Nitrosamines in EU Cosmetics: The In-Formulation Risk That Every CPSR Must Address Under EC Regulation 1223/2009

Most reformulation conversations centre on what you take out of a formula — a restricted preservative here, a flagged UV filter there. Far fewer address what the formula quietly creates on its own, over months, at low pH and elevated temperature. Nitrosamines fall into that second category. And their treatment under Regulation (EC) No 1223/2009 means that overlooking them in your Cosmetic Product Safety Report isn’t a paperwork technicality. It’s a substantive compliance gap that a qualified safety assessor — and a DGCCRF inspector — will both spot.

When Compliant Ingredients Combine to Create a Prohibited Substance

The underlying chemistry is straightforward, even if the regulatory consequences are not. Nitrosamines — formally N-nitroso compounds — form when secondary or tertiary amines react with nitrosating agents. Those agents include nitrites, oxides of nitrogen, and certain nitrogen-releasing preservatives that can introduce nitrite impurities into a formula. The reaction doesn’t require extreme conditions. It proceeds at room temperature, its rate peaks around pH 3.4, and it continues throughout the product’s shelf life, meaning that a product clean at manufacture can test positive six months later under normal storage.

The most extensively documented case in cosmetics is N-nitrosodiethanolamine (NDELA), which forms when diethanolamine (DEA) or DEA-derived surfactants are present alongside a nitrosating co-ingredient. DEA has been widespread in cosmetic formulations for decades — used as an emulsifier, foam booster, pH adjuster, and functional ingredient in shampoos, body washes, conditioners, and moisturisers. The problem is never DEA in isolation. It’s DEA in combination with the right reaction partner, packaged in conditions that favour nitrosation.

What makes this difficult for formulators and safety assessors alike is that both ingredients can individually satisfy an Annex III review. It’s the combination — and the transformation product that results — that creates the compliance problem. Annex II of Regulation (EC) No 1223/2009 explicitly lists several N-nitroso compounds as substances prohibited in finished cosmetic products. NDELA is among them. A brand can pass every ingredient-level check and still ship a product that violates Annex II. That’s the core of the risk.

What EC Regulation 1223/2009 and the SCCS Require

The regulatory response to nitrosamine risk in cosmetics has been layered, building over more than a decade.

The Scientific Committee on Consumer Safety (SCCS) published its evaluation of diethanolamine in 2016 (SCCS/1568/16), concluding that DEA presents a safety concern linked to NDELA formation — particularly in leave-on products, where dermal absorption over sustained contact time elevates systemic exposure estimates. Acting on that opinion, the European Commission amended Annex III of Regulation (EC) No 1223/2009 to restrict DEA across cosmetic product types: it is not authorised in leave-on formulations, and subject to specific maximum concentration limits in rinse-off hair products where contact time is shorter and rinsing reduces residual exposure. Brands that hadn’t proactively reformulated found that replacing DEA-based surfactants required re-validating stability, pH profile, and preservation efficacy from scratch. The reformulation workload was substantial.

But the regulatory picture extends well beyond DEA. Annex I of Regulation 1223/2009 defines what a Cosmetic Product Safety Report (CPSR) must contain. Part A requires information on “impurities of the substances used and traces from the manufacturing process, including information relating to the chemical structure.” Nitrosamines, where they can plausibly form in your formula, represent exactly this kind of in-situ impurity — one that emerges not from poor raw material quality alone, but from the interaction dynamics of the finished system.

The qualified safety assessor signing off on Part B (who must hold a degree in pharmacy, medicine, toxicology, or an equivalent discipline under Article 10 of the Regulation) is expected to address this proactively. The SCCS has published methodological guidance on assessing genotoxic impurities, including application of the Threshold of Toxicological Concern (TTC) principle. For DNA-reactive carcinogens — the category into which many N-nitroso compounds fall — acceptable daily exposure thresholds are stringent, measured in low microgram-per-person-per-day ranges. For a leave-on body cream applied to a large surface area, even trace nitrosamine concentrations can push the systemic exposure calculation above what the SCCS considers tolerable. A CPSR that doesn’t show this calculation has a gap.

Which Formulation Archetypes Carry the Highest Risk

Not every product format presents equal nitrosamine risk. Identifying where the exposure is highest helps prioritise both reformulation decisions and testing resources.

Low-pH leave-on products with amine-bearing actives. Alpha hydroxy acid creams, glycolic acid toners, and vitamin C serums routinely operate at pH values between 3.0 and 4.5 — precisely the window where nitrosation kinetics are most favourable. If those formulas also contain secondary amine-bearing ingredients (certain peptide actives, amino acid derivatives, or botanical extracts with naturally occurring free amines), the conditions for nitrosamine formation are present. The combination of low pH and prolonged skin contact in a leave-on format is the highest-risk scenario the SCCS identifies.

