" DISCLAIMER: The ILO does not take responsibility for content presented on this web portal that is presented in any language other than English, which is the language used for the initial production and peer-review of original content. Certain statistics have not been updated since the production of the 4th edition of the Encyclopaedia (1998)."

Saturday, 19 February 2011 03:29

Pesticides

Written by
Rate this item
(0 votes)

Adapted from 3rd edition, Encyclopaedia of Occupational Health and Safety. Revision includes information from A. Baiinova, J.F. Copplestone, L.A. Dobrobolskij, 

F. Kaloyanova-Simeonova, Y.I. Kundiev and A.M. Shenker.

The word pesticide generally denotes a chemical substance (which may be mixed with other substances) that is used for the destruction of an organism deemed to be detrimental to humans. The word clearly has a very wide meaning and includes a number of other terms, such as insecticides, fungicides, herbicides, rodenticides, bactericides, miticides, nematocides and molluscicides, which individually indicate the organisms or pests that the chemical or class of chemicals is designed to kill. As different types of chemical agents are used for these general classes, it is usually advisable to indicate the particular category of pesticide.

General Principles

Acute toxicity is measured by the LD50 value; this is a statistical estimate of the number of mg of the chemical per kg of body weight required to kill 50% of a large population of test animals. The dose may be administered by a number of routes, usually orally or dermally, and the rat is the standard test animal. Oral or dermal LD50 values are used according to which route has the lower value for a specific chemical. Other effects, either as a result of short-term exposure (such as neurotoxicity or mutagenicity) or of long-term exposure (such as carcinogenicity), have to be taken into account, but pesticides with such known properties are not registered for use. The WHO Recommended Classification of Pesticides by Hazard and Guidelines to Classification 1996-1997 issued by the World Health Organization (WHO) classifies technical products according to the acute risk to human health as follows:

  • Class IA—extremely hazardous
  • Class IB—highly hazardous
  • Class II—moderately hazardous
  • Class III—slightly hazardous.

 

The guidelines based on the WHO Classification list pesticides according to toxicity and physical state; these are presented in a separate article in this chapter.

Poisons enter the body through the mouth (ingestion), the lungs (inhalation), the intact skin (percutaneous absorption) or wounds in the skin (inoculation). The inhalation hazard is determined by the physical form and solubility of the chemical. The possibility and degree of percutaneous absorption varies with the chemical. Some chemicals also exert a direct action on the skin, causing dermatitis. Pesticides are applied in many different forms—as solids, by spraying in dilute or concentrated form, as dusts (fine or granulated), and as fogs and gases. The method of use has a bearing on the likelihood of absorption.

The chemical may be mixed with solids (often with food used as bait), water, kerosene, oils or organic solvents. Some of these diluents have some degree of toxicity of their own and may influence the rate of absorption of the pesticide chemical. Many formulations contain other chemicals which are not themselves pesticides but which enhance the effectiveness of the pesticide. Added surface-active agents are a case in point. When two or more pesticides are mixed in the same formulation, the action of one or both may be enhanced by the presence of the other. In many cases, the combined effects of mixtures have not been fully worked out, and it is a good rule that mixtures should always be treated as more toxic than any of the constituents on their own.

By their very nature and purpose, pesticides have adverse biological effects on at least some species, human beings included. The following discussion provides a broad overview of the mechanisms by which pesticides can act, and some of their toxic effects. Carcinogenicity, biological monitoring and safeguards in the use of pesticides are discussed in more detail elsewhere in this Encyclopaedia.

Organochlorine Pesticides

The organochlorine pesticides (OCPs) have caused intoxication following skin contact, ingestion or inhalation. Examples are endrin, aldrin and dieldrin. The rate of absorption and toxicity differ depending on the chemical structure and the solvents, surfactants and emulsifiers used in the formulation.

The elimination of OCPs from the body takes place slowly through the kidneys. Metabolism in the cells involves various mechanisms—oxidation, hydrolysis and others. OCPs have a strong tendency to penetrate cell membranes and to be stored in the body fat. Because of their attraction to fatty tissues (lipotropic properties) OCPs tend to be stored in the central nervous system (CNS), liver, kidneys and the myocardium. In these organs they cause damage to the function of important enzyme systems and disrupt the biochemical activity of the cells.

OCPs are highly lipophilic and tend to accumulate in fatty tissue as long as exposure persists. When exposure ceases, they are released slowly into the bloodstream, often over a period of many years, from whence they can be transported to other organs where genotoxic effects, including cancer, may be initiated. The great majority of US residents, for example, have detectable levels of organochlorine pesticides, including breakdown products of DDT, in their adipose (fatty) tissue, and the concentrations increase with age, reflecting lifetime accumulations.

A number of OCPs that have been used throughout the world as insecticides and herbicides are also proven or suspected carcinogens to humans. These are discussed in more detail in the Toxicology and Cancer chapters of this Encyclopaedia.

Acute intoxications

Aldrin, endrin, dieldrin and toxaphene are most frequently implicated in acute poisoning. Delay in the onset of symptoms in severely acute intoxications is about 30 minutes. With lower toxicity OCPs it is several hours but not more than twelve.

Intoxication is demonstrated by gastrointestinal symptoms: nausea, vomiting, diarrhoea and stomach pains. The basic syndrome is cerebral: headache, dizziness, ataxia and paraesthesia. Gradually tremors set in, starting from the eyelids and the face muscles, descending towards the whole body and the limbs; in severe cases this leads to fits of tonic-clonic convulsions, which gradually extend to the different muscle groups. Convulsions may be connected with elevated body temperature and unconsciousness and may result in death. In addition to the cerebral signs, acute intoxications may lead to bulbar paralysis of the respiratory and/or vasomotor centres, which causes acute respiratory deficiency or apnoea, and to severe collapse.

Many patients develop signs of toxic hepatitis and toxic nephropathy. After these symptoms have disappeared some patients develop signs of prolonged toxic polyneuritis, anaemia and haemorrhagic diathesis connected with the impaired thrombocytopoiesis. Typical of toxaphene is an allergic bronchopneumonia.

Acute intoxications with OCPs last up to 72 hours. When organ function has been seriously impaired, the illness may continue up to several weeks. Complications in cases of liver and kidney damage can be long-lasting.

Chronic poisoning

During the application of OCPs in agriculture as well as in their production, poisoning is most commonly chronic—that is, low doses of exposure over time. Acute intoxication (or high-level exposures at a particular instant) are less common and are usually the result of misuse or accidents, both in the home and in industry. Chronic intoxication is characterized by damage to the nervous, digestive and cardiovascular systems and the blood-formation process. All OCPs are CNS stimulants and are capable of producing convulsions, which frequently appear to be epileptic in character. Abnormal electroencephalographic (EEG) data have been recorded, such as irregular alpha rhythms and other abnormalities. In some cases bitemporal sharp-peaked waves with shifting localization, low voltage and diffuse theta activity have been observed. In other cases paroxysmal emissions have been registered, composed of slow sharp-peaked waves, sharp-peaked complexes and rhythmic peaks with low voltage.

Polyneuritis, encephalopolyneuritis and other nervous system effects have been described following occupational exposure to OCPs. Tremor of the limbs and alterations in the electromyograms (EMGs) have also been observed in workers. In workers handling OCPs such as BHC, polychloropinene, hexachlorobutadiene and dichloroethane, non-specific signs (e.g., diencephalic signs) have been observed and very often develop together with other signs of chronic intoxication. The most common signs of intoxication are headache, dizziness, numbness and tingling in the limbs, rapid changes in blood pressure and other signs of circulatory disturbances. Less frequently, colic pains below the right ribs and in the region of the umbilicus, and dyskinesia of the bile ducts, are observed. Behavioural changes, such as disturbances of sensory and equilibrium functions, are found. These symptoms are often reversible after cessation of the exposure.

