In a previous subchronic oral toxicity study with
potassium nitrite,
hypertrophy of the adrenal zona glomerulosa was observed for all
nitrite levels examined including the lowest level of 100 mg/litre. This present study was carried out, therefore, to establish a no-observed-effect 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/litre or NaNO2 at levels of 81 or 2432 mg/litre in the
drinking water for 13 wk. The
nitrite content of the
drinking water in the latter two groups was equal to that of the 100 and 3000 mg KNO2/litre groups, respectively.
Potassium and
sodium concentrations were equalized in the corresponding test groups with KCl and NaCl, respectively. General health, behaviour and survival were not affected by the ingestion of
nitrite.
Body weight and food and liquid intake were slightly decreased in the 3000 mg KNO2/litre and 2432 mg NaNo2/litre groups for both sexes. Methaemoglobin 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 levels were slightly decreased in males with 2432 mg NaNO2/litre and plasma
corticosterone in females with 3000 mg KNO2/litre but not in wk 13. Systolic blood pressure was not affected by
nitrite. Microscopic examination 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 90-day study. The effects with
sodium nitrite were similar to those observed with
potassium nitrite. The
biological significance of the adrenal zona glomerulosa
hypertrophy is discussed. It is concluded that the NOEL of KNO2 is 50 mg/litre in the
drinking water, equivalent to about 5 mg/kg
body weight/day.