Understanding the Acceptable Daily Intake of Nitrosamines

November 14, 2025 •

4 min read

According to the European Food Safety Authority (EFSA), nitrosamines could pose a significant health risk, prompting health authorities worldwide to establish exposure limits for these compounds. Determining the acceptable daily intake of nitrosamines is a complex task, as it depends on the specific compound, its potency, and the context of exposure, such as in medicines or food.

Quick Summary

The acceptable daily intake of nitrosamines varies depending on the specific compound and its potential for harm. Regulatory agencies establish limits, particularly for pharmaceuticals, to keep exposure within a negligible cancer risk. For foods, the focus is on minimization rather than a single numerical limit, due to widespread and complex presence.

Key Points

Compound-Specific Limits: The acceptable daily intake of nitrosamines is not a single number but depends on the specific nitrosamine and its potency, with regulators like the FDA setting distinct limits for different compounds.
Pharmaceutical vs. Food Regulation: Regulatory approaches differ significantly; pharmaceuticals have precise, compound-specific daily limits, while food safety focuses on minimizing overall exposure rather than defining a strict threshold.
Negligible Risk for Medicines: In the pharmaceutical sector, limits are calculated to represent a negligible cancer risk (e.g., 1:100,000) over a person's lifetime of drug exposure.
Dietary Minimization: For dietary nitrosamines from sources like cured meats and beer, the primary strategy is minimization, as exposure from food is widespread and a 'safe' level has not been established.
Role of Antioxidants: Consuming antioxidants like Vitamin C and Vitamin E can help inhibit the endogenous formation of nitrosamines in the stomach, balancing the intake of nitrite-containing foods.
Multiple Sources of Exposure: Nitrosamines are found not only in food and medicines but also in other sources such as tobacco smoke, cosmetics, and certain water supplies.

What is the acceptable daily intake of nitrosamines?

The term acceptable daily intake of nitrosamines refers to a set of varying, compound-specific limits rather than a single, universal value. These limits are established by health authorities such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to manage and mitigate health risks associated with chronic exposure to these potent, potentially carcinogenic compounds. The limits vary based on the specific nitrosamine's toxicological profile and the route of exposure, with distinct regulatory approaches for pharmaceuticals and food products.

How regulatory agencies determine acceptable intake

Regulatory bodies approach the risk assessment of nitrosamines by focusing on minimizing long-term exposure. In the pharmaceutical industry, a more prescriptive approach is taken due to the controlled nature of manufacturing and dosage. The FDA and EMA have adopted guidelines based on the International Council for Harmonisation (ICH) M7, which addresses mutagenic impurities.

The acceptable intake (AI) for a specific nitrosamine in a drug product is calculated to approximate a 1:100,000 excess cancer risk over a 70-year lifetime of exposure. For example, the FDA has set an AI limit of 96 ng/day for N-nitrosodimethylamine (NDMA) and 26.5 ng/day for N-nitrosodiethylamine (NDEA), reflecting the different carcinogenic potencies of these compounds. For nitrosamines without robust toxicological data, a default AI of 26.5 ng/day is often applied, corresponding to the most potent known nitrosamine.

The Carcinogenic Potency Categorization Approach (CPCA)

The CPCA is a tiered system used by regulatory bodies to assign an AI limit to a new or unstudied nitrosamine based on its chemical structure. The approach categorizes nitrosamines into five tiers of potency, each with a corresponding acceptable intake level:

Category 1: 26.5 ng/day (most potent)
Category 2: 100 ng/day
Category 3: 400 ng/day
Category 4: 1500 ng/day
Category 5: 1500 ng/day (least potent)

This method allows for a rapid yet scientifically grounded risk assessment for new drug substance-related impurities (NDSRIs).

Nitrosamine exposure from food products

Unlike the strict, compound-specific limits for pharmaceuticals, regulating nitrosamines in food is more complex. The EFSA notes that nitrosamines are formed from the reaction of nitrites and secondary amines, which are naturally present or added during processing. They are found in cured meats, beer, fish, processed vegetables, and tobacco smoke. For food, the governing principle is minimization, as it is impractical to establish a harmless threshold for every possible dietary source.

Common sources of dietary nitrosamines:

Processed and cured meats: Hot dogs, sausages, bacon, and luncheon meats, which contain added nitrites.
Beer: Formed during the kilning (drying) of malt.
Fish: Can contain naturally occurring amines that react with nitrites during processing.
Tobacco smoke: A significant source of nitrosamine exposure.
Cosmetics and drinking water: Trace levels of nitrosamines have been detected in some products and disinfected water.

