Human Health Effects:
Evidence for Carcinogenicity:
Evaluation: There is inadequate evidence in humans for the carcinogenicity of dichlorvos. There is sufficient evidence in experimental animals for the carcinogenicity of dichlorvos. Overall evaluation: Dichlorvos is possibly carcinogenic to humans (2B).
CLASSIFICATION: B2; probable human carcinogen. BASIS FOR CLASSIFICATION: Significant increases in forestomach tumors in female and male B6C3F1 mice and leukemias and pancreatic acinar adenomas in Fischer 344 rats. Supporting evidence included observation of tumors at other sites in the rat and observation of mutagenicity for both dichlorvos and a major metabolite dichloroacetaldehyde. A structurally related material, dichloropropene , also induces forestomach tumors in rodents. HUMAN CARCINOGENICITY DATA: None. ANIMAL CARCINOGENICITY DATA: Sufficient.
A4; Not classifiable as a human carcinogen.
Human Toxicity Excerpts:
HUMANS EXPOSED AT CONCN ... VARYING FROM 0.14 TO 0.33 MG/CU M FOR 30 MIN EACH HR, 10 HR A DAY FOR 14 DAYS, SHOWED NO CHANGES IN CHOLINESTERASE OR IN NUMBER OF PHYSIOLOGICAL FUNCTIONS. ... ON THE OTHER HAND, WHEN 28 HUMAN VOLUNTEERS WERE EXPOSED TO DICHLORVOS BY INHALATION AT A CONCN OF 1 MG/CU M, SINGLE EXPOSURES OF 7.5-8.5 HR RESULTED IN PLASMA CHOLINESTERASE DEPRESSION OF 20-25%.
... PESTICIDE WORKERS HANDLING DICHLORVOS /WERE SEEN TO HAVE A/ REDUCTION ... IN BLOOD CHOLINESTERASE AS WELL AS LEUKOCYTOSIS, NEUTROPHILIA, & DECR IN LYMPHOCYTES & MONOCYTES. THESE WERE BACK TO NORMAL @ A 2 WK FOLLOW-UP FOLLOWING EXPOSURE.
After inhalation of dichlorvos, breathing and eye effects are the first to appear. These include tightness of the chest, wheezing, a bluish discoloration of the skin, small pupils, aching in and behind the eyes, blurring of vision, tearing, runny nose, headache, and watering of the mouth. After /ingestion/ of dichlorvos, loss of appetite, nausea, vomiting, abdominal cramps, and diarrhea may appear within two hours. After skin absorption, sweating and twitching in the area of absorption may occur ... within 15 minutes to four hours. With severe intoxication by all routes, in addition to all the symptoms /previously mentioned/, weakness, generalized twitching, and paralysis may /result/ and breathing may stop. In addition, dizziness, confusion, staggering, slurred speach, generalized sweating, irregular or slow heart beat, convulsions, and coma /may result/.
RAPID DEGRADATION ... BOTH IN AIR & IN BODY, IS PROBABLY RESPONSIBLE FOR WIDE MARGIN BETWEEN THAT CONCN WHICH CAUSES DETECTABLE EFFECT ON MOST SENSITIVE INDICATOR OF EXPOSURE, PLASMA CHOLINESTERASE, & CONCN WHICH PRODUCES NOTICEABLE SYMPTOMS OF ILLNESS.
The potency of dichlorvos to inhibit human complement (C') activities of a panel of normal human sera was investigated in a modified assay using human complement mediated lysis of sheep red cells (1) incorporating suboptimal concn of sensitizing antibody, and (2) exhibiting incr sensitivity to serine esterase inhibitors. Dichlorvos was added to diluted sera 2 hr prior to incorporation into human complement reaction mixtures. Potencies to inhibit human complement and serum cholinesterase were compared to potencies of diisopropylfluorophosphate, a potent serine esterase inhibitor and a standard probe for human complement esterases. At 0.5 to 3.0 mM, dichlorvos produced a dose dependent inhibition of lysis. Mean IC50 for inhibition of cholinesterase (a marker for occupational exposure to organophosphates and carbamates) by dichlorvos was 1.0x10-7 M. Potency of the insecticide to inhibit cholinesterase did not predict absolute or relative potency to inhibit serum human complement activity.
In man, dichlorvos inhibits plasma cholinesterase more readily than red cell cholinesterase.
