I-6

Pos te r Sess ion I (4-5 March 1981) A29

TOXICOLOGICAL ASPECTS OF PRENISTEINE, A NEW PRODUCT WITH EXPECTORANT ACTIVITY

C.SANFELIU, J.Zapatero and L.Bruseghini.

Investigaci6n T~cnica y Aplicada S.A. Santiga. Barcelona. (Spain).

Acute and chronic toxicities of Prenisteine, a new product with expectorant ac- tivity was studied in several animal species. Acute toxicity was tested in Wistar rats and NMRI mice and chronic toxicity in Wistar rats for I and 6 months and also in Beagle dogs for 6 months. The acute toxicity was very low. The LDs0 by oral route was greater than 4000 mg/kg in rat and mouse. By intraperitoneal route the LDs0 was 2100 in NMRI mouse and 3100 in Wistar rat. Prenisteine was administered to Wistar rats during I and 6 months in two diffe- rents trials at doses of 100, 300 and 1000 mg/kg. Administration for I month only produced a slight increment of liver and kidney weights without macro or microscopical alterations. Bromehexine was used as standard product at dose of 1000 mg/kg and produced a smaller increment of body weight. In the chronic toxicity for 6 months a smaller increment of weight was observed in male rats treated with Prenisteine at 1000 mg/kg. A slight increment of kidney weight was registered in male rats treated at 1000 mg/kg. Prenisteine was well tolerated and hematological, biochemical, or his- tological alterations were not observed. Prenisteine was administered during 6 months to Beagle dogs at dose 25, 75 and 225 mg/kg. At the dose of 225 mg/kg a slight decrement of body weight was observed, toge- ther with a slight anaemia. At the doses of 75 and 25 mg/kg none alterations were observed. Biochemicals, oftalmological and E.C.G. analysis were normal for all the dogs, as the organs weight and histopatological studies.

I-7 EFFECT OF CHELATION TREATMENT ON" VANADIUM EXCRETION IN RATS

TOR VIGGO HANSEN, M.D. and JAN AASETH,M.D.

Institute of Occupational Health,Box 8149 Dep.,Oslo l,Norway

Vanadium (V) is widely distributed in nature, and is an element

of substantial toxic potential,with lungs and kidneys as target

organs.

In this study the inter-organ distribution of V was investigated

after a single i.p. injection of VOSO 4 (4,9~mol/kg) to rats.

The organs with the highest levels of V were kidneys and liver,

which contained 24,9 nmol/g and 4,2 nmol/q,respectively, as

measured two days after injection.

Immediate treatment with desferrioxamine B or Ca-DTPA (lOO~mol/

kg) decreased the kidney levels to 64% and 56%,respectively, of

control values. The liver levels were lowered to 64% and 62%,

espectively, by the same treatment. Desferrioxamine B raised

the urinary excretion of V,whereas Ca-DTPA acted by raisinq

the faecal V excretion. The observed increased V elimination

mav result from chelate formation in the circulating blood,

since both complexing aqents were found to remove V from trans-

ferrin in vitro.