Category Example Effects and Disease Associations

Insecticides Organochlorines Neurotoxicity; hepatotoxicity

••DDT

••Chlordane

••Lindane

••Methoxychlor

Organophosphates Neurotoxicity; delayed neuropathy

••Parathion

••Diazinon

••Malathion

Carbamates Neurotoxicity (reversible)

••Aldicarb

••Carbaryl

Botanical agents Paresthesia; lung irritant; allergic dermatitis

••Nicotine

••Pyrethrins

••Rotenone

Herbicides Arsenic compounds Hyperpigmentation; gangrene; anemia; sensory neuropathy; cancer

Dinitrophenols Hyperthermia; sweating

Chlorophenoxy herbicides

••2,4-D and 2,4,5-T ? Lymphoma; sarcoma

••TCDD Fetotoxicity; immunotoxicity; cancer

Paraquat Acute lung injury

Atrazine ? Cancer

Alachlor ? Cancer

Fungicides Captan ? Reproductive toxicity

Maneb

Benomyl

Rodenticides Fluoroacetate Cardiac and respiratory failure

Warfarin Hemorrhage

Strychnine Respiratory failure

Fumigants Carbon disulfide Cardiac toxicity

Ethylene dibromide Neurotoxicity

Phosphine Lung edema; brain damage

Chloropicrin Eye irritation; lung edema; arrhythmias

Data from Hodgson E: Introduction to toxicology. In Hodgson E, Levi PE (eds): A Textbook of Modern Toxicology. Stamford, CT, Appleton & Lange, 1997, p. 1; and Levi PE: Classes of

toxic chemicals. In Hodgson E, Levi PE (eds): A Textbook of Modern Toxicology. Stamford, CT, Appleton & Lange, 1997, p. 229.

soil and water supplies. Environmental contamination is a threat to wildlife; some pesticides undergo bioaccumulation and persist in wildlife and humans for decades. Bioaccumulation and

biopersistence are characteristic of organochlorines, such as DDT (dichlorodiphenyltrichloroethane), and dioxins, such as TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin). There is

considerable controversy about the adverse health effects of these persistent pesticides and their metabolites, especially concerning their relationship to breast cancer,[48] reproductive

abnormalities,[49] and cognitive deficits.[50]

Agricultural pesticides are divided into five categories, depending on the target pest: insecticides, herbicides, fungicides, rodenticides, and fumigants ( Table 9-14 ). All pesticides are toxic

to some plant or rodent species; at higher doses, they can also be toxic to farm animals, pets, and humans. In general, herbicides used to control weeds have low acute toxicity for

mammals; fungicides are characterized as moderately toxic. Acute toxicity of insecticides for mammals ranges from low to high. For example, DDT was widely used as an insecticide in

the 1940s and 1950s because it has low acute toxicity for humans. However, DDT persists in the environment and accumulates in the food chain. Birds that ingested DDT-contaminated

insects and fish suffered reproductive defects. DDT and its major metabolite, DDE

(1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene), accumulate in fat tissue and have been detected in human milk. Organochlorines, as well as industrial chemicals such as polychlorinated

biphenyls (PCBs), are weakly estrogenic. Some of these chemicals are carcinogenic in rodents and cause reproductive dysfunction in amphibians, birds, and fish.[48] Although several

epidemiologic studies have not found increased levels of DDE or PCBs in women with breast cancer compared with matched control subjects, there is still concern that these persistent

organochlorines, other potentially estrogenic pesticides, and natural phytoestrogens in plants such as soybeans may have adverse reproductive effects in humans. The mechanisms of action

of these xenoestrogens, alone or in combination, in the development of cancer and in reproductive dysfunction are unknown.[48] [49]

The major health effects of the most common agricultural pesticides are summarized in Table 9-14 . Selected examples are discussed here.

• Organochlorines, such as DDT, have low acute toxicity for humans; however, they bioaccumulate and persist in the environment and in fat tissue. These chemicals are absorbed

through the skin, gastrointestinal tract, and lungs. As alluded to earlier, the role of DDT and its metabolites as an endocrine-disrupting agent is controversial. Chlordane is

representative of cyclodienes that are used to control termites and other soil insects. Acute toxicity causes hypothermia, tremor, and convulsions. Chlordane also causes immune

dysfunction and may act as a nongenotoxic carcinogen. These effects may contribute to the increased incidence of lymphoma observed in some farm workers. Lindane is an isomer

of benzene hexachloride that is used to control lice and scabies, as a wood preservative, and as a household fumigant. It has been reported to cause immune dysfunction and

reproductive problems in women.

• Organophosphates are irreversible inhibitors of cholinesterases resulting in abnormal transmission at peripheral and central nerve endings. These chemicals are absorbed through

the skin, gastrointestinal tract, and lungs. Up to 40% of farm workers in the United States show measurable inhibition of red blood cell or plasma cholinesterase activity; fatalities

have been reported from organophosphate exposure. Carbamates are reversible inhibitors of cholinesterase that produce acute neurotoxic effects similar to those of

organophosphate insecticides. Carbaryl (Sevin) is potentially mutagenic and teratogenic because it poisons the mitotic spindle.

• Herbicides like the dioxin TCDD has received much attention. During the Vietnam War, the defoliant Agent Orange was contaminated with TCDD. A chemical factory explosion

in Seveso, Italy, in 1976 caused local environmental contamination and human exposure to TCDD, resulting in chloracne and an increased incidence of leukemia, lymphoma, and

sarcomas. TCDD and structurally similar dioxins are also produced in the paper pulp industry using chlorine bleach and by waste incinerators. Low doses of dioxin are present in

our food, soil, and water. In some laboratory animals, TCDD is highly toxic, immunosuppressive, teratogenic, and carcinogenic. The sensitivity of some strains of laboratory mice

to dioxin is linked to the aryl hydrocarbon hydroxylase receptor. TCDD can induce liver cytochrome P-450 enzyme activity, increase estrogen metabolism, and interfere with

development of the male reproductive tract. TCDD also decreases thyroxine levels in adult rats. Extrapolation of these multiple adverse effects observed in laboratory animals to

low-dose exposure of humans is difficult.[51]

• Rodenticides are highly toxic chemicals with restricted use. The major health threat is death from suicidal or accidental ingestion.

TABLE 9-15-- Natural Toxins

Date: 2016-04-22; view: 917