Phenols are a broad chemical class, and they do not all have the same toxicological profile.

The No Nines™ exclusion is directed at specific phenolic chemistries that have been used in consumer, antimicrobial, plastic, preservative, and industrial applications — including triclosan, certain chlorophenols, and bisphenols such as BPA, BPS, and BPF.

We leave them out for different reasons.

Triclosan has been shown in animal studies to alter thyroid-hormone homeostasis, and laboratory research has demonstrated mechanisms by which bacterial exposure to triclosan can select for triclosan resistance and, in some organisms, reduced susceptibility to antibiotics.¹⁻⁶

Bisphenol A (BPA) is biologically active in endocrine systems, including estrogen and thyroid-hormone signaling. Experimental studies demonstrate interference with thyroid-receptor-mediated signaling, while human observational research has reported associations between BPA exposure and altered thyroid measurements.⁷˒⁸

Replacing BPA with another bisphenol does not necessarily remove that concern. Bisphenol S (BPS) and bisphenol F (BPF) have demonstrated hormonal activity in experimental studies, including estrogenic, androgenic, antiestrogenic, antiandrogenic, and thyroid-signaling effects.⁹˒¹⁰

And for certain chlorophenols, the concern is different again. Pentachlorophenol has been classified by the International Agency for Research on Cancer as carcinogenic to humans, while 2,4,6-trichlorophenol has been classified as possibly carcinogenic to humans.¹¹ EPA separately characterizes pentachlorophenol as “likely to be carcinogenic to humans” and historically classified 2,4,6-trichlorophenol as a probable human carcinogen based on sufficient evidence in experimental animals.¹²˒¹³

These are not interchangeable findings, and they should not be presented as though every phenol causes every effect.

For No Nines™, the practical question is simpler:

Do we need these chemistries to make an effective product?

We do not.

So we leave them out.

No Nines™ Standard™

Effective chemistry doesn't require unnecessary exposure.

Our ingredient decisions consider not only whether an ingredient can perform a function, but also how much is required, how people are exposed to it, what happens when it is misused, and whether a different chemistry can accomplish the intended purpose with a more favorable exposure profile.

“Phenols” Are Not One Chemical

The word phenol describes a chemical structural feature: a hydroxyl group attached directly to an aromatic ring.

That structure occurs in a very large number of compounds. Some occur naturally. Others are synthesized for antimicrobial, preservative, plastic, pesticide, or industrial purposes.

Simply belonging to the broad phenolic chemical family does not establish that two substances will behave identically in the human body or have the same toxicological profile.

Toxicity depends on the specific molecule — including what other chemical groups are attached to it — as well as dose, route of exposure, metabolism, duration of exposure, and biological target.

That distinction is especially important here because the compounds included in the No Nines™ phenols category raise different scientific concerns.

Triclosan

A chlorinated phenolic antimicrobial historically incorporated into antibacterial soaps and other consumer products.

Chlorophenols

Phenols containing one or more chlorine atoms. This group includes compounds with very different uses and toxicological profiles, among them pentachlorophenol and 2,4,6-trichlorophenol.

Bisphenols

Compounds containing two phenolic structures. BPA has been widely used in polycarbonate plastics and epoxy resins, while BPS and BPF have been used as structural alternatives to BPA.

The shared structural chemistry matters, but it does not make these substances toxicologically identical.

That is why No Nines™ evaluates the actual chemicals — not simply the family name.

Triclosan: An Antimicrobial That Can Select for Resistance

Triclosan is a chlorinated phenolic compound developed for its antimicrobial activity.

At lower concentrations, an important bacterial target of triclosan is enoyl-acyl carrier protein reductase, or FabI, an enzyme involved in bacterial fatty-acid synthesis.²

That specificity is significant because bacteria are capable of adapting to triclosan.

Laboratory research has identified multiple mechanisms associated with reduced triclosan susceptibility, including:

• alteration of the antimicrobial target;
• increased production of the target enzyme;
• increased activity of bacterial efflux pumps that remove chemicals from the cell; and
• broader stress-response and multidrug-resistance mechanisms.²˒³

Some of those same biological mechanisms also participate in resistance to therapeutic antibiotics.

For example, McMurry and colleagues demonstrated that overexpression of the bacterial marA, soxS, or acrAB systems reduced susceptibility to triclosan in Escherichia coli. The AcrAB system is a multidrug efflux system capable of affecting susceptibility to multiple compounds.³

A broader scientific review of triclosan resistance mechanisms concluded that several mechanisms responsible for triclosan resistance overlap with mechanisms involved in antibiotic resistance and that laboratory isolates have demonstrated cross-resistance between triclosan and antibiotics.²

This does not mean every bacterium exposed to triclosan becomes antibiotic resistant.