OCPs cause liver and kidney damage. Microsomal enzyme induction has been observed, and increased ALF and aldolase activity have also been reported. Protein synthesis, lipoid synthesis, detoxification, excretion and liver functions are all affected. Reduction of creatinine clearance and phosphorus reabsorption are reported in workers exposed to pentachlorophenol, for example. Pentachlorophenol, along with the family of chlorophenols, are also considered possible human carcinogens (group 2B as classified by the International Agency for Research on Cancer (IARC)). Toxaphene is also considered to be a group 2B carcinogen.

Cardiovascular disturbances have been observed in exposed persons, most frequently demonstrated as dyspnoea, high heart rate, heaviness and pain in the heart region, increased heart volume and hollow heart tones.

Blood and capillary disturbances have also been reported following contact with OCPs. Thrombopenia, anaemia, pancytopenia, agranulocytosis, haemolysis and capillary disorders have all been reported. Medullar aplasia can be complete. The capillary damage (purpura) can develop following long- or short-term but intensive exposures. Eosinopenia, neutropenia with lymphocytosis, and hypochromic anaemia have been observed in workers subjected to prolonged exposures.

Skin irritation is reported to follow from skin contact with some OCPs, particularly chlorinated terpenes. Often chronic intoxications are clinically demonstrated by signs of allergic damage.

Organophosphate Pesticides

The organophosphorus pesticides are chemically related esters of phosphoric acid or certain of its derivatives. The organic phosphates are also identified by a common pharmacological property—the ability to inhibit the action of the cholinesterase enzymes.

Parathion is among the most dangerous of the organophosphates and is discussed in some detail here. In addition to parathion’s pharmacological effects, no insect is immune to its lethal action. Its physical and chemical properties have rendered it useful as an insecticide and acaricide for agricultural purposes. The description of parathion’s toxicity applies to other organophosphates, although their effects may be less rapid and extensive.

The toxic action of all organic phosphates is on the CNS through inhibition of the cholinesterase enzymes. Inhibiting these cholinesterases produces excessive and continuous stimulation of those muscle and gland structures which are activated by acetylcholine, to a point where life can no longer be sustained. Parathion is an indirect inhibitor because it must be converted in the environment or in vivo before it can effectively inhibit cholinesterase.

Organophosphates can generally enter the body by any route. Serious and even fatal poisoning may occur by ingesting a small amount of parathion while eating or smoking, for example. Organophosphates may be inhaled when dusts or volatile compounds are even briefly handled. Parathion is easily absorbed through the skin or the eye. The ability to penetrate the skin in fatal quantities without the warning of irritation makes parathion especially difficult to handle.

Signs and symptoms of organophosphate poisoning can be explained on the basis of cholinesterase inhibition. Early or mild poisoning may be hard to distinguish because of a number of other conditions; heat exhaustion, food poisoning, encephalitis, asthma and respiratory infections share some of the manifestations and confuse the diagnosis. Symptoms can be delayed for several hours after the last exposure but rarely longer than 12 hours. Symptoms most often appear in this order: headaches, fatigue, giddiness, nausea, sweating, blurred vision, tightness in the chest, abdominal cramps, vomiting and diarrhoea. In more advanced poisoning, difficult breathing, tremors, convulsions, collapse, coma, pulmonary oedema and respiratory failure follow. The more advanced the poisoning, the more obvious are the typical signs of cholinesterase inhibition, which are: pinpoint pupils; rapid, asthmatic type breathing; marked weakness; excessive sweating; excessive salivation; and pulmonary oedema.

In very severe parathion poisoning, in which the victim has been unconscious for some time, brain damage from anoxia may occur. Fatigue, ocular symptoms, electroencephalogram abnormalities, gastrointestinal complaints, excessive dreams and exposure intolerance to parathion have been reported to persist for days to months following acute poisoning. There is no evidence that permanent impairment occurs.

Chronic exposure to parathion may be cumulative in the sense that repeated exposures closely following each other can reduce cholinesterase faster than it can be regenerated, to the point where a very small exposure can precipitate acute poisoning. If the person is removed from exposure, clinical recovery is usually rapid and complete within a few days. The red blood cells and plasma should be tested for cholinesterase inhibition when phosphate ester poisoning is suspected. Red cell cholinesterase activity is most often reduced and close to zero in severe poisoning. Plasma cholinesterase is also severely reduced and is a more sensitive and more rapid indicator of exposure. There is no advantage in chemical determinations of parathion in the blood because metabolism of the pesticide is too rapid. However, p-nitrophenol, an end-product of the metabolism of parathion, can be determined in the urine. Chemical examination to identify the pesticide can be made on contaminated clothing or other material where contact is suspected.

Carbamates and Thiocarbamates

The biological activity of carbamates was discovered in 1923 when the structure of the alkaloid eserine (or physostigmine) contained in the seeds of Calabar beans was first described. In 1929 physostigmine analogues were synthesized, and soon such derivatives of dithiocarbamic acid as thiram and ziram were available. The study of carbamic compounds began in the same year, and now more than 1,000 carbamic acid derivatives are known. More than 50 of them are used as pesticides, herbicides, fungicides and nematocides. In 1947 the first carbamic acid derivatives having insecticide properties were synthesized. Some thiocarbamates have proved effective as vulcanization accelerators, and derivatives of dithiocarbamic acid have been obtained for the treatment of malignant tumours, hypoxia, neuropathies, radiation injuries and other diseases. Aryl esters of alkylcarbamic acid and alkyl esters of arylcarbamic acid are also used as pesticides.

Some carbamates can produce sensitization in exposed individuals, and a variety of foetotoxic, embryotoxic and mutagenic effects have also been observed for members of this family.

Chronic effects

The specific effects produced by acute poisoning have been described for each substance listed. A review of the specific effects gained from an analysis of published data makes it possible to distinguish similar features in the chronic action of the different carbamates. Some authors believe that the main toxic effect of carbamic acid esters is the involvement of the endocrine system. One of the peculiarities of carbamate poisoning is the possible allergic reaction of exposed subjects. The toxic effects of carbamates may not be immediate, which can present a potential hazard because of lack of warning. Results from animal experiments are indicative of embryotoxic, teratogenic, mutagenic and carcinogenic effects of some carbamates.

Baygon (isopropoxyphenyl-N-methylcarbamate) is produced by reaction of alkyl isocyanate with phenols, and is used as an insecticide. Baygon is a systemic poison. It causes inhibition of the serum cholinesterase activity up to 60% after oral administration of 0.75 to 1 mg/kg. This highly toxic substance exerts a weak effect on the skin.

Carbaryl is a systemic poison which produces moderately severe acute effects when ingested, inhaled or absorbed through the skin. It may cause local skin irritation. Being a cholinesterase inhibitor, it is much more active in insects than in mammals. Medical examinations of workers exposed to concentrations of 0.2 to 0.3 mg/m3 seldom reveal a fall in cholinesterase activity.

Betanal (3-(methoxycarbonyl)aminophenyl-N-(3-methylphenyl) carbamate; N-methylcarbanilate) belongs to the arylcarbamic acid alkyl esters and is used as a herbicide. Betanal is slightly toxic for the gastrointestinal and respiratory tracts. Its dermal toxicity and local irritation are insignificant.

