Brian Skellie, APP Medical Liaison
June 12, 2019
GENTIAN VIOLINS?
GENTIAN VIOLENCE?
Stop use and dispose of gentian violet immediately?
Piercers in Canada were recently informed by Health Canada that they were not allowed to use products containing gentian violet.1 A recall was put in place due to a link to cancer risk. At least one manufacturer voluntarily discontinued sales of their products and their license was cancelled.
The piercers who were notified, exercised prudence to stop use immediately, then learned more about the concerns and responded with questions. They reviewed the toxicology evidence provided which was based on high levels of oral consumption and presented a logical case for safe use as a marking product. The health authorities reviewed these responses, interacted with manufacturers of surgical marking pens, and came to the conclusion that little to no gentian violet is released to the human body in this application due to the dilution of the product and short duration of exposure.
HISTORY
History of surgical skin-marking technique2
[My sketch of the chemical formula from PubChem— NIH3]
Gentian violet was identified as genotoxic carcinogen by the Safe Drinking Water and Toxic Enforcement Act of 1986 (Proposition 65)4. This regulation requires the State of California to publish a list of chemicals known to cause cancer or reproductive toxicity and to update the list at least annually. Studies have tended to focus on the carcinogenicity of the oral rather than topical route of exposure and toxic environmental effects5.
“No evidence of risk” is not the same as “evidence of no risk”
International experts issued a warning to prevent human exposure to gentian violet in food due to cancer risk which triggered the 2018 review by Health Canada as described in their announcement:
In 20146, the FAO/WHO Joint Expert Committee on Food Additives (JECFA) completed an assessment (toxicological evaluation) of certain veterinary drugs (including gentian violet) residues in food. They concluded that gentian violet can alter genetic material and cause cancer (genotoxic carcinogen). Therefore, an acceptable daily intake (ADI) cannot be established. Based on the JECFA’s conclusion, the Codex Alimentarius Commission, which develops international food standards to protect consumer health and to facilitate fair trading practices in foods, recommended in 2018 that regulatory authorities prevent exposure to residues of gentian violet in food7. Following this recommendation, Health Canada decided to review the risk of cancer with the use of gentian violet-containing human health products, in addition to veterinary products.
Because this is the most common skin marking product on the market, there was an immediate inquiry as to the rationale behind this requirement, and if pens or toothpicks with a very small dose were still allowed for topical use, in consideration that the only medical devices were stated to pose little to no risk.
These products do not pose an increased risk of cancer when used for a short time and in most people. [ibid]
Health Canada has reassured us that skin markers made with gentian violet are allowed, but initially replied that containers of liquid were not and must be returned to the pharmacy for disposal. With the rational persistence of Jason Friday, Jesse Villemaire and colleagues, by June 22nd the reasonable topical use of liquid for our purposes of skin marking was clarified and accepted.
Dear Jason, in follow up to your recent telephone request.
The current recall of gentian violet non-prescription drugs and veterinary drugs does not impact compliant sales of medical devices containing gentian violet in Canada. Markers used in the tattoo and piercing industry are not subject to the Medical Devices Regulations or the Food and Drug Regulations. These items maybe medical devices used off-label, and the exposures may be higher depending on the individual circumstances. But are not expected to be toxic if not ingested. Business owners should discuss any potential risks with their clients.
Health Canada reviewed the potential for toxicity from gentian violet in medical devices and concluded that based on the limited exposure to Gentian Violet in wound dressings and surgical markers they are not associated with an increase in excess cancer risk.
The current summary safety reviews and information updates published by Health Canada document an unacceptable toxic response to the potential oral ingestion of gentian violet in human non-prescription drugs and veterinary drugs for feed and companion animals.
Please contact me directly if you have further questions or concerns.
Sincerely Mary-Jane
Mary-Jane Bell, Ph.D.
Science Advisor, Medical Devices Bureau, Health Products and Food Branch
Health Canada | Government of Canada
Yes, we can continue to use gentian violet based sterile surgical markers and non-sterile skin markers because the limited exposure has a low probability of a dangerous dose. Mark the area prior to your final application of antiseptic, or use sterile gloves and a sterile marking implement after the final antiseptic has been applied and dried.
Some risk remains with liquid gentian violet
Please note that the use of liquid gentian violet in bottles has several disadvantages: intrinsic contamination8, extrinsic contamination of a multidose container from use and airborne exposure, added complexity of effective sterilization9, superpotency10, and the possibility that a harmful dose can be delivered by accident, or the inconvenience of an accidental spill.
“Surprisingly, no acute toxic side effects were reported after administration of large amounts of gentian violet-treated blood. Gentian violet is a mutagen, a mitotic poison, and a clastogen. The carcinogenic effects of gentian violet in rodents have been reported recently.”
Don’t panic!
We should not be discouraged by the scrutiny of our gentian violet use, and may be pleased to explore alternatives where possible. Here are some options:
Some skin markers are made without gentian violet. Stick with skin markers and surgical markers, rather than permanent ink pens and markers at the incision site. Gentle, direct pressure with the jewelry or the back of the needle, can make clearly defined indentations to mark the location of the piercing for the client. These pressure marks are another option that does not require ink and can be made in seconds and repositioned accurately. This pressure can help acclimate the area to stimulation, and minimize the shock of the piercing to the client. As with other methods, you may either mark the area prior to your final application of antiseptic with a nonsterile implement or use sterile gloves and a sterile marking implement after the final antiseptic has been applied and dried12.