It does mean that an antimicrobial incorporated into everyday products can create selective pressure favoring organisms equipped to survive that antimicrobial environment — and that some of those survival mechanisms may also influence antibiotic susceptibility.

For an antimicrobial chemical that is unnecessary to the performance of a No Nines™ formulation, that is a meaningful consideration.

FDA and Triclosan in Consumer Antibacterial Washes

Triclosan was once common enough in consumer antibacterial products that the U.S. Food and Drug Administration specifically addressed it during its review of over-the-counter antiseptic washes.

In 2016, FDA issued its final rule covering OTC consumer antiseptic wash products intended to be used with water.

The agency determined that 19 active ingredients — including triclosan and triclocarban — were not demonstrated to be generally recognized as safe and effective for those consumer antiseptic-wash uses.¹

The rule was published as:

Safety and Effectiveness of Consumer Antiseptics; Topical Antimicrobial Drug Products for Over-the-Counter Human Use

81 Federal Register 61106–61130
September 6, 2016
21 CFR Part 310
Docket No. FDA-1975-N-0012
RIN 0910-AF69
Federal Register Document 2016-21337

The rule became effective September 6, 2017.¹

It is sometimes summarized by saying that FDA “banned triclosan,” but that wording is broader than the actual regulatory action.

The final rule addressed OTC consumer antiseptic washes used with water. It did not prohibit every conceivable use of triclosan.

That regulatory distinction is important.

The formulation decision for No Nines™ is equally straightforward:

Triclosan is not necessary for us to make an effective product, so we do not formulate with it.

Triclosan and Thyroid Hormone Homeostasis

Triclosan has also been studied extensively for its potential effects on thyroid-hormone regulation.

A 2007 study conducted by researchers associated with the U.S. Environmental Protection Agency exposed young female rats to triclosan for four days and found a dose-dependent decrease in circulating total thyroxine, or T4.⁴

Researchers subsequently investigated how that effect occurred.

In a 2010 study, Paul and colleagues again observed dose-dependent reductions in circulating T4 in rats. Triclosan also increased activity and expression of liver pathways involved in the metabolism and clearance of thyroid hormone.⁵

Those findings provided a biologically plausible mechanism by which triclosan exposure could lower circulating thyroid hormone in the experimental animals.

Developmental research produced similar findings.

Pregnant rats exposed to triclosan from gestation through lactation showed decreased T4 concentrations in the mothers and in neonatal offspring at particular developmental stages.⁶

These findings matter because thyroid hormones play fundamental roles in metabolism, growth, and neurological development.

Human evidence is less consistent.

For example, a controlled 2009 study in 12 adults found that 14 days of triclosan-containing toothpaste substantially increased plasma triclosan concentrations but did not produce statistically significant changes in the thyroid hormones measured.¹⁴

Human observational studies conducted subsequently have reported some associations between triclosan exposure and particular thyroid measurements, while other measurements or study populations have shown little or no relationship.

The evidence therefore does not justify saying that ordinary consumer exposure to triclosan has been proven to cause human thyroid disease.

What the research does establish is that triclosan is biologically capable of altering thyroid-hormone homeostasis in experimental systems, adding another consideration to the use of an antimicrobial ingredient that No Nines™ does not require.

BPA: A Plastic Chemical With Endocrine Activity

Bisphenol A, or BPA, is probably the best known of the bisphenols.

It has been used for decades in the manufacture of polycarbonate plastics and epoxy resins.

The scientific interest in BPA extends far beyond its physical role in plastic.

BPA has demonstrated activity within endocrine-signaling systems, including estrogen-receptor and thyroid-hormone pathways.

In 2002, Moriyama and colleagues examined the interaction between BPA and thyroid-hormone receptors. Their experiments demonstrated that BPA could interfere with thyroid-hormone-receptor-mediated transcription and act as an antagonist of thyroid-hormone signaling under the experimental conditions studied.⁷

That finding helped establish that BPA's endocrine activity was not limited to estrogen signaling.

Researchers have also examined whether BPA exposure is associated with thyroid measurements in people.

An analysis of the 2007–2008 U.S. National Health and Nutrition Examination Survey, including 1,346 adults and 329 adolescents, evaluated urinary BPA concentrations in relation to a panel of serum thyroid measurements. The researchers reported suggestive relationships between BPA exposure and some thyroid measures, although the pattern was not uniform across all hormones or age groups.⁸

Because that was a cross-sectional observational study, it could identify associations but could not establish that BPA caused those changes.

