Related Experiment Video
Updated: Aug 15, 2026

11:28
Analytical Techniques for Assaying Nitric Oxide Bioactivity
Published on: June 18, 2012
Nitrite-induced adrenal effects in rats and the consequences for the no-observed-effect level
Summary
The no-observed-effect level (NOEL) for potassium nitrite (KNO2) in drinking water was established at 50 mg/litre. This study determined the safe intake level of nitrite, finding adrenal zona glomerulosa hypertrophy at higher doses.
Area of Science:
- Toxicology
- Endocrinology
- Environmental Health
Background:
- Previous studies indicated adrenal zona glomerulosa hypertrophy in rats exposed to potassium nitrite.
- Establishing a no-observed-effect level (NOEL) for nitrite is crucial for risk assessment.
Purpose of the Study:
- To determine the no-observed-effect level (NOEL) for nitrite exposure in Wistar rats.
- To assess the dose-response relationship of nitrite on adrenal gland morphology and other physiological parameters.
Main Methods:
- Rats were administered varying doses of potassium nitrite (KNO2) or sodium nitrite (NaNO2) in drinking water for 13 weeks.
- General health, body weight, food/liquid intake, hematology (methaemoglobin, red blood cells), kidney weights, hormone levels, and blood pressure were monitored.
- Adrenal glands were examined microscopically for hypertrophy of the zona glomerulosa.
Main Results:
- No effects on general health, behavior, or survival were observed.
- Higher doses (3000 mg/L KNO2, 2432 mg/L NaNO2) caused decreased body weight, food/liquid intake, and increased kidney weights.
- Significant methaemoglobin increases and slight red blood cell changes occurred at high doses. Adrenal zona glomerulosa hypertrophy was dose-dependent, observed at 100 mg/L KNO2 and 81 mg/L NaNO2 and above.
Conclusions:
- The no-observed-effect level (NOEL) for potassium nitrite (KNO2) was determined to be 50 mg/litre in drinking water, equivalent to approximately 5 mg/kg body weight/day.
- The hypertrophy of the adrenal zona glomerulosa is a dose-dependent effect of nitrite exposure.
- Sodium nitrite (NaNO2) exhibited similar toxicological effects to potassium nitrite (KNO2).
Related Concept Videos
2° Amines to N-Nitrosamines: Reaction with NaNO2
Secondary amines react with nitrous acid to form N-nitrosamines, as depicted in Figure 1. Nitrous acid, a weak and unstable acid, is formed in situ from an aqueous solution of sodium nitrite and strong acids, such as hydrochloric acid or sulfuric acid, in cold conditions. In the presence of an acid, the nitrous acid gets protonated. The subsequent loss of water results in the formation of the electrophile known as nitrosonium ion.
Toxicity Testing in Animals
Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...

