Health Implications of p‑Phenylenediamine: The Aromatic Amine in Permanent Hair Dye

By Hugo Francisco de SouzaReviewed by Benedette Cuffari, M.Sc.

Introduction
How PPD works in permanent hair dyes
Health implications of PPD use in cosmetics
Toxicological profile and systemic risks
Regulatory status and safety assessments
Safer alternatives and future directions
Conclusions
References
Further reading

This article explains how p-phenylenediamine (PPD) is used in permanent hair dyes, its health risks, including allergies and rare links to cancer, and the regulatory landscape. It highlights that while PPD is highly effective for coloring hair, its main health risks are allergic reactions, occupational dermatitis, and acute poisoning in developing countries.

Image Credit: hedgehog94 / Shutterstock.com

Introduction

Current estimates suggest that 50-80% of women and 10% of men 40 years of age and over in the United States and Europe use permanent hair dye products. The aromatic amine p-phenylenediamine (PPD) is present in about 80% of permanent hair dyes used in the U.S. and Europe.¹

The International Agency for Research on Cancer (IARC) has classified occupational exposure to hair dyes as "probably carcinogenic to humans" (Group 2A), but found that personal use of hair dyes is "not classifiable as to its carcinogenicity to humans" (Group 3). Despite its widespread use, PPD has a complex and hazardous toxicological profile, with growing evidence linking the molecule to severe allergic reactions and associations with some cancers in specific subgroups, though causality is unproven. Acute poisoning and deaths related to PPD are overwhelmingly a problem of intentional ingestion (often for self-harm) in developing countries, rather than chronic use in cosmetic contexts. This article examines the function, mechanism, and multifaceted health risks associated with PPD based on evidence from toxicology, epidemiology, and regulatory studies.^1,3,7

How PPD works in permanent hair dyes

PPD is an aromatic amine known for its ability to create stable, natural-looking, and long-lasting color in permanent hair dye formulations. In addition to its critical role in cosmetics, PPD is also used to produce high-strength polymers like Kevlar, as a rubber antioxidant, and in photographic development.²

The efficacy of permanent hair dyes relies on a controlled, multistep in-situ chemical reaction. Initially, an alkalizing agent, typically ammonia, is used to increase hair pH, which causes the protective outer cuticle to expand and separate. This opening allows small precursor molecules, including PPD, to penetrate the inner cortex of the hair fiber.³

Following entry, the mixture of these precursor molecules with hydrogen peroxide triggers an oxidative reaction, which oxidizes the initially colorless PPD into highly reactive intermediates. These intermediates rapidly react with other aromatic compounds in the mixture to form a diverse array of large, colored polymer molecules that become trapped within the cortex. As a result, the dye becomes resistant to washing and drying.³

Unfortunately, this mechanistic process simultaneously generates hazardous byproducts. PPD and hydrogen peroxide, for example, create hydroxyl radicals, which are potent reactive oxygen species (ROS) capable of causing DNA damage and promoting mutations.³

PPD intermediates can also self-condense to form Bandrowski's base (2,5-bis(4-aminophenylimino)-1,4-cyclohexadien-1,4-diimine), a tricyclic amine and confirmed potent mutagen in vitro; however, its formation and significance in vivo in human hair dye users remains uncertain and may be limited.⁴

Health implications of PPD use in cosmetics

Cosmetic users report a greater prevalence of allergic disorders, the most common of which includes allergic contact dermatitis (ACD), a delayed hypersensitivity reaction resulting in severe inflammation. ACD is triggered by several specific skin irritants, of which PPD is a potent member.⁵

Between 24-72 hours after skin exposure, PPD is oxidized into a reactive hapten that binds to skin proteins, which leads to immune sensitization and severe inflammation characterized by redness, swelling, blistering, and intense itching.⁴

An estimated 1.5% of the global human population is susceptible to PPD sensitization, with this estimate rising to 6% in dermatitis patients. Due to repeated exposure, hairdressers are at an exceptionally high occupational risk, with sensitization rates of up to 21.3%. Similar high rates have been reported internationally among professional hairdressers (19.7% in East Europe, 20.4% in Italy).^5,6

