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Carbaryl. Caroline Cox. Journal of Pesticide Reform, Volume 13, Number 1, Spring 1993. Northwest Coalition for Alternatives to Pesticides, Eugene, OR.


Carbaryl

By Caroline Cox

Many pesticides have gained their notoriety because of a 
particular human or environmental health problem. The 
organochlorine insecticide DDT, for example, is well known 
because of its ability to bioconcentrate in carnivorous 
animals,1 and the fumigant dibromodichloropropane (DBCP) made 
headlines when it caused sterility in men who worked with 
it.2 The insecticide carbaryl, however, is striking because 
its use has been associated with such a large number of 
health problems. From acute toxicity, suppression of immune 
system functions, and behavioral pro-blems to cancer, genetic 
damage, and reproductive problems in both males and females, 
carbaryl's adverse effects span an enormous range.

Carbaryl (1-naphthyl methyl carbamate) is one of the three 
most commonly used insecticides in the United States with an 
estimated annual use of between 10 and 15 million pounds.3 
(See Figure 2 for agriculture use by state.) It is a broad-
spectrum insecticide and is registered for use on more than 
100 different crops, animals, ornamental plants, and indoor 
areas.4 Carbaryl is also sometimes used as a chemical 
thinning agent for apples.5,6  It has been registered in the 
U.S. since 1958.4 Previously manufactured by Union Carbide,7 
the primary U.S. manufacturer is now Rhone Poulenc 
Agricultural Company; many of its carbaryl-containing 
products are marketed under the brand name Sevin.8 

Mode of Action

Carbaryl is a carbamate insecticide. Like all members of this 
chemical family, it inhibits the action of an enzyme that is 
an essential component of insect, fish, bird, and mammal 
nervous systems. The enzyme, acetyl cholinesterase (AChE), 
controls the chemical reaction that transforms acetylcholine 
into choline after acetylcholine has been used to transmit 
nerve impulses across the junctions between nerves. Without 
functioning AChE, acetylcholine accumulates and prevents the 
smooth transmission of nerve impulses.9 This causes loss of 
normal muscle control, and ultimately death. The AChE 
inhibition is said to be reversible because the carbaryl 
disassociates from the AChE within several hours. This 
happens even if death has already occurred. Insecticides in 
the organophosphate family (malathion and diazinon, for 
example) also inhibit AChE, but the inhibition is not as 
readily reversible.10

Carbaryl can also affect a number of other enzyme systems in 
living things. For example, the carboxylesterases 
(detoxification enzymes),11 lactic dehydrogenase (enzymes 
that utilize sugar),12 and serine esterases (enzymes 
important to the function of certain immune system 
components)13 are all inhibited by carbaryl.

Acute and Subchronic Toxicity

Symptoms of acute carbaryl exposure in humans are malaise, 
muscle weakness, dizziness, sweating, headache, salivation, 
nausea, diarrhea, incoordination, and slurred speech. 
Depression of breathing ability combined with an excess of 
fluid in the lungs (pulmonary edema) is the usual cause of 
death when exposure is high.10 

Carbaryl's acute oral LD50 (the dose that causes death in 50 
percent of a population of test animals) in rats is 255 
milligrams per kilogram (mg/kg) of body weight.5 Extrapolated 
to the weight of an average 70 kilogram (154 pound) human who 
is assumed to be as sensitive to carbaryl as are rats, this 
means that a dose of about 18 grams or two-thirds of an ounce 
would be fatal. 

