Human & Experimental Toxicology

1 Uptake of the herbicide paraquat (PQ), by rat proximal tubular cells (PTC) in primary culture grown on a collagen coated support was investigated.

2 The uptake of PQ by PTC was predominantly from the basolateral side. The basolateral uptake of PQ was saturable with time and increasing concentrations, energy dependent and could be inhibited by certain organic cations. Using Michaelis Menten kinetics, the apparent Km was 778 ± 241 μM and V_max was 0.97 ± 0.24 pmol/μg protein/15 min for the basolateral uptake of PQ. Cimetidine (5.7 ± 0.4 pg/μg protein/ 30 min, P < 0.001) was the most potent inhibitor of PQ uptake, followed by quinine (6.5 ± 0.4 pg/μg pro tein/30 min, P < 0.01) and then tetraethylammonium (8.2 ± 0.5 pg/μg protein/30 min, P < 0.05) when com pared with control (11 ± 1 pg/μg protein/30 min). N- methylnicotinamide, p-aminohippurate and putres cine did not inhibit the basolateral uptake of PQ. The sodium hydrogen exchange inhibitors, amiloride and its analogue, 5-(N,N hexamethylene) amiloride (HMA) inhibited both the apical and basolateral uptake of PQ.

3 The apical uptake of PQ was not saturable with increasing concentrations and was not inhibited by 2,4-dinitrophenol, but it was reduced by cimetidine (P < 0.01), quinine (P < 0.05) and a sodium potassium ATPase inhibitor, ouabain (P<0.01).

4 It is concluded that PQ was taken up from the basolateral side of primary cultured rat PTC by an energy dependent transport system.

1 This study was conducted with the aim of evaluating the impact on health produced by the use of different types of pesticides in greenhouses. It is based on the need to practice and develop biological monitoring techniques to assess exposure and predict health risk in workers occupationally exposed to pesticides.

2 Two groups of greenhouse workers with either high or low exposure to a combination of pesticides was taken in Almeria, a Spanish province where cultures under plastic are very extended.

3 One hundred and five sprayers were interviewed to collect information about symptoms and signs related to past exposures. Each pesticide sprayer was exam ined by a physician, and a blood sample was drawn for plasma and red blood cell cholinesterases, complete blood count, and liver and renal function tests.

4 Exposure of workers to a combination of pesticides resulted in 37% of the workers showing toxic signs and symptoms. The main toxic effects observed were a high incidence of spontaneous abortion, depression, and certain neurologic disorders like headache, tremor and paraesthesia.

5 The major analytical change was a decrease of the mean corpuscular haemoglobin concentration in 38% of the cases. However, no significant decrease in both serum and erythrocyte cholinesterase activities was observed.

6 The sprayers were not usually aware of the potential hazards of pesticides and did not try their best to maintain personal hygiene.

Sulfur mustard (SM) represents a potential chemical warfare agent. In order to characterize SM-induced airway epithelial damage, we studied the effects of an intratracheal injection of 0.3 mg/kg of SM in guinea pigs, 5 h, 24 h, 14 days and 35 days after exposure. During the acute period, lesions prevailed in tracheal epithelium exhibiting intra-epithelial blisters, inflammatory cell infiltration and columnar cell shedding with exposure of basal cells. Fourteen days after intoxication, tracheal epithelium appeared disorganized and showed a signifi cant decrease in height and cell density. Tracheal epithelium recovery was still not complete even 35 days after SM-intoxication. At day 14, in SM-intoxicated guinea pigs treated with betamethasone from day 7 to day 14, epithelium height, cell density and cell proliferation (evaluated by immunohistochemistry) were significantly increased compared to untreated guinea pigs. In conclu sion, the lesions observed in SM-intoxicated guinea pigs seem to be in accordance with clinical human observa tions and are relevant to the study of airway epithelial damage induced by SM. This animal model could be used to illustrate tracheal epithelium regeneration mainly derived from basal cells and to show glucocorticoid effects on airway epithelial recovery after chemical aggression.

1 Inhibition of cholinesterases (ChE) and carboxyles terases (CaE) by paraoxon (Px) was studied in vitro in the serum, liver, lung and muscle of mouse, guinea pig, rabbit and man (serum only). Moreover, the role ofPx hydrolyzing enzyme (Pxase) in the detoxification of Px was studied by inhibiting its activity with EDTA.

2 The ChE and CaE activities as well as their sensitivity to Px varied in different tissues and species. The ChEs were more sensitive than CaEs to Px except in the liver. The CaE activity in human and rabbit sera was low and resistant to Px, indicating that it may have a minor importance for the binding of Px.

3 The Px-inhibited ChEs were spontaneously reactivated in the mouse and rabbit sera during 24 h. In mouse, also the CaE activity was recovered. The presence of EDTA in the incubation medium prevented this reactivation indicating that Pxase takes part in the reactivation process.

4 In rabbit, the serum Pxase activity was very high suggesting a good Px detoxifying capacity of the rabbit serum.

5 The results show that amounts and sensitivities of esterases to OPs in rodents may markedly differ from that in man. Possible species-related differences in the affinity of ChEs and CaEs for OPs and the OP hydrolyzing activity should be taken into the con sideration, when animal data are extrapolated to man.