How the body forms nitrosamines

Nitrosamines can also form endogenously, meaning inside the human body. In the acidic environment of the stomach, nitrites (from food or saliva) can react with amines to create nitrosamines. This process can be inhibited by antioxidants like Vitamin C (ascorbic acid) and Vitamin E, which is why food manufacturers often add them to processed meats.

Comparison: Pharmaceuticals vs. Food Regulation


Feature	Pharmaceutical Nitrosamine Regulation	Food Nitrosamine Regulation
Regulatory Approach	Compound-specific Acceptable Intake (AI) limits for each nitrosamine impurity.	Minimization principle; focus is on reducing levels as much as reasonably achievable.
Guiding Principles	Based on ICH M7 to ensure negligible risk (e.g., 1:100,000 excess cancer risk) for lifetime exposure.	No set limit considered harmless. Minimizing dietary intake is the primary strategy.
Limit Specificity	Precise limits in ng/day based on toxicological data or a categorization approach (CPCA).	General guidelines and monitoring, with some guidance values for specific foods like malt and beer.
Mitigation Strategy	Manufacturers implement strict quality control measures to reduce formation during synthesis and storage.	Consumers are advised to limit intake of cured meats and increase consumption of antioxidant-rich foods.
Risk Assessment	Detailed risk assessments required for drug applications to identify and quantify potential impurities.	Broader monitoring studies conducted to assess overall population exposure.

Mitigation and reduction of exposure

For consumers, minimizing nitrosamine exposure involves a multi-pronged approach:

Reduce intake of cured and processed meats: Limit consumption of hot dogs, sausages, and bacon, which often contain sodium nitrite.
Eat a balanced, antioxidant-rich diet: Vitamin C, Vitamin E, and other antioxidants can help inhibit nitrosamine formation in the stomach. A glass of orange juice or a serving of antioxidant-rich vegetables can be beneficial when consuming cured meats.
Opt for organic products: Organic packaged foods and meats are not permitted to use synthetic nitrates or nitrites as preservatives.
Be mindful of other sources: Be aware of potential exposure from tobacco smoke (both active and passive) and, in some cases, certain cosmetics.

Conclusion

The acceptable daily intake of nitrosamines is not a single value but a nuanced regulatory concept that varies between pharmaceuticals and food products. For medicines, precise, compound-specific limits are set based on a negligible lifetime cancer risk, with rigorous assessment during manufacturing. In contrast, the approach for food emphasizes minimization due to the wide variety of sources and the difficulty of establishing a universal safe threshold. By understanding the different regulatory contexts and adopting prudent dietary and lifestyle habits, consumers can take steps to manage their exposure to these potentially harmful compounds.

For more detailed regulatory guidance, refer to the FDA's official page on nitrosamine impurities in medicines.

Frequently Asked Questions

The U.S. Food and Drug Administration (FDA) has set an acceptable intake (AI) limit of 96 nanograms per day (ng/day) for N-nitrosodimethylamine (NDMA) in drug products.

Acceptable intake limits for nitrosamines in medicines are determined using toxicological data to calculate a daily exposure that approximates a negligible cancer risk, such as 1:100,000 over a lifetime.

There is no universal limit because the carcinogenic potency varies significantly between different nitrosamine compounds. Regulatory agencies assess each compound individually, or use a categorization approach, to set appropriate limits.

No, formal acceptable daily intake limits are not typically set for food. Instead, the guiding principle for food is minimization, as it is difficult to determine a harmless threshold for nitrosamines from diverse dietary sources.

Nitrosamines are found in processed and cured meats (e.g., hot dogs, bacon), beer, some fish products, and processed vegetables. They can also form during cooking, particularly at high temperatures.

You can reduce your dietary intake by minimizing consumption of processed and cured meats, choosing organic options when possible, and eating a diet rich in antioxidants like Vitamin C and E.

Yes, nitrosamines can be formed endogenously in the stomach from the reaction of nitrites and amines present in food. This process can be inhibited by antioxidants.

Because nitrosamines are classified as possible or probable carcinogens, particularly with long-term exposure, regulatory efforts focus on minimizing intake as much as possible rather than identifying a 'safe' level.