Percutaneous toxicity of uranyl nitrate: its effect in terms of exposure area and time.

Different groups have undertaken research work focusing their attention on the biological effects of uranium and have described kidney and bone to be the main target organs in uranium poisoning. In this study we used the skin as the route of entry of uranium. We carried out two sets of experiments in adult rats: in one of them topical applications with uranyl nitrate (UN) over different areas were performed; in the other topical applications with UN on a given area over different times were carried out. In the latter experiment the exposure to UN was stopped by removing it from skin with soap and water. Kidney and bone samples were removed for histological studies. This work is based on the determination of the survival rate of the exposed animals and on the effects elicited in kidney and bone. There is a relation between the area of the surface exposed to uranium and the time of exposure and the subsequent percutaneous toxicity. There were no surviving animals following topical application of UN to an 8 cm2 area nor when the time of exposure was 24 h. The survival rate of the animals increased when either the topical area or the time of exposure to UN was reduced. Although the inhibition of bone formation in metaphysical bone has been previously described by our group as a result of UN poisoning, this is the first time that such an effect is found after percutaneous exposure for such short periods of time. The general toxic effects of UN, evidenced as kidney histological alterations, increased in severity as either one of the two variables studied increased. This is a condition that could be considered as hazardous for those workers engaged in uranium processing and purification. It is noteworthy that a simple method such as washing with soap and water is an effective method to reduce the lethality of UN percutaneous intoxication.

Bone growth is impaired by uranium intoxication.

Acute and chronic uranium intoxication leads to the inhibition of bone formation and impaired bone modeling and remodeling. As these are processes directly involved in bone growth the aim of this paper is to present a biometric study of bone growth--tibiae and mandibles of rats intoxicated with uranium. Wistar ratios weighing 60-80 g were used as follows, a) one intraperitoneal injection (IPI, 2 mg/Kg of body weight)) of uranyl nitrate; b) 30 daily applications on the dorsal skin of aliquots of a mixture of U308, concentrated at 2% and at 4%--percutaneous absorption(PA)-. Tibia and mandible length were smaller in both experimental groups than in their respective controls. Some of the mandibular parameters were lower in intoxicated animals than their controls which in turn results in the alteration of the mandibular shape. We conclude that impairment in bone growth can be achieved by uranium intoxication.

Ethane 1-hydroxy-1, 1-diphosphonate (EHDP) counteracts the inhibitory effect of uranyl nitrate on bone formation.

The beneficial effect of ethane 1-hydroxy-1, 1-diphosphonate (EHDP) in restoring the inhibition of bone formation in cases of acute uranium intoxication is presented. Bone formation was studied histomorphometrically in a model of alveolar bone healing. After tooth extraction, 40 rats were divided into 4 groups that received (1) no further treatment, (2) 10 daily intraperitoneal injections of 7.5 mg/kg of body weight of EHDP, (3) an intraperitoneal injection of 2.0 mg/kg of body weight of uranyl nitrate, and (4) the same treatment as was provided rats in groups 2 and 3. The results showed that the healing of bone did not occur in exposed animals, whereas healing in EHDP-treated exposed animals did not differ from that of nonexposed controls. This effect might result from a blocking and/or competitive action of EHDP and/or the stimulation that EHDP elicits at the doses and in the administration period studied.