NITRITE-INDUCED ADRENAL EFFECTS IN RATS AND THE CONSEQUENCES FOR THE NO-OBSERVED-EFFECT LEVEL

In a previous subchronic oral toxicity study with potassium nitrite, h ypertrophy of the adrenal zona glomerulosa was observed for all nitrit e levels examined including the lowest level of 100 mg/litre. This pre sent study was carried out, therefore, to establish a no-observed-effe ct level (NOEL) for nitrite. Groups of 10 male and 10 female 6-wk-old Wistar rats received KNO2 at levels of 12.5, 25, 50, 100 or 3000 mg/li tre or NaNO2 at levels of 81 or 2432 mg/litre in the drinking water fo r 13 wk. The nitrite content of the drinking water in the latter two g roups was equal to that of the 100 and 3000 mg KNO2/litre groups, resp ectively. Potassium and sodium concentrations were equalized in the co rresponding test groups with KCI and NaCl, respectively. General healt h, behaviour and survival were not affected by the ingestion of nitrit e. Body weight and food and liquid intake were slightly decreased in t he 3000 mg KNO2/litre and 2432 mg NaNo2/litre groups for both sexes. M ethaemoglobin concentration was significantly elevated in rats of both high-dose nitrite groups in wk 4 and 12, while slight increases in a number of red blood cell variables occurred with 3000 mg KNO2/litre in females in wk 12. Relative kidney weights were increased in both high -dose nitrite groups; In wk 4, plasma aldosterone and corticosterone l evels were slightly decreased in males with 2432 mg NaNO2/litre and pl asma corticosterone in females with 3000 mg KNO2/litre but not in wk 1 3. Systolic blood pressure was not affected by nitrite. Microscopic ex amination revealed slight hypertrophy of the adrenal zona glomerulosa in animals of the 100 and 3000 mg KNO2/litre and of the 81 and 2432 mg NaNO2/litre groups, the incidence and degree being dose related. The results obtained with 100 and 3000 mg KNO2/litre in the drinking water were comparable with those found at the same levels in the previous 9 0-day study. The effects with sodium nitrite were similar to those obs erved with potassium nitrite. The biological significance of the adren al zona glomerulosa hypertrophy is discussed. It is concluded that the NOEL of KNO2 is 50 mg/litre in the drinking water, equivalent to abou t 5 mg/kg body weight/day. (C) 1997 Elsevier Science Ltd.