Isoplan is a highly toxic member of the group, its action, like that of Sevin and others, being characterized by the inhibition of acetylcholinesterase activity. Isoplan is used as an insecticide. Pyrimor (5,6-dimethyl-2-dimethylamino-4-pyrimidinyl methylcarbamate) is a derivative of arylcarbamic acid alkyl esters. It is highly toxic for the gastrointestinal tract. Its general absorption and local irritative effect are not very pronounced.

Thiocarbamic Acid Esters

Ronite (sym-ethylcyclohexylethyl thiocarbamate; Eurex); Eptam (sym-ethyl-N,N-dipropyl thiocarbamate); and Tillam (sym-propyl-N-ethyl-N-butylthiocarbamate) are esters which are synthesized by reaction of alkylthiocarbamates with amines and of alkaline mercaptides with carbamoyl chlorides. They are effective herbicides of selective action.

The compounds of this group are slightly to moderately toxic, and the toxicity is reduced when they are absorbed through the skin. They can affect the oxidative processes as well as the nervous and endocrine systems.

Dithiocarbamates and bisdithiocarbamates include the following products, which have much in common as regards their use and their biological effects. Ziram is used as a vulcanization accelerator for synthetic rubbers and, in agriculture, as a fungicide and seed fumigant. This compound is very irritant to the conjunctiva and upper airway mucous membranes. It can cause extreme pain in the eyes, skin irritation and liver function disorders. It has embryotoxic and teratogenic effects. TTD is used as a seed fumigant, irritates the skin, causes dermatitis and affects the conjunctiva. It increases sensitivity to alcohol. Nabam is a plant fungicide and serves as an intermediate in the production of other pesticides. It is irritating to the skin and mucous membranes, and it is a narcotic in high concentrations. In the presence of alcohol it can cause violent vomiting. Ferbam is a fungicide of relatively low toxicity, but may cause renal function disorders. It irritates the conjunctiva, the mucous membranes of the nose and upper airways, and the skin.

Zineb is an insecticide and fungicide that can cause irritation of the eyes, nose and larynx, and is harmful if inhaled or swallowed. Maneb is a fungicide that can cause irritation of the eyes, nose and larynx, and is harmful if inhaled or swallowed. Vapam (sodium methyldithiocarbamate; carbation) is white crystalline powder of unpleasant smell similar to that of carbon disulphide. It is an effective soil fumigant which destroys weed seeds, fungi and insects. It irritates the skin and mucous membranes.

Rodenticides

Rodenticides are toxic chemicals used for the control of rats, mice and other pest species of rodents. An effective rodenticide must conform to stringent criteria, a fact that is borne out by the small number of compounds that are currently in satisfactory use.

Poisoned baits are the most generally effective and widely used means of formulating rodenticides, but some are used as “contact” poisons (i.e., dusts, foams and gels), where the toxicant adheres to the fur of the animal and is ingested during subsequent grooming, while a few are applied as fumigants to burrows or infested premises. Rodenticides may conveniently be divided into two categories, depending on their mode of action: acute (single dose) poisons and chronic (multiple dose) poisons.

Acute poisons, such as zinc phosphide, norbormide, fluoracetamide, alpha-chloralose, are highly toxic compounds, with LD50s that are usually less than 100 mg/kg, and can cause death after a single dose consumed during a period not longer than a few hours.

Most acute rodenticides have the disadvantages of producing symptoms of poisoning rather quickly, of being generally rather non-specific, and lacking satisfactory antidotes. They are used at relatively high concentrations (0.1 to 10%) in bait.

Chronic poisons, which may act, for example, as anticoagulants (e.g., calciferol), are compounds that, having a cumulative mode of action, may need to be eaten by the prey over a succession of days to cause death. Anticoagulants have the advantage of producing symptoms of poisoning very late, usually well after the target species has eaten a lethal dose. An effective antidote to anticoagulants is available for those accidentally exposed. Chronic poisons are used at relatively low concentrations (0.002 to 0.1%).

Application

Rodenticides intended for use in baits are available in one or more of the following forms: technical grade material, concentrate (“master-mix”) or ready-to-use bait. Acute poisons are usually acquired as the technical material and mixed with the bait-base shortly before use. Chronic poisons, because they are used at low concentrations, are normally sold as concentrates, where the active ingredient is incorporated into a finely powdered flour (or talc) base.

When the final bait is prepared, the concentrate is added to the bait-base at the relevant rate. If the bait-base is of a coarse consistency, it may be necessary to add a vegetable or mineral oil at a prescribed rate to act as a “sticker”, thus ensuring that the poison adheres to the bait-base. It is commonly compulsory for a warning dye to be added to concentrates or ready-to-use baits.

In control treatments against rats and mice, poisoned baits are laid at frequent intervals throughout the infested area. When acute rodenticides are used, better results are obtained when unpoisoned bait (“prebait”) is laid for a few days before the poison is given. In “acute” treatments, poisoned bait is presented for a few days only. When anticoagulants are used, prebaiting is unnecessary, but the poison should remain in position for 3 to 6 weeks to achieve complete control.

Contact formulations of rodenticides are especially useful in situations where baiting is difficult for any reason, or where the rodents are not being drawn satisfactorily off their normal diet. The poison is usually incorporated in a finely divided powder (e.g., talc), which is laid on runways or around bait points, or is blown into burrows, wall cavities and so on. The compound may also be formulated in gels or foams, which are inserted into burrows.

The use of contact rodenticides relies on the target animal ingesting the poison while grooming itself. Because the amount of dust (or foam, etc.) adhering to the fur may be small, the concentration of the active ingredient in the formulation is usually relatively high, making it safe to use only where the contamination of food and so on cannot occur. Other specialized formulations of rodenticides include water baits and wax-impregnated blocks. The former, which are aqueous solutions of soluble compounds, are especially useful in dry environments. The latter are made by impregnating the toxicant and bait-base in molten paraffin wax (of low melting point) and casting the mixture into blocks. Wax-impregnated baits are designed to withstand wet climates and insect attack.

Hazards of rodenticides

Although toxicity levels of rodenticides may vary between target and non-target species, all poisons must be presumed to be potentially lethal to humans. Acute poisons are potentially more dangerous than chronic ones because they are rapid in action, non-specific and generally lack effective antidotes. Anticoagulants, on the other hand, are slow and cumulative, allowing adequate time for the administration of a reliable antidote, such as vitamin K.

As stated above, the concentrations of active ingredients in contact formulations of a given poison are higher than those in bait preparations, thus making operator hazard considerably greater. Fumigants present a special danger when used to treat infested premises, holds of ships and so on, and should be used only by trained technicians. The gassing of rodent burrows, although less hazardous, must also be carried out with extreme caution.

Herbicides

Grassy and broad-leaved weeds compete with crop plants for light, space, water and nutrients. They are hosts to bacteria, fungi and viruses, and hamper mechanical harvesting operations. Losses in crop yields as a result of weed infestation can be very heavy, commonly reaching 20 to 40%. Weed-control measures such as hand weeding and hoeing are ineffective in intensive farming. Chemical weedkillers or herbicides have successfully replaced mechanical methods of weed control.

In addition to their use in agriculture in cereals, meadows, open fields, pastures, fruit growing, greenhouses and forestry, herbicides are applied on industrial sites, railway tracks and power lines to remove vegetation. They are used for destroying weeds in canals, drainage channels and natural or artificial pools.

