WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE
VBC/PDS/DS/85.56
ORIGINAL: ENGLISH
DATA SHEET ON PESTICIDES No. 56
CARBOFURAN
CLASSIFICATION:
Primary use: Insecticide
Secondary use: Nematocide
Chemical Group: Carbamate
Date issued:
It must be noted that the issue of a Data Sheet for a
particular pesticide does not imply endorsement of the pesticide by
WHO or FAO for any particular use, or exclude its use for other
purposes not stated. While the information provided is believed to
be accurate according to data available at the time when the sheet
was compiled, neither WHO nor FAO are responsible for any errors or
omissions, or any consequences therefrom.
The issue of this document does Ce document ne constitue pas une
not constitute formal publication. Il ne doit faire
publication. It should not be l'objet d'aucun compte rendu ou
reviewed, abstracted or quoted résumé ni d'aucune citation sans
without the agreement of the l'autorisation de l'Organisation
Food and Agriculture des Nations Unies pour
Organization of the United l'Alimentation et l'Agriculture
Nations or of the World Health ou de l'Organisation Mondiale de
Organization. la Santé.
1. GENERAL INFORMATION
1.1 COMMON NAME: Carbofuran (ISO, BSI and ANSI)
1.1.1 Identity:
IUPAC: 2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate
CAS No. 1: 2,3-dihydro-2,2-dimethyl-7-benzofuranyl
methylcarbamate
CAS Reg. No.: 1563-66-2
Molecular formula: C12H15NO3
Molecular weight: 221.3
Structural formula:
1.1.2 Synonyms: Bay 70143; Carbofuran; CuraterrR; ENT 27,164;
FMC 10242; FuradanR; Niagara 10242R; YaltoxiR.
1.2 SYNOPSIS: Carbofuran is a broad spectrum, non-cumulative carbamate
insecticide; a cholinesterase inhibitor with contact and stomach
action and highly toxic to mammals. It is a systemic with no
phytotoxic action.
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics - Carbofuran is a colourless (white)
crystalline solid. It has a melting point of 150-152°C, a
density (d204) of 1.180. The technical material contains 98.8%
active ingredient. It is non-corrosive and non-flammable.
1.3.2 Solubility - Water 700 mg/l, 25°C
1-methyl-2-pyrrolidione 300 g/kg, 25°C
Dimethylformamide 270 g/kg, 25°C
Dimethylsufoxide 250 g/kg, 25°C
Acetone 150 g/kg, 25°C
Acetonitrile 140 g/kg, 25°C
Methylene chloride 120 g/kg, 25°C
Cyclohexanone 90 g/kg, 25°C
Benzene 40 g/kg, 25°C
Ethanol 40 g/kg, 25°C
Carbofuran is virtually insoluble in conventional solvents of
agricultural formulations.
1.3.3 Stability - It is stable under neutral or acidic conditions but
unstable in alkaline media.
1.3.4 Vapour pressure - 2.66 x 10-6 kPa (2 x 10-5 mmHg), 33°C
1.33 x 10-5 kPa (1 x 10-4 mmHg), 50°C
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
1.4.1 Common formulations - Flowables (100, 120, 300, 350, 480 g
a.i./l) granules (20, 30, 50, 100 and 150 g a.i./kg).
1.4.2 Pests controlled - Carbofuran is effective against a wide range
of foliar-feeding and soil pests including nematodes, corn
rootworm, rice water weevil, wireworms, sugar-cane borer, alfalfa
weevil, alfalfa snout beetle, armyworms, European corn borer,
flea beetle, aphids, thrips, hornworms and others.
1.4.3 Use pattern - Carbofuran may be applied to alfalfa, corn,
peanuts, peppers, strawberries, tobacco, bananas, sorghum,
potatoes, cottonwood trees, sugar-cane, and rice. It may be
applied to foliage at 0.25-1.0 kg a.i./ha; in a 7 inch band or in
seed furrows at planting time at 0.5-4.0 kg/ha; and, as a soil
treatment incorporated into the top 1 inch of soil. On rice,
apply before or within 21 days after flooding. It is compatible
with other non-alkaline pesticides and fertilizers.
1.4.4 Unintended effects - Carbofuran is not phytotoxic when used as
directed.
1.5 PUBLIC HEALTH USE - No recommended use.
1.6 HOUSEHOLD USE - No recommended use.
2. TOXICOLOGY AND RISKS
2.1 TOXICOLOGY - MAMMALS
2.1.1 Absorption - Carbofuran may be absorbed from the gastrointestinal
tract; minimally through the intact skin; and, by inhalation of
spray mists or dusts.