The importance of the finding is therefore not a single epidemiological association by itself.

It is that human biomonitoring findings exist alongside a larger body of experimental evidence demonstrating that BPA is capable of interacting with endocrine pathways.

Regulatory Safety and Biological Activity Are Different Questions

BPA is also a good illustration of an important distinction in toxicology.

A chemical can demonstrate biological activity in laboratory studies while a regulatory agency determines that a particular approved use, at estimated exposure levels, meets its regulatory safety standard.

Those statements address different questions.

The U.S. Food and Drug Administration currently states that available information continues to support the safety of BPA for its currently approved uses in food containers and packaging.¹⁵

That determination concerns exposure from specified authorized food-contact applications.

It does not mean BPA lacks endocrine activity.

Conversely, demonstrating endocrine activity in an experimental system does not, by itself, establish that every real-world exposure causes an adverse health effect.

The No Nines™ Standard™ asks another question entirely:

Is this chemistry necessary in our formulation?

When it is not, we choose not to add the exposure.

“BPA-Free” Does Not Necessarily Mean Bisphenol-Free

As concern surrounding BPA increased, manufacturers began replacing BPA with structurally related chemicals.

Two of the most prominent substitutes are bisphenol S (BPS) and bisphenol F (BPF).

The substitution produced products that could accurately be labeled “BPA-free.”

But removing BPA does not necessarily eliminate bisphenol chemistry.

That became an important research question:

Are BPS and BPF biologically inactive replacements, or do they retain some of the endocrine activity associated with BPA?

The evidence indicates that they are not biologically inert.

BPS and BPF: Similar Structure, Similar Questions

In 2015, Rochester and Bolden published a systematic review examining the hormonal activity of BPS and BPF.

The review identified 32 experimental studies available at that time — 25 conducted only in vitro and seven including in-vivo testing.⁹

Across those studies, BPS and BPF demonstrated several forms of hormonal activity, including:

• estrogenic activity;
• antiestrogenic activity;
• androgenic activity; and
• antiandrogenic activity.⁹

The authors reported that many observed effects occurred within the same general order of magnitude as BPA and concluded that BPS and BPF were hormonally active BPA substitutes.⁹

Research has also addressed thyroid-hormone signaling specifically.

In 2018, Zhang and colleagues directly compared BPA, BPS, and BPF using receptor-binding tests, thyroid-receptor-mediated transcription assays, cell-based experiments, and an in-vivo amphibian model.¹⁰

BPS and BPF interacted with thyroid-hormone signaling pathways, although the potency and particular effects varied among the chemicals, concentrations, and experimental systems.¹⁰

This does not mean BPS, BPF, and BPA are toxicologically identical.

It does mean that replacing one bisphenol with another structurally related bisphenol cannot automatically be assumed to eliminate endocrine activity.

The Problem of Substituting Within a Chemical Family

This is sometimes described in environmental-health research as regrettable substitution.

A chemical attracts concern and is removed.

A closely related molecule is substituted because it performs the same technical function.

Only afterward does research establish that the replacement retains some of the biological properties that motivated concern about the original chemical.

That is one reason the No Nines™ Standard™ is built around broader ingredient categories rather than simply maintaining a list of individual banned names.

For us, “BPA-free” is not the same as saying that a formulation contains no bisphenol chemistry of concern.

Our exclusion includes BPA, BPS, and BPF.

Chlorophenols: A Different Toxicological Issue

Chlorophenols demonstrate particularly well why “phenols” cannot be treated as a single toxicological entity.

Adding chlorine atoms to a phenolic structure produces a range of compounds with different physical properties, environmental behavior, uses, and toxicological profiles.

Two well-studied examples are:

Pentachlorophenol — PCP
CAS Registry No. 87-86-5

and

2,4,6-Trichlorophenol — 2,4,6-TCP
CAS Registry No. 88-06-2

Both have histories of pesticide, preservative, wood-treatment, or industrial use.

For these particular chlorophenols, carcinogenicity has been formally evaluated by major scientific and regulatory bodies.

Pentachlorophenol and Cancer Classification

The International Agency for Research on Cancer, or IARC, is the specialized cancer agency of the World Health Organization.

In IARC Monographs Volume 117, published in 2019, IARC evaluated pentachlorophenol and related compounds.¹¹

IARC classified “pentachlorophenol as Group 1 — carcinogenic to humans.”¹¹

That classification is a hazard identification. It means the evidence supports the conclusion that the chemical is capable of causing cancer under some exposure circumstances; it is not a statement that every exposure carries the same cancer risk.

The U.S. Environmental Protection Agency has independently evaluated pentachlorophenol through its Integrated Risk Information System, or IRIS.

