Human Health Effects:
Toxicity Summary:
Food represents the major source of carbaryl intake for the general population. ... The general population can be exposed to carbaryl during pest control operations in both the home & recreation areas. Workers can be exposed to carbaryl during its manufacture, formulation, packing, transportation, storage, & during & after application. ... Significant dermal exposure may occur in industrial & agricultural workers if protective measures are inadequate. Carbaryl is rapidly absorbed in the lungs & digestive tract. ... The principal metabolic pathways of carbaryl are ring hydroxylation & hydrolysis. As a result, numerous metabolites are formed & subjected to conjugation with the formation of water-soluble sulfates, glucuronides, & mercapturates, excreted in the urine. Hydrolysis results in the formation of 1-naphthol, carbon dioxide & methylamine. Hydroxylation produces 4-hydroxycarbaryl, 5-hydroxycarbaryl, N-hydroxymethylcarbaryl, 5-6-dihydro-5-6-dihydroxycarbaryl & 1,4-naphthalendiol. The principal metabolite in humans is 1-naphthol. Under normal exposure conditions, the accumulation of carbaryl in animals is unlikely. Carbaryl is excreted primarily via the urine, since the product of its hydrolysis, 1-naphthol, is mainly detoxified to water-soluble conjugates. Enterohepatic cycling of carbaryl metabolites is also considerable, especially after oral administration. ... Carbaryl metabolites are also present in a small percentage of the absorbed doses in saliva & milk. ... The acute toxicity for birds is low. ... Carbaryl is very toxic for honey-bees & earthworms. ... The acute toxicity ... varies considerably according to species, formulation & vehicle. ... Carbaryl is a mild eye irritant & has little or no sensitizing potential. ... Carbaryl has a low cumulative potential. Carbaryl has been shown to affect mammalian reproduction & perinatal development adversely in a number of species. Effects on reproduction include impairment of fertility, decreased litter size, & reduced postnatal viability. Developmental toxicity is seen as increased in utero death, reduced fetal weight, & the occurrence of malformation. With the exception of a small number of studies, all adverse reproductive & developmental effects were noted only at doses that caused overt maternal toxicity, &, in a number of cases, the maternal animal was more sensitive to carbaryl than the conceptus. The maternal toxic effects included lethality, decreased growth, & dystocia. ...The available evidence indicates that carbaryl does not have any DNA-damaging properties. ... Negative results were obtained in tests for gene mutations in a large number of bacterial assays ... The available database does not support the presumption that carbaryl poses a risk of inducing genetic changes in ... humans. Carbaryl has been studied for its carcinogenic potential in numerous studies on rats & mice. The results of most of these studies were negative ... The effects of carbaryl on the nervous system are primarily related to cholinesterase inhibition & are usually transitory. ... Carbaryl has been reported to affect coagulation ... Carbaryl binds free blood amino acids. Disturbances have been reported in the carbohydrate metabolism & protein synthesis & detoxification function of the liver in mammals. Carbaryl is a weak inducer of hepatic microsomal drug-metabolizing activity. ... Carbaryl has been reported to incr the gonadotropic function of the hypophysis of rats. Carbaryl is an inhibitor of cholinesterase activity. This effect is dose-related & quickly reversible. ... All identified metabolites of carbaryl are appreciably less active cholinesterase inhibitors than carbaryl itself. Carbaryl is easily absorbed /in humans/ through inhalation & via the oral route & less readily by the dermal route. Since the inhibition of cholinesterase is the principal mechanism of carbaryl action, the clinical picture of intoxication is dominated by ... symptoms, such as: increased bronchial secretion, excessive sweating, salivation, & lacrimation; pinpoint pupils, bronchoconstriction, abdominal cramps (vomiting & diarrhea); bradycardia; fasciculation of fine muscles (in severe cases, diaphragm & respiratory muscles also involved); tachycardia; headache, dizziness, anxiety, mental confusion, convulsions, & coma; & depression of the respiratory center. Signs of intoxication develop quickly after absorption & disappear rapidly after exposure ends.... In cases of occupational overexposure to carbaryl, mild symptoms are observed long before a dangerous dose is absorbed, which is why severe cases of occupational intoxication with carbaryl are rare. During agricultural application, dermal exposure may play an important role. ... The appearance of a skin rash after accidental splashing with carbaryl formulations has been described. ... The most sensitive biological indicator of carbaryl exposure is the appearance of 1-naphthol in the urine & the decr of cholinesterase activity in the blood. ... The hazards of carbaryl for human beings are judged to be low, because of its low vapor pressure, rapid degradation , rapid spontaneous recovery of inhibited cholinesterase, & the fact that symptoms usually appear well before a dangerous dose has accumulated in the body. ...