Mortality surveys and death certificate studies have suggested an association between leukemia and farming. To investigate whether exposure to carcinogens in an agricultural setting is related to risk of leukemia, a population based control interview study of 578 white men with leukemia and 1245 controls living in Iowa and Minnesota /was conducted/. Consistent with recent mortality studies, there were slight, but significant, elevations in risk for all leukemia (odds ratio 1.2) and chronic lymphocytic leukemia (odds ratio 1.4) for farmers compared to nonfarmers. There were no significant associations with leukemia for exposure to specific fungicides, herbicides (including 2,4-D and 2,4,5-T), or crop insecticides. However, significantly elevated risks for leukemia of \ 2.0 were seen for exposure to specific animal insecticides including the organophosphates crotoxyphos (odds ratio 11.1), dichlorvos (odds ratio 2.0), and famphur (odds ratio 2.2) and the natural product pyrethrins (odds ratio 3.7) and the chlorinated hydrocarbon methoxychlor (odds ratio 2.2). There were also smaller, but significant, risks associated with exposure to nicotine (odds ratio 1.6) and DDT (odds ratio 1.3). This finding of elevated risks for insecticides used on animals deserves further evaluation.
MUTAGENICITY: SISTER CHROMATID EXCHANGE - IN VITRO CHROMOSOMAL EFFECT STUDIES, HUMAN: NEGATIVE.
Skin, Eye and Respiratory Irritations:
Dichlorvos is not known to be an eye irritant.
Drug Warnings:
VET: DO NOT USE IN CONJUNCTION WITH OR WITHIN FEW DAYS OF (BEFORE &/OR AFTER) ANY OTHER CHOLINESTERASE INHIBITORS & AVOID USE WITH PHENOTHIAZINE, PHENOTHIAZONE TRANQUILIZERS, ARSENICALS, PURGATIVES, OR DRUGS PRODUCING PURGATION AS SIDE EFFECT.
DO NOT ADMINSTER TASK /A FORMULATION/ ... DOG ANTHELMINTIC IN CONJUNCTION WITH OTHER ANTHELMINTICS, TAENIACIDES, ANTIFILARIAL AGENTS (DIETHYLCARBAMAZINE EXCEPTED), MUSCLE RELAXANTS OR TRANQUILIZERS. /TASK/
DO NOT ADMIN TO DOGS SHOWING SIGNS OF SEVERE CONSTIPATION, MECHANICAL BLOCKAGE OF INTESTINAL TRACT, IMPAIRED LIVER FUNCTION, CIRCULATORY FAILURE, OR TO DOGS RECENTLY EXPOSED TO OR SHOWING SIGNS OF INFECTIOUS DISEASES.
Medical Surveillance:
A complete history and physical examination. ... Examination of the respiratory system, nervous system, cardiovascular system, and attention to the cholinesterase levels in the blood should be stressed. The skin should be examined for chronic disorders. ... The cholinesterase activity in the serum and erythrocytes should be determined by using acceptable biochemical tests prior to any new period of exposure. ... Medical examinations should be repeated on annual basis, with the exception of cholinesterase determination which should be performed quarterly or at any time overexposure is suspected or signs or symptoms of toxicity occur.
... Workers ... must undergo an annual medical exam at the beginning of each agricultural season. Contraindications for work with organophosphorus pesticides are organic diseases of the CNS, mental disorders & epilepsy, pronounced endocrine & vegetative disorders, pulmonary tuberculosis, bronchial asthma, chronic respiratory diseases, cardiovascular diseases and circulatory disorders, gastrointestinal diseases (peptic ulcer), gastroenterocolitis, diseases of the liver & kidneys, eye diseases (chronic conjunctivitis and keratitis). Blood cholinesterase activity must be determined before work starts. In the event of prolonged work periods, this activity should be determined at intervals of 3-4 days. Persons exhibiting a fall in cholinesterase activity of 25% or more must be transferred to other work where they are not exposed ... until /cholinesterase level/ is completely restored. /Organophosphorus pesticides/
PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/
SERUM OR PLASMA: The literature search did not reveal reports of monitoring tests for assessment of organophosphate pesticide absorption. Reference Ranges: Normal - Not established; Exposed - Not established; Toxic - Not established. /Organophosphate pesticides/
URINE: The assessment of organophosphate pesticide exposure can be accomplished through measurement of the following alkyl phosphate metabolites: dimethylphosphate (DMP), diethylphosphate (DEP), dimethylthiophosphate (DMTP), diethylthiophosphate (DETP), dimethyldithiophosphate (DMDTP), and diethyldithiophosphate (DEDTP). Detection of dimethylphosphate and diethylphosphate have been found to be directly attributable to pesticide exposure. Detection of dimethyldithiophosphate and diethyldithiophosphate is difficult since they are rapidly degraded and are less directly associated with pesticide exposure, while dimethylthiophosphate and diethylthiophosphate levels can be produced from other non-pesticide sources, limiting their usefulness as markers for pesticide absorption. The one limitation to measurement of urinary alkyl metabolites is that this test is only useful for assessing recent exposure, due to the short half-life of organophosphate pesticides. In addition, there are tests for specific urinary phenolic metabolites of certain organophosphate pesticides such as parathion (metabolite, p-nitrophenol). However, since each pesticide gives rise to a different phenol metabolite, it is probably not feasible to identify each urinary metabolite. Reference Ranges: Normal - Not established; Exposed - Not established; Toxic - Not established. /Organophosphate pesticides/