2.1.2 Mode of action - Carbofuran is a reversible, direct inhibitor of
cholinesterases through carbamoylation of the esteratic site of
the enzyme. Accumulation of acetylcholine at nerve synapses and
myoneural junctions causes the toxic effects. The carbamoylated
enzyme undergoes spontaneous and rapid reactivation. Carbofuran
and its ester metabolites are active.
2.1.3 Excretion products - The metabolism and excretion of carbofuran
have been well studied in rats, mice and lactating cows. The per
oral dose is rapidly absorbed, degraded and eliminated. In
mammals mixed function oxidases are chiefly responsible for
metabolism; 3-hydroxycarbofuran and 3-ketocarbofuran are the most
common carbamate metabolites. 3-Hydroxy-N-hydroxycarbofuran is
also produced to some extent in all the test animals except the
mouse. Hydrolysis of the carbamoyl ester bond also occurs,
producing 3-ketocarbofuran phenol followed by carbofuran phenol
and 3-hydroxyphenol. These degradation products are primarily
excreted as conjugates of glucuronic acid and sulfate.
In rats, 87% of the radioactivity from carbonyl 14C labelled
carbofuran (p.o.) is eliminated within 48 hours, 45% as C02 in
expired air, 38% in urine and 4% in faeces. When ring-labelled
carbofuran is fed to cows and rats, nearly all of the 14C is
eliminated in urine (92% in 32 hours), none is exhaled and less
than 3% is found in faeces. In milk cows, less than 3% is found
in milk following per oral and fistula administration.
2.1.4 Toxicity, single dose
Oral LD50:
Rat (M, F) 8.8 mg/kg bw (technical)
Rat (weanling male) 8.06 mg/kg bw (technical)
Rat (weanling female) 5.91 mg/kg bw (technical)
Dog +15.38 mg/kg bw (technical)
Mouse 14.4 mg/kg bw (technical)
Cat 2.5-3.5 mg/kg bw (technical)
Rabbit 7.5 mg/kg bw (technical)
Guinea-pig 9.2 mg/kg bw (technical)
Dermal LD50:
Rat 2 000 mg/kg bw* (technical)
Rabbit 2 000 mg/kg bw* (technical)
Inhalation LC50:
1 hour
Rat (M) 0.091-0.108 mg/l (dust)
Rat (F) 0.080 mg/l (dust)
4 hours
Rat (M, F) 0.120 mg/l (50 W.P.)
Rat (M, F) 0.085 mg/l (80 W.P.)
Dog (M) 0.052 mg/l (50 W.P.)
Guinea-pig (M, F) 0.053 mg/l (75 W.P. aerosol)
Guinea-pig (M, F) 0.043 mg/l (75 W.P. dust)
I.P. LD50:
Rat (M) 8.2 mg/kg bw (75% W.P.)
Rat (F) 2.8 mg/kg bw (75% W.P.)
* Manufacturer provided information.
In an acute intubation study using female rats, it was found that
brain cholinesterase was more sensitive to carbofuran than plasma
and erythrocyte cholinesterase respectively.
2.1.5 Toxicity, repeated doses
Oral: Groups of female rats were administered carbofuran by
gavage at a dosage level of 1.0 mg/kg/day for 28 days.
Cholinesterase activity was monitored at 1, 2, 6 and 24 hours
after administration on days 14 and 28. Brain cholinesterase
activity was the most affected, reaching maximal depression by
six hours on both testing days; erythrocyte activity was least
affected. The treatment activity values appeared comparable to
control values at 24 hours post treatment. Similar results were
observed in a 90-day intubation study with male and female rats
receiving dosage levels of 0, 0.1, 0.3, 1.0 and 3.0 mg/kg bw/day.
In this study, maximum erythrocyte and plasma activity
depressions at the highest dosage level (3.0 mg/kg bw/day)
occurred within one hour of administration after three weeks of
treatment. Normal activity was re-established within 24 hours.
No changes were observed at levels of 0.3 mg/kg bw or below.
These studies demonstrated the rapid and transient nature of
in vivo cholinesterase depression by carbofuran.
Dermal: Groups of male and female rabbits received dermal
applications of carbofuran 50% wettable powder at dosage levels
of 0, 0.5, 1.0 and 2.0 mg/kg bw/day for 20 successive days.
Mortality appeared to be dose-related. Decreased body weights,
inflammatory skin lesions and decreased general activity were
observed in all treatment groups during the test period. The
lesions disappeared within five days of cessation of treatment
and there were no treatment-related biochemical or
histopathological changes.