Herbicides are sprayed or dusted on weeds or on the soil they infest. They remain on the leaves (contact herbicides) or penetrate into the plant and so disturb its physiology (systemic herbicides). They are classified as non-selective (total—used to kill all vegetation) and selective (used to suppress the growth of or kill weeds without damaging the crop). Both non-selective and selective can be contact or systemic.

Selectivity is true when the herbicide applied in the correct dose and, at the right time, is active against certain species of weed only. An example of true selective herbicides are the chlorophenoxy compounds, which affect broad-leaved but not grassy plants. Selectivity can also be achieved by placement (i.e., by using the herbicide in such a way that it comes into contact with the weeds only). For example, paraquat is applied to orchard crops, where it is easy to avoid the foliage. Three types of selectivity are distinguished:

1. physiological selectivity, which relies upon the plant’s ability to degrade the herbicide into non-phytotoxic components

2. physical selectivity, which exploits the particular habit of the cultivated plant (e.g., the upright in cereals) and/or a specially fashioned surface (e.g., wax-coating, resistant cuticule) protecting the plant against herbicide penetration

3. positional selectivity, in which the herbicide remains fixed in the upper soil layers adsorbed on colloidal soil particles and does not reach the root zone of the cultivated plant, or at least not in harmful quantities. Positional selectivity depends on the soil, precipitation and temperature as well as the water solubility and soil adsorption of the herbicide.

Some commonly used herbicides

Following are brief descriptions of acute and chronic effects associated with some commonly used herbicides.

Atrazine gives rise to decreased body weight, anaemia, disturbed protein and glucose metabolism in rats. It causes occupational contact dermatitis due to skin sensitization. It is considered a possible human carcinogen (IARC group 2B).

Barban, in repeated contact with 5% water emulsion, causes severe skin irritation in rabbits. It provokes skin sensitization in both experimental animals and agricultural workers, and causes anaemia, methaemoglobinaemia and changes in lipid and protein metabolism. Ataxia, tremor, cramps, bradycardia and ECG deviations are found in experimental animals.

Chlorpropharm can produce slight dermal irritation and penetration. In rats, exposure to atrazine causes anaemia, methaemoglobinaemia and reticulocytosis. Chronic application causes skin carcinoma in rats.

Cycloate causes polyneuropathia and liver damage in experimental animals. No clinical symptoms have been described after occupational exposure of workers for three consecutive days.

2,4-D poses moderate dermal toxicity and skin irritancy risks to exposed persons. It is highly irritating to the eyes. Acute exposures in workers provoke headache, dizziness, nausea, vomiting, raised temperature, low blood pressure, leucocytosis, and heart and liver injury. Chronic occupational exposure without protection may cause nausea, liver functional changes, contact toxic dermatitis, irritation of airways and eyes, as well as neurological changes. Some of the derivatives of 2,4-D are embryotoxic and teratogenic for experimental animals in high doses only.

2,4-D and the related phenoxy herbicide 2,4,5-T are rated as group 2B carcinogens (possible human carcinogens) by the IARC. Lymphatic cancers, particularly non-Hodgkin lymphoma (NHL), have been associated in Swedish agricultural workers with exposure to a commercial mixture of 2,4-D and 2,4,5-T (similar to the herbicide Agent Orange used by the US military in Viet Nam during the years 1965 to 1971). Possible carcinogenicity is often ascribed to contamination of 2,4,5-T with 2,3,7,8-tetrachloro-dibenzo-p-dioxin. However, a US National Cancer Institute research group reported a risk of 2.6 for adult NHL among Kansas residents exposed to 2,4-D alone, which is not thought to be dioxin-contaminated.

Dalapon-Na can cause depression, an unbalanced gait, decreased body weight, kidney and liver changes, thyroid and pituitary dysfunctions, and contact dermatitis in workers who are exposed. Diallate has dermal toxicity and causes irritation to the skin, eyes and mucous membranes. Diquat is an irritant to the skin, eyes and upper respiratory tract. It can cause a delay in the healing of cuts and wounds, gastrointestinal and respiratory disturbances, bilateral cataract and functional liver and kidney changes.

Dinoseb presents dangers because of its toxicity through dermal contact. It can cause moderate skin and pronounced eye irritation. The fatal dose for humans is about 1 to 3 g. After an acute exposure, Dinoseb causes central nervous system disturbances, vomiting, reddening (erythema) of the skin, sweating and high temperature. Chronic exposure without protection results in decreased weight, contact (toxic or allergic) dermatitis and gastrointestinal, liver and kidney disturbances. Dinoseb is not used in many countries because of its serious adverse effects.

Fluometuron is a moderate skin sensitizer in guinea-pigs and humans. It has been observed to cause decreased body weight, anaemia, and liver, spleen and thyroid gland disturbances. The biological action of diuron is similar.

Linuron causes mild irritation to the skin and eyes, and has low cumulative toxicity (threshold value after single inhalation 29 mg/m3). It causes CNS, liver, lung and kidney changes in experimental animals, as well as thyroid dysfunction.

MCPA is highly irritant to skin and mucous membranes, has low cumulative toxicity and is embryotoxic and teratogenic in high doses in rabbits and rats. Acute poisoning in humans (an estimated dose of 300 mg/kg) results in vomiting, diarrhoea, cyanosis, mucus burns, clonic spasms, and myocardium and liver injury. It provokes severe contact toxic dermatitis in workers. Chronic exposure without protection results in dizziness, nausea, vomiting, stomach aches, hypotonia, enlarged liver, myocardium dysfunction and contact dermatitis.

Molinate can reach a toxic concentration after single inhalation of 200 mg/m3 in rats. It causes liver, kidney and thyroid disturbances, and is gonadotoxic and teratogenic in rats. It is a moderate skin sensitizer in humans.

Monuron in high doses can result in liver, myocardium and kidney disturbances. It causes skin irritation and sensitization. Similar effects are shown by monolinuron, chloroxuron, chlortoluron and dodine.

Nitrofen is a strong skin and eye irritant. Chronic occupational exposure without protection results in CNS disturbances, anaemia, raised temperature, decreased body weight, fatigue and contact dermatitis. It is considered a possible human carcinogen (group 2B) by the IARC.

Paraquat has dermal toxicity and irritant effects on skin or mucous membranes. It causes nail damage and nose bleeding in occupational conditions without protection. Accidental oral poisoning with paraquat has resulted when it was left within reach of children or transferred from the original container into a bottle used for a beverage. Early manifestations of such intoxication are corrosive gastrointestinal effects, renal tubular damage and liver dysfunction. Death is due to circulatory collapse and progressive pulmonary damage (pulmonary oedema and haemorrhage, intra-alveolar and interstitial fibrosis with alveolitis and hyaline membranes), clinically revealed by dyspnoea, hypoxaemia, basal rales and roentgenographic evidence of infiltration and athelectasis. The renal failure is followed by lung damage, and accompanied in some cases by liver or myocardium disturbances. Mortality is higher with poisoning from liquid concentrate formulations (87.8%), and lower from granular forms (18.5%). The fatal dose is 6 g paraquat ion (equivalent to 30 ml Gramoxone or 4 packets of Weedol), and no survivors are reported at greater doses, irrespective of the time or vigour of treatment. Most survivors had ingested less than 1 g paraquat ion.

Potassium cyanate is associated with high inhalation and dermal toxicity in experimental animals and humans due to the metabolic conversion to cyanide, which is discussed elsewhere in this Encyclopaedia.