BAT for Acetylcholinesterase inhibitors (sampling time is end of exposure or end of shift, or for long-term exposures sampling time is after several shifts: both measured as acetylcholinesterase in erythrocytes): Reduction of activity to 70% of reference value. /Organophosphate pesticides/
BEI (sampling time is discretionary): 70% of individual's baseline. /Organophosphate pesticides/
Urine Albumin: Albuminuria has been shown to be a specific marker of glomerular dysfunction. Tubular damage, however, can also result in increased levels of albumin in the urine. /Organophosphate pesticides/
Urinary Beta-2-Microglobulin and/or Retinal Binding Protein (RBP): Measurements for the presence of either of these low molecular weight proteins are useful in detection of early impairment of proximal tubular function. However, beta-2-microglobulin is unstable at urinary pH less than 6, and may degrade in the bladder prior to collection and subsequent neutralization of the urine sample. Measurement of RBP appears to be a better marker for early tubular dysfunction due to its stability in the urine subsequent to collection and analysis. However, RBP is produced in the liver and not a constitutive protein of the kidney, so that its presence in the kidney provides only indirect evidence of tubular damage.
Urinary Alpha and Pi Isoenzymes of Glutathione S-Transferase: Radio-immunological and Elisa techniques have been developed for quantitation of and isoenzymes of glutathione S-transferase (GST), which are constitutive proteins in the kidney. The isoenzyme is located only in the proximal tubule, while the isoenzyme is located in the distal convoluted tubule, the loop of Henle, and the collecting ducts of the kidney. Damage to epithelial cell membranes can result in the increased excretion of these isoenzymes in the urine. This test for assessing renal tubular damage appears to have many advantages over other available tests, such as: (1) the alpha and pi isoenzymes are constitutive proteins in the kidney; (2) these isoenzymes are stable in the urine; (3) the test is simple and reproducible; and (4) due to selective localization of the isoenzymes, differential diagnosis of specific tubular damage is possible. In addition, increased levels of these isoenzymes were seen in patients previously exposed to nephrotoxicants where conventional tests for kidney function were normal, indicating a high degree of sensitivity. /Organophosphate pesticides/
Urinary Enzyme N-acetylglucosaminidase: This lysosomal enzyme has shown promise in assessment of subclinical nephrotoxic injury. This enzyme is not normally filtered at the glomerulus due to its high molecular weight. In the absence of glomerular injury, this enzyme will be detected in the urine as a result of leakage or exocytosis from damaged, stimulated, or exfoliated renal cells. The sensitivity of measurement for this enzyme has not been thoroughly studied, but its usefulness has shown some promise. However, this enzyme is unstable at urinary pH greater than 8, which could diminish the sensitivity of measurement due to enzyme degradation. /Organophosphate pesticides/
Routine Urinalysis: Performing a routine urinalysis including parameters such as specific gravity, glucose, and a microscopic examination may be useful for assessing renal toxicity. /Organophosphate pesticides/
Evaluation of Peripheral Neuropathy: nerve conduction study, electromyography (EMG), quantitative sensory testing, thermography. /Organophosphate 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 test. 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. /Organophosphate pesticides/
Evaluation of Cranial Neuropathies: Evaluation of cranial nerve damage, as evidenced by symptoms such as loss of balance, visual function, smell, taste, or sensation on the face, can be accomplished through a physical examination focusing on tests such as: smell assessment - standardized odor threshold and identification testing; vision assessment - standard acuity test, visual field tests, contrast sensitivity, and color vision measurements (vision assessment); facial and trigeminal nerve assessment - blink reflex (pontogram); vestibular assessment - pure tone audiometry for bone- and air-conducted sounds, threshold decay at 4 kHz, speech discrimination and speech reception thresholds, tympanograms and acoustic thresholds, electronystagmograms; hearing assessment - audiometry testing. /Organophosphate pesticides/
Populations at Special Risk:
... Persons with a history of reduced pulmonary function, convulsive disorders, or recent exposure to anticholinesterase agents would be expected to be at increased risk from exposure.
DICHLORVOS IS RAPIDLY INACTIVATED BY ... LIVER ENZYMES. ... PATIENTS WITH HEPATIC INSUFFICIENCY MAY BE LESS TOLERANT TO THE TOXIC EFFECTS OF DICHLORVOS.
