Acetyl Hexapeptide-8: What It Is, and Why 500 ppm

Acetyl hexapeptide-8 is a six-amino-acid peptide sold under the trade name Argireline. Its sequence copies one end of SNAP-25, a protein nerve endings use to release their signal. re:firm-8 carries it at 500 ppm, which is 0.05 percent of the finished formula. This guide covers the sequence, the published record, and what a percentage on a label can mean.

What is acetyl hexapeptide-8?

It is a synthetic peptide, built in a lab from six amino acids in fixed order.

The 2025 Cosmetic Ingredient Review safety assessment records the sequence as Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2. The molecule weighs 889.1 daltons. It is a white powder, soluble in water, with a log P of -6.3. The same assessment describes manufacture by solid phase peptide synthesis.

You will see five names for the same material. Acetyl hexapeptide-8, acetyl hexapeptide-3, acetyl hexapeptide-24, acetyl hexapeptide-24 amide and acetyl hexapeptide-8 amide all share CAS number 616204-22-9. Argireline is the trade name. A label listing two of these is listing one ingredient twice.

How acetyl hexapeptide-8 works: SNAP-25 and the SNARE complex

It competes for a seat in the machinery that releases neurotransmitter.

A nerve ending signals a muscle by fusing a vesicle with its own membrane. Three proteins pull that fusion together: syntaxin, VAMP and SNAP-25. Together they form the SNARE complex. No complex, no fusion, no signal.

Acetyl hexapeptide-8 is patterned on the N-terminal end of SNAP-25. A 2025 review in the International Journal of Molecular Sciences describes the competition. The peptide contends with SNAP-25 for binding to VAMP. The three-part complex destabilizes.

Blanes-Mira and colleagues published the original paper in 2002. The peptide inhibited neurotransmitter release in their laboratory models. They traced it to interference with the formation or stability of the SNARE complex. Those authors developed the peptide, which is worth knowing when you read their numbers.

Peptides work by sequence, not by strength. Our guide to peptides in skincare covers the other families.

Why the injectable comparison is overstated

Two molecules touch the same protein. Almost nothing else about them matches.

Botulinum toxin type A is an enzyme. It cuts SNAP-25 apart inside the nerve terminal, and a cut protein does not reassemble. Acetyl hexapeptide-8 cuts nothing. It occupies a binding site while it is present in useful amounts.

The second difference is delivery. An injection places the molecule where the nerve meets the muscle. A topical peptide lands on dead cells and has to travel.

Property	Botulinum toxin type A	Topical acetyl hexapeptide-8
Molecule	Bacterial protein, about 150 kilodaltons	Synthetic peptide, 889 daltons
Action on SNAP-25	Cleaves it	Competes for a binding site
Route to the nerve	Needle, direct placement	Must cross the outer skin layer
Found in the dermis, human cadaver skin, 24 hours	Not applicable	None detected (Kraeling, 2015)
Where you get it	A clinic, by injection	A shelf, in a bottle

The developers said it plainly in their own 2002 paper. The peptide matched the toxin on potency in their assay. It showed much lower efficacy. Anyone selling you a needle-free equivalent is skipping that sentence.

What "10 percent" means on an acetyl hexapeptide-8 label

It may mean 10 percent of a dilute solution rather than 10 percent peptide.

This is the most misread number in the category. The CIR assessment records how the raw material ships. It ships as a powder. It also ships as a water solution holding 0.5 grams of that powder per liter. Half a gram per liter is 0.05 percent. It is 500 ppm.

The panel noted a consumer product purported to hold 10 to 30 percent acetyl hexapeptide. Whether that product is a drug or a cosmetic, the report says, remains unknown. The report does not say what a percentage on a label refers to. Reading it as the supplier solution is our inference, not the panel's.

Run the arithmetic. Put that solution into a serum at 10 percent and the bottle holds 50 ppm of peptide. Put it in at 30 percent and you reach 150 ppm. A big number on the front may describe the carrier, not the active.

What the label says	Peptide present, if the label means the supplier solution
10 percent of the supplier solution	50 ppm (0.005 percent)
30 percent of the supplier solution	150 ppm (0.015 percent)
The supplier solution, undiluted	500 ppm (0.05 percent)

500 ppm is what a supplier solution holds before anyone dilutes it. re:firm-8 carries acetyl hexapeptide-8 at 500 ppm. That is the spec, and the safety section below sets out what CIR did and did not review. For the units themselves, read what ppm means in skincare.

One honest consequence. The published papers we cite read their 10 percent as 10 percent peptide. We take them at their word. On a consumer label we cannot rule out the supplier-solution reading. That reading would put the peptide at a two-thousandth of the figure. This is our inference, not a finding in any source.

What the published studies actually measured

Less than the headlines suggest, and each lab measured a different thing.