Evidence for Carcinogenicity:
No data are available in humans. Inadequate evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 3: The agent is not classifiable as to its carcinogenicity to humans.
A4; Not classifiable as a human carcinogen.
Human Toxicity Excerpts:
MALE VOLUNTEERS WHO CONSUMED DOSES UP TO 0.13 MG/KG/DAY FOR 6 WK HAD NO SUBJECTIVE EFFECTS THAT COULD BE RELATED TO CARBARYL, ALTHOUGH THEY EXHIBITED SLIGHT, TRANSIENT DECR IN THEIR ABILITY TO REABSORB AMINO ACIDS.
INHIBITION OF MITOSIS & SPINDLE FIBER FORMATION HAS ... BEEN REPORTED IN CULTURED HUMAN EMBRYONIC FIBROBLASTS. AFTER TREATMENT WITH 20-80 UG/ML OF A TECHNICAL PRODUCT CONTAINING 84% CARBARYL.
SYMPTOMATOLOGY: Except for diminished intensity and duration, particularly of the central nervous signs and symptoms, carbamate poisoning resembles parathion intoxication in its clinical manifestations. 1. Nausea, vomiting, abdominal cramps, diarrhea, and excessive salivation (sialorrhea) and sweating. 2. Lassitude and weakness. 3. Rhinorrhea and a sensation of tightness in the chest may occur with respiratory exposures. 4. Blurring or dimness of vision, miosis (with fixed pinpoint pupils), tearing, ciliary muscle spasm, loss of accommodation, and ocular pain. None of these eye signs, however, is dependable for diagnosis. Mydriasis may be seen secondary to sympathoadrenal discharge. 5. Loss of muscle coordination, slurring of speech, fasciculations and twitching of muscles. 6. Difficulty in breathing, excessive secretions of saliva and of respiratory tract mucus, oronasal frothing, cyanosis, pulmonary rales and rhonchi, and hypertension (presumably due to asphyxia). 7. Random jerky movements, incontinence, convulsions, and coma. 8. Death primarily due to respiratory arrest of central origin, paralysis of the respiratory muscles, intense bronchoconstriction, or all three.
... Epidemiological studies have not demonstrated delayed neurotoxic effects, dysmorphic sperm, or viral enhancement in humans exposed to carbaryl.
Male human volunteers were given daily po doses of either 0.06 or 0.12 mg/kg of carbaryl. After six weeks of exposure, no EEG changes were found attributable to carbaryl exposure.
The observation of neurotoxicity in a subject with long-term exposure to high levels of carbaryl has prompted the review of the potential for carbaryl to cause toxicity. The information available about carbaryl's disposition in humans is inadequate to interpret the relevance of animal studies to humans. Published information on the effects of long-term exposure to carbaryl in humans is limited and has not identified any adverse effects. It is concluded that not enough information is available to exclude the possibility that sustained high levels of exposure to carbaryl could be associated with neurotoxic or myotoxic responses in humans.
Carbaryl, a widely used insecticide, is reputed to have a wide safety margin. It can induce acute cholinesterase poisoning, which is rapidly reversible on discontinuation of exposure. Long-term sequelae from long-term exposure have not previously been described in humans. This report describes the experience of a 75-year-old man who had long-term excessive exposure to carbaryl and in whom a debilitating syndrome, including headaches, memory loss, proximal muscle weakness, muscle fasciculation, muscle cramps, and anorexia with marked weight loss developed. At the time of diagnosis, serum pseudocholinesterase levels were low, and his major symptoms resolved on termination of exposure. Late clinical features were sleep apnea and progressive development of a periheral neuropathy. The difficulty in diagnosing the cause of a group of relatively nonspecific symptoms raises the question of whether chronic carbaryl neurotoxicity might be occurring more frequently than previously suspected.