Lower doses of carbaryl over a longer period of time cause a 
variety of adverse effects. In humans, ingestion of 0.13 
mg/kg/day (less than a thousandth of the LD50) caused 
abdominal cramps and a decrease in the ability of the kidneys 
to resorb amino acids.14 In rats, decreases in weight and 
body temperature occurred following single injections of 
doses of less than one-twentieth of the LD50.15 Similar doses 
given for two years caused kidney abnormalities in rats as 
well as dogs.16 In addition, drinking water contaminated with 
10 parts per million (ppm) of carbaryl caused liver 
pathologies and reduced blood clotting activity in rats17 and 
single sublethal doses in rabbits reduced their heart rate 
and caused changes in their electrocardiograms.18 

Behavioral and           Neurological Effects

Given that carbaryl's primary mode of action disturbs the 
nervous system, it is not surprising that researchers have 
measured a variety of neurological and behavioral effects of 
carbaryl exposure. Case reports of human exposures tell some 
compelling stories. For example, a professor of medicine at a 
New England university reported that his twice daily 
applications of a commercial tick powder with active 
ingredient carbaryl to his cat had dramatic effects on the 
cat's personality. The pet, who had never been much of a 
hunter, began attacking large numbers of birds and mice. The 
professor's personality underwent a parallel change (in spite 
of the gloves and mask he wore while dusting the cat) and he 
was described as being in a "continual rage." Ending the tick 
powder treatments brought an end to the aggressive behavior 
in both doctor and cat within a week.19 Two other reports 
describe patients with a neurological condition called 
delayed peripheral neuropathy following carbaryl exposure. 
This condition, normally associated with certain 
organophosphates and not carbamates like carbaryl, causes 
nerve degeneration and paralysis of arms or legs several 
weeks after exposure.20 One of the patients had been exposed 
through ingestion of a relatively large quantity of carbaryl-
containing insecticide.21 The other patient was exposed when 
his basement was treated for fleas with a carbaryl-containing 
dust.22 

Carbaryl exposure has also caused behavioral and neurological 
problems in studies of laboratory animals. In rats, single 
doses of ten mg/kg (less than one-twentieth of the LD50) or 
less caused decreases in the responses to a battery of 
behavioral tests,15,23 increased tolerance for electrical 
shock, and decreased desire to drink water.24 Smaller doses 
given for two weeks slowed the speed that rats were able to 
run a maze and increased the number of errors that they 
made.25 Single sublethal injections of carbaryl reduced the 
success of monkeys in performing a learning task.26 In pigs, 
long-term (over 70 days) feeding of sublethal carbaryl doses 
caused incoordination of movements followed by extensive 
degeneration of nerves in the brain and muscles.27 

Effects on the Immune System

Carbaryl's ability to decrease the effectiveness of the 
immune system has been documented in a variety of laboratory 
studies. A review of some of the immune system literature 
published during the 1960s and 1970s cited seven studies that 
found adverse effects of carbaryl in immune system function 
of rats and rabbits;28 a second review identified three more 
studies.29 The studies measured decreases in the cellular 
activity of the immune system, a reduction in the resistance 
to infection by certain diseases, a decrease in antibody 
development, and a decrease in the size of a part of the 
spleen important in immune system function. Doses were well 
below lethal toxic doses. 

More recent studies show similar results. Rats fed carbaryl 
at doses as low as 1/100 of the LD50 and then infected with a 
bacteria had a mortality rate almost twice as high as 
unexposed rats.30 In goldfish cell cultures, synthesis of the 
immunologically important compound interferon was reduced, 
leading to enhanced replication of a virus.31,32 In mice cell 
cultures, carbaryl inhibited enzymes that were essential to 
proper functioning of macrophages, the cells that engulf and 
consume foreign bodies.33 Finally, at doses too low to cause 
inhibition of AChE, carbaryl exposure of human cell cultures 
reduced proliferation of immune system cells called large 
granular lymphocytes. This was caused by effects on another 
immunologically important compound, interleukin. These 
lymphocytes "contribute significantly to protection against 
tumor cell growth and infections,"34 so their suppression can 
have significant consequences. Taken together, the studies 
suggest striking effects of carbaryl on proper immune system 
function.

Effects on Reproduction

Ever since the late 1960s, when two researchers showed that 
female beagle dogs fed carbaryl had more stillbirths and 
infant deaths, decreased litter size, smaller pups, and more 
pups with birth defects than did unexposed mothers,35 
carbaryl's reproductive hazards have been of concern.29 
Adverse effects in the beagle study were found at doses 
approximately 1/50 of the LD50. Studies since that time have 
demonstrated that carbaryl can affect reproduction in a 
variety of species and in both sexes.