EPA's assessment, last updated September 30, 2010, characterizes pentachlorophenol as: “Likely to be carcinogenic to humans.”¹²

EPA identifies pentachlorophenol as:
CASRN 87-86-5
DTXSID 7021106

and bases its cancer assessment on the agency's 2005 Guidelines for Carcinogen Risk Assessment.¹²

That is substantially stronger evidence than the generalized phrase “carcinogenic potential” might suggest.

For this particular chlorophenol, formal carcinogenic hazard classifications exist.

2,4,6-Trichlorophenol

The evidence for 2,4,6-trichlorophenol differs from the evidence for pentachlorophenol.

IARC classified 2,4,6-trichlorophenol as: Group 2B — possibly carcinogenic to humans.¹¹

EPA's older IRIS cancer assessment classified 2,4,6-trichlorophenol under its then-current 1986 cancer guidelines as: B2 — probable human carcinogen, based on sufficient evidence of carcinogenicity in animals.¹³

EPA notes that the assessment was based on an absence of adequate human data and sufficient animal evidence, including increased incidences of lymphomas or leukemias in male rats and liver tumors in male and female mice.¹³

EPA identifies the compound as:

CASRN 88-06-2
DTXSID 5021386

with the cancer assessment last updated June 1, 1990.¹³

That date is worth identifying because EPA's terminology has changed over time.

The designation “B2 probable human carcinogen” belongs to EPA's older 1986 classification framework. It should not be presented as though it were a newly issued 2026 classification.

The underlying IRIS assessment nevertheless remains part of EPA's published toxicological record.

Why We Do Not Say “All Phenols Are Carcinogenic”

This distinction matters.

The cancer classifications for pentachlorophenol and 2,4,6-trichlorophenol cannot simply be transferred to:

• triclosan;
• BPA;
• BPS;
• BPF;
• or the enormous universe of phenolic compounds generally.

That would be scientifically inaccurate.

Instead, the evidence supports a more specific statement:

Certain chlorophenols have formal carcinogenic hazard classifications.

That is both stronger and more precise than implying that the entire phenol category has one cancer classification.

Different Chemicals. Different Evidence. One Formulation Decision.

The compounds grouped under the No Nines™ phenols exclusion do not present one uniform hazard.

They illustrate several different reasons we evaluate ingredients before deciding they belong in a formulation.

Triclosan

Research demonstrates bacterial resistance mechanisms, including mechanisms capable of affecting susceptibility to other antimicrobial agents, together with experimental evidence of altered thyroid-hormone homeostasis.

BPA

A substantial experimental literature demonstrates endocrine activity, including interference with estrogen and thyroid-hormone signaling, while human observational studies have examined associations with endocrine measurements.

BPS and BPF

Research demonstrates that replacing BPA with structurally similar bisphenols does not necessarily eliminate endocrine activity.

Certain chlorophenols

Pentachlorophenol and 2,4,6-trichlorophenol have undergone formal cancer-hazard evaluations, with pentachlorophenol receiving the strongest IARC classification: carcinogenic to humans.

These are different chemicals.

They have different uses.

They have different exposure patterns.

And they have different toxicological evidence.

What they have in common under the No Nines™ Standard™ is much more practical:

We do not need them to make our products work.

Effective chemistry does not require us to include an antimicrobial such as triclosan simply because it kills bacteria.

It does not require BPA, BPS, or BPF simply because bisphenol chemistry can provide a useful material property.

And it does not require chlorophenols with toxicological profiles we have no reason to introduce into a No Nines™ formulation.

When a product can accomplish its intended purpose without those chemistries, we choose the more favorable exposure profile.

That is why phenols are one of the nine ingredient categories we leave out.

No Nines™. No compromise.

Published Sources & Further Reading

1. U.S. Food and Drug Administration. Safety and Effectiveness of Consumer Antiseptics; Topical Antimicrobial Drug Products for Over-the-Counter Human Use. Final Rule. Federal Register. September 6, 2016;81:61106–61130. 21 CFR Part 310. Docket No. FDA-1975-N-0012; formerly part of Docket No. 1975N-0183H. RIN 0910-AF69. Federal Register Document 2016-21337. Effective September 6, 2017.

2. Schweizer HP. Triclosan: a widely used biocide and its link to antibiotics. FEMS Microbiology Letters. 2001;202(1):1–7. DOI: 10.1111/j.1574-6968.2001.tb10772.x. PMID: 11506900.