A SINGLE ORAL DOSE OF 250 MG (ABOUT 2.8 MG/KG) CARBARYL PRODUCED MODERATE ILLNESS IN A MAN.
Carbaryl ... appears to have caused no eye disturbance except in one case of suicidal poisoning in which disturbance of vision was complained of but not explained. ... Splash contact of an insecticide liquid containing both carbaryl & dimethoate in one patient on two different occasions caused transient injury of the corneal epithelium & much swelling of the lids, but recovery was rapid & complete. This suggests that carbaryl is not particularly dangerous to the eye.
A patient ingested 21 g (500 mg/kg) of carbaryl (1-naphthyl N-methylcarbamate. After he recovered from acute cholinergic toxicity, acute weakness of arms and legs was accompanied by electrophysiologic findings consistent with axonal peripheral neuropathy. Recovery began at 1 week and continued for 9 months. A similar delayed neuropathy has been described with organophosphates.
Carbamate insecticides and herbicides were tested for their ability to affect human blood platelet aggregation and arachidonic acid metabolism in platelets. The herbicides of the carbamate type have no, or only little, influence up to a concentration of 100 uM; the carbamate insecticides, however, inhibit both aggregation and arachidonic acid metabolism in a dose- and time-dependent manner. Carbaryl, the most effective compound, inhibits platelet aggregation and cyclooxygenase activity completely at 10 uM. The liberation of arachidonic acid from phospholipids and the lipoxygenase pathway are not affected, whereas the products of the cyclooxygenase pathway are drastically decreased. By using (14)C-carbaryl labelled in the carbamyl or in the ring moiety, it was shown that the carbamyl residue binds covalently to platelet proteins. In contrast with acetylsalicylic acid, which acetylates only one protein, carbaryl carbamylates a multitude of platelet proteins. One of the carbamylated proteins was found to be the platelet cyclooxygenase, indicating that carbaryl resembles in this respect acetylsalicylic acid, which is known to inhibit this enzyme specifically by acetylation.
The usual symptoms include headache, giddiness, nervousness, blurred vision, weakness, nausea, cramps, diarrhea, and discomfort in the chest. Signs include sweating, miosis, tearing, salivation and other excessive respiratory tract secretion, vomiting, cyanosis, papilledema, uncontrollable muscle twitches followed by muscular weakness, convulsions, coma, loss of reflexes, and loss of sphincter control. The last four signs are seen only in severe cases but do not preclude a favorable outcome if treatment is prompt and energetic. Cardiac arrhythmias, various degrees of heart block, and cardiac arrest may occur ... /Organic phosphorus pesticides/
Skin, Eye and Respiratory Irritations:
Irritating to skin & eyes.
Medical Surveillance:
Initial Medical Examination: A complete history and physical examination: The purpose is to detect pre existing conditions that might place the exposed employee at increased risk, and to establish a baseline for future health monitoring. Examination of the respiratory system, cardiovascular system, and central nervous system should be stressed. The skin should be examined for evidence of chronic disorders. Urinalysis: Carbaryl may cause kidney damage. A urinalysis should be performed to include, at a minimum, specific gravity, albumin, glucose, and a microscopic /examination/ of centrifuged sediment. Medical warning: Exposure should be minimized during pregnancy. Periodic Medical Examination: The aforementioned medical examinations should be repeated on an annual basis.
Intact carbaryl is not routinely measured in human blood. ... Exposure to anticholinesterase agents such as carbaryl is frequently monitored by determination of blood cholinesterase activity. A preexposure cholinesterase level should be obtained for each employee so that the postexposure level may be expressed as a percentage of that subject's normal cholinesterase activity. A postexposure blood cholinesterase level that is less than 70% of normal is considered indicative of excessive exposure to carbaryl.