Prometryn exhibits moderate dermal toxicity and skin and eye irritation. It provokes decreased clotting and enzyme abnormalities in animals and has been found to be embryotoxic in rats. Exposed workers may complain of nausea and sore throat. Analogous effects are shown by propazine and desmetryne.

Propachlor’s toxicity is doubled at high environmental temperatures. Skin and mucous membrane irritation and mild skin allergy are associated with exposure. The toxic concentration after single inhalation is 18 mg/m3 in rats, and it is thought to exhibit moderate cumulative toxicity. Propachlor causes polyneuropathies; liver, myocardium and kidney disturbances; anaemia; and damage to testes in rats. During spraying from the air, the concentration in the spray cabin has been found to be about 0.2 to 0.6 mg/m3. Similar toxic properties are shown by propanil.

Propham exhibits moderate cumulative toxicity. It causes haemodynamic disturbances, and liver, lung and kidney changes are found in experimental animals.

Simazine causes slight irritation of the skin and mucous membranes. It is a moderate skin sensitizer in guinea-pigs. It also causes CNS, liver and kidney disturbances and has mutagenic effect in experimental animals. Workers may complain of weariness, dizziness, nausea and olfactory deviations after application without protective equipment.

2,4,5-T causes pronounced irritation and embryotoxic, teratogenic and carcinogenic effects in animals; there are also data on its gonadotoxic action in women. Because the extremely toxic chemical dioxin can be a contaminant of the trichlorophenoxy acids, use of 2,4,5-T is prohibited in many countries. Agricultural, forestry and industrial workers exposed to mixtures of 2,4-D and 2,4,5-T have been reported at increased risk for both soft-tissue sarcomas and non-Hodgkin lymphomas.

Trifluralin causes slight irritation of skin and mucous membranes. An increased incidence of liver carcinoma has been found in hybrid female mice, probably due to contamination with N-nitroso compounds. Trifluralin causes anaemia and liver, myocardium and kidney changes in experimental animals. Extensively exposed workers have developed contact dermatitis and photodermatitis.

Fungicides

Some fungi, such as rusts, mildews, moulds, smuts, storage rots and seedling blights, are able to infect and cause diseases in plants, animals and humans. Others can attack and destroy non-living materials such as wood and fibre products. Fungicides are used to prevent these diseases and are applied by spraying, dusting, seed dressing, seedling and soil sterilization, and fumigation of warehouses and greenhouses.

Fungi causing plant diseases can be arranged into four sub-groups, which differ by the microscopic characters of the mycelium, the spores and the organs on which the spores were developed:

1. phycomycetes—soil-borne organisms causing club rot of brassicae, wart diseases of potatoes and so on
2. ascomycetes—perithecia-forming powdery mildews and fungi causing apple scab, black currant leaf spot and rose black spot
3. basidiomycetes, including loose smut of wheat and barley, and several rusts species
4. fungi imperfecti, which includes the genera Aspergillus, Fusarium, Penicillium and so on, that are of great economic importance because they cause significant losses during plant growth, at harvest, and after harvest. (e.g., Fusarium species infect barley, oats and wheat; Penicillium species cause brown rot of pomaceous fruit).

Fungicides have been used for centuries. Copper and sulphur compounds were the first to be used, and Bordeaux mixture was applied in 1885 to vineyards. A great number of widely differing chemical compounds with fungicidal action are used in many countries.

Fungicides can be classified into two groups according to their mode of action: protective fungicides (applied at a time prior to the arrival of the fungal spores—e.g., sulphur and copper compounds) or eradicant fungicides (applied after the plant has become infected—e.g., mercury compounds and nitroderivatives of the phenols). The fungicides either act on the surface of the leaves and seeds or penetrate into the plant and exert their toxic action directly on the fungi (systemic fungicides). They can also alter the physiological and biochemical processes in the plant and thus produce artificial chemical immunization. Examples of this group are the antibiotics and the rodananilides.

Fungicides applied to seed act primarily against surface-borne spores. However, in some cases they are required to persist on the seed coat long enough to be effective against the dormant mycelium contained within the seed. When applied to the seed before sowing, the fungicide is called seed disinfectant or seed dressing, though the latter term may include treatment not intended to counter seed-borne fungi or soil pests. To protect wood, paper, leather and other materials, fungicides are used by impregnation or staining. Special drugs with fungicidal action are also used to control fungal diseases in humans and animals.

Specific field applications include:

  • Seed dressing. This is a simple and economically efficient method for the control of plant diseases. The pests are destroyed on the seeds and in the soil during the development of the seed. Despite the availability of efficient alternative compounds, the mercury fungicides are still used to a considerable extent for this purpose. Dithiocarbamates, and particularly thiuram, are widely used. Chloranil and dichlone of the quinone group, hexachlorobenzene, formaldehyde and some antibiotics are also used for seed dressing. The seeds can be treated by either the dry or the wet method.
  • Soil disinfection. This is a more general action, with fungicides incorporated into the soil as solid or liquid formulations that liberate volatile or easily soluble components (e.g., chloropicrin, methyl bromide, dibromomethane, formaldehyde, vapam, dazomet, allyl alcohol, pentachloronitrobenzene and chloroneb). These fungicides are used most intensively on greenhouse soil. Several of them are known or suspected carcinogens.
  • Application on plants. To control airborne diseases, fungicides are used on annual field crops, fruit trees and berry crops. Almost all fungicide groups are used for this purpose. Copper compounds, dithiocarbamates, aromatic nitro derivatives, quinones, phthalamides, guanidines and chlorinated hydrocarbons are the most frequently used; some heterocyclics, nickel compounds and some antibiotics are also used.

 

Hazards of fungicides

The fungicides cover a great variety of chemical compounds differing widely in their toxicity. Highly toxic compounds are used as fumigants of foods and warehouses, for seed dressing and for soil disinfection, and cases of poisoning have been described with organomercurials, hexachlorobenzene and pentachlorobenzene, as well as with the slightly toxic dithiocarbamates. These and several other chemicals are discussed in more detail elsewhere in this article, chapter and Encyclopaedia. Some are briefly reviewed here.

Chinomethionate has a high cumulative toxicity and inhibits thiol groups and some enzymes containing them; it lowers phagocytic activity and has antispermatogenic effects. It is irritant to the skin and the respiratory system. It can damage the CNS, the liver and the gastrointestinal tract. Glutathione and cysteine provide protection against the acute effects of chinomethionate.

Chloranil is irritating to the skin and the upper respiratory tract; it can also cause depression of the CNS and dystrophic changes in the liver and kidney. The biological monitoring of exposed persons has shown an increased level of the urinary phenols, both free and bound.

Dazomet is used also as a nematocide and a slimicide. This compound and its decomposition products are sensitizers and mild irritants of the eye, nose, mouth and skin. Poisoning is characterized by a variety of symptoms, including anxiety, tachycardia and quick breathing, hypersalivation, clonic cramps, impaired movement coordination, sometimes hyperglycaemia and cholinesterase inhibition. The main pathomorphological findings are enlargement of the liver and degenerative changes of the kidney and other internal organs.

Dichlofluanid inhibits thiol groups. In experimental animals it caused histological changes in liver, proximal tubules of the kidney and adrenal cortex, with the reduction of the lymphatic tissue in the spleen. It is a moderate irritant of the skin and mucous membranes.

Diclone, in addition to sharing the irritant and blood depressant properties common to quinones, is an experimental animal carcinogen.

