Carbaryl
| 1. NAME |
| 1.1 Substance |
| 1.2 Group |
| 1.3 Synonyms |
| 1.4 Identification numbers |
| 1.4.1 CAS number |
| 1.4.2 Other numbers |
| 1.5 Main brand names, main trade names |
| 1.6 Manufacturers, Importers |
| 2. SUMMARY |
| 2.1 Main risks and target organs |
| 2.2 Summary of clinical effects |
| 2.3 Diagnosis |
| 2.4 First-aid measures and management principles |
| 3. PHYSICO-CHEMICAL PROPERTIES |
| 3.1 Origin of the substance |
| 3.2 Chemical structure |
| 3.3 Physical properties |
| 3.3.1 Colour |
| 3.3.2 State/Form |
| 3.3.3 Description |
| 3.4 Hazardous characteristics |
| 4. USES |
| 4.1 Uses |
| 4.1.1 Uses |
| 4.1.2 Description |
| 4.2 High risk circumstances of poisoning |
| 4.3 Occupationally exposed populations |
| 5. ROUTES OF EXPOSURE |
| 5.1 Oral |
| 5.2 Inhalation |
| 5.3 Dermal |
| 5.4 Eye |
| 5.5 Parenteral |
| 5.6 Others |
| 6. KINETICS |
| 6.1 Absorption by route of exposure |
| 6.2 Distribution by route of exposure |
| 6.3 Biological half-life by route of exposure |
| 6.4 Metabolism |
| 6.5 Elimination by route of exposure |
| 7. TOXICOLOGY |
| 7.1 Mode of Action |
| 7.2 Toxicity |
| 7.2.1 Human data |
| 7.2.1.1 Adults |
| 7.2.1.2 Children |
| 7.2.2 Relevant animal data |
| 7.2.3 Relevant in vitro data |
| 7.2.4 Workplace standards |
| 7.2.5 Acceptable daily intake (ADI) |
| 7.3 Carcinogenicity |
| 7.4 Teratogenicity |
| 7.5 Mutagenicity |
| 7.6 Interactions |
| 8. TOXICOLOGICAL ANALYSES & BIOMEDICAL INVESTIGATIONS |
| 8.1 Material sampling plan |
| 8.1.1 Sampling and specimen collection |
| 8.1.1.1 Toxicological analyses |
| 8.1.1.2 Biomedical analyses |
| 8.1.1.3 Arterial blood gas analysis |
| 8.1.1.4 Haematological analyses |
| 8.1.1.5 Other (unspecified) analyses |
| 8.1.2 Storage of laboratory samples & specimens |
| 8.1.2.1 Toxicological analyses |
| 8.1.2.2 Biomedical analyses |
| 8.1.2.3 Arterial blood gas analysis |
| 8.1.2.4 Haematological analyses |
| 8.1.2.5 Other (unspecified) analyses |
| 8.1.3 Transport of laboratory samples &specimens |
| 8.1.3.1 Toxicological analyses |
| 8.1.3.2 Biomedical analyses |
| 8.1.3.3 Arterial blood gas analysis |
| 8.1.3.4 Haematological analyses |
| 8.1.3.5 Other (unspecified) analyses |
| 8.2 Toxicological Analyses and Their Interpretation |
| 8.2.1 Tests on toxic ingredient(s) of material |
| 8.2.1.1 Simple Qualitative Test(s) |
| 8.2.1.2 Advanced Qualitative Confirmation Test(s) |
| 8.2.1.3 Simple Quantitative Method(s) |
| 8.2.1.4 Advanced Quantitative Method(s) |
| 8.2.2 Tests for biological specimens |
| 8.2.2.1 Simple Qualitative Test(s) |
| 8.2.2.2 Advanced Qualitative Confirmation Test(s) |
| 8.2.2.3 Simple Quantitative Method(s) |
| 8.2.2.4 Advanced Quantitative Method(s) |
| 8.2.2.5 Other Dedicated Method(s) |
| 8.2.3 Interpretation of toxicological analyses |
| 8.3 Biomedical investigations & their interpretation |
| 8.3.1 Biochemical analysis |
| 8.3.1.1 Blood, plasma or serum |
| 8.3.1.2 Urine |
| 8.3.1.3 Other fluids |
| 8.3.2 Arterial blood gas analyses |
| 8.3.3 Haematological analyses |