Carbaryl is known to be metabolized by N-demethylation, ring hydroxylation, hydrolysis & conjugation. The hydrolysis pathway results in the urinary excretion of free & conjugated 1-naphthol, which accounts for over 20% of an ingested dose & which may be measured as an index of exposure to the chemical. Another 4% of a dose is excreted as conjugated p-hydroxycarbamyl. Urine concn of 1-naphthol in unexposed subjects avg less than 0.01 mg/l & do not exceed 0.23 mg/l. Exposed but asymptomatic workers exhibited 1-naphthol urine concn of less than 0.1 to more than 42 mg/l; air concn of carbaryl during these exposures ranged from 0.2 to 31 mg/cu m. In another study of formulating plant workers, asymptomatic individuals excreted 1-naphthol in urine at concn of 0.2 to 65 mg/l, avg 8.9 mg/l. ... Although standards have not been developed for carbaryl metabolites in urine, it is probable that urinary 1-naphthol concentrations in excess of 4 mg/l represent significant exposure to carbaryl.
Whole Blood Reference Ranges: Normal - not established; Exposed - not established; Toxic - not established. Serum or Plasma Reference ranges: Normal - not established; Exposed - not established; Toxic - not established. Urine Reference Ranges: Normal - not established; Exposed - not established; toxic - not established. /Carbamate pesticides/
Respiratoty Symptom Questionnaires: Questionnaires have been published by the American Thoracic Society (ATS) and the British Medical Research Council. These questionnaires have been found to be usead in identiEcation of people with chronic bronchitis, however certain pulmonary function tests such as FEV1 (see pulmonary function test section) have been found to be better predictors of chronic airflow obstruction. /Carbamate pesticides/
Chest Radiography: This test is widely used for assessing pulmonary disease. Chest radiographs have been found to be useful for detection of early lung cancer in asymptomatic people, especially for detection of peripheral tumors such as adenocarcinomas. However, even though OSHA mandates this test for exposure to some toxicants such as asbestos, there are conflicting views on its efficacy in detection of pulmonary disease. /Carbamate pesticides/
Pulmonary Function Tests: The tests that have been found to be practical for population monitoring include: Spirometry and expiratory flow-volume curves; Determination of lung volumes; Diffusing capacity for carbon monoxide; Single-breath nitrogen washout; inhalation challenge tests; Serial measurements of peak expiratory flow; Exercise testing. /Carbamate pesticides/
Sputum Cytology: Sputum cytology along with chest radiographs have been the standard procedures for detecting early lung cancer in asymptomatic patients. Sputum cytology has been found to be useful for detection of central tumors, especially squamous carcinomas. For this test to be effective. exfoliated respiratory mucosal cells must be present in the expectorated specimen. Pooling of sputum collected over 2-3 days may enhance the sensitivity of this test by increasing the yield of exfoliated cells in the specimen. /Carbamate pesticides/
Evaluation of Peripheral Neuropathy: Nerve conduction study; Electromyography (EMG); Quantitative sensory testing; Thermography. /Carbamate pesticides/
Evaluation of Central Nervous System Effects: Evaluation of CNS effects can be performed through neuropsychological assessment, which consists of a clinical interview and administration of standardized personality and neuropsychological tests. The areas that the neuropsychology test batteries focus on include the domains of memory and attention; visuoperceptual, visual scanning, visuospatial, and visual memory; and motor speed and reaction time. There is limited data on which components of the test batteries are best indicators of early CNS effects. /Carbamate pesticides/
Evaluation of Cranial Neuropathies: Evaluation of cranial nerve damage, as evidenced by symptoms such as loss of balance, visual function, smell, taste, orsensation on the face, can be accompolished through a physical examination focusing on tests such as: Smell assessment ... Vision assessment ... Facial and Trigeminal Nerve assessment ... Vestibular assessment .. Hearing assessment. /Carbamate pesticides/
Probable Routes of Human Exposure:
Workers engaged in production, formulation and application of carbaryl as a contact insecticide for fruits, vegetables, cotton, and other crops.
Mean dermal exposure to carbaryl ranged from 0.50 mg/hr (lower arms) - 1.90 mg/hr (hands) in strawberry harvesters(1). Individuals performing production, collection, and bagging of carbaryl were exposed to 0.23-31 mg dust/cu m(2). The hourly dermal exposure (HDE) of agricultural workers to carbaryl applied by air or ground equipment was studies. HDE was highest for the aerial flagger, next highest for the mixed loader, followed by the applicator and the bystander. The exposure of the three types of workers was limited mainly to the hands. The hand exposure of the mixed loader was greater when gloves were not worn. HDE on hands of thinners working in apple orchard treated with carbaryl correlated with total extractable from apple leaves(4). The mean rates of carbaryl exposure for professional applicators were 3.85 and 0.26 ug/sq cm-hr, respectively for outside of the clothing and the skin beneath the clothing. The hand exposures for the applicators were 2.36 and 24.9 ug/cm-hr, respectively for gloved and bare hands. The max air concentration in application area was 0.28 ug/l(3). The mean dermal and respiratory exposure for applicators was 59.4-128 mg/hr and 0.1 mg/hr(5).