Other products have been used with mixed results. Tattoo pigment have been reported to leave permanent stains in some cases when used for marking. Food coloring dye may not work for clients with related allergies.
Related science in regulation
Ongoing scientific review to assess the safety and effectiveness data gaps of health care antiseptics went into effect by the FDA on December 20, 201813. In this case and with other antiseptics under review when a product has out of date or insufficient evidence for market, updated evidence can become a regulatory requirement. Now they want proof of no harm, or predictable minimal harm, which is different from “no proof of harm” shifting of responsibility. We can anticipate more interaction from regulatory authorities in regard to the antiseptic products we use as piercers and body artists.
I prefer to find an alternative if clinically significant or regulatory disadvantages apply to a product. There are quite a number of grey areas in our business practices and the products we use that deserve both scrutiny and further discussion into the ethical decision-making process. When it comes to regulatory requirements, it’s a hard stop and switch to something else until we can prove safety through the required means. Some aspects of our work practices are more based on theoretical rationale than evidence. When it comes to products, there is a choice between evidence to prove safety and the theoretical rationale or regulatory limits, evidence first, limits imposed, then negotiated rationale.
*Sometimes it just takes an educational push to get rationale supported by evidence or at least move regulatory limits in the right direction for us. In this case, it was a success for our industry.
For another example, Statim autoclaves are sometimes confusing to regulatory authorities when they are presented as a separate category of sterilizer, even though they are proven substantially equivalent to other autoclaves plus a few features. When educational information is provided, their function and operation are as easy to understand as any other autoclave.
**Jewelry standards have had a similar level of analysis in terms of evidence requirements for material safety. Also, a similar level of misunderstanding that we are working on correcting through educational outreach.
Resources
1“Health Canada warns Canadians of potential cancer risk associated with gentian violet,” Recalls and safety alerts, Health Canada, accessed August 4, 2019, https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2019/70179a-eng.php.
2 ”Surgical skin-marking techniques,” PubMed.gov, NCBI, accessed August 4, 2019, https://www.ncbi.nlm.nih.gov/pubmed/2434965.
3 “Gentian Violet,” Chemical Compound, PubChem, National Library of Medicine, accessed April 16, 2020, https://pubchem.ncbi.nlm.nih.gov/compound/Gentian-violet.
4 ”Gentian Violet,” Chemicals Considered or Listed Under Proposition 65, OEHHA: California Office of Environmental Health Hazard Assess- ment, accessed April 16, 2020, https://oehha.ca.gov/proposition-65/chemicals/gentian-violet.
5 ”Exposure to Crystal Violet, Its Toxic, Genotoxic and Carcinogenic Effects on Environment and Its Degradation and Detoxification for Environ- mental Safety,” PubMed.gov, NCBI, accessed August 4, 2019, https://www.ncbi.nlm.nih.gov/pubmed/26613989.
6 ”Toxicological evaluation of certain veterinary drug residues in food / prepared by the seventy-eighth meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA),” Institutional Repository for Information Sharing, World Health Organization, accessed August 5, 2019, https://apps.who.int/iris/handle/10665/128550.
7 “Codex Alimentarius Commission: 02-06 July 2018,” News, Food and Agriculture Organization of the United Nations, accessed August 4, 2019, http://www.fao.org/news/story/en/item/1143286/icode/.
8 Thomas J. Safranek, M.D., William R. Jarvis, M.D., Loretta A. Carson, Lucy B. Cusick, Lee A. Bland, Jana M. Swenson, and Vella A. Silcox, “Myco- bacterium chelonae Wound Infections after Plastic Surgery Employing Contaminated Gentian Violet Skin-Marking Solution,” (July 23, 1987): accessed August 4, 2019, https://www.nejm.org/doi/full/10.1056/NEJM198707233170403.
9 ”Precautions with gentian violet: Skin marking made sterile, effective, and economical,” Resources, Brian W. Skellie – Sharing Ideas, accessed August 4, 2019,
10 “FDA Recalls & Court Actions: Dec. 18 & 26, 1991,” News, Scrip > Informa Pharma Intelligence, accessed August 4, 2019, https://scrip.pharmaintelligence.informa.com/PS020249/FDA-RECALLS-amp-COURT-ACTIONS-Dec-18-amp-26-1991.
11 “The metabolism and mode of action of gentian violet,” PubMed.gov, NCBI, accessed August 4, 2019, https://www.ncbi.nlm.nih.gov/pubmed/2272286.
12 “Marking for procedures,” (April 20, 2012), Shares, Brian W. Skellie – Sharing Ideas, accessed August 4, 2019, https://brnskll.com/shares/marking-for-procedures/.
13 “Safety and Effectiveness of Health Care Antiseptics; Topical Antimicrobial Drug Products for Over-the-Counter Human Use,” (December 20, 2017), A Rule by the Food and Drug Administration, Federal Register, accessed August 5, 2019, https://www.federalregister.gov/docu– ments/2017/12/20/2017-27317/safety-and-effectiveness-of-health-care-antiseptics-topical-antimicrobial-drug-products-for.