| 8.3.4 Interpretation of biomedical investigations |
| 8.4 Other biomedical investigations |
| 8.5 Overall Interpretation |
| 8.6 References |
| 9. CLINICAL EFFECTS |
| 9.1 Acute poisoning |
| 9.1.1 Ingestion |
| 9.1.2 Inhalation |
| 9.1.3 Skin exposure |
| 9.1.4 Eye contact |
| 9.1.5 Parenteral exposure |
| 9.1.6 Other |
| 9.2 Chronic poisoning |
| 9.2.1 Ingestion |
| 9.2.2 Inhalation |
| 9.2.3 Skin exposure |
| 9.2.4 Eye contact |
| 9.2.5 Parenteral exposure |
| 9.2.6 Other |
| 9.3 Course, prognosis, cause of death |
| 9.4 Systematic description of clinical effects |
| 9.4.1 Cardiovascular |
| 9.4.2 Respiratory |
| 9.4.3 Neurological |
| 9.4.3.1 Central Nervous System (CNS) |
| 9.4.3.2 Peripheral nervous system |
| 9.4.3.3 Autonomic nervous system |
| 9.4.3.4 Skeletal and smooth muscle |
| 9.4.4 Gastrointestinal |
| 9.4.5 Hepatic |
| 9.4.6 Urinary |
| 9.4.6.1 Renal |
| 9.4.6.2 Others |
| 9.4.7 Endocrine & reproductive systems |
| 9.4.8 Dermatological |
| 9.4.9 Eye, ears, nose, throat: local effects |
| 9.4.10 Haematological |
| 9.4.11 Immunological |
| 9.4.12 Metabolic |
| 9.4.12.1 Acid-base disturbances |
| 9.4.12.2 Fluid & electrolyte disturbances |
| 9.4.12.3 Others |
| 9.4.13 Allergic reactions |
| 9.4.14 Other clinical effects |
| 9.4.15 Special risks |
| 9.5 Others |
| 9.6 Summary |
| 10. MANAGEMENT |
| 10.1 General principles |
| 10.2 Life supportive procedures |
| 10.3 Decontamination |
| 10.4 Enhanced elimination |
| 10.5 Antidote treatment |
| 10.5.1 Adults |
| 10.5.2 Children |
| 10.6 Management discussion |
| 11. ILLUSTRATIVE CASES |
| 11.1 Case reports from literature |
| 12. ADDITIONAL INFORMATION |
| 12.1 Specific preventive measures |
| 12.2 Other |
| 13. REFERENCES |
| 14. AUTHOR(S), REVIEWER(S), DATES |
CARBARYL
International Programme on Chemical Safety
Poisons Information Monograph 147
Chemical
1. NAME
1.1 Substance
Carbaryl
1.2 Group
Hydrocarbons, polycyclic, carbamate naphtalene derivative
1.3 Synonyms
1-Naphthyl - N - methylcarbamate;
alpha - Naphthyl N - methylcarbamate;
1-Napthalenol methyl - carbamate;
methylcarbamic acid;
1-naphthyl ester
1.4 Identification numbers
1.4.1 CAS number
63-25-2
1.4.2 Other numbers
UN Number: 2757
RTECS Number: FC5950000
1.5 Main brand names, main trade names
Sevin, Arilat, Carbatox, Dicarbam
1.6 Manufacturers, Importers
2. SUMMARY
2.1 Main risks and target organs
Carbaryl is a reversible cholinesterase inhibitor.
Carbaryl is absorbed via inhalation and the oral route, and
less well absorbed by the dermal route.
2.2 Summary of clinical effects
The clinical picture of intoxication is secondary to by
cholinesterase inhibition. Symptoms may include increased
bronchial secretion, exessive sweating, salivation, and
lacrimation, pinpoint pupils, bronchoconstriction, abdominal
cramps, vomiting, diarrheoa, bradycardia, muscle
fasciculation, diaphragm and respiratory muscles paralysis,
tachycardia, headache, dizziness, anxiety, mental confusion,
convulsion, coma, and depression of the respiratory
centre.
