E X T O X N E T
Extension Toxicology Network
A Pesticide Information Project of Cooperative Extension Offices of
Cornell University, Michigan State University, Oregon State University, and
University of California at Davis. Major support and funding was provided
by the USDA/Extension Service/National Agricultural Pesticide Impact
Assessment Program.
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Pesticide
Information
Profile
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Maneb
Publication Date: 9/93
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TRADE OR OTHER NAMES
Some trade names include Dithane M-22, Manesan, Manex, Manzate,
Nereb, Newspor. A chemical name for maneb is manganese ethylene
bisdithiocarbamate (26).
REGULATORY STATUS
Maneb is registered as a general use pesticide by the U.S.
Environmental Protection Agency (EPA). In July 1987, the Environmental
Protection Agency announced the initiation of a special review of the
ethylene bisdithiocarbamates (EBDCs), a class of chemicals to which
maneb belongs. This Special Review was initiated because of concerns
raised by laboratory tests on rats and mice. The EPA was concerned
about
- potential effects on the general population from dietary exposure to residues left on food crops and
- potential occupational health risks to workers who handle and/or apply EBDC pesticides.
As
part of the Special Review, EPA reviewed data from market basket surveys
and concluded that actual levels of EBDC residues on produce purchased
by consumers are too low to affect human health. The EPA concluded its
Special Review in April, 1992 with new label requirements for protective
clothing to be worn by industrial and agricultural workers, and with the
establishment of a 24-hour reentry period for agricultural workers.
Many homegarden uses of EBDCs have been canceled because the EPA has
assumed that home users of these pesticides do not wear protective
clothing during application (31). Toxicity data reviewed by the EPA as
part of their Special Review of EBDCs are included in this document
under "Toxicological Effects."
Containers of maneb must bear the signal word "CAUTION" (1).
INTRODUCTION
The EBDCs are fungicides used to prevent crop damage in the field
and to protect harvested crops from deterioration in storage or
transport (26). Maneb is used in the control of early and late blights
on potatoes and tomatoes and many other diseases of fruits, vegetables
and field crops and ornamentals (25). Maneb controls a wider range of
diseases than any other fungicide (8). It is available as granular,
wettable powder, flowable concentrate, and ready-to-use formulations
(26).
Maneb is one of the chemicals of a class called the ethylene-
bisdithiocarbamates ('EBDCs') that are noted for their instability in
the environment. The application of heat can break these chemicals down
into a number of metabolites. In addition to natural environmental
processes that break down EBDCs, cooking of vegetables that are
contaminated with these fungicides can also change them into different
metabolites. Ethylenethiourea, an EBDC metabolite that is considered to
be cancer-producing, is formed when maneb-treated vegetables are cooked
(11, 26).
TOXICOLOGICAL EFFECTS
ACUTE TOXICITY
Maneb is moderately toxic to humans (29). Occasional signs of
local irritation or inflammation of the skin, eyes, or respiratory tract
have been experienced upon contact with maneb. Acute inhalation of
large amounts of maneb dust or spray may cause irritation of the mucous
membranes, resulting in a scratchy throat, sneezing, cough, and
inflammation of the linings of the nose and upper respiratory tract.
Signs of poisoning from large amounts of maneb may include nausea,
vomiting, diarrhea, loss of appetite, weight loss, headache, confusion,
drowsiness, coma, slowed reflexes, respiratory paralysis and death (5).
Maneb is a mild eye and skin irritant (24, 29).
Maneb is of moderately low toxicity to laboratory animals (6).
Single toxic doses of maneb in rats induced hypotonia, slowed breathing
and heart beat, functional abnormalities of the thyroid and liver,
infiltrations in the lungs, bronchitis and tracheitis (29). The amount
of a chemical that is lethal to one-half (50%) of experimental animals
fed the material is referred to as its acute oral lethal dose fifty, or
LD50. The oral LD50 for maneb in rats is 3,000 to 7,990 mg/kg, in mice
is 2,600 mg/kg, and in guinea pigs is 7,500 mg/kg. The dermal LD50 for
rats is greater than 5,000 mg/kg (1, 9, 12).