Inhalation: Groups of mice and female guinea-pigs were exposed to
carbofuran aerosol formulation at a concentration level of 0.01
mg/m3 (air) for four hours a day, five days a week for three
weeks. There were no compound-related changes in mortality
rates, behaviour, haematology, biochemistry or histopathology.
Sensitization: No sensitization reactions were produced in
guinea-pigs following challenge doses administered two weeks
after daily subcutaneous injections of carbofuran.
Cumulation of compound: Carbofuran is not accumulated in body
tissue.
Cumulation of effect: Carbofuran did not produce any cumulation
of effect in several studies with multiple dosing.
2.1.6 Dietary studies
Short-term: Groups of male and female rats were offered varying
levels of carbofuran in the diet for 90 days. Initially,
carbofuran was incorporated into the diet at dosages of 0, 0.1,
0.4, 2.0, 10 and 25 mg/kg diet. Subsequently, the dietary levels
of carbofuran were progressively increased on days 22-35, 36-49
and 50-90 to yield final concentrations of 0, 1.6, 6.4, 32, 160
and 1600 mg/kg diet. No mortality occurred during the study
period. Intermittent tremors and episodes of incontinence were
observed among females receiving the 1600 mg/kg diet. Depressed
growth rates were noted at dietary levels of 100 mg/kg and above
and persisted to the end of the test period at levels of 160, 400
and 1600 mg/kg diet. However, this finding appeared to be
related to poor diet palatability. Haematological and urological
values were unaffected and gross and microscopic pathological
findings were comparable. Cholinesterase activity was not
monitored. No effects were observed among the three lowest
dosage groups.
A 14-day feeding study was conducted with carbofuran using
groups of male and female rabbits. Dietary concentrations of 0,
70, 210 and 700 ppm did not produce mortality or untoward
behavioural effects. Body weight reductions were observed within
the group receiving the 700 ppm diet.
Carbofuran was administered at dosages of 0, 0.025, 0.25, 1.25,
2.5 and 5.0 mg/kg/day by gelatin capsule to groups of male and
female dogs for 93 continuous days. Clinical signs of
acetylcholine poisoning were observed within the groups receiving
either 2.5 or 5.0 mg/kg/day. Plasma and erythrocyte
cholinesterase activities were within normal limits when
monitored four hours before and one hour after daily dosing. At
5.0 mg/kg, some depression of plasma and erythrocyte
cholinesterase activities were observed when samples were drawn
15, 30, 45 and 60 minutes following carbofuran administration
on day 72 and after extended dosing, again on day 113.
Long-term: In a two year study, groups of male and female rats
were offered diets containing 0, 10, 20 or 100 ppm of carbofuran.
Males exposed to 100 ppm exhibited slightly lower group mean
body weights. Depressed plasma, erythrocyte and brain
cholinesterase activity values were noted for animals receiving
the 100 ppm diet; no effects were observed at the 10 or 20 ppm
levels. There were no treatment-related effects on mortality,
food consumption, ophthalmology, haematology and clinical
chemistry parameters, urinalysis and histopathology. The no-
effect level (NOEL) was considered to be 20 ppm.
Groups of male and female mice were exposed to carbofuran at
dietary concentrations of 0, 20, 125 and 500 ppm for two years.
Decreased body weights were noted at the 500 ppm level during
weeks 1-65 for males and weeks 1-78 for females. However, this
effect was not observed at study termination. Brain
cholinesterase activity was depressed at the 6, 12 and 18 month
intervals and at termination for animals exposed to 125 or 500
ppm carbofuran. No treatment-related effects were reported for
mortality, haematology and clinical chemistry parameters,
urinalysis and histopathology. The no-effect level (NOEL) was
considered to be 20 ppm.
Carbofuran was administered to groups of male and female beagle
dogs via dietary inclusion for two years. Initially, carbofuran
was incorporated into the diet at concentrations of 0, 1, 10, 50
and 100 ppm and a level to establish the maximum tolerated dose
(100 ppm for days 1-14 and 200 ppm during days 15-267). The 50
ppm diet was increased to contain 100 ppm of carbofuran on day
143 while all of the other dietary concentrations were fortified
on day 268 yielding dietary levels of 0, 2, 20, 100, 200 and 400
ppm through termination. Mortality was reported for one female
exposed to the 400 ppm diet; three males in the 400 ppm dietary
group were sacrificed in extremis after at least 518 days on
study. At 100 ppm, occasional coughing and gagging were
observed; at 200 and 400 ppm, more severe signs of cholinergic
toxicity were observed daily. Reduced mean body weights were
also exhibited at the 400 ppm level. There were no treatment-
related effects associated with food consumption, haematology and
clinical chemistry parameters (cholinesterase activity was not
monitored), urinalysis and histopathology. The no-effect level
(NOEL) was considered to be 50 ppm.