Signs of intoxication develop quickly after absorption.
In cases of occupational exposure to carbaryl, mild symptoms
are observed long before a dangerous dose is absorbed.
During agricultural application, dermal exposure may play an
important role. No local irritation is usually observed,
however, skin rash after accidental exposure to liquid
formulations has been described.
2.3 Diagnosis
Diagnosis is based on the history of exposure and the
characteristic presentation of muscarinic, nicotinic, and
central nervous system effects of an excess of
acetylcholine.
2.4 First-aid measures and management principles
Evaluation and support airway, breathing and
circulation.
In the case of ingestion, administer activated charcoal, or,
if the patient is obtunded within one hour of ingestion,
gastric lavage with endotracheal intubation may be
undertaken. Do not induce emesis because of the risk of
sudden seizures, coma, or respiratory depression. Specific
treatment is the use of atropine intramuscularly or
intravenously 0.5 to 2 mg every 15 minutes until the symptoms
are reversed. It is important to maintain airway potency.
When dermal exposure occurs, decontamination procedures
include removal of contaminated clothes and copious
irrigation.
Extensive eye irrigation with water or saline should also be
performed after acute exposure.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Carbaryl was initially synthesized in 1953, and is a
synthetic devivative of carbamic acid (H2 N-COOH).
3.2 Chemical structure
Structural names:
1-Naphtalenol methyl carbamate
methyl carbamic acid 1-naphtylester
Molecular formula: C12H11NO2
Molecular weight: 201.22
3.3 Physical properties
3.3.1 Colour
White to greyish
3.3.2 State/Form
Solid-crystals
3.3.3 Description
Boiling Point: Decomposes
Melting Point:142 °C
Flash Pont: 173 °C
Autoignition: 625 °C
Vapour Pressure < 4.10-5 mm Hg at 25 °C
Solubility in water: Practically insoluble (4mg/100mL
@ 20 °C)
Solubility in alcohol: Soluble in ethanol
Solubility in ether: Soluble in petroleum ether and
diethylether
Conversion factor: 1 ppm = 8.22 mg/m3 of air
1 mg/m3 = 0.12 ppm
3.4 Hazardous characteristics
Stable to heat, light, acids; hydrolyzed in alkalies;
non corrosive.
4. USES
4.1 Uses
4.1.1 Uses
Pesticide
Insecticide
4.1.2 Description
Carbaryl is a contact and stomach insecticide
with slight systemic properties, for use against many
insect pests of cotton, fruit, vegetables, and other
crops. It is available for household lawn and garden
pest control, and in veterinary practice carbaryl is
used on cattle, poultry and pets especially to control
flies, mosquitos, ticks and lice (WHO, 1994).
4.2 High risk circumstances of poisoning
Occupational exposure during the manufacture,
formulation, packing, storage, and transportation.
Occupational exposure during agricultural application.
4.3 Occupationally exposed populations
Farmers and plant workers are at risk for occupational
hazard of poisoning.
The general population can be exposed to carbaryl during pest
control operations in both the home and recreational areas.
Workers can be exposed to carbaryl during its manufacture,
formulation, packing, transportation, storage, and
application. Significant dermal exposure may occur in
industrial and agricultural workers if protective measures
are inadequate.
5. ROUTES OF EXPOSURE
5.1 Oral
Carbaryl is absorbed via the oral route (WHO, 1994)
5.2 Inhalation
Carbaryl is easily absorbed via inhalation (WHO, 1994)
5.3 Dermal
Carbaryl can be slowly absorbed through the skin (NIOSH,
1994; WHO, 1994).
5.4 Eye
No data
5.5 Parenteral
No data.
5.6 Others
No data.
6. KINETICS
6.1 Absorption by route of exposure
In rats, absorption of carbaryl from the
gastrointestinal tract is rapid (Casper & Pekas, 1971).
When applied to the forearm of humans, C14 labeled carbaryl
was slowly but almost completely absorbed (Feldman & Maibach,
1974).
