegetables, and for seed- and plant- bed treatment. Also used as a fungicide in paints and plastics, and for treatment of internal and external structural surfaces of buildings (1). Incompatible with strongly alkaline preparations, such as lime sulfur (1). The Signal Word for products containing folpet is "Warning" (2).

TOXICOLOGICAL EFFECTS

ACUTE TOXICITY

The acute oral toxicity for male and female rats is >10 g/kg. The acute oral toxicity for mice is 2,440 mg/kg. The acute dermal toxicity for rabbits is > 5.0 g/kg. Primary eye irritation in rabbits causes reversible corneal opacity, which is prevented by immediately washing the exposed eye. It is not considered an eye irritant to rabbits and is a dermal sensitizer in the guinea pig (10). Folpet does cause irritation of the skin and mucous membranes in rabbits (1).

Acute inhalation exposure to folpet may cause irritation of the mucous membranes. Acute inhalation data for rats reported an LC50 >5 mg/l/2 hr. The LC50 for the mouse was >6 mg/l/2 hr. Folpet is considered slightly toxic by ingestion (4).

A dermal LD50 of 22,600 mg/kg was reported for rabbits. Inhalation of dust or spray mists and contact with the eyes can also result in local irritation (7).

CHRONIC TOXICITY

A one-year chronic oral toxicity study in dogs at doses of 10, 60 or 120 mg/kg/day administered in gelatin capsules caused non-significantly reduced mean body weight gains in both males and females at 60 and 120 mg/kg/day. Mean food consumption was also reduced in these animals. Cholesterol, total protein, albumin, and globulin values were decreased in mid- and high-dose males and high-dose females. There were no organ weight changes or histologic findings that were considered to be associated with administration of folpet. Based on changes in body weight and clinical biochemistry, the Lowest Observed Effects Level (LOEL) was 60 mg/kg/day, and the No Observable Effect Level (NOEL) was 10 mg/kg/day (9).

In another study, a cumulative dose of 10,000 ppm fed to dogs and rats for 17 months produced no adverse effects on the major organs. Carcinogenic tumors of the gastrointestinal tract were produced in mice from continuous administration of 437 mg/kg for 2 years (4). Another study found that feeding folpet to rats at 3,200 mg/kg or to dogs at 1,500 mg/kg for 17 months produced no adverse effects (1).

In 17-month feeding trials, no adverse effects, histopathological changes or significant differences in tumor incidence were noted in albino rats receiving 10,000 mg/kg folpet via the diet. Prolonged or repeated exposure to the skin may cause dermatitis, while prolonged exposure to the eyes may cause conjunctivitis (4).

Reproductive Effects

A 2-generation reproductive study in rats produced a parental NOEL of 34.5 mg/kg/day (10). The same study showed decreased weight gain in F1 offspring. The NOEL in F2 matings was 40 mg/kg/day based on decreased body weight gain, decreased fertility of males and a Lowest Effect Level (LEL) of 180 mg/kg/day (10). Another study reported no significant effect on reproductive performance over three generations in rats at 1,000 mg/kg diet.

The result from one study of pregnant hamsters given a single dose of between 500 and 900 mg/kg on days seven or eight of gestation, was an increase in fetal mortality and the production of some abnormal fetuses (4).

Chronic administrations to pregnant rabbits of a cumulative dose of 488 mg/kg for 13 days produced adverse effects on fertility.

Treatment of male mice by Bateman's dominant lethal procedure did not induce dominant lethal mutations as measured by increase in early post- implantation deaths (7). Chronic inhalation exposure to folpet showed an increase of fetal mortality in an inhaltion study of pregnant mice exposed to 491 mg/m3/4 hours/day for 8 days (4)

Teratogenic Effects

Folpet was found to be positive in producing developmental effects in both rabbits and rats.

In rabbits, the developmental NOEL was 10 mg/kg and the LEL was 20 mg/kg (hydrocephalus, domed skull, and irregularly shaped fontanelles). In rats, the NOEL was 60 mg/kg and the developmental LEL was 360 mg/kg (5, 10).

Mutagenic Effects

In both E. coli and S. typhimurium, reverse mutations occurred, with a positive direct acting mutagen. In vivo, the Drosophila sex-linked recessive assay was positive using folpet.

In a mouse somatic cell mutation assay, the results were negative, although a significant pup mortality occurred at all dose levels (9, 10).

Carcinogenic Effects

In a carcinogenicity study in mice, folpet was found to be a carcinogen with a dose-related increased incidence of adenocarcinomas in the duodenum (a rare neoplasma in CD-1 mice) in all dose groups (142.9, 714.3 and 1714.2 mg/kg/day respectively) (9, 10).

Another carcinogenicity study in mice also found folpet to be a positive carcinogen with a dose-related increased incidence of adenocarcinomas in the duodenum (a rare neoplasma in B6C3F1 mice) in all dose groups (142.9, 714.3 and 1428.6 mg/kg/day respectively) (9, 10).

In another study, Sprague-Dawley rats were fed a diet of 200, 800, or 3,200 ppm of folpet. No carcinogenic effects were reported (10).

