PESTICIDES KILL YOUR NERVOUS SYSTEM

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Health impacts of pesticide exposure and approaches to prevention

Fengsheng He, Shuyang Chen

P.R. China

Abstract

Pesticides are used worldwide to control pests that destroy crops and

transmit diseases to people and animals. Agriculture, horticulture, vector

control and forestry and livestock production account for the greatest use of

pesticides. Acute pesticide poisoning has for some time now been an important

occupational and public health problem, particularly in the developing

countries. In recent years, the development of resistance in pest species has

resulted in increased dosages and the application of new compounds or

pesticide mixtures, thereby leading to increased risks of occupational and

accidental poisoning. Legislative control, sound pest management practices,

the

proper training of users and the continued development of safer compounds are

essential for the prevention of hazardous effects of pesticides on human

health.

Single and combined pesticide exposure

The term 'pesticide' covers a wide range of compounds including insecticides,

fungicides, herbicides, rodenticides, molluscacides, nematocides, plant

growth regulators and others. Thus far, more than

1,000 active substances have been incorporated in the approximately 35,000

preparations which are known as pesticides. Insecticides represent by far the

greatest proportion of pesticides used in

developing countries, whereas herbicide sales have been greater than those of

other pesticides in industrialized countries.

It has been estimated that the use of pesticides in developing countries

approximately doubled every ten years between 1945 and 1995. Organochlorine

insecticides, which had been used successfully in

controlling a number of diseases, such as typhus and malaria, were banned or

restricted after the 1960s because of their adverse effects on the ecosphere.

The introduction of other synthetic insecticides - including organophosphates

in the 1960s, carbamates in the 1970s and pyrethroids in the 1980s - and the

introduction of herbicides and fungicides in the 1970s-1980s, contributed

greatly to pest control and to increased yields in the case of cereal crops

and cotton (1,2).

In China, the number of registered pesticide formulations was about 1,600 in

1996. Insecticides account for the highest proportion (60%) of total

pesticide usage, followed by fungicides and herbicides. The principal classes

of compounds that have been used as insecticides are

organophosphates, pyrethroids, carbamates and some others. In addition, more

than 600 kinds of pesticide mixture preparations, mainly containing

organophosphorus insecticides, have been produced and applied in China in

recent years. The trend towards the development of combined

pesticides is mainly due to the resistance of pests to single pesticides.

Occupational and non-occupational exposure

Occupational exposure to pesticides occurs in manufacturing processes, such

as mixing, loading, packaging and storage. Workers involved in pest control

in agriculture and vector-borne disease prevention programmes are usually

exposed to pesticides during mixing and spraying. Accidental

exposure often results from the misuse of pesticides, and suicide attempts

are another cause of exposure. The situation as regards non-occupational

exposure to pesticides differs greatly from one country to the other.

If one shares the common belief that pests are responsible for a loss of one

third of pre-harvest yields and that the use of pesticides can increase rice

yield by 50%, one can expect that chemical pesticides will probably continue

to be the principal component of pest control programmes in agriculture in

the foreseeable future (1). However, the effects of pesticide exposure have

resulted in problems for human health, and these are of growing concern.

Acute pesticide poisoning

Worldwide estimates suggest that there are about 3 million acute pesticide

poisonings and 220,000 deaths each year. Most of the poisonings and 99% of

the deaths are believed to occur in developing

countries (1). In the Asian region, a survey of acute pesticide poisoning

among agricultural workers revealed that occupational pesticide poisonings

accounted for about 1.9% of the cases in Indonesia

and as many as 31.9% in Sri Lanka, while suicides accounted for 62.6% of the

cases in Indonesia, 67.9% in Malaysia, 36.2% in Sri Lanka and 61.4% in

Thailand (3). In China, 52,287 cases of acute pesticide poisoning with 6,281

deaths were reported from 27 provinces in 1993. Of the total

cases, occupational pesticide poisoning accounted for 17.8% and intentional

poisoning cases for 82.2%. However, in Latin America, it appears that most

cases of pesticide poisoning are occupational. For example, in Costa Rica

67.8% were work-related compared with 6.4% that

were suicide-related. In Nicaragua, 91% of the reported cases of pesticide

poisoning were occupational, 8% involved other accidents, and 1% were

intentional (3). The causal factors contributing to acute occupational

pesticide poisoning include sloppy handling during the

preparation and spraying of pesticides, using highly toxic pesticides or high

concentrations of pesticides, spraying every row, direct contact with sprayed

crops, going forward into the wind during spraying, lack of personal

protection, and poor personal hygiene (4).