6.2 Distribution by route of exposure
Carbaryl is distributed in liver, stomach, intestines,
kidneys, lungs, bone marrow and brain (WHO, 1994). Animal
studies showed that placental transfer occurs in the first
hour after administration. Carbaryl concentration in the eye,
liver, and brain of the fetus was relatively constant from 8
to 96 hours(Declume & Derache, 1976, 1977; Declume & Benard,
1977 a,b, 1978).
6.3 Biological half-life by route of exposure
Given intravenously to volunteers, the estimated half-
life was 9 hours (Feldman & Maibach, 1974).
6.4 Metabolism
Metabolic reactions include: hydroxylation, hydrolysis,
and conjugation. Hydrolysis results in the formation of 1-
naphtol, carbon dioxide, and methylamine. Metabolites of
carbaryl were identified in the urine of human volunteers
after the ingestion of a 2 mg/kg dose. (Andrawes & Myers,
1976)
Entero hepatic cycling of carbaryl metabolites is also
considerable, especially after oral administration.
Only traces of the unchanged carbaryl could be detected in
the urine indicating rapid metabolism. The only detectable
metabolites in urine samples taken from workers exposed to
carbaryl dust were 1-naphthylglucoronide and sulfate (Knaak
et al., 1965).
Carbaryl is metabolized by hepatic microsomal enzymes.
6.5 Elimination by route of exposure
The elimination of metabolized carbaryl is rapid.
Carbaryl is generally excreted entirely within 24 to 96 hours
after absorption. Elimination takes place via the urine,
faeces and respiration. Carbaryl is mainly excreted as its
product of hydrolysis, 1-naphthol, as a soluble glucuronide
(Carpenter et al., 1961), and as a sulfate (Whitehurst et
al., 1963). It is excreted in trace amounts as unchanged
carbaryl.
Carbaryl's metabolites are less active than the parent
compound.
7. TOXICOLOGY
7.1 Mode of Action
Carbaryl is an inhibitor of cholinesterase enzymes.
In normal nervous system function, a burst of the
neurotransmitter acetylcholine is released from a nerve cell
terminal, diffuses across the synaptic cleft and transmits a
nerve impulse to a specific cholinergic receptor. To end
stimulation and restore the sensitivity of the receptor to
new transmitter, acetylcholine at the receptor must
continually be eliminated; this function is fulfilled by the
enzyme acetylcholinesterase, which hydrolyzes acetylcholine
to choline and acetic acid. By inhibiting
acetylcholinesterase, anticholinesterase carbamates allow
acetylcholine to accumulate at cholinergic junctions (Hayes &
Laws, 1991).
This effect is dose-related and reversible.
Chronic exposure may cause a cumulative effect. All
identified metabolites of carbaryl are less active
cholinesterase inhibitors than carbaryl itself.
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
Carbaryl was ingested once by
individual men at dosages of 0.5, 1.0 and
2.0, mg/kg. Neither subjective nor objective
effects were noted (Wills et al., 1968). In a
further study, five men took a dosage of 0.06
mg/kg/day for 6 weeks, and six men took from
0.12 to 0.13 mg/kg/day for the same duration.
No abnormalties other than a slight,
reversible increase in the ratio of amino
acid nitrogen to creatinine in the urine were
seen (Wills et al., 1968).
An adult male ingested 250 mg of carbaryl
(approx. 2.8 mg/kg). Twenty minutes later he
experienced the very sudden onset of violent
epigastric pain. A little later he began to
sweat profusely. A 1 mg dose of atropine
produced little improvement; he gradually
developed great lassitude and vomited twice.
One hour after taking carbaryl and following
a total of 3 mg atropine, he was feeling
better (Hayes, 1982).
An ingestion of 500 mg/kg resulted in the
development of a delayed peripheral
neuropathy (Dickoff et al., 1987).
An ingestion of 400 g resulted in severe
pulmonary edema and death in a 39 year old
male (Farago, 1969).
7.2.1.2 Children
A nineteen month old infant
developed miosis, salivation and muscular
inco-ordination despite gastric lavage within
half an hour of ingestion of an unknown
amount of carbaryl. A single 0.3 mg dose of
atropine sulphate was effective and recovery
apparently was complete in at hours (Best &
Murray, 1962).