There is no evidence of 'neurotoxicity,' nerve tissue destruction
or behavior change, from the EBDCs (30). However, EBDCs are partially
chemically broken down, or metabolized, to carbon disulfide, a
neurotoxin capable of damaging nerve tissue (7). EBDC residues in or on
foods convert readily to ETU during commercial processing or home
cooking (26).
CHRONIC TOXICITY
Prolonged exposure to large concentrations of maneb spray or dust
may cause dermatitis (13, 29).
Feeding maneb to rats at 250 mg/kg for two years caused no
injurious health effects (9). After several months of daily doses of
200 mg/kg, experimental dogs developed signs of toxicity such as
tremors, weakness, lack of energy, gastrointestinal disturbances, and
incoordination (5).
Rats were fed daily doses of 0, 1.25, 12.5, 62.5 or 125 mg/kg of
maneb. After 97 days, those given the 62.5 mg/kg dose showed
significant increases in thyroid weight (i.e. goiter) and reduced growth
rate. After one year, rats at the 62.5 mg/kg dose also exhibited
increased thyroid weight. The NOEL for this study was 12.5 mg/kg/day
(26).
Rats which received 1500 mg/kg/day for 10 days showed weight loss,
weakness of the hind legs and increased mortality. Rats given 0.25%
maneb in the diet for 2 years developed thyroid abnormalities and
goiter. Other effects observed in studies of lab animals exposed to
chronic doses of maneb include depression of reflexes, paralysis,
impaired kidney function, and benign lung tumors (29).
Ethylene bisdithiocarbamate pesticides (EBDCs), which include
maneb, are generally considered to have low short-term mammalian
toxicity. A major toxicological concern, however, is ethylenethiourea
(ETU), an industrial contaminant and a breakdown product of maneb and
other EBDC pesticides. In addition to having the potential to cause
goiter, a condition in which the thyroid gland is enlarged, this
metabolite has produced birth defects and cancer in experimental
animals. ETU has been classified as a probable human carcinogen by the
EPA (31). ETU can be produced when EBDCs are used on stored produce,
and also when fruit or vegetables with residues of these fungicides are
cooked (24).
Conversion of EBDCs into ETU can occur inside of spray tanks,
during cooking of produce or processing of crops bearing EBDC residues,
or as EBDCs are metabolized within the body. Residues of the EBDCs and
of ETU can readily be removed from produce by washing or peeling (11, 26).
Disulfiram is an EBDC which is used in the treatment of alcoholics
to produce an intolerance to alcohol. Ingestion of disulfiram and
alcohol together causes symptoms of nausea, vomiting, headache,
excessive sweating and chills. Other EBDC compounds may cause similar
symptoms when combined with alcohol (24).
Reproductive Effects
Maneb had a negative effect on the course of gestation in female
rats that were given 50 mg/kg body weight every other day during this
period. There were increased numbers of embryo deaths, stillborn
offspring, and newborns incapable of survival (16). Rats given a single
dose of 770 mg/kg of maneb, the lowest dose tested, on the 11th day of
gestation exhibited adverse effects on reproductive fertility and
development. These effects included early fetal deaths and fetal
abnormalities of the eye, ear, body wall, central nervous system, and
musculoskeletal system (13, 29). The lowest oral toxic dose in mice
which caused fetotoxicity when given under the same conditions as
previously mentioned, was 1420 mg/kg (12).
Teratogenic Effects
Maneb is metabolized to ethylenethiourea, ETU, a known teratogen.
Rats given an oral dose of 2,000 to 4,000 mg/kg of ETU on days 11 or 13
of gestation showed a high incidence of skeletal malformations and
defects in the closing of the neural tube, an embryonic tube that
eventually forms the brain and spinal cord (14). A single dose of ETU
produced teratogenic effects in rats and mice (6, 13).
In pregnant rats fed ETU at 5.0 mg/kg/day, the lowest dose tested,
developmental toxicity was observed in the form of delayed hardening if
the bones of the skull in offspring. ETU has also been shown to be
teratogenic in hamsters, but not in mice (31).
Mutagenic Effects
Several tests have shown that maneb is not mutagenic (26). Maneb
is metabolized to ethylenethiourea, a suspected mutagen (7).
Carcinogenic Effects
All of the EBDC pesticides can be degraded or metabolized into ETU,
which has been classified as a probable human carcinogen by the EPA (26, 31).