2.1.7 Supplementary studies of toxicity
Carcinogenicity: In the long-term rat and mouse dietary studies
described in section 2.1.6, carbofuran did not demonstrate any
carcinogenic or tumorigenic potential at dietary levels up to and
including 100 ppm for rats and 500 ppm for mice. No evidence of
carcinogenicity or tumorigenicity was observed in the dog at
dietary levels up to 400 ppm.
Teratogenicity: Carbofuran was administered daily by gavage to
groups of pregnant female rats at dosages of 0 (corn oil only),
0.25, 0.50 and 1.20 mg/kg/day on gestation days 6 through 15.
Caesarean sections were performed on all females on day 20 of
presumed gestation. Foetuses were examined for soft tissue and
skeletal abnormalities. Survival was 100% in all groups. All
maternal and foetal parameters were comparable among the groups.
Carbofuran was not teratogenic when administered by gavage at a
dosage of 1.20 mg/kg/day.
Groups of pregnant female rabbits were administered carbofuran at
dosage levels of 0, 0.12, 0.50 and 2.0 mg/kg/day by gavage during
gestation days 6 through 18. On gestation day 29, all surviving
dams were subjected to a Caesarean section and the foetuses were
examined for skeletal and soft tissue abnormalities. At the 2.0
mg/kg/day dosage group, one dam died on gestation day 11.
Depressed mean maternal body weight gains were also reported for
the 2.0 mg/kg/day dosage group. All other maternal and foetal
parameters were comparable among the groups. There was no
evidence of teratogenicity in this study at a dosage of 2.0
mg/kg/day.
A teratology and postnatal dietary study was conducted with
carbofuran in the rat. Carbofuran was incorporated into the diet
at concentrations of 0, 20, 60 and 160 ppm and administered to
pregnant female rats only during gestation days 6 through 19. On
gestation day 20, approximately half of the dams from each dosage
group were submitted to Caesarean section and the foetuses were
examined for skeletal and visceral abnormalities. The remaining
dams were allowed to deliver and care for the pups for 21
post-partum days. At the end of the lactation period (post-
partum day 21), the dams and pups were submitted to necropsy.
Mean food consumption was slightly reduced in the 160 ppm group
during the treatment period. Apparent dose-related mean maternal
body weight losses occurred in the 60 and 160 ppm groups during
the first two days of treatment (gestation days 6 and 7) and
during the first 7 days of lactation.
A statistically significant (P < 0.05) reduction in mean pup body
weight for the 160 ppm group animals was reported on lactation
days 0, 4, 7, 14 and 21. Examination of the foetuses and pups
did not reveal any teratogenic response in this study at a
dietary concentration of 160 ppm.
Mutagenicity: A dominant lethal test was conducted with groups
of male mice receiving intraperitoneal injections of carbofuran
suspended in corn oil at dosages of 0.25 and 0.50 mg/kg. A
vehicle control group received corn oil only while a positive
control group was administered 100 mg/kg of methyl methane-
sulfonate by the same route. Immediately following treatment,
each male was housed with three untreated, virgin females and
allowed to mate. This procedure was repeated weekly with a new
group of untreated, virgin females for a total of six consecutive
weeks. Mated females were sacrificed in mid-gestation for
uterine examination. Carbofuran did not affect mating ability,
frequency of pregnancy, the incidence of resorptions,
preimplantation losses or the number of embryos per dam.
Therefore, carbofuran was not considered to be mutagenic.
Carbofuran was evaluated for its mutagenic potential in a mitotic
recombination assay using Saccharomyces cervisiae D3.
Weight/volume concentrations of 0.1, 0.5, 1.0 and 5.0% were
tested in the presence and absence of metabolic activation;
1,2,3,4-diepoxybutane (positive control) and a negative control
were also tested. Carbofuran was considered to be non-mutagenic
in this assay since it did not cause an increase in the number of
absolute or relative mitotic recombinants. An Ames assay was
conducted with carbofuran using five tester strains of Salmonella
typhimurium. Two trials were conducted with six concentrations
each, ranging between 1 and 1000 µg/plate and 10 to 5000
µg/plate, both in the presence and absence of metabolic
activation. Positive controls (2-anthramine and N-methyl-N'-
nitro-N-nitrosoguanidine) and a negative control were also
tested. There was no increase in the number of revertants per
plate for any of the tester strains in the presence or absence of
metabolic activation. These results indicate that carbofuran was
not considered to be mutagenic.