7.2.2 Relevant animal data
LD50 (oral, rat): 500 to 600 mg/kg (WHO, 1986);
250 mg/kg (Budavari, 1996); 230 to 850 mg/kg (Hayes &
Laws, 1991)
LD50 (sc, rat) > 4000 mg/kg (Cranmer, 1986)
LD50 (sc, rabbit) > 2000 mg/kg (WHO, 1986)
LD50 (oral, monkey) > 1000 mg/kg (Cranmer, 1986)
LD50 (dermal, rabbit) > 4000 mg/kg (WHO, 1978)
Toxic to fish, lesser toxicity to most birds, more
toxic to bees and crustaceans.
Cloudy swelling of cells in the proximal convoluted
tubules of the kidneys was noted in rats and dogs fed
400 ppm of carbaryl in their diets for several months
(Carpenter et al, 1961).
Eye irritation: rabbit, 45% concentration of carbaryl
produced mild irritation with complete recovery
(Cranmer, 1986).
Skin: several studies showed that carbaryl does not
produce allergic skin reactions (Cranmer, 1986).
Immunogenicity: carbaryl inhibited the action of the
immune system but severe inhibition occured only at
high doses which also produce neurotoxic effects.
These effects were completely reversible once the
exposure was stopped (Cranmer, 1986). These results
have been questioned (WHO, 1994).
7.2.3 Relevant in vitro data
Carbaryl produced a marked concentration
dependent inhibition of Inter Leukin 2 driven
proliferation of mouse CTLL2 cells (Gasale et al.,
1993).
7.2.4 Workplace standards
TWA 5 mg/m3 Australia
TWA 5 mg/m3 UK
STEL 10 mg/m3 UK
TWA 5 mg/m3 USA
7.2.5 Acceptable daily intake (ADI)
The acceptable daily intake is 0.01 mg/kg body
weight per day (WHO, 1994). Food represents the major
source of carbaryl intake for the general population.
Residues in total dietary samples are relatively low,
ranging from trace amounts to 0.05 mg/kg in the
USA.
7.3 Carcinogenicity
No human information about carbaryl carcinogenicity is
available. Animal studies show inadequate evidence, although
N-nitroso carbaryl is carcinogenic when administered in high
doses but does not represent a significant risk factor
(Cranmer, 1986; WHO, 1994).
7.4 Teratogenicity
Animal studies showed that placental transfer occurs in
the first hour after administration. Radio active carbon
concentration in the eye, liver, and brain of the fetus was
relatively constant from 8 to 96 hours.
(Declume & Derache, 1976, 1977; Declume & Benard, 1977 a,b,
1978)
Monkeys given doses of carbaryl of 0.2, 2, or 20 mg/kg body
weight from day 18 to day 40 of gestation, did not have any
teratogenic effects (Dougherty et al, 1971).
Mammalian studies on the reproductive or developmental
toxicity of carbaryl clearly show that this compound is
capable of inducing adverse effects in utero and during the
reproductive process. These effects are always seen only at
dose levels at which there is concurrent maternal toxcicity,
with the possible exception of a few studies on the rat which
have not been replicated by other workers (WHO, 1994).
No human information available.
7.5 Mutagenicity
The available evidence indicate that Carbaryl does not
have any DNA-damaging properties. There have been no reports
of confirmed induction of recombination, gene conversion, and
UDS in prokaryotes. (H. influenza, B. subtilis) and
eukaryotes (S.cereviside, A.nidulans, Cultured human
lymphocytes and rat hepatocytes) in vitro (WHO, 1994).
However, chromosomal damage with high doses of carbaryl has
been reported in vitro in human, rats, and hamster, and
plants (WHO, 1994).
N-nitrosocarbaryl does bind to DNA and induces mitotic
recombination and gene conversion (WHO, 1994).
7.6 Interactions
Carbaryl is a weak inducer of hepatic microsomal drug
metabolizing activity. This has been suggested to have
clinical importance. There is evidence that hepatic enzyme
inducers may decrease toxicity, and hepatic enzyme inhibitors
increase toxicity, especially chronic neurotoxicity. Low
protein diet increases acute toxicity (WHO, 1994).
Carbaryl metabolism is inhibited by cimetidine in the
isolated perfused rat liver (Ward et al., 1988).