Marked increases in the incidence of liver tumors were observed in
mice fed 646 ppm of ETU daily for 80 weeks. Rats fed 175 or 350 ppm
daily for 18 months developed malignant thyroid tumors. In rats fed ETU
at doses of 0.1, 1.25, 6.25, 12.5, or 25 mg/kg for nearly 2 years, a
dose related increase in thyroid tumors was observed at the 12.5 or 25
mg/kg doses. Female mice fed doses of 17 or 50 mg/kg ETU for up to 2
years exhibited a 58 or 96% incidence of malignant liver tumors,
respectively. In this same study, there was also a significant increase
in the incidence of thyroid tumors at the 59 mg/kg dose level (13, 31).
Chronic administration of cumulative oral doses of 62,980 mg/kg of
ETU to rats, intermittently for 94 weeks, caused tumors of the
gastrointestinal tract, skin, and appendages. Oral administration of
ETU produced malignant thyroid tumors in rats and increased the
incidence of liver cell tumors in two strains of mice (10, 26). In
another study, maneb did not display significant carcinogenicity in
laboratory tests with experimental animals (6, 17). Malignant tumors
were observed in one study in which rats were given scrotal injections
of 12.5 mg/kg body weight of 82.6% pure maneb (16).
Organ Toxicity
Poisoning from maneb may adversely affect the thyroid, kidneys and
heart (13). Dogs that received oral doses of 200 mg/kg/day for three or
more months showed damage to the spinal cord but not the thyroid gland
(10). Rats given 0.25% maneb in food for two years showed abnormalities
and/or excessive growth of thyroid cells (16).
Several studies of the effects of EBDCs on test animals have shown
rapid reduction in the uptake of iodine and swelling of the thyroid
(i.e. goiter). In one study, a marked reduction of iodine uptake was
measured 24-hours after administration of a large dose of maneb. A 90-
day study of the effects of ETU, a common metabolite of the EBDCs on rat
thyroids revealed a NOEL of 5 ppm (0.25 mg/kg/day) (24, 26, 30).
Fate in Humans and Animals
Research results vary on the fate of maneb in humans and animals.
While nearly fifty-five percent of an oral dose of a radioactive form of
maneb (14-C) in rats was excreted in the form of metabolites in the
urine and feces within three days, after 24 hours, body organs contained
1.2% of the original dose as metabolites. On the 5th day, less than
0.18% remained (16). In another study with rats fed radio-labeled
maneb, 20 to 30% of the administered dose was excreted in the urine and
feces within two hours after dosage. The major metabolite of maneb was
ethylenethiourea (ETU). By the seventh day after dosage, 70% had been
excreted and the remaining radioactivity was concentrated in the
thyroid, kidneys and liver (26). In other studies, maneb was not found
in the tissues of rats that were fed as much as 2,500 parts per million
(ppm) for two years. There was also no evidence of maneb in tissues of
dogs which received 75 mg/kg/day for one year (10).
The EBDC pesticides break down in mammalian tissues into ETU, a
metabolite which has caused goiter and cancer in laboratory animals (9, 31).
ECOLOGICAL EFFECTS
Harmful Effects on Birds
Maneb is practically non-toxic to birds (26). The 5-day LC50 for
maneb in bobwhite quail and mallard ducklings is greater than 10,000 ppm
(4).
Effects on Aquatic Organisms
Maneb is highly toxic to fish. The lethal concentration fifty, or
LC50, is that concentration of a chemical in air or water that kills
half of the experimental animals exposed to it for a set time period.
The 96-hour LC50 for maneb is 1 ppm in bluegill sunfish. Its 48-hour
LC50 is 1.9 ppm in rainbow trout. Its 58-hour LC50 is 1.8 ppm in carp
(4, 9, 26). Water can be contaminated by the inappropriate storage,
use, or disposal of maneb (1).
Effects on Other Animals (Nontarget species)
Maneb-treated crop foliage must not be fed to livestock (15). The
fungicide is not thought to be toxic to bees (9). Its 72-hour LC50 is
more than 40 ppm in crayfish. In tadpoles, the 48-hour LC50 is 40 ppm
(4).