Escherichia coli WP2 was used in a reverse mutation assay with
carbofuran. Concentrations ranging between 1 and 1000 µg/plate
and 10 to 5000 µg/plate were tested in the presence and absence
of metabolic activation in two trials. Positive controls (2-
anthramine, AF-2 and N-methyl-N'-nitrosoguanidine) and a negative
control were also evaluated. Carbofuran did not cause an
increase in the number of revertants in the presence or absence
of metabolic activation and was not considered to be mutagenic.
DNA repair assays were conducted using DNA repair-proficient and
repair-deficient strains of Bacillus subtilis (H17 and M45,
respectively) and Escherichia coli (W3110 and p3478,
respectively) to evaluate the mutagenic and genotoxic potentials
of carbofuran. Concentrations of 0.01, 0.10, 1.0 and 5.0 mg/disc
were used in both bacterial assays. Chloramphenicol was used as
the negative control, while 1-phenyl-3,3-dimethyltriazine served
as the positive control. Carbofuran was not considered to be
mutagenic or genotoxic in either bacterial assay.
Carbofuran was tested to assess its ability to induce unscheduled
DNA synthesis in cultured human fibroblast cells (WI-38).
Concentrations of 0.1, 1.0, 10, 100 and 1000 µg carbofuran/ml
solvent were evaluated in the presence and absence of metabolic
activation. In addition to a negative (solvent) control,
dimethylnitrosamine and 4-nitroquinoline N-oxide were used as
positive contols in the presence and absence of metabolic
activation, respectively. The rate of unscheduled DNA synthesis
was not increased in the presence or absence of metabolic
activation by carbofuran.
Reproduction: Groups of male and female rats were maintained on
diets containing concentrations of 0, 20 and 100 ppm of
carbofuran for three generations (two litters per generation).
Reproductive and general toxicological parameters were monitored.
Mean parental body weights and food consumption were consistently
lower within the 100 ppm dietary group. Reduced survival of F1a,
F2a and F3a litters on lactation day 4 and consistently lower pup
body weights in all litters occurred within the 100 ppm group.
Dehydration was noted among some of the 100 ppm group F3a and F3b
litters.
Fertility, gestation time, general behaviour, appearance and
survival (parents only) were unaffected. At the completion of
each generation, all parental animals and pups from the F2b and
F3b litters were sacrificed and necropsied. No compound-related
gross or microscopic changes were reported. Carbofuran did not
produce any adverse effects on reproduction. The no-effect level
(NOEL) in this study was 20 ppm. A one-generation reproduction
study in beagle dogs was conducted with carbofuran at dietary
levels of 0, 20 and 50 ppm. Natural mating was allowed during
the second oestrus cycle. Survival, behaviour, body weights,
food consumption, oestrus cycles, mating performance and
gestation and lactation parameters were monitored for the
parental animals. At birth, litter size, pup viability,
survival, nursing ability, general behaviour and physical
appearance were reported for each litter. Physical and
neurological examinations were also conducted on each of the pups
at birth. After one week of age, the pups were examined by X-
rays to evaluate skeletal structure and general development.
Gross pathological examinations were performed on one male and
female pup per litter.
Carbofuran did not affect reproductive performance. There were
no adverse effects attributed to carbofuran in the parental
animals or progeny. The no-effect level (NOEL) in this study was
50 ppm.
Neurotoxicity: Carbofuran was evaluated to determine its
potential to induce delayed neurotoxicity. A group of mature
hens was orally administered 38.9 mg/kg (LD50) of carbofuran and
observed for signs of delayed neurotoxicity for 21 days. A
positive control group received TOCP orally, at a dosage of 50
mg/kg. The dosage and observation period were repeated in the
surviving birds since neurotoxicity was not observed during the
initial 21-day observation period. The lack of neurotoxic effect
after the second administration and 21-day observation period
indicated that carbofuran does not induce delayed neurotoxicity.
2.1.8 Modification of toxicity - Equitoxic mixtures of carbofuran and
other anticholinesterase agents were administered orally to male
rats to determine if a potentiation effect on acute toxicity
would result. The LD50 values were determined for carbofuran and
the other compounds (Systox, Guthion, Trithion, Ethion,
Phosphamidon, Dibrom, Diazinon, EPN, Delnau, Schradan, methyl
parathion, sevin, RE 5353 and Phosdrin). The theoretical
additive LD50 value for each mixture was calculated and compared
to the value obtained in vivo. The results of these trials
indicated that the acute oral toxicity of carbofuran was not
potentiated when administered in combination with other
anticholinesterase agents.