3. McMurry LM, Oethinger M, Levy SB. Overexpression of marA, soxS, or acrAB produces resistance to triclosan in laboratory and clinical strains of Escherichia coli. FEMS Microbiology Letters. 1998;166(2):305–309. DOI: 10.1111/j.1574-6968.1998.tb13905.x. PMID: 9770288.

4. Crofton KM, Paul KB, DeVito MJ, Hedge JM. Short-term in vivo exposure to the water contaminant triclosan: evidence for disruption of thyroxine. Environmental Toxicology and Pharmacology. 2007;24(2):194–197. DOI: 10.1016/j.etap.2007.04.008. PMID: 21783810.

5. Paul KB, Hedge JM, DeVito MJ, Crofton KM. Short-term exposure to triclosan decreases thyroxine in vivo via upregulation of hepatic catabolism in young Long-Evans rats. Toxicological Sciences. 2010;113(2):367–379. DOI: 10.1093/toxsci/kfp271. PMID: 19910387. PMCID: PMC2902919.

6. Paul KB, Hedge JM, DeVito MJ, Crofton KM. Developmental triclosan exposure decreases maternal and neonatal thyroxine in rats. Environmental Toxicology and Chemistry. 2010;29(12):2840–2844. DOI: 10.1002/etc.339. PMID: 20954233.

7. Moriyama K, Tagami T, Akamizu T, Usui T, Saijo M, Kanamoto N, Hataya Y, Shimatsu A, Kuzuya H, Nakao K. Thyroid hormone action is disrupted by bisphenol A as an antagonist. Journal of Clinical Endocrinology & Metabolism. 2002;87(11):5185–5190. DOI: 10.1210/jc.2002-020209. PMID: 12414890.

8. Meeker JD, Ferguson KK. Relationship between urinary phthalate and bisphenol A concentrations and serum thyroid measures in U.S. adults and adolescents from the National Health and Nutrition Examination Survey (NHANES) 2007–2008. Environmental Health Perspectives. 2011;119(10):1396–1402. DOI: 10.1289/ehp.1103582. PMID: 21749963. PMCID: PMC3230451.

9. Rochester JR, Bolden AL. Bisphenol S and F: a systematic review and comparison of the hormonal activity of bisphenol A substitutes. Environmental Health Perspectives. 2015;123(7):643–650. DOI: 10.1289/ehp.1408989. PMID: 25775505. PMCID: PMC4492270.

10. Zhang YF, Ren XM, Li YY, Yao XF, Li CH, Qin ZF, Guo LH. Bisphenol A alternatives bisphenol S and bisphenol F interfere with thyroid hormone signaling pathway in vitro and in vivo. Environmental Pollution. 2018;237:1072–1079. DOI: 10.1016/j.envpol.2017.11.027. PMID: 29146198.

11. International Agency for Research on Cancer. Pentachlorophenol and Some Related Compounds. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 117. Lyon, France: International Agency for Research on Cancer; 2019. ISBN-13 978-92-832-0155-7 and 978-92-832-0184-7. Evaluations include pentachlorophenol and 2,4,6-trichlorophenol.

12. U.S. Environmental Protection Agency, Integrated Risk Information System. Pentachlorophenol. CASRN 87-86-5; DTXSID 7021106. IRIS Toxicological Review and Chemical Assessment Summary. Noncancer and cancer assessments last updated September 30, 2010. Cancer weight-of-evidence characterization: “Likely to be carcinogenic to humans” under U.S. EPA's 2005 Guidelines for Carcinogen Risk Assessment. Accessed October 2, 2026.

13. U.S. Environmental Protection Agency, Integrated Risk Information System. 2,4,6-Trichlorophenol. CASRN 88-06-2; DTXSID 5021386. IRIS Chemical Assessment Summary. Cancer assessment last updated June 1, 1990. Cancer classification: B2 — probable human carcinogen, based on sufficient evidence of carcinogenicity in animals, under U.S. EPA's 1986 Guidelines for Carcinogen Risk Assessment. Inhalation assessment last updated July 1, 1991. Accessed October 2, 2026.

14. Allmyr M, Panagiotidis G, Sparve E, Diczfalusy U, Sandborgh-Englund G. Human exposure to triclosan via toothpaste does not change CYP3A4 activity or plasma concentrations of thyroid hormones. Basic & Clinical Pharmacology & Toxicology. 2009;105(5):339–344. DOI: 10.1111/j.1742-7843.2009.00455.x. PMID: 19686543.

15. U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition. Questions & Answers on Bisphenol A (BPA) Use in Food Contact Applications. FDA consumer and regulatory information on currently authorized BPA food-contact uses. FDA states that available information continues to support the safety of BPA for currently approved uses in food containers and packaging. Accessed October 2, 2026.