"Organophosphate-based pesticides have been associated with pathology and chromosomal damage in humans. There are also epidemiological links between organophosphate-based pesticides and cancer. Currently low-level chemical exposure receives less attention than does acute poisoning and the few screening tests for low level occupational exposure are of doubtful sensitivity. This investigation evaluated four methods and undertook a pilot study of safe-handling practices among a group of workers with occupational exposure to organophosphate-based pesticides in the Riverina area, Australia. Blood samples were studied from ten farmers before and after occupational exposure to the pesticides and from five unexposed controls."

"that Howell-Jolly body and chromosome breakage analysis are sensitive indicators of cell nuclear damage resulting from low level occupational exposure to organophosphates. Such nuclear damage could be implicated in carcinogenesis; the development of bladder cancer is one such example.

In addition, it was found that despite the education of 70% of the farmers tested, not one of them abided by all of the safety procedures recommended. The design of protective clothing may need to be reevaluated in order to increase compliance."

The organophosphate-based chemicals act as anti-cholinesterase substances and are widely used throughout the world (1). Organophosphate-based chemicals are most commonly insecticides but they are also used in fungicides and herbicides, and have common usage in agriculture. Specifically, they have been used to control insect numbers in commercial crops, as well as to control parasites on animals such as sheep and cattle (eg. fly-strike control). One significant advantage organophosphate chemicals offer over other insecticide agents such as organochlorines (eg. DDT) is that they are much less persistent in the environment (2). Despite the advantages the application of these pesticides has to offer, there is also the potential for considerable adverse affects to those exposed over extended periods of time (2).

A variety of short term and chronic effects may be experienced following repeated or prolonged exposure to organophosphate-based pesticide exposure including difficulty in breathing, involuntary muscle contractions, blurred vision, tear formation, bleeding in the eye, nausea, headache, confusion and slurred speech (1, 3). Little information has been gathered with respect to long term effects of sublethal doses over a period of time but reports

of depression, memory loss and chronic fatigue syndrome have been presented (1, 3, 4); there is also evidence of a possible carcinogenic effect of organophosphate-based pesticides (5, 6).

Considerable attention has been given to the indicators of genetic damage such as chromosomal aberrations, sister-chromatid exchanges and micronuclei to observe human populations occupationally exposed to organophosphate-based pesticides (5, 7, 8, 9). The precise effects of these chromosomal aberrations induced by occupational exposure to organophosphate-based pesticides are not fully known, but the increase in the number of these aberrations following exposure suggests an increase in the likelihood of cancer development induced by chromosomal damage (6, 8, 10).

There are 118 locations in human chromosomes that have been recognised as having a susceptibility to breakage and these are known as fragile sites. These sites can be observed in the laboratory as chromosomal breaks and gaps following the application of particular chemicals. The number of sites expressed varies between individuals and they show a Mendelian pattern of inheritance. Chromosome breakage is a common occurrence and is usually repaired before cell division proceeds.

The scoring of fragile sites can detect exposure to DNA damaging agents (clastogens) such as X-rays and certain chemicals such as nitrogen mustard or diepoxybutane because the number of fragile sites can be increased in these situations. An even more sensitive test can be obtained when a recognised chromosomal damaging agent is applied in the laboratory to blood samples collected from subjects who have been suspected of being environmentally exposed to a DNA damaging agent. Even mild exposure to clastogenic agents can be detected with this method (11)..

Aphidicolin is the usual inducing agent employed for environmental studies (11, 13, 14, 15, 16); in this context it can induce 67% of the recognised fragile sites in the human genome (12). In 1995 Sbrana and Musio (11) reported an increase in the expression of aphidicolin induced chromosomal fragile sites following occupational exposure to pesticides. This observation reinforced the existence of a link between exposure to clastogenic agents (eg. organophosphate-based pesticides) and fragile site induction. Furthermore, the analysis of the breakage effects of different carcinogens on fragile site regions appeared to be significant in the carcinogenic process of many cancers. Enhanced expression of particular fragile sites were implicated in cancers such as the leukaemias, and non-Hodgkin’s lymphoma and those sites were also the locations of numerous tumour suppressor genes and oncogenes (11, 16). These authors also reported that fragile site expression was a reproducible cell response to human exposure to pesticides (16).

Farmers are one occupational group with a high usage of organophosphate-based pesticides, and thus form a group of potential high risk to the types of genetic damage described above. In this connection, a number of studies have shown an increase in cancer incidence of numerous tumour types among the farming population. These included: bladder cancer (17, 18), prostate cancer (17, 19, 20, 21), non-Hodgkin’s lymphoma (19, 20, 22), multiple myeloma (19, 20), skin cancer (20, 23) kidney cancer (17) and lung cancer (23). Our group looked particularly at bladder cancer, because there is a greater incidence of this type of cancer in our area, the Riverina (6th most common in males) compared to the state of New South Wales in general (8th most common in males) (24)."

"Toxicology of the Organophosphates

Human toxicity to organophosphorus compound has been known since 1899, when neurotoxicity to to phospho-creosole (then used in the treatment of tuberculosis) was reported. The study of the toxicity is extensive with two very well established mechanisms on esterases and on neurotoxic esterases(NTE)"