2.2 TOXICOLOGY - MAN
2.2.1 Absorption route - Carbofuran may be absorbed from the
gastrointestinal tract; through the intact skin; and, by
inhalation of spraymist or dusts.
2.2.2 Dangerous doses
Single: The acute oral LD50 is reported to be approximately 11
mg/kg bw, the dermal LD50 to be 10 000 mg/kg. The probable oral
lethal dose is reported to be 5-50 mg/kg bw.
Repeated: Not known; because of rapid metabolism it probably
differs little from the single dangerous dose.
2.2.3 Observations on occupationally exposed workers - Typical cases
involving blurred vision, nausea, excessive perspiration and a
sense of weakness have been reported among formulators and
applicators. Uneventful recovery is reported to occur within a
few hours even without therapy but it was faster when atropine
was administered.
2.2.4 Observations on exposure of the general population - No
information available, if recommended agricultural practices are
followed, the general population will not be exposed to hazardous
amounts of carbofuran.
2.2.5 Observations on volunteers - No information available.
2.2.6 Reported mishaps - In one episode, 142 boys and girls aged 13-16
were employed to remove tassles from corn the day after a field
had been erroneously sprayed with carbofuran (carbofuran is not
recommended for this purpose). By early afternoon 74 teenagers
complained of symptoms of carbofuran poisoning, 40 of them were
treated with atropine, 28 remained in hospital for a few hours
and one patient remained overnight. The onset of symptoms was
rapid but mild, recovery was also rapid.
2.3 TOXICITY TO NON-MAMMALIAN SPECIES
2.3.1 Fish - Carbofuran is very toxic to fish.
LC50 (96 hours): Bluegill 80 µg/l
Yellow perch 147 µg/l
Brown trout 280 µg/l
Lake trout 164 µg/l
Mosquito fish 300 µg/l
Coho salmon 524 µg/l
Steelhead 600 µg/l
2.3.2 Birds - Carbofuran is very toxic to birds and has been used as an
avicide.
Oral LD50: Domestic hen 6.0 mg/kg bw
Bobwhite quail 5.04 mg/kg bw
Ring-neck pheasant 4.15 mg/kg bw
Japanese quail (M) 1.9 mg/kg bw
Japanese quail (F) 1.7 mg/kg bw
House sparrow 1.3 mg/kg bw
Mallard duck 36 hours old 0.37 mg/kg bw
1 week old 0.63 mg/kg bw
4 weeks old 0.51 mg/kg bw
6 months old 0.42 mg/kg bw
Quella 0.42 mg/kg bw
Red-wing blackbird 0.42 mg/kg bw
Dermal LD50: House sparrow 100 mg/kg bw
Quella 100 mg/kg bw
Dietary: The cumulative LD50 (10 days for pheasants) was 960 mg a.i.
(as 10% granular)/kg of diet.
2.3.3 Other species - Carbofuran is highly toxic to a variety of
beneficial invertebrates, the LD50 for honeybees is 0.16 µg/bee.
3. FOR REGULATORY AUTHORITIES
3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY
(For definition of categories see the Introduction to data sheets)
Liquid formulations of 4% and over, Category 2
Other liquid formulations, Category 3
Solid formulations of 16% and over, Category 2
Other solid formulations, Category 3
3.2 TRANSPORTATION AND STORAGE
All formulations - Should be transported and stored in labelled
impermeable containers under lock and key, and secure from access
by children and other unauthorized persons. No food or drink
should be stored in the same compartment.
3.3 HANDLING
All formulations - Full protective clothing (see paragraph 4.3 in
part 4) should be used by those handling the compound. Adequate
washing facilities should be available at all times during the
handling and should be close to the site of handling. Eating,
drinking and smoking should be prohibited during handling and
before washing after handling.
3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS
All formulations - Container must either be burned or crushed and
buried below topsoil. Care must be taken to avoid subsequent
contamination of water sources. Decontamination of containers in
order to use them for other purposes should not be permitted.
3.5 SELECTION AND TRAINING AND MEDICAL SUPERVISION OF WORKERS
All formulations - Pre-employment medical examination of workers
necessary. Workers suffering from active hepatic or renal disease
should be excluded from contact. Pre-employment and periodic
cholinesterase test for workers desirable. Special account should
be taken of the workers' mental ability to comprehend and follow
instructions. Training of workers in techniques to avoid contact
is essential.
