What research says about skin
How aniline and N-methylaniline affect the skin
What happens when these two impurities left in synthetic indigo reach the skin, summarised from human studies and regulatory assessments. Useful background before you read the test results table below.
It stays inside synthetic indigo
Commercial synthetic indigo contains up to 0.6% aniline (6,000 mg/kg) and up to 0.4% N-methylaniline (4,000 mg/kg). Both are locked inside the indigo crystals and are not removed by acid washing or solvent extraction.
Cordin et al., Sci Rep 2021
It moves from fabric into sweat
When 42 commercial pairs of jeans were soaked in artificial sweat, indigo dye migrated at 3.2 to 7.8 mg per gram of fabric, more from dark shades. The study measured the dye only, not the aniline within it.
Herrero et al., Environ Res 2019
It passes through intact skin
Aniline is absorbed through unbroken skin as a liquid and as vapour. In human volunteers, aniline in water was absorbed at 0.2 to 1.2 mg per cm² of skin per hour; in excised human skin, 20 to 38% of the applied dose passed through within 24 hours. Workers with irritated skin carried higher internal doses.
Baranowska-Dutkiewicz 1982 · Wellner et al. 2008 · Korinth et al. 2007
It stops blood from carrying oxygen
Inside the body both substances turn haemoglobin into methaemoglobin, which cannot carry oxygen. Lips and skin turn bluish (cyanosis), headache, dizziness and breathlessness follow, and severe cases lose consciousness. Symptoms can appear hours after exposure.
ATSDR · Lee et al. 2013 · Bernasconi et al. 2026
Skin reactions and long-term risk
Under the EU harmonised classification aniline may cause an allergic skin reaction (Skin Sens. 1), and both substances are classed as toxic in contact with skin. In 2020 the International Agency for Research on Cancer (IARC) classified aniline as probably carcinogenic to humans (Group 2A).
EU CLP harmonised classification · IARC Monographs 127
What has happened to people
46.8%
blood methaemoglobin
A 25-year-old worker splashed with about 200 mL of aniline on his face and upper body. Cyanosis spread over his whole body after 90 minutes and he was treated with methylene blue; burns and contact dermatitis remained on the skin.
Lee et al., Ann Occup Environ Med 2013 (Korea)
82 patients
severe methaemoglobinaemia
Migrants whose skin sat for hours in fuel-contaminated seawater. N-methylaniline or its metabolites were found in 37 of 39 patients tested, and two died. The investigators identified dermal absorption as the likely cause.
Bernasconi et al., N Engl J Med 2026 (Italy)
Blood methaemoglobin level and symptoms
- below 1%normal range
- 15–30%skin and lips turn bluish
- 30–50%headache, fatigue, dizziness, rapid pulse
- 50–70%stupor, depressed breathing, arrhythmia, risk of cardiac arrest
ATSDR (US Agency for Toxic Substances and Disease Registry), Medical Management Guidelines for Aniline
Key paperScientific Reports (Nature Portfolio)Open access (CC BY 4.0)
Quantification of aniline and N-methylaniline in indigo
Michael Cordin · Thomas Bechtold · Tung Pham
Research Institute of Textile Chemistry and Textile Physics, University of Innsbruck (Dornbirn, Austria)
26 October 2021 · Volume 11, article 21135
doi:10.1038/s41598-021-00634-7
Read the paper↗ (opens in a new tab) What the paper found
- Commercial synthetic indigo contains up to 0.6% aniline and up to 0.4% N-methylaniline by weight, and these impurities are trapped inside the indigo crystals as they form.
- Because neither acid washing nor solvent extraction removes them, the authors present a new method: reduce indigo to leuco-indigo to dissolve it, extract with acid and quantify by HPLC (quantitation limit 0.010%).
- Commercial indigo samples measured with this method contained 0.3 to 0.6% aniline and 0.1 to 0.3% N-methylaniline. The two values rise and fall together, pointing to the same degradation reaction during synthesis.
- The weak mutagenic effect seen in synthetic indigo is most probably due to these impurities, which are also released into waste water during indigo production and dyeing.
- The authors conclude that, because of the effects on human health, an efficient purification process that removes these impurities is important.
Blugene test result
Aniline and N-methylaniline both not detected — below the method detection limit of 5 mg/kg (KOTERI, KS K 0734 2019). The table below shows the result alongside nine commercial samples.
Not detected means below the detection limit of the test method. It does not mean that skin safety has been proven.