ENVIRONMENTAL FATE
The ethylenebisdithiocarbamates (EBDCs), including maneb, are noted
for their instability in the environment (21). They are generally
unstable in the presence of moisture, oxygen, and in biological systems
(26). The EBDCs rapidly degrade to ETU. This rapid degradation lowers
the need for concern about the environmental fate of EBDCs and focuses
such concern on ETU. The EPA has either called for or is currently
reviewing data on the behavior of ETU in the environment (9, 21, 26).
Breakdown of Chemical in Soil and Groundwater
Maneb is nearly insoluble in water (0.5 ug/ml). It adsorbs
strongly to soil particles. Thus, despite its lengthy soil half life
(60 days), maneb is not expected to contaminate groundwater. It may
enter surface waters if erosion of soil with adsorbed maneb occurs (32).
Maneb breaks down under both aerobic and anaerobic soil conditions (26).
Maneb's half-life in soil, or the time that it takes for half of
the amount of the fungicide in soil to be broken down by natural
processes , was found to be four to eight weeks. Metabolites were found
in soil 15 days after treatment of beans and tomatoes (11). Residues of
a traceable form of maneb did not leach below the five-inch soil depth
(2).
ETU, a metabolite of maneb, has been detected at 16 ppb in only one
out of 1,295 drinking water wells tested (31).
Breakdown of Chemical in Water
Maneb degraded completely within one hour under anaerobic aquatic
conditions (26).
Breakdown of Chemical in Vegetation
The main metabolite of maneb in plants is ethylenethiourea (ETU);
this is then rapidly metabolized further (9). Maneb residues were
higher on beans than on tomatoes when they were measured at intervals up
to 15 days after treatment. The heating of maneb residues in vegetables
can result in the formation of the metabolic carcinogen, ETU.
Significant amounts of ETU were found in cooked vegetables that had been
experimentally treated with maneb (11). Some varieties of apple,
morello cherry and pumpkin can be negatively affected by maneb (9).
Young greenhouse tomato and tobacco seedlings have also been injured
(15).
PHYSICAL PROPERTIES AND GUIDELINES
Maneb is a yellow powder with a faint odor. Maneb is a flammable,
combustible material which may decompose, heat up, or self-ignite if it
is exposed to air or moisture. Fire may produce irritating or poisonous
gases such as toxic oxides of nitrogen and sulfur. Runoff from fire
control or dilution may cause pollution. Maneb should be kept away from
flames and sparks (9, 18, 29).
Maneb must be stored in sealed original containers in well-
ventilated places. The fungicide must not be allowed to become wet
during storage (15). Its temperature should not exceed 25-30 degrees C.
Water, feed, or food can be contaminated by inappropriate storage or
disposal of maneb. Containers must be stacked in a way that permits
free flow around piles (1). While maneb is stable under normal storage
conditions, it decomposes more or less rapidly when it is exposed to
moisture or acidic conditions.
Long-term skin, eye, and respiratory tract exposure to small
quantities of maneb should be avoided (9). Protective equipment should
be worn by workers involved in the manufacture or agricultural
application of maneb; those who spray crops should wear eye protection
and respirators (16). Empty containers should not be reused; they
should be buried in a safe place far from water supplies. Open dumping
is prohibited (1).
Occupational Exposure Limits:
| OSHA ceiling: | 5 mg/m3 |
| ACGIH TWA: | 1 mg/m3: NIOSH recommended TWA |
| NIOSH recommended STEL: | 3 mg/m3 (29) |
Physical Properties:
| CAS #: | 12427-38-2 |
| H20 solubility: | nearly insoluble in water: 0.5 ug/ml (29) |
| Solubility in other solvents: | soluble in chloroform and pyridine (13, 22, 29) |
| Melting point: | Decomposes before melting (pure compound) (23, 29) |
| Vapor pressure: | negligible, less than 10 to the minus 7 power mbar at 20 degrees C (9) |
| Chemical Class/Use: | carbamate; ethylenebisdithiocarbamate |
| ADI: | 0-0.005 mg/kg body weight (16) |
BASIC MANUFACTURER(S)
Atochem North America, Inc.
Three Parkway
Philadelphia, PA 19102
Review by Basic Manufacturer:
Comments solicited: January, 1992
Comments received:
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