8. TOXICOLOGICAL ANALYSES & BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
Cholinesterase activity in blood or
brain, which has been found to correlate with
carbaryl concentration in theses tissues may
be determined by colorimetry (Fleisher &
Pope, 1954) or by an electrometric method
(Michel, 1949), Carbaryl itself has been
analysed in biological specimens by a
nonspecific colorimetric technique involving
diazotisation (Farago, 1969) and by electron
capture gas chromatography after
derivitization with heptafluorobutyric
anhydride (Mount and Oehme, 1980). The
measurement of 1-naphthol in urine is
generally accomplished by colorimetry (Best &
Murray, 1962) or by gas chromatography
(Shafik et al., 1971).
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples & specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified) analyses
8.1.3 Transport of laboratory samples &specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis
8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple Qualitative Test(s)
8.2.1.2 Advanced Qualitative Confirmation Test(s)
8.2.1.3 Simple Quantitative Method(s)
8.2.1.4 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
8.2.2.1 Simple Qualitative Test(s)
8.2.2.2 Advanced Qualitative Confirmation Test(s)
8.2.2.3 Simple Quantitative Method(s)
8.2.2.4 Advanced Quantitative Method(s)
8.2.2.5 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations & their interpretation
8.3.1 Biochemical analysis
8.3.1.1 Blood, plasma or serum
8.3.1.2 Urine
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations
8.4 Other biomedical investigations
8.5 Overall Interpretation
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
Serious effects occur by ingestion of the
substance in high doses.
In the early stage, a muscarinic syndrome occurs
including nausea, vomiting, abdominal cramps and
diarrhea. Symptoms may also include increased
bronchial secretion, excessive sweating, salivation,
and lacrimation, pinpoint pupils (miosis), and
bronchoconstriction. Then a nicotinic syndrome
develops with bradycardia, muscle fasciculation,
followed by signs of CNS toxicity including:
dizziness, anxiety, mental confusion, convulsion and
coma, and depression of respiratory centre (WHO,
1994).
9.1.2 Inhalation
Carbaryl has a very low tendency to evaporate,
and vapour concentrations are normally too low to pose
an inhalation hazard. While exposure can occur by
inhalation of mist, serious or harmful symptoms have
not been reported (CHEMINFO, 1995).
9.1.3 Skin exposure
Dust or liquid can produce mild irritation and
a burning sensation (Hayes et al., 1982).
Carbaryl can be slowly absorbed through the skin at
levels which can result in systemic symptoms (NIOSH,
1994).
9.1.4 Eye contact
Liquid or dust can probably produce mild
temporary irritation. Splash contact with a liquid
containing both carbaryl and dimethoate produced mild
temporary swelling of the eyelids and mild irritation
of the cornea. Recovery was rapid and complete (Grant
et al., 1986).
9.1.5 Parenteral exposure
No data
9.1.6 Other
No data
9.2 Chronic poisoning
9.2.1 Ingestion
Animal models show decreased survival, weight
gain, decreased erythrocytes, increased liver weight
with chronic high dose exposure (WHO, 1994).
It has been reported that the urinary amino acid
nitrogen/creatinine ratios were increased in a group
of human volunteers who ingested daily doses of
carbaryl of 0,12 mg/kg/day for several weeks (Wills et
al., 1968).
9.2.2 Inhalation
Long term exposure has occasionaly been
reported to decrease cholinesterase activity, which is
dependent on the dose and frequency of repeated
exposures. These exposures are usually not associated
with symptoms (WHO, 1994).
9.2.3 Skin exposure
Long term exposure has occasionaly been
reported to decrease cholinesterase activity, which is
dependent on the dose and frequency of repeated
exposures. These exposures are usually not associated
with symptoms (WHO, 1994).
9.2.4 Eye contact
Can result in visual disturbances, miosis, and
temporary irritation.
9.2.5 Parenteral exposure
No data available
9.2.6 Other
No data available
9.3 Course, prognosis, cause of death
The onset of the symptoms of cholinesterase inhibition
is usually rapid, with a good prognosis for survival without
sequelae. Death can occur secondary to respiratory depression
or pulmonary edema. Long term peripheral neurotoxicity has
been reported.