Organ Toxicity

In a 90-day feeding study in rats, the NOEL was established at 3,000 ppm and the LEL was 10,000 ppm. Noted effects were decreased brain weight and decreased total blood protein including albumin (9, 10).

Fate in Humans and Animals

An in vitro study of folpet stability in human blood showed that the half-life of folpet in human blood is about one minute, degrading rapidly to phthalimide and ultimately to phthalic acid and ammonia (10).

ECOLOGICAL EFFECTS

Effects on Birds

Acute oral studies indicated that folpet is slightly toxic to upland game bird species. Subacute dietary toxicity studies with bobwhite quail and mallard ducks also indicate that folpet is slightly toxic to birds when it is ingested in the diet of these birds. The avian reproductive studies indicate that technical folpet is not expected to cause reproductive impairment (9).

Folpet is considered slightly toxic to avian species. The LC50 for bobwhite quail is >2,510 mg/kg and the LC50 for the mallard duck is >5,000 ppm (10).

Effects on Aquatic Organisms

Studies with typical end-use products indicate that folpet is highly toxic to both rainbow trout and bluegill sunfish. Rainbow trout were the most sensitive species and the folpet product tested was classified in the very highly toxic range of toxicity for this species (9).

The 96-hr LC50 for bluegill sunfish is 675 ppb and the 96-hr LC50 for rainbow trout is 185 ppb (10). Folpet is characterized as being "highly toxic" to both coldwater and warmwater fish (1, 10).

Data from a study with a typical end-use product of folpet indicate that folpet is toxic to aquatic invertebrtates (9).

The 48-hr LC50 for Daphnia magna is 0.60 ppm, which is considered very highly toxic to aquatic invertebrates (10).

Effects on Other Animals (Nontarget species)

Folpet is considered relatively non-toxic to honeybees (1, 9).

ENVIRONMENTAL FATE

Breakdown of Chemical in Soil and Groundwater

Degradation is probably the same as that of captan, in which three chlorine atoms are removed under the influence of endogenous thiol compounds, with the formation of the trithiocarbonate, thiophosgene, and phthalimide (1).

Breakdown of Chemical in Surface Water

No information currently available.

Breakdown of Chemical in Vegetation

Some injury to crops due to phytotoxicity has been noted, especially during extended dry periods (3).

PHYSICAL PROPERTIES and GUIDELINES

Exposure Guidelines:

TLV-TWA: None (8)
WHO-ADI: 0.01 mg/kg

Physical Properties:

CAS No.: 133-07-3 (1)
Chemical name: N-[(Trichloromethyl)thio]phthalimide (2, 10)
Chemical Class/Use: carboximide compound/protective foliage fungicide (3)
Solubility in water: practically insoluble in water (1); 1 mg/l water (6)
Solubility in other solvents: slightly soluble in organic solvents, e.g. 3-4% in alphatic ketones and 0.1-1 % in hydrocarbons. In chloroform 8.7, benzene 2.2, isopropanol 1.25 (all in g/100 ml at 20 degrees C) (1)
Melting point: 177-180 degrees C (1, 2); 351 degrees F (4)
Vapor pressure: <1.3 x 10 to the minus 9 mbar at 20 degrees C

BASIC MANUFACTURER

Zeneca Ag Products
1800 Concord Pike
Wilmington, DE 19897
Fax: 302-886-1552
Telephone: 800-759-4500
Emergency: 800-759-2500

Review by Basic Manufacturer:

Comments solicited: October, 1994
Comments received:

REFERENCES

  1. The Agrochemicals Handbook. 1983. The Royal Society of Chemistry, The University, Nottingham, England.
  2. Farm Chemicals Handbook. 1994. Meister Publishing Co. Willoughby, OH.
  3. Thomson, W. T. 1990. Agricultural Chemicals. Book IV: Fungicides. Thomson Publications, Fresno, CA.
  4. OHS Database. March, 1993. MSDS for Folpet. MDL Information Systems Inc., San Leandro, CA.
  5. U.S. Environmental Protection Agency. 1986. Office of Pesticides. TOX Oneliners -- Folpet. February, 1986.
  6. CENET. 1994. Pesticide Management and Education. Chemical Profiles Library.
  7. Worthing, C. R. (ed.) 1979. The Pesticide Manual: A World Compendium, 6th ed. The British Crop Protection Council, Croydon, England. 655 pp.
  8. Clayton, G. D. and F. E. Clayton (eds.) 1981. Patty's Industrial Hygiene and Toxicology, Volume 2A: Toxicology, 3rd ed. John Wiley and Sons, Inc. NY. 2878 pp.
  9. U.S. Environmental Protection Agency. June, 1987. Guidance for the Reregistration of Pesticide Products Containing Folpet as the Active Ingredient. US EPA, Office of Pesticide Programs, Washington, DC.
  10. U.S. Environmental Protection Agency. June, 1987. Pesticide Fact Sheet Number 215: Folpet. US EPA, Office of Pesticides and Toxic Substances, Office of Pesticide Programs, Washington, DC.