This is a review on the research work undertaken by the cooperative study group (chief: T. Wakatsuki) from 1986 to 1988.
The results of many studies including clinical case study, epidemiological study and experimental study as well were presented and discussed.

Acute toxic effects from pesticides are fairly easily recognized, whereas the effects that result from long-term exposure to low doses are often difficult to distinguish. The chronic pesticide poisoning may occur theoretically, but as for the reported cases of pesticide poisoning and disorders the majority are generally acute pesticide poisoning and skin lesions.
To make a proposal for the study of the chronic pesticide poisoning and disorders, the author have discussed about the subjects of general speech in the annual meeting of the Japanese Association of Rural Medicine and some nationwide reports on the chronic effects from pesticides. From the results, there are many controversial points to be improve as the confusion of the concepts and terminology used, overestimation of the decrease in serum and plasma cholinesterase activity for diagnosis of pesticide poisoning, fairly limited epidemiological study for evaluation of the chronic health effects associated with pesticide exposure, and so forth.
Many detailed studies will be recommended as the following:
1) Establishment of the approaches to causal relationship between situation of pesticide exposure and health effects; 2) To seize the exposure levels of pesticides in the presentand the past; 3) The development of the methods of accurate examination and diagnosis, and their concrete application to a field study; 4) Establishment of the better designed of epidemiological study; 5) Enforcement of systematic study of health effects of occupational groups exposed to pesticides for long periods; 6) Establishment of the appropriate methods of toxicity testing and their well fitted extrapolation to health effects; 7) Opening to the general public of data on the toxicity testing and on the survey in an enterprise; 8) Cooperation and collaboration in studying among researchersand field workers, and others.

Research work of the Special Research Group for Survey of Pesticide Poisoning (Chief: T. Matsushita) was presented and discussed.
The main items are as follows:
1) Long term years of nation-wide survey for clinical cases of pesticide poisoning (disorders) in Japan from 1967 to 1989, which was carried out by the Research Group of the Pesticide Poisoning under the Japanese Association of Rural Medicine, was reconsidered. And, revised systems of this survey including new survey forms were proposed.
2) Results of methodological research work of our group for epidemiological study to clarify health disturbance from pesticides were indicated and a personal protocol was also presented.

Data concerning clinical cases of pesticide poisoning (disorders) were collected from members of the Japanese Association of Rural Medicine during 1996-1997 FY throughout the nation using a new prescribed form, and were analyzed statistically.
1) A total of 232 cases of poisoning (disorders) by agricultural chemicals were reported from 38 hospitals and other medical institutions.
2) By types of clinical manifestations, the majority of the cases were acute or subacute pesticide poisoning (70.3%), which was followed by acute dermatitis (20.7%).
3) Suicide accounted for 53.4% of the pesticide poisoning (disorders) cases. Poisoning caused after spraying in fields or green houses accounted for 17.2%, during spraying 15.9%, and so forth.
4) Organophosphate insecticides were the most frequent inducers of the clinical cases (35.8%), which was followed by a herbicide bipyridylium (16.8%) and a fungicide fluazinum (15.5%).
5) Main factors contributing to the onset of pesticide poisoning (disorders) excluding suicide were nature of agricultural chemicals (32.7%), insufficient protective clothing (25.7%), overconfidence (21.8%), carelessness (16.8%), ignorance (16.8%), and so forth.
6) Epidemiological features such as by sex, age, seasons, and prognoses were also analyzed and discussed.

The authors reviewed the English language papers concerning chronic health effects of agricultural chemicals, focusing on the incidence of cancer in pesticide users. These papers were collected using MEDLINE between 1988 and 1998 as a referencetool. According to the standard study design, the epidemiological literature is classified into cohort studies and case-control studies. These studies suggested the association between pesticides and various types of cancer such as soft tissue sarcoma, non-Hodgkin's lymphoma, lung cancer, and breast cancer. Categories of pesticides included in these studies, varied greatly, including herbicides and insecticides.
In this paper, we discussed about such problems as the selection of control groups and the assessment of pesticide exposure levels, which may pose some problems in conducting epidemiological research on the relationship between pesticides and cancer.
A model for a method of epidemiological study of health hazards due to pesticide exposure was also presented.

An epidemiolgical survey as well as a case study on the skin hazards due to dithiocarbamate fungicides, such as Maneb and Manzeb (Mancozeb), were carried out. The results were summarized as follows;
1. From the epidemiological survey, the incidence rate of skin lesions due to the dithiocarbamates in three areas were 42.4%(39/92), 43.3%(113/261) and 27.6%(42/151), respectively.
2. The skin lesions appeared generally in face, hands and nape of neck and collar areas and also in covered areas of the body such as breast, back and so forth.
3. By patch testing with a dithiocarbamate “Maneb” the positive reactions in 40 cases tested were observed in 18%, 23% and 15% of the subject with 0.1%, 0.05% and 0.025% preparations, respectively.
The results suggested that allergic type of contact dermatitis is involved in the skin hazard due to the dithiocarbamate fungicides.

