Tattoos and Cancer Why should anyone think about it?

1. Tattoos and CancerWhy should anyone think about it? EuropeanCongress on Tattoo and Pigment research 26-28 March 2019, Bern, Switzerland Milena Foerster, PhD foersterm@fellows.iarc.fr

2. Is there any existing proven relationship between tatoos and cancer? This paper estimates 4 additional cases of bladder cancer per 10 000 people tattooed with pigment yellow 14 (tattoo size 400 cm2, 20 y decomposition time) This paper - Restricted to skin cancer Number of reported cases not higher as expected by chance

3. Why aren’t there studies on tattoos and cancer? 1. Tattoos are as old as mankind 2. Mankind did not always get as old as it gets now 3. Cancer risk increases with age Source: NCI

4. Why aren’t there studies on tattoos and cancer?4. Tattooed population used to be small and co-exposed 5. Cancer usually needs some incubation time 6. Only recently tattoos got mainstream Large exposed population = even small effect has a large impact on public health ANY research on tattoos and health is important Source: Dalia Research, 2018

5. Why might there be an association with cancer? Exposure to carcinogens environmental pollutants industrial chemicals metals Mutation Cancer • Carcinogens identified in Tattoo ink • 7 substances classified as carcinogenic to humans • 17 substances probably/possibly carcinogenic to humans (for these usually no human evidence) • Many of these are directly genotoxic •  dermal or respiratory exposure to some of these substances caused cancer How does this relate to subcutaneous tattoo exposure ? Dermal + X?

6. How might the body react / interact to injected tattoo inks? Acute inflammatory reaction occurs immediately after tattooing on the injection site  high acute exposure to carcinogens? A large part of tattoo pigments will accumulate in the draining lymph nodes  low constant exposure to carcinogens? THE LYMPHATIC SYSTEM • Ensures proper functioning of immune system •  healthy immune system is important to fight cancer • Lymphocytes produce antibodies to fight and filter toxins and stop infections from spreading. • React to foreign bodies • by “eating” (phagocytose) and elimination • by inflammation • Can learn to recognise external threats (adaptive immunity)

7. How might the body react / interact to injected tattoo inks? Hypothesised carcinogenic mechanism of chronic exposure to tattoo inks Exposure to particles Production of cytotoxic agents Clearance of particles Deposition of particles What is the manageable amount of pigments? Mutations Uptake of particles by phagocytes and other cells Cancer Skin Lymphatic …? Inflammation Cell injury Cell proliferation Adopted from IARC monograph 93 Carbon Black and Titanium Dioxide (both Group 2B)

8. Is there some evidence for tattoos causing chronic inflammation ? Black inks associated with production of cytotoxic agents like reactive oxygen species Høgsberg et al, 2013; Regensburger et al, 2010 TiO and Carbon Black nanoparticles in mice induce oxidative stress  chronic inflammation  mutations (Trouiller et al (2009), Driscoll et al 1997) Alternatively: Tattoos as immune-vaccines? Enhanced secretory immunoglobulin A in people with more tattoo experience (Lynn et al, 2016)

9. Conclusion No evidence does not necessarily mean no association: very limited studies on tattoos and cancer Necessity to conduct studies on potential mechanisms and epidemiological research Studies are needed to investigate whether tattooscause chronic inflammation in humans

10. Wolfgang Baeumler, University Of Regensburg Ines Schreiver, German Federal Institute of Risk Assessment UrsHauri, Cantonal Laboratory of Basel David Kriebel, University of Massachusetts The Environment and Radiation Section at the IARC Milena Foerster, PhD foersterm@fellows.iarc.fr

11. Volume 49 (1990) Chromium, Nickel and Welding: Volume 52 (1991) Chlorinated Drinking-water; Chlorination By-products; Some Other Halogenated Compounds; Cobalt and Cobalt Compounds Volume 57 (1993) Occupational Exposures of Hairdressers and Barbers and Personal Use of Hair Colourants; Some Hair Dyes, Cosmetic Colourants, Industrial Dyestuffs and Aromatic Amines Volume 73 (1999) Some Chemicals that Cause Tumours of the Kidney or Urinary Bladder in Rodents and Some Other Substances Volume 82 (2002) Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene Volume 87 (2006) Inorganic and Organic Lead Compounds Volume 93 (2010) Carbon Black, Titanium Dioxide, and Talc Volume 92 (2010) Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Exposures Volume 100C (2012) Arsenic, Metals, Fibres, and Dusts Volume 100F (2012) Chemical Agents and Related Occupations Supplement 7 (1987) Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42

12. First projects planned Evaluating the pharmakokinetics of PAAs and metals in the 24hours after tattooing Validation of metal and TiO2 concentration in lymphatic tissue as exposure proxy for tattoo exposure in studies on lymphatic cancers Identification of suitable cohort for including questions on tattoo exposure

13. Carcinogenic potential of tattoo inks Group 1 Carcinogenic to humans Group 2A Probably carcinogenic to humans Group 2B Possibly carcinogenic to humans Group 3 Not classifiable as to its carcinogenicity to humans

15. Commonly proposed mechanism of carcinogenesis: Genotoxic and/or mutagenic substances -> DNA damage/mutations -> cancer Questions to answer: How does the respiratory/dermal exposure levels relate to the subcutaneous exposure to tattoo inks? May it be considered as dermal + X