Males: Two studies at a carbaryl manufacturing facility have 
shown that carbaryl exposure affects the quantity and quality 
of sperm produced by the workers. One study found that more 
exposed workers had very low sperm counts than in a control 
group of unexposed workers.36 This result was significant 
based on one statistical test, but has been criticized 
because a second statistical test only "closely approached 
significance." A second study of the same sperm samples found 
that the number of sperm abnormalities was increased in 
workers who were being exposed to carbaryl while the study 
took place.37 

Studies of laboratory animals have shown similar effects. A 
1980 U.S. Environmental Protection Agency (EPA) review cited 
four studies (three in rats, one in another rodent) showing 
decreases in sperm numbers, an increase in sperm 
abnormalities, and a decrease in sperm mobility caused by 
carbaryl exposure.38 A 1986 review cited three other studies 
of rats with similar results.29 Some of these studies found 
effects at low doses. For example, 7 mg/kg per day (about 
1/35 of the LD50) given over a period of nine months  reduced 
sperm mobility and  the  numbers of sperm-forming cells.39

Females: Female laboratory animals of a number of species fed 
carbaryl suffer from reproductive problems. A 1986 review 
summarized 25 studies that had found reproductive problems 
caused by carbaryl in eight different kinds of animals. These 
problems included reduced fertility, increased fetal 
mortality, low birth weights, reduced growth and survival of 
babies, and birth defects.29 Some effects occur at 
surprisingly low doses. For example, rats fed carbaryl in 
doses equivalent to 1/35 of the LD50 for one year had estrous 
cycles significantly longer than unexposed control rats39 and 
pregnant monkeys given daily doses as low as 1/100 of the 
acute lethal dose had increased rates of spontaneous 
abortions.40 

The most recent laboratory study of reproductive effects that 
NCAP has found (1991) shows a variety of reproductive 
hazards.41 Rats exposed to carbaryl had smaller litters, 
smaller babies, and more resorbed fetuses than unexposed 
rats. (See Figure 4.) These results were found  in mice 
receiving a single carbaryl dose during pregnancy, as well as 
in those exposed for most of the pregnancy. The study also 
found an increased frequency of birth defects, including eye, 
kidney, and skeletal abnormalities, in the fetuses of 
carbaryl-treated mothers.

Carcinogenicity

Several recent epidemiology studies have associated exposure 
to agricultural and household use of carbaryl with an 
increased risk of cancer in humans. Farmers in Minnesota and 
Iowa who had ever handled carbaryl had an increased risk of 
non-Hodgkin's lymphoma; this increased risk was statistically 
significant for those farmers who had handled the chemical 
prior to 1965 (with a risk almost four times as high as that 
of unexposed Minnesota and Iowa residents) or had handled 
carbaryl without using protective clothing (with a risk about 
double that of unexposed Minnesotans and Iowans).42 A similar 
elevated risk associated with exposure to carbamate 
insecticides as a group was found in a study of Nebraska 
farmers.43 Exposure to carbaryl used in gardens or backyard 
orchards in Missouri is associated with an increased risk 
(2.5-fold) of childhood brain cancer.44 

Some of the concerns about carbaryl's carcinogenicity come 
from the carcinogenicity of nitrosocarbaryl, a compound that 
forms when carbaryl is combined with certain nitrogen-
containing compounds (sodium nitrite, for example). 
Nitrosocarbaryl belongs to a family of compounds called N-
nitrosamines of which 70 percent have been found to be 
carcinogenic in laboratory tests.45 Nitrosocarbaryl has been 
shown to form in the stomach of guinea pigs (animals whose 
stomachs are as acid as human stomachs) when the guinea pigs 
are given carbaryl and sodium nitrite.46 Nitrosocarbaryl 
causes skin cancers when painted on the skin of mice47 and 
cancers of the forestomach in rats.48,49 

At least fifteen laboratory studies have been done of 
carbaryl's carcinogenicity.29,50,51 Three of these studies 
showed that carbaryl exposure caused an increase in cancer 
incidence: a 1970 study of rats,52 a 1982 study of carbaryl's 
ability to enhance lung tumor formation in mice by the 
carcinogen benzo[a]pyrene,51 and a 1992 study of carbaryl's 
ability to initiate tumors when painted on the skin of 
mice.50 The other studies found no relationship between 
carbaryl exposure and cancer incidence. 