A simple and sensitive method for the determination of residual Nicarbazin (NCZ) by high performance liquid chromatography (HPLC) was examined to apply to livestock products. And the detection of residual NCZ in commercial chickens was also investigated.
1. The method that the acetonitrile extracts of meat homogenate were injected directly into HPLC was able to apply to determine the residual NCZ by adding process of degreasing and dehydration of the extracts. The average recovery of NCZ added to the chicken muscle (0.4 μg/g) were 89.13±6.61%(N =5) and detection limit in this analytical procedure was 0.02μg/g.
2. Using the above method for the analysis of NCZ in commercial samples, the frequency of detection was 13.0% and the range of concentration was 0.03-0.30μg/g in samples collected from Kagoshima city (N =131). The residual NCZ in commercial chickens showed a tendency to increase in summer season. The similar levels of frequency (12.5%) and concentrations (0.03-0.43μg/g) were found in samples collected from other prefectures (N=40).

In order to clarify the actual conditions and mechanism of contact dermatitis from pesticides, a field survey including patch testing with 11 pesticides and formaldehyde was carried out on 111 subjects who engaged in farming in the plastic greenhouse mainly. The relationship between skin sensitization due to pesticides and conditions of pesticide exposure was also studied. The results were as follows;
1) About half of subjects (52%) have been suffered from health hazards due to pesticides. Among the symptoms complained, dermatitis was most frequent (32%) as compared with acute poisoning such as headache (12%), general fatigue (9 %) and so on. The causative pesticides of those dermatitis were mainly Difolatan (72%), Daconil (8 %), and Gramoxone (8%).
2) Relatively higher rates of positive reaction of patch testing were observed in Difolatan (43%) in male, and Difolatan (25%), Topsin M (24%), Rovral (24%) in female. A positive reaction with more than one substance tested were seen in 31 males (55%) and 31 females (55%).
3) Among 11 kinds of pesticides tested, positive correlations between the skin reaction of patch testing and the use of corresponding pesticides were found only in Orthocide (r = 0.233) and Daconil (0.203).
4) From the Cluster Analysis, 16 kinds of using pesticides were classified into 3 clusters with similarity to patch test reactions. It was also suggested from the Dendrogram that there might be cross reactions among patch testing pesticides.
5) By Multiple Regression Analysis, no factor which contributed remarkably to skin sensitization was clarified. And, it was suggested that many kinds of factor were complicatedly related to skin sensitization.

The outbreak of skin hazards from okra cultivation was studied by a field survey. About a half (46.2 %) of 186 workers investigated (male, 76 ; female, 110) reported to have experienced pastly or annually skin hazards from okra cultivation.The sites of lesion complained were mostly the arms (47.5%), neck (41.3%), fingers (32.5%) and so forth in total number. The degree of lesions were generally itching (85.0%) and flare (61.3%), but severe cases like vanishing fingerprints (16.3%) and fissures on the fingers (11.3 %) were also revealed. Portion of okra responsible for skin hazards seemed to be mainly leaves, trichomes and pods.
Positive patch test reactions with preparations of immature okra pods in 46 workers (male, 12 ; female, 34), compared to 112 control subjects (male, 84 ; female, 28), were significantly higher in okra workers than in controls, which were 25% in males and 20% in total group.
These results show that okra components cause irritant contact dermatitis and allergic contact dermatitis as well.

Statistical analyses were made on a total of 242 clinical cases of skin disordersfrom agricultural chemicals in Japanese farmers, using data recorded by physicians on standard forms in 41 hospitals and other medical institutions during the 1982-89 period. The majority of the cases were acute dermatitis (72.3%), followed by chronic dermatitis (19.0%), chemical burns (7.4%) and photosensitive dermatitis (2.1%). Organophosporus insecticides were the most frequent inducer of occupational skin lesions (24.8%), followed by sulfur fungicides (20.7%), polyhaloalkylthio-fungicides (16.1%), and soil disinfectants (7.9%). Main factors contributing to the onset of skin lesions were insufficient clothing on the part of users (46.7%), carelessness (21.9%), unsuitable weather (strong wind) (9.9%) and so forth. Epidemiological features such as sex, age, season, complications, affected sites and prognoses were also analyzed and discussed.