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
Bradycardia, decreased stroke volume, atrio-
ventricular block, hypo or hypertension, and QT
prolongation have been reported (Leikin & Paloucek,
1996).
9.4.2 Respiratory
Respiratory effects include difficulty in
breathing, increased bronchial secretion, tachypnoea,
pulmonary oedema, diaphragmatic paralysis, and
respiratory depression.
9.4.3 Neurological
9.4.3.1 Central Nervous System (CNS)
The primary effect of carbaryl on
the central nervous system is related to
cholinesterase inhibition. Symptoms include
dizziness, headache, anxiety, mental
confusion, convulsions, coma, and depression
of the respiratory centre (WHO,
1994).
9.4.3.2 Peripheral nervous system
Peripheral neuropathy has been
reported in one case (Dickoff et al.,
1987).
9.4.3.3 Autonomic nervous system
Increased bronchial secretion,
excessive sweating, salivation and
lacrimation.
Pinpoint pupils, bronchoconstriction,
abdominal cramps, and bradycardia (WHO,
1994).
9.4.3.4 Skeletal and smooth muscle
Muscle fasciculation, in severe
cases, diaphragm and intracostal muscles may
be affected (WHO, 1994).
9.4.4 Gastrointestinal
Symptoms may include abdominal cramps, vomiting
and diarrhoea (WHO,1994).
9.4.5 Hepatic
A syndrome similar to acute intermittent
porphyria was described 2 to 23 days after ingestion
of an unknown amount of carbaryl in one case (Sargin
et al., 1992).
9.4.6 Urinary
9.4.6.1 Renal
It has been reported that the
urinary amino acid nitrogen/creatinine ratios
were increased in a group of human volunteers
who ingested daily doses of carbaryl of 0.12
mg/kg/day for several weeks (Wills et al.,
1968).
9.4.6.2 Others
No data
9.4.7 Endocrine & reproductive systems
With chronic male workplace exposure no
reproductive system toxicity was observed (WHO, 1994).
In the animal adverse effects on reproduction are seen
with severe toxicity (WHO, 1994).
9.4.8 Dermatological
Liquid or dust can produce mild irritation,
burning sensation, and a skin rash (Hayes et al.,
1982).
9.4.9 Eye, ears, nose, throat: local effects
In some animal tests, carbaryl produced slight
temporary eye irritation which cleared in 2 to 3 days
(Cranmer, 1986).
9.4.10 Haematological
In in vitro studies, hypo or hyper
coagulation were reported (Krug et al., 1988).
Carbaryl produces oxidative stress to G-6-PD deficient
red blood cells.
It produced a decrease in the level of haemoglobin,
red blood cells and platelets (Calabrese & Geiger,
1986).
9.4.11 Immunological
Carbaryl inhibited the inter leukin 2 mediated
proliferation of mouse CTLL2 cells, and resulted in
proliferation and enhancement of natural killer cells
(Gasale et al., 1993).
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
Carbaryl can produce metabolic
acidosis in severe intoxication.
9.4.12.2 Fluid & electrolyte disturbances
No data
9.4.12.3 Others
No data available.
9.4.13 Allergic reactions
Generally not associated with skin rashes or
allergic skin reactions (WHO, 1994).
9.4.14 Other clinical effects
The intermediate syndrome of delayed
peripheral nerve toxicity has been reported similar to
organophosphates.
9.4.15 Special risks
No data available.
9.5 Others
No data available.
9.6 Summary
10. MANAGEMENT
10.1 General principles
Specific treatment is the use of atropine
intramuscularly or intravenously 0.5 to 2 mg every 15 minutes
(0,01 to 0.05 mg/kg for children) until symptoms are
reversed. It is important to maintain airways potency.
Pralidoxime should not be used unless there is evidence of
nicotinic toxicity without muscarinic effects.
Administer activated charcoal. Do not induce emesis because
of the risk of sudden seizures, coma, or respiratory
depression. Gastric lavage is probably not necessary
following small ingestions if activated charcoal is given
promptly (Olson, 1994).
Closely observe the patient during the early stages of
treatment, the principle concerns being those of convulsion,
coma or respiratory distress.