3.6 ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT
All formulations - Pilots and loaders should have special training
in application methods and early symptoms of poisoning, and must
wear a suitable respirator. Use of flagmen not recommended.
Flagmen, if used, should wear protective clothing and be located
well away from the dropping zone.
3.7 LABELLING
All formulations - "DANGER - POISON" (skull and cross-bones
insignia). Carbofuran is a carbamate compound which inhibits
cholinesterase enzymes. It is extremely toxic. Contact with the
skin, inhalation of dust or spray, or swallowing should be
avoided. Wear protective gloves, clean protective clothing, and a
respirator of the organic-vapour type when handling this material.
Bathe immediately after work.
Ensure that containers are stored under lock and key. Empty
containers must be disposed of in such a way as to prevent all
possibility of accidental contact with them. Keep the material
out of reach of children and well away from foodstuffs, animal
feed and their containers.
In case of contact, immediately remove contaminated clothing and
wash the skin thoroughly with soap and water; for eyes, flush with
water for 15 minutes.
If poisoning occurs, call a physician. Atropine sulfate is a
specific antidote and repeated doses may be necessary. Artificial
respiration may be needed.
3.8 RESIDUES IN FOOD
Maximum residue levels - Maximum residue levels have been
recommended by the Joint FAO/WHO Meeting on Pesticides Residues.
4. PREVENTION OF POISONING IN MAN AND EMERGENCY AID
4.1 PRECAUTIONS IN USE
4.1.1 General - Carbofuran is a carbamate pesticide of very high
toxicity. It is an acute poison, absorbed by inhalation of dust
and spray mist; from the gastrointestinal tract; and, to a lesser
extent, through the intact skin. Most formulations should be
handled by trained personnel wearing suitable protective
clothing.
4.1.2 Manufacture and formulation - TLV - (ACGIH) 2.5 mg/m3.
Formulation should not be attempted without advice from the
manufacturer. Although volatility is low, vapour and dusts
should be controlled preferably by mechanical means. Protective
equipment for the skin and respiratory protection is necessary.
4.1.3 Mixers and applicators - When opening the container and when
mixing, protective impermeable boots, clean overalls, gloves and
a respirator should be worn. Beware of possible positive
pressure build-up, especially with liquid formulations in metal
containers with inverted pour spouts. Mixing, if not mechanical,
should always be carried out with a paddle of appropriate length.
When spraying tall crops or during aerial application, a
respirator should be worn as well as an impermeable hood,
protective clothing, boots and gloves. The applicator should
avoid working in spray mist and avoid contact with the mouth.
Particular care is needed when equipment is being washed after
use. All protective clothing should be washed immediately after
use, including the inside of the gloves. Splashes must be washed
immediately from the skin or eyes with large quantities of water.
Before eating, drinking or smoking, hands and other exposed skin
should be washed.
4.1.4 Other associated workers (including flagmen in aerial operations)
- Persons exposed to carbofuran and associated with its
applications should wear protective clothing and observe the
precautions described above in 4.1.3 under "Mixers and
applicators".
4.1.5 Other populations likely to be affected - With good agricultural
practice subject to 4.2 below, other populations should not be
exposed to hazardous amounts of carbofuran.
4.2 ENTRY OF PERSONS INTO TREATED AREAS - Unprotected persons should
be kept out of treated areas for at least one day.
4.3 SAFE DISPOSAL OF CONTAINERS AND SPILLAGE - Residues in containers
should be emptied in a diluted form into a deep pit taking care
to avoid contamination of ground waters. The empty container may
be decontaminated by rinsing two or three times with water and
scrubbing the sides. An additional rinse should be carried out
with 5% sodium hydroxide solution which should remain in the
container overnight. Impermeable gauntlets should be worn during
this work and a soakage pit should be provided for the rinsings.
Decontaminated containers should not be used for food and drink.
Spillage of carbofuran and its formulations should be removed by
washing with 5% sodium hydroxide solution and then rinsing with
large quantities of water.
4.4 EMERGENCY AID
4.4.1 Early symptoms of poisoning - Early symptoms of poisoning may
include headache, weakness, giddiness and nausea. Later there may
be perspiration, stomach pains, blurred vision, excessive
salivation, slurred speech, and muscle twitching, tremor,
diarrhoea and vomiting.