Dinobuton, like dinitro-o-cresol (DNOC), disturbs cell metabolism by inhibiting oxidative phosphorylation, with the loss of energy-rich compounds such as adenosintriphosphoric acid (ATP). It can cause severe liver dystrophy and necrosis of the convoluted tubules of the kidneys. The clinical manifestations of the intoxication are high temperature, methaemoglobinaemia and haemolysis, nervous disturbances and irritation of the skin and mucous membranes.

Dinocap can increase the blood level of alkaline phosphatase and is a moderate irritant of the skin and mucous membranes. It produces distrophic changes in the liver and kidney, and hypertrophy of the myocardium. In acute poisoning, disturbances in thermoregulation, clonic cramps and breathing difficulties have been observed.

Hexachlorobenzene (HCB) is stored in the body fat. It interferes with porphyrin metabolism, increasing the urinary excretion of coproporphyrins and uroporphyrins; it increases also the levels of transaminases and dehydrogenases in the blood. It can produce liver injury (hepatomegaly and cirrhosis), photosensitization of the skin, a porphyria similar to porphyria cutanea tarda, arthritis and hirsutism (monkey disease). It is a skin irritant. Chronic poisoning needs long-term treatment, mainly symptomatic, and it is not always reversible on cessation of exposure. It is classified as a possible human carcinogen (group 2B) by the IARC.

Milneb can cause gastrointestinal disturbances, weakness, decrease of the body temperature and leukopoenia.

Nirit has haemotoxic properties and causes anaemia and leucocytosis with toxic granulation of the leucocytes, in addition to degenerative changes in the liver, spleen and kidneys.

Quinones, in general, cause blood disturbances (methaemoglobinaemia, anaemia), affect the liver, disturb vitamin metabolism, particularly that of ascorbic acid, and are irritant to the respiratory ways and the eye. Chloranil and dichlone are the quinone derivatives most widely used as fungicides.

Thiabendazole has caused thymus involution, colloid depletion in the thyroid and increase in liver and kidney size. It is also used as an anthelmintic in cattle.

Safety and Health Measures

Labelling and storage

The requirements regarding the labelling of pesticides laid down in national and international legislation should be strictly applied to both imported and locally produced chemicals. The label should give the following essential information: both the approved name and the trade name of the chemical; the name of the manufacturer, packager or supplier; the directions for use; the precautions to be taken during use, including details of protective equipment to be worn; the symptoms of poisoning; and the first-aid treatment for suspected poisoning.

The greater the degree of toxicity or hazard of the chemical, the more precise should be the wording on the label. It is sound practice for the different classes to be clearly distinguished by background colours on the label and, in the case of compounds of high or extreme hazard, for the appropriate danger symbol to be incorporated. It often occurs that an adequately labelled quantity of pesticide in bulk is locally repacked into smaller containers. Each such small package should bear a similar label, and repacking in containers which have held, or are easily identifiable with, containers used for food should be absolutely forbidden. If small packages are to be transported, the same rules apply as for the carriage of larger packages. (See the chapter Using, storing and transporting chemicals.)

Pesticides of moderate or higher hazard should be so stored that only authorized persons can have access to them. It is particularly important that children should be excluded from any contact with pesticide concentrates or residues. Spillages often occur in storage and repacking rooms, and they must be cleaned up with care. Rooms used only for storage should be soundly constructed and fitted with secure locks. Floors should be kept clear and the pesticides clearly identified. If repacking is carried out in storage rooms, adequate ventilation and light should be available; floors should be impervious and sound; washing facilities should be available; and eating, drinking and smoking should be prohibited in the area.

A few compounds react with other chemicals or with air, and this has to be taken into account when planning storage facilities. Examples are cyanide salts (which react with acid to produce hydrogen cyanide gas) and dichlorvos (which vaporizes in contact with air). (Dichlorvos is classified as a group 2B possible human carcinogen by the IARC.).

Mixing and application

Mixing and application may comprise the most hazardous phase of the use of pesticides, since the worker is exposed to the concentrate. In any particular situation, only selected persons should be responsible for mixing; they should be thoroughly conversant with the hazards and provided with the proper facilities for dealing with accidental contamination. Even when the mixed formulation is of such a toxicity that it can be used with a minimum of personal protective equipment (PPE), more elaborate equipment may need to be provided for and used by the mixer.

For pesticides of moderate or higher hazard, some type of PPE is almost always necessary. The choice of particular items of equipment will depend on the hazard of the pesticide and the physical form in which it is being handled. Any consideration of PPE must also include not only provision but also adequate cleaning, maintenance and replacement.

Where climatic conditions preclude the use of some types of PPE, three other principles of protection can be applied—protection by distance, protection by time and protection by change of working method. Protection by distance involves modification of the equipment used for application, so that the person is as far away as possible from the pesticide itself, bearing in mind the likely routes of absorption of a specific compound.

Protection by time involves limitation of hours of work. The suitability of this method depends on whether the pesticide is readily excreted or whether it is cumulative. Accumulation of some compounds occurs in the body when the rate of excretion is slower than the rate of absorption. With some other compounds, a cumulative effect may occur when the person is exposed to repeated small doses which, taken individually, may not give rise to symptoms.

Protection by change of working method involves a reconsideration of the whole operation. Pesticides differ from other industrial processes in that they can be applied from the ground or the air. Changes of method on the ground depend largely on the choice of equipment and the physical nature of the pesticide to be applied.

Pesticides that are applied from the air can be in the form of liquids, dusts or granules. Liquids may be sprayed from very low altitudes, frequently as fine droplets of concentrated formulations, known as ultra-low volume (ULV) applications. Drift is a problem particularly with liquids and dusts. Aerial application is an economical way of treating large tracts of land but entails special hazards to pilots and to workers on the ground. Pilots can be affected by leakage from hoppers, by pesticides carried into the cockpit on clothes and boots, and by flying back through the swathe just released or through the drift from the swathe. Even minor degrees of absorption of some pesticides or their local effects (such as may be caused, for instance, by an organophosphorus compound in the eye) can affect a pilot to the extent that he or she cannot maintain the high degree of vigilance necessary for low flying. Pilots should not be allowed to engage in pesticide operations unless they have been specially trained in the items listed above, in addition to any special aviation and agricultural operational requirements.

On the ground, loaders and flaggers may be affected. The same principles apply to loaders as to others dealing with pesticides in bulk. Flaggers mark the swathe to be flown and can be severely contaminated if the pilot misjudges the moment of release. Balloons or flags can be placed in position before or ahead of the operation, and workers should never be used as flaggers within the flight pattern.

Other restrictions

The hazards associated with pesticides do not end with their application; with the more toxic compounds it has been shown that there is a danger to workers entering a sprayed crop too soon after application. It is therefore important that all workers and members of the general public should be informed concerning the areas where a toxic pesticide has been applied and the earliest date on which it is safe to enter and work in these areas. Where a food crop has been sprayed, it is also important that the crop not be harvested until a sufficient period has elapsed for degradation of the pesticide to take place, in order to avoid excessive residues on food.

Disposal of pesticides and containers. Spillage of pesticides at any stage of their storage or handling should be treated with great care. Liquid formulations may be reduced to solid phase by evaporation. Dry sweeping of solids is always hazardous; in the factory environment, these should be removed by vacuum cleaning or by dissolving them in water or other solvent. In the field they may be washed away with water into a suitable soak-hole. Contaminated topsoil should be removed and buried if any domestic animals or fowls are in the area. Soak-holes should be used for disposing of washing waters from cleaning application equipment, clothing or hands. These should be at least 30 cm deep and sited well away from wells or watercourses.