Acute organophosphorus insecticide poisoning

The main classes of pesticides responsible for acute poisoning in many

developing countries have been identified as organophosphate insecticides.

Acute organophosphate (OP) poisoning accounts for 78.8% of total pesticide

poisonings in China, 69.1% in Sri Lanka, and 53.6% in Malaysia (3).

The organophosphorus insecticides are neurotoxic. The neurotoxic effects of

acute OP poisoning include three categories of clinical syndromes:

1. Acute cholinergic crisis

Organophosphates cause acute toxic effects by inhibiting the enzyme

acetylcholinesterase (AChE); this leads to the accumulation of acetylcholine

at all cholinergic transmission sites in the peripheral

and central nervous system.

Symptoms and signs resulting from mild acute OP poisoning include dizziness,

headache, nausea, vomiting, miosis (small pupils), excessive sweating and

tracheobroncheal and salivary secretions. Muscular fasciculations and

shortness of breath appear in cases of moderate poisoning, while patients

with severe poisoning develop coma, pulmonary oedema and respiratory

depression.

The cholinergic effects of acute OP poisoning usually correlate with blood

AChE inhibition at the initial stage (5). Early treatments are necessary,

with atropine and oxime cholinesterase reactivators at

repeated and sufficient dosages, in addition to the rapid removal of toxic

compounds.

The fatality rate of occupational OP poisoning in China was 0.9%, whereas the

fatality of intentional OP poisoning was 14.2%.

2. Organophosphate-induced delayed polyneuropathy

Some organophosphates induce a delayed polyneuropathy (OPIDP), which occurs

following a latent period of 2-4 weeks after the cholinergic crisis and is

independent of AChE inhibition. The neuropathy target esterase (NTE) is

thought to be the primary target protein for OPIDP which has recently been

purified (6).

The main symptoms and signs of OPIDP include distal weakness of the feet and

hands, calf pain preceding the weakness, and paraesthesia in the distal parts

of limbs. Wasting of distal muscles is frequent. In severe cases, signs of

spinal cord involvement (spasticity, increased tendon reflexes and

pathological reflexes) appear after several weeks or months after poisoning.

In China, 218 cases of OPIDP were reported in the Chinese medical journals in

the period 1960-1990. They were mainly induced by exposure to methamidophos

and by suicide attempts involving dichlorvos, trichlorphon, dimethoate,

isocarbophos, etc.

A follow-up study on patients with acute methamidophos poisoning indicated an

OPIDP prevalence of 9.1%, while the prevalence of OPIDP caused by other kinds

of OPs was found to be 4.2% in severe cases. Treatments are mainly

symptomatic, and recovery from OPIDP is variable in degree. Severe cases of

OPIDP are usually irreversible and lead to lifelong disability.

3. Intermediate myasthenia syndrome (IMS)

The " intermediate syndrome " (IMS) is another outcome of severe acute OP

poisoning; it was first reported by Senanayake and Karalliedde in 1987. IMS

is characterized by muscle weakness, which usually occurs at 24-96 h after

acute poisoning after the victim has recovered from the

cholinergic crisis and is conscious, but before the expected onset of the

delayed polyneuropathy.

The cardinal clinical feature is muscle weakness affecting predominantly the

neck flexors, proximal limb muscles, muscles innervated by motor cranial

nerves and respiratory muscles. Respiratory insufficiency usually draws

attention to the onset of the IMS and is also the cause of death if not

recognized early and adequately treated by means of artificial ventilation.

The fatality rate of IMS was reported to be about 20%. Repetitive nerve

stimulation at 20 Hz and 30 Hz revealed a marked decrement of evoked compound

muscle potentials, indicating the existence of post-synaptic block of

neuromuscular transmission (7).