Self-tanning products. Dihydroxyacetone (DHA), the reactive tanning agent in most self-tanners, undergoes Maillard-type reactions with amino groups. In the formulation itself, under certain conditions and in the presence of secondary amine co-ingredients, DHA can participate in reactions that generate nitrosamine precursors. The self-tanner format — typically a lotion or mousse at mildly acidic pH — warrants routine finished-product screening, not just ingredient-level review.

Formulas using formaldehyde-releasing preservatives. The industry’s broad move away from parabens has accelerated adoption of preservatives like DMDM hydantoin, imidazolidinyl urea, and diazolidinyl urea. These systems function in part by releasing low levels of formaldehyde. Formaldehyde can react with secondary amines to generate nitrosamines under certain conditions, particularly when nitrite traces are present as raw material impurities. The positioning of these alternatives as “cleaner” or “more natural” doesn’t eliminate nitrosamine risk — in some formulations, it relocates it. Safety assessors reviewing preservative system switches should flag this explicitly.

Rinse-off products retaining DEA-derived surfactants above permitted thresholds. Shampoos and conditioners that still contain DEA surfactants in quantities exceeding Annex III limits remain obvious market surveillance targets. DGCCRF in France conducts structured cosmetics sampling programmes, and products that fail Annex II or Annex III checks in the laboratory trigger formal administrative follow-up. A withdrawal or recall based on a prohibited substance finding carries a different weight than a label correction — the reputational damage tends to extend well beyond the initial notification.

Building Nitrosamine Risk Into Your CPSR and GMP Controls

There are four practical areas where the nitrosamine assessment needs to be visible — in documentation, in testing, and in manufacturing practice.

Formulation compatibility screening before stability testing begins. Before committing to a 12- or 24-month real-time stability programme, screen the full ingredient list for amine/nitrosating agent pairs. This initial review doesn’t require a mass spectrometer — a structured analysis of every ingredient’s functional group chemistry and known raw material impurity profiles will flag combinations that warrant laboratory verification. If you’re working with a contract manufacturer, ask them directly whether nitrosating agent impurities have been assessed across all raw material specifications. The answer will tell you a great deal about their quality system.

Targeted finished-product analytical testing. GC-MS with nitrogen-phosphorus detection (GC-NPD) or GC-MS with a thermal energy analyser (GC-TEA) are established reference methods for nitrosamine screening in cosmetic matrices. LC-MS/MS offers lower detection limits — routinely below 10 μg/kg (10 ppb) — and is increasingly used for confirmatory quantification in ISO 17025-accredited labs. Testing should be performed on finished product stored under accelerated stability conditions (40°C/75% RH for a minimum of three months) to simulate worst-case shelf-life scenarios. Testing only freshly manufactured product misses the formation dynamics that drive the actual consumer exposure.

A clear risk narrative in Part B of the CPSR. Part B is where the safety assessor demonstrates overall safety and signs off on their professional judgement. If any ingredient in the formula has nitrosamine formation potential, the assessor should state it explicitly: describe the combination assessed, reference the SCCS methodology applied to the systemic exposure calculation, note the analytical results from finished-product testing, and confirm that any detected nitrosamine impurity falls within acceptable risk limits. Assessors who address this only implicitly, or skip it because concentrations appear low, leave a gap that is specifically the kind of thing national competent authority auditors are trained to identify.

Manufacturing controls under ISO 22716. Good Manufacturing Practice for cosmetics (ISO 22716) requires that production equipment be maintained to prevent contamination. This matters for nitrosamines because certain industrial lubricants, elastomeric gaskets, and nitrogen-pressurised filling systems can introduce low-level nitrosating agents into the manufacturing environment. Document your equipment qualification records and, if you use nitrogen blanketing during filling or bulk storage, specify acceptable purity grades and test incoming nitrogen against that specification. It’s a small operational requirement with a disproportionately important documentation footprint in a GMP audit.

The Practical Takeaway

The formula you submit for safety assessment isn’t a static chemistry snapshot — it’s a dynamic system that continues to react across its shelf life, under the temperature and light conditions of actual distribution and use. Any formulation containing secondary amines should be treated as a potential nitrosamine-generating system until analytical data confirms otherwise. The obligation under Regulation (EC) No 1223/2009 is clear; the practical consequence of ignoring it, given DGCCRF market surveillance activity and EU-wide rapid alert coordination through Safety Gate (formerly RAPEX), is not abstract. Build the nitrosamine risk assessment into your safety strategy at the ingredient selection stage — not as an afterthought during the pre-launch documentation sprint.

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Written by Nour Abochama, Quality & Regulatory Advisor, Care Europe | VP Operations, Qalitex. Learn more about our team

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• Cosmetic Product Testing to ISO 17025 Standards — Qalitex Laboratories provides accredited analytical testing for nitrosamines and other cosmetic impurities, including GC-MS/NPD and LC-MS/MS methods.
• Exporting Cosmetics to Canada: Health Canada Compliance Essentials — Androxa outlines what European cosmetics brands must address when entering the Canadian market, including impurity documentation requirements.