10.2 Life supportive procedures
Airway, breathing, and circulation should be evaluated
and supported as necessary.
Artificial ventilation via endotracheal intubation may be
required for severe respiratory distress (WHO, 1994).
10.3 Decontamination
Skin and eyes: remove all contaminated clothing and
wash exposed skin copiously with soap and water, including
hair and under nails. Irrigate exposed eyes with copious
water or saline (Olson, 1994).
Ingestion: administer activated charcoal. Do not induce
emesis because of the risk of sudden seizures, coma, or
respiratory depression. Gastric lavage is probably not
necessary following small ingestions if activated charcoal is
given promptly (Olson, 1994).
10.4 Enhanced elimination
Dialysis and hemoperfusion are not indicated because
the duration of toxicity is brief and effective antidotal
therapy available (Olson, 1994).
10.5 Antidote treatment
10.5.1 Adults
Atropine is recommended for the treatment of
carbaryl poisoning, starting with 0,5 to 2 mg
intravenously (IV) repeated every 15 minutes until
symptoms (especially pulmonary) resolve, or there is
evidence of atropine toxicity (dilated pupils, skin
flushing, dry mouth) (WHO, 1994).
Diazepam has been recommended for treating anxiety,
and is suggested to improve other CNS symptoms (WHO,
1994).
Pralidoxime should not be used unless there is
isolated evidence of severe nicotinic
symptoms.
10.5.2 Children
Atropine dose is 0,01 to 0.05 mg/kg every 15
minutes (Olson, 1994).
10.6 Management discussion
Not relevant.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
A 23 year old man ingested 500 mg/kg of carbaryl (the
approximate LD50 in rats) and survived, but developed a
severe delayed peripheral neuropathy (Dickoff et al.,
1987).
Death due to respiratory failure was reported after ingestion
of an unknown amount of carbaryl in an adult (Sargin et al.,
1992).
A drunken 39 year old man swallowed approximately 500 mL of
an 80% solution of carbaryl. When he was hospitalized 1.5
hours later he was confused but still able to answer
questions. Gastric lavage was performed and drugs to
stimulate circulation were administered. However, the patient
became worse; he complained of disturbance of vision and
developed pulmonary oedema. Atropine was given intravenously
and intramuscularly at half hours intervals for a total dose
of 6 mg. A slight amelioration occured, buttere was no sign
of full atropinization. Three hours after ingestion, 250 mg
of 2-PAM were administered. Thereafter, pulmonary oedema
progressed rapidly and the patient died six hours later after
ingestion (Farago, 1969).
A nineteen months old child developed miosis, salivation and
muscular incoordination in spite of gastric lavage within
half an hour after ingestion of carbaryl. The dose was not
known but the symptoms were promptly relieved by 0.3 mg of
atropine and recovery apparently was complete in 12 hours
(Best & Murray, 1962).
12. ADDITIONAL INFORMATION
12.1 Specific preventive measures
No data available.
12.2 Other
No data available.
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14. AUTHOR(S), REVIEWER(S), DATES
Authors: Amal Mutawai
School of Pharmacy. University of Otago
Box 913
Dunedin. New Zealand
Dr Wayne A Temple
National Toxicology Group. University of Otago
Box 913
Dunedin. New Zealand
Phone: 64-3-4797244
Fax: 64-3-4770509
E-mail: wtemple@gandalf.otago.ac.nz
Dr Nerida A Smith
School of Pharmacy. University of Otago
Box 913
Dunedin. New Zealand
Phone: 64-3-4797239
Fax: 64-3-4770509
E-mail: nerida.smith@stonebow.otago.ac.nz
Date: 11 December 1996
Reviewer: MO Rambourg Schepens
Centre Anti-Poisons de Champagne Ardenne
Centre Hospitalier Universitaire
F-51092 Reims cedex France
E-mail: marie-odile.rambourg@wanadoo.fr
Date: July 1997
Peer review: INTOX-10 Meeting, Rio, Brazil, September, 1997 (Drs
M Kowalczyk, L Lubomirov, R McKeown, P Rosen, W Watson)
Finalization/Edition: MO Rambourg Schepens. M Ruse (IPCS,
Geneva)
Date: October 1997