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Higher yield and performance in plant and animal production will depend on reinforced use of pesticides, particularly alkyl phosphate esters and insecticidal carbamates. Prenatal toxic action of the pesticides used today may be detrimental to human and animal health. Prenatal-toxicological tests, using parathion-methyl, were conducted on the basis of known but modified experimental methods. The vulnerability of a rat strain was tested by applying to it teratogenic model substances (trypan blue and cyclophosphamide). Several oral applications of parathion-methyl (3 ppm) during the sensitive phases of germ formation and growth (fifth to ninth and eleventh to fifteenth or eleventh to nineteenth days from conception) were followed by clear embryotoxic effects, such as retardation and increased resorption. The average number of resorption sites grew from nine in the control group to 20 in the experimental group. Postnatal malformations were not observed.

In an epidemiological study in the Neubrandenburg district among 316 long-term exposed pesticide workers the incidence of tumors was investigated. There were 30 cases of tumors, of which 11 were lung cancers. The incidence of lung cancers was in contrast to age-specific population twenty times higher. The average exposure against pesticides amounted to 14.1 +/- 4.7 (6-23) years, the latency period between exposition start and tumor manifestation to 17.9 +/- 6.0 (6-23) years. The exposure occurred mainly to the following agents: herbicides, such as derivatives of phenoxyacetic acid (2,4 D and MCPA); insecticides, such as chlorinated hydrocarbons (DDT, HCH and Toxaphen), organic phosphorus compounds (Parathion) and organic nitro derivatives (DNOC) as well as fungicides, such as copper containing and organic synthetic agents. Between 1950 and 1956 some pesticide workers were also exposed to arsenic containing agents. As the workers were exposed to various chemical compounds simultaneously or alternatively, no carcinogenic effect can be determined by specific individual pesticides. The investigations are discussed in detail on the today knowledge about cancer hazards associated with exposure to pesticides, and respective conclusions are drawn for preventive measures.

After oral administration of pesticides Parathion-methyl, Carbaryl, Lindane and their combinations were investigated the activities of enzyme SGOT, SGPT, Alkaline Phosphatase and Cholinesterase. Results concerning SGOT-activity demonstrated a significant increase in all groups. The cause of this rise can be found in its effect on liver, muscle and/or heart. The activity of cholinesterase is significantly lower in the combinations of Parathion-methyl/Lindane, Lindane/Carbaryl and Carbaryl/Parathion-methyl. In future the extent of these investigations concerning the subacute toxicity, chronical toxicity, the additive or cumulative effects of pesticide--combinations, combinations of pesticides with drugs and/or xenobiotics etc. must be enhanced in any case.

The growing use of a diversity of pesticides in agricultural practice calls for studies into the toxicity of pesticides when used in combinations. Fundamental studies were conducted into the acute toxicity of pesticide combinations in rat and showed that double or triple combinations of parathion-methyl, carbaryl, and Lindan could aggravate or mitigate toxicity, depending on the active ingredients involved. The above findings were obtained from acute animal experiments, but it may well be necessary to develop proper screening models for optimum information and to study subchronic toxicity as well.

A new thin-layer chromatography method was developed to detect parathion-methyl (0.0-dimethyl-0-p-nitrophenyl phosphorothioate) and its metabolite methyl-paraoxon and the degradation produce p-nitrophenol in samples of animal and plant origin. Coupling with Bratton-Marshall reagent, as used in colorimetry, was employed to detect the compounds on the chromatography plate. Pretreatment of the samples was simplified by preparing a crude extract and separating unwanted substances from the pesticide compounds by thin-layer chromatography.

Tyrosine-amino transferase, an enzyme induced to the liver via glucocorticoids, caused clearly measurable activity rises in either sex, 24 hours after 1 and 2 applications. Increased levels continued to recordable from males on the 3rd day from application, whereas enzyme activities in females had already returned to normal by that time. Histological examination of liver sections, following 1 and 2 applications of parathion methyl (PM), revealed the tissue pattern of clearly manifest toxic hepatosis with detectable mesenchymal reactions. Histologically detectable damage reached its maximum on the 2nd and 3rd days from application. Sex-related differences were not recordable. Damage in response to the 2nd application was characterised by faster mesenchymal activation and higher frequency of cell necroses. The morphological picture of the liver was rated as having returned to normal, 14 days after 1 and 2 applications of PM. These results should not be interpreted as evidence to the involvement of specific, non-cholinergic mechanisms in the processes of damage observed. The alterations might rather be attributed to unspecific disorders in the energy balance or to the effect of "stress" during intoxication.

Reference is made to the first communication made under this heading. The haematological parameters did not undergo any visible change in response to the chosen experimental arrangement. Further studies should be undertaken, with the view to elucidating the possibility of bone marrow change. The blood glucose levels were strongly increased two hours from application of parathion-methyl, carbaryl/Lindan, and carbaryl/Lindan/parathion-methyl and strongly decreased 24 hours after application. Complementary experiments should cover chronic and subchronic situations.

Clearly pronounced changes in plasma enzyme activities were observed 24 hours after one and two applications of parathion methyl (PM). The most strongly pronounced rise was in activity of aspartate-amino transferase and was recorded from both sexes. PM application caused sizeable changes in male rats. Comparison between reactions after one and two applications revealed more intensive changes in males after the 1st application. Somewhat larger differences were recordable in some cases between the 1st and 2nd applications. Closer agreement between reaction intensities after the 1st and 2nd PM applications was recordable from female rats. In either sex in response to one single and repeated application parameters returned to normal within nearly one and the same period of time. No secured relationships between activities prior to and after application of PM could be derived from the assays of gamma-glutamyl transpeptidase (gamma-GT). Both increase and decrease of determined enzyme activities were actually recorded. Activities were highly variable in the control groups. Extreme rises were recordable in some cases from both control and experimental groups. No conclusions so far can be drawn as to "normal values" in rat plasma, possible sex-related differences, and behaviour of enzyme activity in response to one single or repetitive applications. Hence, within common investigations of acute toxicity of alkylphosphates, gamma-GT was found to be not suitable for detection of damage to the liver or other organs.

Acute toxicity of methylparathion male mice is reduced by DET in dose-range from 50 to 300 mg/kg. Mean survival time in LD100 range of methylparathion is significantly prolonged. Inhibition of AChE in vivo is reduced, too. The observed dose-effect-relations show an approx. 10-fold increase in equi-effective doses after DET-pretreatment. DET has no protective effect both in vivo and in vitro, if methylparathion is added to the brain homogenate of mice. As probable mechanism of action a change in methylparathion-metabolism induced by DET in the system of mixed functional oxidases is discussed.

The effect of 5 organophosphorus pesticids on the rat intestine and serum was investigated with histochemical and biochemical methods. The results of both methods were corresponding in nonspecific esterases of rat intestine. They differ in cholinesterases. Furthermore the effect on serum esterases of rat and man was investigated. With few exceptions the results corresponded too. We concluded, that the intestine is a suitable object for testing antiesterase action histochemically. General statements about total toxicity of a pesticid, however, are not possible.