Empty pesticide containers should be collected with care, or disposed of safely. Plastic liners, and paper or card containers should be crushed and buried well below the topsoil or burned, preferably in an incinerator. Metal containers of some pesticides can be decontaminated according to the instructions of the pesticide manufacturers. Such drums should be clearly marked “Not to be used for food or for water for drinking or domestic use”. Other metal containers should be punctured, crushed or buried.

Hygiene and first aid

Where a pesticide is of moderate or higher hazard and can be readily absorbed through the skin, special precautions are necessary. In some situations where workers may become accidentally contaminated with large quantities of concentrate, such as in factory situations and mixing, it is necessary to provide a shower bath in addition to the usual washing facilities. Special arrangements for cleaning clothing and overalls may be necessary; in any case, these should not be left for the worker to wash at home.

Since pesticides are often applied outside the factory environment, depending on the chemical used, special care may have to be taken to provide washing facilities at the workplace, even though this may be in remote fields. Workers must never bathe themselves in canals and rivers, the water from which may be subsequently used for other purposes; the washing water provided should be disposed of with care as outlined above. Smoking, eating and drinking before washing should be absolutely prohibited when any pesticide of moderate or higher toxicity is being handled or used.

Where an antidote exists which can be readily used as a first-aid measure for a specific pesticide (e.g., atropine for organophosphorus poisoning), it should be readily available to workers, who should be instructed in the method of its use. When any pesticide is being used on a substantial scale, medical personnel in the area should be informed by the persons responsible for distribution. The nature of the chemical used should be well defined so that medical facilities can be equipped and will know the specific antidotes, where these are applicable and how to recognize cases of poisoning. Facilities should also be available in order to make proper differential diagnosis, even if these are of the simplest type, such as test papers for determining cholinesterase levels. Strict routine medical supervision of workers heavily exposed to concentrates, as in the manufacture and packing of pesticides, is essential and should include laboratory tests and routine surveillance and record keeping.

Training

While all workers using pesticide formulations of moderate or higher hazard should be thoroughly trained in their use, such training is particularly important if the pesticide is extremely toxic. Training programmes must cover: toxicity of compounds used and routes of absorption; handling of concentrates and formulations; methods of use; cleaning of equipment; precautions to be taken and PPE to be worn; maintenance of PPE; avoidance of contamination of other crops, foods and water supplies; early symptoms of poisoning; and first-aid measures to be taken. All training should be strictly relevant to the pesticide actually being used, and, in the case of extremely hazardous compounds, it is wise to license operators following an examination to show that they have, in fact, a good understanding of the hazards and the procedures to be followed.

Public health measures

When pesticides are used, every effort must be made to avoid contamination of water supplies, whether these are officially recognized supplies or not. This not only concerns the actual application (when there may be immediate contamination) but must also include consideration of remote contamination by run-off through rainfall on recently treated areas. While pesticides in natural watercourses may be diluted to such a degree that the contaminated water may not be hazardous in itself, the effect on fish, on water vegetables used as food and grown in the watercourses, and on wild life as a whole must not be overlooked. Such hazards may be economic rather than directly related to health, but are no less important.

 

Back

Read 6215 times Last modified on Thursday, 19 May 2011 08:33

Contents

Preface
Part I. The Body
Part II. Health Care
Part III. Management & Policy
Part IV. Tools and Approaches
Biological Monitoring
Resources
Epidemiology and Statistics
Ergonomics
Occupational Hygiene
Personal Protection
Record Systems and Surveillance
Toxicology
Part V. Psychosocial and Organizational Factors
Part VI. General Hazards
Part VII. The Environment
Part VIII. Accidents and Safety Management
Part IX. Chemicals
Part X. Industries Based on Biological Resources
Part XI. Industries Based on Natural Resources
Part XII. Chemical Industries
Part XIII. Manufacturing Industries
Part XIV. Textile and Apparel Industries
Part XV. Transport Industries
Part XVI. Construction
Part XVII. Services and Trade
Part XVIII. Guides

Biological Monitoring Additional Resources

Click the Button below to view additional resources for this topic.

button

Biological Monitoring References

Alcini, D, M Maroni, A Colombi, D Xaiz, and V Foà. 1988. Evaluation of a standardised European method for the determination of cholinesterase activity in plasma and erythrocytes. Med Lavoro 79(1):42-53.

Alessio, L, A Berlin, and V Foà. 1987. Influence factors other than exposure on the levels of biological indicators. In Occupational and Environmental Chemical Hazards, edited by V Foà, FA Emmett, M Maroni, and A Colombi. Chichester: Wiley.

Alessio, L, L Apostoli, L Minoia, and E Sabbioni. 1992. From macro- to micro-doses: Reference values for toxic metals. In Science of the Total Environment, edited by L Alessio, L Apostoli, L Minoia, and E Sabbioni. New York: Elsevier Science.

American Conference of Governmental Industrial Hygienists (ACGIH). 1997. 1996-1997 Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, Ohio: ACGIH.

—. 1995. 1995-1996 Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, Ohio: ACGIH.

Augustinsson, KB. 1955. The normal variation of human blood cholinesterase activity. Acta Physiol Scand 35:40-52.

Barquet, A, C Morgade, and CD Pfaffenberger. 1981. Determination of organochlorine pesticides and metabolites in drinking water, human blood, serum and adipose tissue. J Toxicol Environ Health 7:469-479.

Berlin, A, RE Yodaiken, and BA Henman. 1984. Assessment of Toxic Agents at the Workplace. Roles of Ambient and Biological Monitoring. Proceedings of the International Seminar held in Luxembourg, December 8-12. 1980. Lancaster, UK: Martinus Nijhoff.

Bernard, A and R Lauwerys. 1987. General principles for biological monitoring of exposure to chemicals. In Biological Monitoring of Exposure to Chemicals: Organic Compounds, edited by MH Ho and KH Dillon. New York: Wiley.

Brugnone, F, L Perbellini, E Gaffuri, and P Apostoli. 1980. Biomonitoring of industrial solvent exposure of workers’ alveolar air. Int Arch Occup Environ Health 47:245-261.

Bullock, DG, NJ Smith, and TP Whitehead. 1986. External quality assessment of assays of lead in blood. Clin Chem 32:1884-1889.

Canossa, E, G Angiuli, G Garasto, A Buzzoni, and E De Rosa. 1993. Dose indicators in farm workers exposed to mancozeb. Med Lavoro 84(1):42-50.

Catenacci, G, F Barbieri, M Bersani, A Ferioli, D Cottica, and M Maroni. 1993. Biological monitoring of human exposure to atrazine. Toxicol Letters 69:217-222.

Chalermchaikit, T, LJ Felice, and MJ Murphy. 1993. Simultaneous determination of eight anticoagulant rodenticides in blood serum and liver. J Anal Toxicol 17:56-61.

Colosio, C, F Barbieri, M Bersani, H Schlitt, and M Maroni. 1993. Markers of occupational exposure to pentachlorophenol. B Environ Contam Tox 51:820-826.

Commission of the European Communities (CEC). 1983. Biological indicators for the assessment of human exposure to industrial chemicals. In EUR 8676 EN, edited by L Alessio, A Berlin, R Roi, and M Boni. Luxembourg: CEC.

—. 1984. Biological indicators for the assessment of human exposure to industrial chemicals. In EUR 8903 EN, edited by L Alessio, A Berlin, R Roi, and M Boni. Luxembourg: CEC.

—. 1986. Biological indicators for the assessment of human exposure to industrial chemicals. In EUR 10704 EN, edited by L Alessio, A Berlin, R Roi, and M Boni. Luxembourg: CEC.