There are a number of reasons why epidemiology and laboratory 
studies give conflicting results. First, none of the 
laboratory studies meets current standards29,53 and properly 
done studies may show significant results. Second, all of the 
laboratory studies used technical grade carbaryl while humans 
in epidemiology studies are exposed to commercial carbaryl 
products which contain a variety of other ingredients in 
addition to carbaryl. (See "Secret 'Inert' Ingredients," 
below) Some of these may be carcinogenic. Third, humans are 
exposed to mixtures of chemicals rather than the single 
chemicals used in laboratory tests. Given the studies showing 
that carbaryl can enhance or initiate cancers caused by other 
compounds, it may be combinations of chemicals that are 
important. Finally, humans may be more sensitive to carbaryl 
than are laboratory animals. For example, human stomachs are  
more acid than rat stomachs, and therefore are more likely to 
promote the formation of nitrosocarbaryl.46 

Mutagenicity

Carbaryl's potential to cause genetic damage (mutagenicity) 
has been called "weak" by EPA.4 The mutagenicity tests 
performed with carbaryl, however, provide a different 
picture. In human cells, carbaryl causes abnormal synthesis 
of DNA (the molecules from which genes are made).54 In 
Chinese hamster cells, carbaryl exposure caused sister 
chromatid exchanges (SCE; exchanges of genetic material 
within a pair of chromosomes),55 chromosomal aberrations,53 
and abnormal cell division.56,57 In a newt, carbaryl exposure 
caused broken DNA in red blood cells.58 Carbaryl has also 
caused an increase in the frequency of lethal mutations in  
fruitflies,59,60 mutations or DNA damage in two species of 
bacteria,61,62 and chromosome aberrations or mutations in two 
species of plants (onions and corn).63,64 

Several derivatives of carbaryl also are known to be 
mutagenic. 1-naphthol, the primary breakdown product of 
carbaryl, caused abnormal mitosis in Chinese hamster cells 
and DNA breakage when combined with naturally occurring 
hypochlorous acid in human cells.65 Nitrosocarbaryl (see 
"Carcinogenicity," above, and Figure 5) was found to be a 
more potent mutation agent than several other nitrosamines in 
three bacteria cultures66,67 and is a "potent" agent causing 
breakage of chromosomes and SCEs in  hamster cells.68

Human Exposure

 People are exposed to carbaryl through using the insecticide 
in homes and gardens, consuming residues on food, drinking 
contaminated water, being contaminated due to drift from 
nearby applications, and working with carbaryl. Detailed 
information about these effects will be published in the next 
issue of JPR (13(2); Summer 1993).

Effects on Nontarget Species

A wide variety of animals, plants, and bacteria are adversely 
affected by carbaryl. Not only acute toxicity, but many 
different kinds of chronic effects have been documented in 
bees, beneficial insects, fish, birds, earthworms, frogs, 
crop plants, nitrogen-fixing bacteria, and other species. 
Some effects occur at surprisingly low doses. Detailed 
information about these effects will be published in the next 
issue of JPR (Summer 1993).

Synergy

The anti-ulcer drug Tagamet (cimetidine) has been shown to 
inhibit the breakdown of carbaryl in both laboratory animals 
and humans.69 This means that people exposed to both 
cimetidine and carbaryl will have longer and more pronounced 
symptoms. For example, a man who was exposed to six home 
treatments of a carbaryl-containing insecticide and who was 
also taking cimetidine suffered from headaches, memory loss, 
muscle weakness and cramps, anorexia, weight loss, and sleep 
apnea for a seven month period. Some neurological symptoms 
persisted for over a year.22 The acute and chronic toxicity 
of niridazole, a drug used to treat schistosomiasis, is also 
enhanced by carbaryl exposure.70