Work ... must not be carried out by young persons under 18 yr, expectant or nursing mothers, or persons for whom work with toxic chemicals is contraindicated on account of their state of health; the same applies to alcoholics. Contraindications for work with organophosphorus pesticides are organic diseases of the CNS, mental disorders & epilepsy, pronounced endocrine & vegetative disorders, pulmonary tuberculosis, bronchial asthma, chronic respiratory diseases, cardiovascular diseases and circulatory disorders, gastrointestinal diseases (peptic ulcer), gastroenterocolitis, diseases of the liver & kidneys, eye diseases (chronic conjunctivitis and keratitis). /Organophosphorus pesticides/
Probable Routes of Human Exposure:
Dichlorvos can affect the body if it is inhaled, if it comes in contact with the eyes or skin, or is swallowed. ...
NIOSH (NOES Survey 1981-1983) has statistically estimated that 11,182 workers (2,182 of these are female) are potentially exposed to dichlorvos in the US(1). The NOES Survey does not include agricultural workers. Occupational exposure to dichlorvos may occur through inhalation of ambient air and dermal contact with this compound at workplaces where dichlorvos is produced or used for household and public health insect control, flea collars and no-pest strips(2,SRC). Similarly, the general population may be exposed to dichlorvos via inhalation of air and dermal contact when no-pest strips, sprays or flea collars containing this insecticide are used. Exposure could also result from ingestion of food which has been prepared in rooms where dichlorvos is used for insect control(SRC). As part of EPA's Non-Occupational Pesticide Exposure Study (NOPES) conducted in the Summer 1986, Spring 1987 and Winter 1988 in Jacksonville, FL and Springfield/Chicopee, MA the estimated mean personal air concn of dichlorvos for Jacksonville residents was 147.6, 40.2, and 21.4 ng/cu m in summer, spring and winter, respectively(3). The estimated spring and winter concns for Springfield/Chicopee residents were 3.7 and 2.1 ng/cu m in spring and winter. In Jacksonville, it was estimated that the percentage of residents with detectable levels of dichlorvos in personal air was 35%, 11%, and 16% in summer, spring and winter, respectively. In Springfield/Chicopee only 2% and 1% of residents were exposed in spring and winter. Exposure from air inhalation was the primary route of exposure to dichlorvos(3).
Dichlorvos was detected in the workplace environment in concns of 77 ppb in air during production and processing of a dichlorvos-releasing vaporizer(1). During spraying of an orchard 130 ppb was detected in air and a rate of skin contamination of 72 ug/100 sq cm/hr was reported(1). After spraying, 114-765 ug/sq m of dichlorvos was deposited on worker's clothing(3). A study was performed to determine the level of exposure to 5 workers after 1.85 kg of dichlorvos was sprayed on an apple orchard for 5.5 hr with an airblast sprayer(4). The air and breathing zone dichlorvos concns were 1.0-15.4 ug/cu m, and 113.6-765.3 ug/cu m, respectively. Ambient air in storage rooms of four North Carolina commercial pest control firms (4 hr period) contained 147-1501 ng/cu m, (617 ng/cu m avg)(2). Ambient air in offices of four North Carolina commercial pest control firms (4 hr period) contained 19-66 ng/cu m, (41 ng/cu m avg)(2). A 1993 study of insecticide concns in the air of 10 North Carolina pest control firms (19 samples) resulted in mean dichlorvos air levels of 1.48 ug/cu m(5). Levels were higher in summer than in winter. In a study to determine the dissipation of dislodgeable residues of dichlorvos on turf, the residue level was 0.10 ug/sq cm immediately post application (<2 hr) and rapidly declined to below the safe level for reentry, 0.06 mg/sq cm after two hours and was undetectable (<1 ug/sample) after 23 hr(5). There was no significant difference in post application dissipation of dislodgeable residues between irrigated and non-irrigated plots. Dichlorvos was detected in air samples immediately post-spray at 1.9 ppb(5). Three hours after application of dichlorvos to greenhouse crops using low-volume (<50 l/ha) techniques, the atmospheric concn of dichlorvos had declined to 12% of the initial concn but was still exceeding the 1000 ug/cu m threshold limit value (TLV)(6).
Body Burden:
Two pest control operators in Japan involved in spraying and mixing a combined emulsifiable concentrate of fenithrothion and dichlorvos to exterminated cockroaches in household construction contained mean and maximum alkyl phosphate levels in urine of 0.099 and 0.22 ug/mg creatinine(1).
Average Daily Intake:
AIR INTAKE: 1.25 ug (Jacksonville, FL; assuming a weighted estimate of average daily air concns of 62.4 ng/cu m(1)); 0.066 ug (Springfield/Chicopee, MA; assuming a weighted estimate of average daily air concns of 3.3 ng/cu m(1)).
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