A major consumer risk factor, particularly in younger individuals, is that of temporary ‘black henna’ tattoos, which are often illegally adulterated with high concentrations of PPD, leading to a very high risk of severe allergic sensitization and reactions even after a single exposure.⁴

Toxicological profile and systemic risks

PPD poisoning presents a stark contrast to cosmetically associated dermatology issues. Herein, oral PPD ingestion causes life-threatening poisoning that frequently occurs in parts of Asia and Africa, where PPD is sometimes used in suicide attempts or accidental poisoning.⁷

PPD ingestion causes rapid and severe multi-organ failure, beginning with massive angioneurotic edema of the neck and airways that can lead to asphyxiation. This is followed by severe muscle breakdown (rhabdomyolysis) and acute renal failure. The mortality rate among hospitalized patients is alarmingly high at 14.5%, with 93.5% of these cases due to suicidal intent.⁷

In normal cosmetic use, systemic absorption of PPD is minimal after oxidation with peroxide, and repeated dermal application in animal studies causes little to no systemic toxicity except mild weight changes at high doses. Chronic effects may include eczematoid dermatitis in some users, but there is no evidence for reproductive or developmental toxicity in humans, and animal studies are negative for teratogenicity. ^2,4

To date, it remains unclear whether hair dye use increases the risk of cancer. In a 2020 36-year prospective cohort study of 117,200 U.S. women, researchers did not identify a statistically significant association between the use of permanent hair dyes and the risk of most cancers or cancer-related mortality.

However, this study identified a positive and dose-dependent association between cumulative hair dye use and an increased risk of specific cancer subtypes including estrogen receptor-negative breast cancer, progesterone receptor-negative breast cancer, and ovarian cancer. Increased risk of basal cell carcinoma and Hodgkin lymphoma in specific subgroups was also observed. Importantly, these findings are associations and not confirmed as causal relationships. Further investigation is needed.¹

Image Credit: Korelidou Mila / Shutterstock.com

Regulatory status and safety assessments

The global regulation of PPD usage is concentrated in the European Union (EU) and United States, wherein these products are evaluated by the Scientific Committee on Consumer Safety (SCCS) and Food and Drug Administration (FDA), respectively.^{4, 8}

The SCCS restricts PPD usage to a maximum on-head concentration of 2% due to its status as an "extreme sensitizer." Comparatively, the FDA considers PPD a "coal tar hair dye," which exempts the molecule from pre-market approval provided that PPD-containing products are labelled with a specific warning recommending a preliminary patch test. However, both the FDA and the CIR panel emphasize that PPD is unsafe for direct application to the skin, including in temporary tattoos, eyelashes, or eyebrows. Only hair dye use on scalp is permitted under current regulations. Industry and independent reviews agree that labeling and patch testing are critical for consumer safety.⁸

Industry-funded research suggests that PPD is safe at regular cosmetic hair dye concentrations but unsafe for direct dermal application including tattoos, eyelashes, and eyebrows. Independent reviews continue to recommend caution due to individual susceptibility and the lack of a defined safe level for all populations.⁴

Safer alternatives and future directions

Increasing public awareness about the toxic properties of PPD has promoted the development of PPD-free products, with p-toluenediamine sulfate (PTDS) marketed as a less allergenic alternative to PPD. PTDS is chemically related to PPD and likely exhibits mechanistic overlap, with cross-reactivity studies reporting that approximately 57% of individuals allergic to PPD will also react to PTDS.⁹

Thus, PTDS is an unsuitable substitute for individuals already sensitized to PPD. Low-sensitizer technologies are in the early stages of development, with no non-toxic alternatives currently available with equivalent performance capabilities. Other emerging alternatives, such as plant-based dyes (e.g., pure henna), generally lack the permanence or color range of PPD-based dyes. At present, no permanent hair dye is free from sensitization risk.^{4, 9}

Conclusions

Public health recommendations suggest that the most effective risk mitigation strategy for consumers is the universal adoption of a 48-hour patch test before every application to screen for sensitization to PPD. For skincare and hairdressing professionals, consistent use of protective gloves is paramount to ensure safety. Improving occupational safety training and glove compliance among hairdressers is essential, as is greater consumer education on patch testing and risk factors.