—. 1987. Biological indicators for the assessment of human exposure to industrial chemicals. In EUR 11135 EN, edited by L Alessio, A Berlin, R Roi, and M Boni. Luxembourg: CEC.

—. 1988a. Biological indicators for the assessment of human exposure to industrial chemicals. In EUR 11478 EN, edited by L Alessio, A Berlin, R Roi, and M Boni. Luxembourg: CEC.

—. 1988b. Indicators for Assessing Exposure and Biological Effects of Genotoxic Chemicals. EUR 11642 Luxembourg: CEC.

—. 1989. Biological indicators for the assessment of human exposure to industrial chemicals. In EUR 12174 EN, edited by L Alessio, A Berlin, R Roi, and M Boni. Luxembourg: CEC.

Cranmer, M. 1970. Determination of p-nitrophenol in human urine. B Environ Contam Tox 5:329-332.

Dale, WE, A Curley, and C Cueto. 1966. Hexane extractable chlorinated insecticides in human blood. Life Sci 5:47-54.

Dawson, JA, DF Heath, JA Rose, EM Thain, and JB Ward. 1964. The excretion by humans of the phenol derived in vivo from 2-isopropoxyphenyl-N-methylcarbamate. Bull WHO 30:127-134.

DeBernardis, MJ and WA Wargin. 1982. High performance liquid chromatographic determination of carbaryl and 1 naphtol in biological fluids. J Chromatogr 246:89-94.

Deutsche Forschungsgemeinschaft (DFG). 1996. Maximum Concentrations At the Workplace (MAK) and Biological Tolerance Values (CBAT) for Working Materials. Report No.28.VCH. Weinheim, Germany: Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area.

—. 1994. List of MAK and BAT Values 1994. Weinheim, Germany: VCH.

Dillon, HK and MH Ho. 1987. Biological monitoring of exposure to organophosphorus pesticides. In Biological Monitoring of Exposure to Chemicals: Organic Compounds, edited by HK Dillon and MH Ho. New York: Wiley.

Draper, WM. 1982. A multiresidue procedure for the determination and confirmation of acidic herbicide residues in human urine. J Agricul Food Chem 30:227-231.

Eadsforth, CV, PC Bragt, and NJ van Sittert. 1988. Human dose-excretion studies with pyrethroid insecticides cypermethrin and alphacypermethrin: Relevance for biological monitoring. Xenobiotica 18:603-614.

Ellman, GL, KD Courtney, V Andres, and RM Featherstone. 1961. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88-95.

Gage, JC. 1967. The significance of blood cholinesterase activity measurements. Residue Rev 18:159-167.

Health and Safety Executive (HSE). 1992. Biological Monitoring for Chemical Exposures in the Workplace. Guidance Note EH 56. London: HMSO.

International Agency for Research on Cancer (IARC). 1986. IARC Monographs On the Evaluation of Carcinogenic Risks to Humans - An Updating of (Selected) IARC Monographs from Volumes 1 to 42. Supplement 6: Genetic and related effects; Supplement 7: Overall evaluation of carcinogenicity. Lyon: IARC.

—. 1987. Method for Detecting DNA Damaging Agents in Humans: Applications in Cancer Epidemiology and Prevention. IARC Scientific Publications, No.89, edited by H Bartsch, K Hemminki, and IK O’Neill. Lyon: IARC.

—. 1992. Mechanisms of Carcinogenesis in Risk Identification. IARC Scientific Publications, No.116, edited by H Vainio. Lyon: IARC.

—. 1993. DNA Adducts: Identification and Biological Significance. IARC Scientific Publications, No.125, edited by K Hemminki. Lyon: IARC.

Kolmodin-Hedman, B, A Swensson, and M Akerblom. 1982. Occupational exposure to some synthetic pyrethroids (permethrin and fenvalerate). Arch Toxicol 50:27-33.

Kurttio, P, T Vartiainen, and K Savolainen. 1990. Environmental and biological monitoring of exposure to ethylenebisdithiocarbamate fungicides and ethylenethiourea. Br J Ind Med 47:203-206.

Lauwerys, R and P Hoet. 1993. Industrial Chemical Exposure: Guidelines for Biological Monitoring. Boca Raton: Lewis.

Laws, ERJ. 1991. Diagnosis and treatment of poisoning. In Handbook of Pesticide Toxicology, edited by WJJ Hayes and ERJ Laws. New York: Academic Press.

Lucas, AD, AD Jones, MH Goodrow, and SG Saiz. 1993. Determination of atrazine metabolites in human urine: Development of a biomarker of exposure. Chem Res Toxicol 6:107-116.

Maroni, M, A Ferioli, A Fait, and F Barbieri. 1992. Messa a punto del rischio tossicologico per l’uomo connesso alla produzione ed uso di antiparassitari. Prev Oggi 4:72-133.

Reid, SJ and RR Watts. 1981. A method for the determination of diaklyl phosphate residues in urine. J Anal Toxicol 5.

Richter, E. 1993. Organophosphorus Pesticides: A Multinational Epidemiologic Study. Copenhagen: Occupational Health Programme and WHO Regional Office for Europe.

Shafik, MT, DE Bradway, HR Enos, and AR Yobs. 1973a. Human exposure to organophosphorous pesticides: A modified procedure for the gas-liquid chromatographic analysis of the alkyl phosphate metabolites in urine. J Agricul Food Chem 21:625-629.

Shafik, MT, HC Sullivan, and HR Enos. 1973b. Multiresidue procedure for halo- and nitrophenols: Measurements of exposure to biodegradable pesticides yielding these compounds as metabolites. J Agricul Food Chem 21:295-298.

Summers, LA. 1980. The Bipyridylium Herbicides. London: Academic Press.

Tordoir, WF, M Maroni, and F He. 1994. Health surveillance of pesticide workers: A manual for occupational health professionals. Toxicology 91.

US Office of Technology Assessment. 1990. Genetic Monitoring and Screening in the Workplace. OTA-BA-455. Washington, DC: US Government Printing Office.

van Sittert, NJ and EP Dumas. 1990. Field study on exposure and health effects of an organophosphate pesticide for maintaining registration in the Philippines. Med Lavoro 81:463-473.

van Sittert, NJ and WF Tordoir. 1987. Aldrin and dieldrin. In Biological Indicators for the Assessment of Human Exposure to Industrial Chemicals, edited by L Alessio, A Berlin, M Boni, and R Roi. Luxembourg: CEC.

Verberk, MM, DH Brouwer, EJ Brouer, and DP Bruyzeel. 1990. Health effects of pesticides in the flower-bulb culture in Holland. Med Lavoro 81(6):530-541.

Westgard, JO, PL Barry, MR Hunt, and T Groth. 1981. A multirule Shewhart chart for quality control in clinical chemistry. Clin Chem 27:493-501.

Whitehead, TP. 1977. Quality Control in Clinical Chemistry. New York: Wiley.

World Health Organization (WHO). 1981. External Quality Assessment of Health Laboratories. EURO Reports and Studies 36. Copenhagen: WHO Regional Office for Europe.

—. 1982a. Field Survey of Exposure to Pesticides, Standard Protocol. Document. No. VBC/82.1 Geneva: WHO.

—. 1982b. Recommended Health-Based Limits in Occupational Exposure to Pesticides. Technical Report Series, No.677. Geneva: WHO.

—. 1994. Guidelines in Biological Monitoring of Chemical Exposure at the Workplace. Vol. 1. Geneva: WHO.