4.4.2 Treatment before person is seen by a physician, if these symptoms
appear following exposure - The person should stop work
immediately, remove contaminated clothing and wash the affected
skin with soap and water, if available, and flush the area with
large quantities of water. If swallowed, vomiting should be
induced immediately if the person is conscious. In the event of
collapse, artificial respiration should be given, preferably by
mechanical means. If mouth-to-mouth resuscitation is used vomit
may contain toxic amounts of carbofuran. If the eyes are
contaminated, flush them with water for at least 15 minutes. If
carbofuran is inhaled, remove victim to fresh air immediately.
5. FOR MEDICAL AND LABORATORY PERSONNEL
5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING
5.1.1 General information - Carbofuran is a carbamate insecticide of
very high toxicity. It is absorbed from the gastrointestinal
tract and by inhalation, and only to a limited extent through the
intact skin. Its mode of action is by reversible inhibition of
acetyl cholinesterase. Erythrocyte cholinesterase is more
inhibited than plasma cholinesterase. Symptoms of mild poisoning
are short lasting and in case of occupational over-exposure occur
without delay and at doses well below the fatal dose. Because of
its rapid metabolism and excretion it does not accumulate in the
tissues.
5.1.2 Symptoms and signs - Symptoms of poisoning include excessive
sweating, headache, chest tightness, weakness, giddiness, nausea,
vomiting, stomach pains, salivation, blurred vision, slurred
speech and muscle twitching. Paraesthesia and mild skin reactions
have also been reported. Diagnosis can be based on a recent
history of activities and non-reactive pupils of the eyes.
5.1.3 Laboratory - Because carbofuran is a reversible inhibitor of
cholinesterase, measurements of cholinesterase activity should be
made by a method which minimizes the reactivation of inhibited
enzyme. Erythrocyte cholinesterase determination is more
informative than either plasma or whole blood cholinesterase, but
the enzyme will only be inhibited for a short time (few hours)
after exposure. The presence of metabolites of carbofuran in
urine is also indicative of exposure.
5.1.4 Treatment - If the pesticide has been ingested, unless the
patient is vomiting, rapid gastric lavage should be performed
using 5% sodium bicarbonate, if available. For skin contact, the
skin should be washed with soap and water. If the compound has
entered the eyes, they should be washed with isotonic saline or
water. Since the symptoms of poisoning with carbofuran are of
short duration, atropine treatment is usually not necessary by
the time the patient reaches a place where this antidote is
available. Where there are manifest symptoms 1-2 mg of atropine
sulfate (adult dose) may be given intramuscularly or even
intravenously and repeated as necessary. Care should be taken to
avoid overdosage of atropine, especially when treating children.
In extreme cases, if the patient is unconscious or is in
respiratory distress, oxygen may be required. Provide patient
support as required, including; suction of secretions,
maintenance of airways, intravenous fluids pro re nata and
bladder catheterization. Morphine, aminophylline,
phenothiazines, reserpine, furosemide and ethacryoic acid are
condraindicated. Pralidoxime chloride is of doubtful value but
if muscle weakness is severe a dilute solution may be given
cautiously intravenously. If convulsions occur diazepam may be
given, the patient must be monitored for respiratory depression
and hypotensive reactions.
5.1.5 Prognosis - If the acute toxic effect is survived, the chances of
complete recovery are very good.
5.1.6 References of previously reported cases - Okeefe, M. & Pierse, C.
(1980), Bull. Environs Contam. Toxicol., 25, 777.
5.2 SURVEILLANCE TESTS - Due to rapid reactivation of inhibited
enzymes, determination of blood cholinesterase levels is of
little, if any, practical value in determining when workers should
be withdrawn to prevent over-exposure. Minor complaints, such as
headache and nausea, generally cause the worker to stop work and
thus prevent further exposure. The worker then quickly recovers,
particularly if appropriate decontamination procedures are
followed.
5.3 LABORATORY METHODS
5.3.1 Detection and assay of compound - Chapman, R. A. & Robinson, J.
R, (1977) J. Chromatogr., 140, 209. Cooke, R. F. et al. (1969)
J. Agric. Food Chem., 17, 277. Cooke, R. F. (1973) Anal.
Methods Pestic. Plant Growth Regul., 7, 187.
5.3.2 Other tests in cases of poisoning - Cholinesterase levels in
blood are unreliable as a routine test to detect poisoning by
carbofuran. However, shortly after absorption inhibition of
erythrocyte cholinesterase may be demonstrated by an appropriate
method. In plasma; Ellman, G. et al. (1961) Biochem.
Pharmacol., 7, 88. In whole blood; Fleischer, J. et al. (1956)
Arch. Indust. Hyg., 14, 510; Wilheim, K. et al. (1973) Bull
Wld. Hlth, Org., 48, 235.