IMS has not yet been widely recognized in clinical practice, is not as rare

as might be expected, and involves the risk of death in patients with

respiratory muscular weakness. For these reasons, we propose naming the

syndrome " Intermediate Myasthenia Syndrome (IMS) " , in order to promote the

recognition of this myasthenia syndrome following acute OP poisoning.

Acute carbamate poisoning

Insecticidal and nematocidal carbamates are also cholinesterase inhibitors

and have a high acute toxicity. In Nicaragua, almost half of the total

pesticide poisonings involved the carbamate insecticides, with figures of

15.9% in Thailand and 10.7% in Malaysia (3). In China, thousands of victims

of acute carbamate poisoning have been reported; such poisoning has been

mainly caused by carbofuran (more than 1,500 cases) and to a lesser extent by

carbaryl, MTMC and isoprocarb (MIPC).

Carbamate insecticides produce a clinical picture of cholinergic excess

similar to that of OP toxicity. However, because of spontaneous hydrolysis of

the carbamylated AChE enzyme, the symptoms are less severe and of shorter

duration. The carbamates penetrate the blood-brain barrier only poorly, and

therefore produce minimal effects on brain ChE activity and few CNS symptoms.

Atropine is the antidote of choice, but the total amount required is usually

less than that for acute OP poisoning. The prognosis is usually good in cases

of occupational carbamate poisoning. Fatal cases nearly all involve

intentional poisoning.

Acute pyrethroid poisoning

Synthetic pyrethroids have a high insecticidal activity and a low toxicity in

mammals. Pyrethroids are unlikely to be of acute toxicity for occupationally

exposed subjects employing good work practices and safety precautions.

However, about two hundred cases of acute occupational pyrethroid poisoning

resulting from inappropriate handling were first reported in China in 1982.

In the period 1983-1998, more than 1,700 cases of acute pyrethroid poisoning

(occupational cases 1/3,

intentional 2/3) were reported in the Chinese medical literature (8). The

majority of cases involved exposure to deltamethrin, followed by fenvalerate,

cypermethrin and other pyrethroids (cyfluthrin,

fenpropathrin). In an epidemiological survey conducted in China, the

prevalence of mild acute pyrethroid poisoning in 3,113 spraymen was 0.38% (4).

The initial symptoms of acute occupational pyrethroid poisoning are burning

and itching sensations in the face or dizziness; these usually develop 4-6 h

after exposure. The symptoms of intentional poisoning often start with

epigastric pain, nausea and vomiting within 10 min - 1 h after ingestion. The

systemic symptoms include dizziness, headache, nausea, anorexia, fatigue,

increased stomal secretion, and muscular fasciculation. Convulsive attacks,

disturbances of consciousness, and

dyspnea, cyanosis and moist rales indicating pulmonary edema occur mainly in

severe cases of intentional poisoning.

The vast majority of patients with acute pyrethroid poisoning recover fully

after symptomatic and supportive treatments lasting 1-6 days. The few fatal

cases reported have been due to misdiagnosis and inappropriate treatments;

they include persons poisoned by pyrethroid-organophosphate

mixtures and treated with an insufficient dosage of atropine, as well as

victims of pure pyrethroid poisoning dying of an overdose of atropine (8).

Acute poisoning due to combined insecticide exposure

Because of the development of resistance in insects to the above-mentioned

single insecticide, there has been an increasing application of combined

insecticides in China in recent years. At present, more than 600 kinds of

pesticide mixture preparations (mainly OP + pyrethroids, OP + OP, OP +

carbamates and some others) are being or have been marketed in China.

Consequently, the reported number of cases of occupational acute poisoning

due to combined insecticide exposure increased from 2.6% of the total annual

reported number of acute occupational pesticide poisonings in 1993 to 5.8% in

1997. The number of cases of acute poisoning due to exposure to

organophosphate + pyrethroid mixtures reported in the Chinese medical

journals in the late 1990s was about 4 times greater than the number reported

in the late 1980s.