NIOSH (NOES Survey 1981-1983) has statistically estimated that 16,544 workers (3,228 of these are female) are potentially exposed to carbaryl in the US(1). The NOES Survey, however, does not include farm workers. Workers engaged in production, formulation and application of carbaryl as a contact insecticide for fruits, vegetables, cotton, and other crops are especially prone to exposure(2). Occupational exposure to carbaryl may occur through inhalation and dermal contact with this compound at workplaces where carbaryl is produced or used(SRC). The general population may be exposed to carbaryl via inhalation of ambient air(3), ingestion of food(4,5) and drinking water(6,7) and pesticide products(8) containing carbaryl(SRC).
To evaluate the exposure of farmers to carbaryl during pesticide application, a study was conducted that measured the personal air, dermal contact, indoor residue content, urine and serum from a single farmer(1). Before carbaryl was applied to the crops, the personal air samples contained 0.008-0.016 ug/cu m carbaryl; a dermal patch contained 0.0014-0.010 ug/sq cm carbaryl; handwipe sample of the farmer and family contained 9-20 ug carbaryl; urine samples contained 270 ug/g creatinine 1-naphthol (breakdown product of carbaryl); while serum samples contained 0.260 ug/l 1-naphthol and 0 detection for carbaryl(1). On the day of application, the carbaryl concns changed to: personal air samples contained 640 ug/cu m; dermal patch contained 11 ug/cm sq; handwipe samples contained 20,100 ug; urine samples contained 140-9,300 ug/g creatinine 1-naphthol; while serum samples contained 510 ug/l 1-naphthol and 0.12 ug/l carbaryl(1). In a year long study, from March 1986 to February 1987, of carbaryl exposure to tree nursery workers in the Pacific Northwest and Central United States, 18 out of 3,134 urine samples analyzed contained detectable amounts of carbaryl(2). Of these, the total amount of carbaryl adsorbed was determined to range from 0.0075-0.0238 mg/kg person(2). Airborne levels of pesticides were measured during and following the mixing, loading, or application of pesticides(3). Measurements included breathing zone air, indoor air of pesticide warehouse facilities and offices, indoor air of residential properties and ambient air of residential properties(3). Approximately 500 samples were taken in 14 cities in the U.S. and Canada(3). Breathing zone air samples contained carbaryl in 8 out of 17 air samples with a time weighted avg of 0.005 mg/cu m(3). Office, operations room and warehouse air samples did not contain any detectable amount of carbaryl in 82 samples(3). For residential indoor air samples, carbaryl was the most frequently detected pesticide with a time waited avg of 0.013 mg/cu m in 16 out of 38 samples(3). Carbaryl was detected in 13 out of 28 residential outdoor ambient air samples with a time waited avg of 0.013 mg/cu m(3).
Body Burden:
Carbaryl does not accumulate in tissues or persist in blood. It is quickly metabolized into a nontoxic compound, 1-naphthol, which is excreted in urine as the glucuronide or sulfate ester(1).
Average Daily Intake:
FOOD: The avg adult daily dietary intake for the years 1980-84 was in the range 0.12-0.032 ug/kg body weight(1-3). Insufficient data are available to calculate avg daily carbaryl intakes from water and air ingestion. Avg daily intake per unit of body weight of carbaryl between 1984-1986 in the United States was 0.0704 ug (age group: 6-11 month), 0.0565 ug (2 yr), 0.0087 ug (14-16 yr female), 0.0088 ug (14-16 yr male), 0.0123 ug (25-30 yr female), 0.010 ug (25-30 yr male), 0.0134 ug (60-65 yr female), and 0.012 ug (60-65 yr male)(4).
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