The common insecticide synergist piperonyl butoxide increases 
carbaryl toxicity. In fish, acute toxicity of a carbaryl-
piperonyl butoxide mixture was over 100 times that of 
carbaryl alone.71 In addition, carbaryl increases the acute 
toxicity of the phenoxy herbicide 2,4-D, the insecticides 
rotenone (a botanical) and dieldrin (an organochlorine) as 
well as the wood preservative pentachlorophenol.72 Sublethal 
effects of the organophosphate insecticide phenthoate are 
also synergized by carbaryl in fish, including AChE 
inhibition73 and both morphological and behavioral changes.74 
While the toxicity of combinations of chemicals is rarely 
studied, the ability of carbaryl to interact with a large 
number of chemical classes is striking.

Manufacturing

One of the intermediaries used in the manufacture of carbaryl 
is the highly reactive compound methyl isocyanate (MIC).9 On 
December 3, 1984 a toxic cloud containing MIC and other 
reaction products escaped from a tank in a Union Carbide 
plant in Bhopal, India that manufactured carbaryl and 
aldicarb (another carbamate insecticide).75 Between 2500 and 
5000 people died as a result of the accident, and up to 
200,000 people were injured. Injuries included respiratory 
problems, eye damage, fetal and newborn deaths, suppression 
of the immune system, and changes in blood chemistry.76 A 
smaller, but similar accident occurred the following year at 
Union Carbide's aldicarb and carbaryl plant in Institute, 
West Virginia and 135 people were hospitalized.75

Secret "Inert" Ingredients

Most carbaryl-containing pesticide products contain "inert" 
ingredients whose identity EPA and the pesticide industry 
claim are trade secrets. There is little publicly available 
information about most of these "inerts." Some carbaryl 
formulations contain crystalline silica as an "inert" and 
others contain petroleum oils.77 EPA has listed petroleum 
hydrocarbons as an inert with high priority for testing 
because some petroleum products are suspected or known 
carcinogens.78 

Crystalline silica causes the chronic lung disease 
silicosis79 and the International Agency for Research on 
Cancer has classified crystalline silica as having "limited 
evidence of carcinogenicity in humans" and "sufficient 
evidence of carcinogenicity" in animals.80 Silica was 
responsible for what has been called "America's worst 
industrial disaster" during the 1930s when over 700 workers 
died of silicosis after working on a tunneling project for 
Union Carbide in West Virginia.81

Other "inerts" in carbaryl formulations also pose 
toxicological problems. For example, exposure of prawns to 
sublethal concentrations of a commercial formulation of 
carbaryl caused more AChE inhibition than did exposure to 
carbaryl alone. The researchers believe that the emulsifier 
in the commercial formulation is responsible for the enhanced 
toxicity.82 

Summary

Carbaryl is a neurotoxic carbamate insecticide. In humans, 
acute effects of carbaryl exposure include headaches, nausea, 
incoordination, and difficulty breathing. Carbaryl can cause 
a variety of behavioral effects, some of which are relatively 
long-term. It also suppresses several functions of the immune 
system. Men exposed to carbaryl have more abnormal sperm and 
lower sperm counts than unexposed men. In female laboratory 
animals, exposure to carbaryl has caused a variety of 
reproductive problems, including birth defects in beagle dogs 
and increased rate of miscarriages in monkeys. Exposure to 
carbaryl has been associated with a higher incidence of the 
cancer non-Hodgkin's lymphoma in farmers and brain cancer in 
children. Nitrosocarbaryl, formed when carbaryl and nitrites 
react, is a potent carcinogen. Both carbaryl and 
nitrosocarbaryl cause genetic damage in some test systems, as 
does carbaryl's primary breakdown product, 1-naphthol. 

Carbaryl acts synergistically with a number of other 
insecticides and herbicides. An enormous industrial accident 
occurred at a carbaryl-manufacturing plant in Bhopal, India 
and other such plants have had significant accidents. Secret 
ingredients in carbaryl formulations include petroleum oils 
and crystalline silica, associated with the lung disease 
silicosis and cancer.   n

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