A cross-sectional survey recently conducted by the authors' team showed that

the prevalence of acute pesticide poisoning in farmers with exposure to

combined insecticides and single OP insecticide was 10.1 and 2.3

respectively; this represented a significant difference (x2=12.460,

p=0.005). The results implied a higher risk of acute poisoning in subjects

exposed to OPs combined with other insecticides than in those exposed to a

single OP insecticide (RR= 4.41).

Since the majority of the pesticide mixtures contain OPs which are more

potent in toxicity than the other ingredients, the main clinical features of

acute poisoning involving pesticide mixtures are similar to those of acute OP

poisoning. In general, the treatments should be given for acute OP pesticide

poisoning first and then supplemented with symptomatic therapies.

Long-term effects of pesticide exposure

Long-term health effects from prolonged exposure to pesticides - including

cancer mortality, reproductive effects and non-cancer health effects - have

been studied in many countries. A comprehensive review reveals evidence of

suppression of spermatogenesis and increased FSH and

LH levels as a result of long-term exposure to dibromochloropropane (DBCP).

However, firm conclusions on other adverse effects of chronic exposure to

pesticides on human health are difficult to draw at present (9). In this

connection, valid measurements of exposure covering relatively long periods

and well-designed epidemiological studies are desperately needed.

Approaches to prevention

About 100 million members of the agricultural population are likely to have

significant exposure to pesticides. In addition, 500 million people may be

exposed to pesticides to a lesser extent (1). In view of the major problem of

acute pesticide poisoning, particularly in the developing countries, efforts

are needed on the part of national authorities, non-governmental

organizations and industries in order to

control the health impacts of pesticide use.

It is important to restrict the use of the most hazardous compounds, to

impart information by means of safety labels, to make workers all the way

down the distribution chain aware of the hazards and to train pesticide users

in appropriate application. In this connection, approaches to the prevention

of pesticide poisoning should include:

1. Establishment of legislation to control the use of pesticides and to set

up an infrastructure for enforcement

2. Utilization of suitable techniques and sound pest-management practices to

control pests and avoid their becoming resistant

3. Establishment and strengthening of training and information activities

concerning pesticide safety for pesticide workers, distributors and users

4. Continued development of safer compounds for both agricultural and public

health use.

References

1. WHO/UNEP Working Group. Public Health Impact of Pesticides Used in

Agriculture. Geneva: World Health Organization, 1990.

2. Forget G. Balancing the need for pesticides with the risk to human health.

In: Forget G, Goodman T, de Villiers A (eds). Impact of Pesticide Use on

Health in Developing Countries. Ottawa: IDRC, 1993:2-16.

3. He F. Occupational neurotoxic diseases in developing countries. In: Costa

LG; Manzo L (eds). Occupational Neurotoxicology. Boca Raton, USA: C.R.C.

Press, 1998:259-69.

4. Chen S, Zhang Z, He F, et al. An epidemiological study on occupational

acute pyrethroid poisoning in cotton farmers. Br J Ind Med 1991;48:77-81.

5. He F. Biological monitoring of occupational pesticides exposure. Int Arch

Occup Environ Health 1993;65:S 69-S 76.

6. Glynn P, Read DJ, Guo R, et al. Synthesis and characterization of a

biotinylated organophosphorus ester for detection and affinity purification

of a brain serine esterase: neuropathy target esterase. Biochem J

1994;301:551-6.

7. He F, Xu H, Qin F, et al. Intermediate myasthenia syndrome following acute

organophosphates poisoning - an analysis of 21 cases. Hum Exp Toxicol

1998;17:40-5.

8. He F, Wang S, Liu L, et al. Clinical manifestations and diagnosis of acute

pyrethroid poisoning. Arch Toxicol 1989;63:54-8.

9. Maroni M, Fait A. Health Effects in Man from Long-Term Exposure to

Pesticides. Amsterdam: Elsevier, 1993.

Fengsheng He, Shuyang Chen

Institute of Occupational Medicine

Chinese Academy of Preventive Medicine

29, Nan Wei Road

Beijing 100050

People's Republic of China

E-mail: <A HREF= " http:// " >hefs@... </A>