Moving forward, a combination of stringent regulatory oversight, continued research into long-term health effects, and clear consumer education is essential to manage the risks of this ubiquitous cosmetic chemical. Global harmonization of regulations and investment in alternative dye technologies are also likely to play a key role in future risk reduction.

References

1. Zhang, Y., Birmann, B. M., Han, J., Giovannucci, E. L., Speizer, F. E., Stampfer, M. J., Rosner, B. A., & Schernhammer, E. S. (2020). Personal use of permanent hair dyes and cancer risk and mortality in U.S. women: prospective cohort study. BMJ, 370, m2942. DOI:10.1136/bmj.m2942, https://www.bmj.com/content/370/bmj.m2942
2. U.S. Environmental Protection Agency. (2000). p-Phenylenediamine Hazard Summary. EPA-452/R-00-005. https://www.epa.gov/sites/default/files/2016-09/documents/p-phenylenediamine.pdf. Accessed 28^th July 2025.
3. He, L., Michailidou, F., Gahlon, H. L., & Zeng, W. (2022). Hair Dye Ingredients and Potential Health Risks from Exposure to Hair Dyeing. Chemical Research in Toxicology, 35(6), 901–915. DOI:10.1021/acs.chemrestox.1c00427, https://pubs.acs.org/doi/10.1021/acs.chemrestox.1c00427
4. Burnett, C. L., Boyer, I. J., Bergfeld, W. F., Belsito, D. V., Hill, R. A., Klaassen, C. D., Liebler, D. C., Marks, J. G., Jr, Shank, R. C., Slaga, T. J., Snyder, P. W., & Heldreth, B. (2025). Amended Safety Assessment of p-Phenylenediamine, p-Phenylenediamine HCl, and p-Phenylenediamine Sulfate as Used in Cosmetics. Cosmetic Ingredient Review. https://www.cir-safety.org/sites/default/files/p-Phenylenediamine_2.pdf. Accessed 28^th July 2025.
5. Alinaghi, F., Bennike, N. H., Egeberg, A., Thyssen, J. P., & Johansen, J. D. (2018). Prevalence of contact allergy in the general population: A systematic review and meta-analysis. Contact Dermatitis, 80(2), 77–85. DOI:10.1111/cod.13119, https://onlinelibrary.wiley.com/doi/10.1111/cod.13119
6. Lee, J. J., Kim, D. Y., Lee, H., Byun, J. Y., Choi, Y. W., Roh, J. Y., & Choi, H. Y. (2025). Clinical Patterns and Risk Factors of Occupational Contact Dermatitis in Hairdressers: A Questionnaire-based Cross-sectional Study. Annals of Dermatology, 37(3), 162. DOI:10.5021/ad.25.019, https://anndermatol.org/DOIx.php?id=10.5021/ad.25.019
7. Bandari, D., Bhagavathula, A., Khan, M., & Shehab, A. (2019). A systematic review and meta-analysis of the prevalence and complications of paraphenylenediamine-containing hair dye poisoning in developing countries. Indian Journal of Pharmacology, 51(5), 302. DOI:10.4103/ijp.ijp_246_17, https://journals.lww.com/iphr/fulltext/2019/51050/a_systematic_review_and_meta_analysis_of_the.3.aspx
8. Scientific Committee on Consumer Products (SCCP). (2006). Opinion on p-Phenylenediamine. European Commission. https://ec.europa.eu/health/ph_risk/committees/04_sccp/docs/sccp_o_069.pdf. Accessed on 28^th July 2025.
9. Scheman, A., Cha, C., & Bhinder, M. (2011). Alternative Hair-Dye Products for Persons Allergic to para-Phenylenediamine. Dermatitis, 22(4), 189–192. DOI:10.2310/6620.2011.00010, https://www.liebertpub.com/doi/10.2310/6620.2011.00010

Further Reading

• All Toxicology Content
• What is Toxicology?
• Toxicity of Metabolites
• What is Toxicogenomics?
• Glyphosate in Food: How Dangerous is it?