Study	Design	Reported finding
Blanes-Mira, 2002	10 women, split face, twice daily, 30 days, 10 percent emulsion	Wrinkle depth down 20 percent by day 15 and 30 percent by day 30 with peptide. Vehicle alone 10 percent, not called statistically significant
Wang, 2013	60 subjects, randomized 3:1 against placebo, 4 weeks	Subjective anti-wrinkle rating 48.9 percent versus 0 percent placebo
Kraeling, 2015	Human cadaver skin, 24 hours, mass spectrometry	0.22 percent of dose in the outer layer, none in the dermis
An, 2019	52 enrolled and 50 completed, 3 arms, split face, dissolving patch, weekly for 29 days	Patch with peptide beat patch alone on wrinkle scores

Read the Wang row again. That 48.9 percent circulates online as "49 percent wrinkle reduction". It is a subjective global rating by assessors. It is not a measured change in wrinkle depth.

The same trial ran an objective arm too. Silicone replicas showed roughness down in the peptide group and flat in placebo. That arm carries no percentage, which is why nobody quotes it.

Read the Blanes-Mira row too. The vehicle with no peptide moved wrinkle depth by 10 percent. The report does not call that change statistically significant. It says the vehicle caused no significant change in skin topography. Ten women is a small group. Our piece on how long skincare takes to work covers why short trials flatter every active.

Why absorption is the whole problem for this peptide

It is too big, too water loving and too charged to cross intact skin well.

Bos and Meinardi proposed the 500 dalton rule in 2000. Molecules above roughly 500 daltons do not pass the outer corneal layer. Acetyl hexapeptide-8 weighs 889 daltons. It is over the line before charge and water solubility are counted.

Charge makes it worse. Lim and colleagues reported in Scientific Reports in 2018. The peptide exists in a zwitterionic form. That charged state hindered its skin permeation. Their fix was to modify the molecule.

The hardest number comes from an FDA laboratory. Kraeling and colleagues applied a 10 percent emulsion to human cadaver skin. Exposure ran 24 hours. Measurement used tandem mass spectrometry. Of the applied dose, 0.22 percent stayed in the outer layer and 0.01 percent reached the epidermis. None was found in the dermis. None reached the fluid beneath the skin.

That is the barrier doing its job. It is the same reason your last serum went nowhere. We cover it in why your serum is not absorbing and what the stratum corneum is.

What the needle studies measured, and what they did not

Two labs used needles to move this peptide. One needled first and then applied. One built the peptide into a dissolving needle. Read both with their limits attached.

Zhang, Qiu and Gao ran acetyl hexapeptide-3 across porcine ear skin in diffusion cells. Passive flux through untreated skin measured 0.014 plus or minus 0.002 micromoles per centimeter per hour. That is the unit the paper prints. After pretreatment with a 150 micrometer needle array, flux measured 0.44 plus or minus 0.12. The authors report that as more than 31 fold in their diffusion cell.

Read the fine print before you carry that figure anywhere. It is pig ear skin in a diffusion cell, not a face. The array was 150 micrometers of solid silicon microneedles. The donor solution was 90 millimoles per liter, far above any cosmetic. It is not a measurement of any re:tones product. No such measurement exists for ours, and we will not print a number we did not make.

The human study is An and colleagues in 2019. Fifty-two Korean women were enrolled and 50 completed the study. They used a dissolving needle patch once a week for 29 days. The trial was split face. Patches carrying acetyl hexapeptide-8 outperformed the same patch without it.

Apply the same caution here. The patch was cross-linked hyaluronic acid worn for four hours. Three arms split 50 completers, so each group was small. It is not a measurement of any re:tones product either. Our overview of transdermal delivery explains the mechanism.

Is acetyl hexapeptide-8 safe?

The published record is reassuring and incomplete. Here are both halves.

The 2025 Cosmetic Ingredient Review assessment reached a conclusion. The ingredient is safe in cosmetics in the present practices of use, at concentrations up to 0.005 percent. Above that level the panel found the available data insufficient. Insufficient describes missing data. It is not a finding of harm.

Two details matter. The 0.005 percent figure came from a 2019 industry survey of reported use. The report notes the panel knew of higher use concentrations. It could not say whether those products are cosmetics. The panel also leaned on the peptide staying out. It cited the log P of -6.3 as evidence against absorption.

re:firm-8 sits at 500 ppm, which is 0.05 percent. The CIR sufficiency finding stops at 0.005 percent, and our level is above that. Insufficient data is what sits above the line, not a finding of harm. Naming that is better than hiding it, so here is the context.

The panel gave two reasons for stopping at 0.005 percent. Use above that level is unsupported by the available safety test data. And the panel wrote that the threshold for an effect on the dermis is not known. It asked for one specific figure, a no-observed-adverse-effect level for type I and type III collagen synthesis. That figure does not exist yet for this ingredient.

Tolerance data exists for the raw material at this percentage, not for our formula. The CIR assessment describes a human repeat insult patch test in 50 subjects. The material was a 0.05 percent aqueous tradename mixture preserved with phenonip. The report describes two such mixtures and does not say which one was tested. No sensitization was reported, and the protocol and results were not published. A patch test sits on ordinary skin, and that mixture is not re:firm-8. The 2002 paper reported no primary irritation at high doses.

No published human study has applied this peptide right after a microneedling device session. Not us, not anyone. Patch test any new product on your arm, and leave a week between sessions.

Safety rules if you are using a needle

Technique carries more risk than the peptide does. This is general guidance for anyone using needles at home.

• Patch test any new leave-on product on your inner arm first.
• Start at the shallowest setting and stay there for several sessions.
• Once a week. A fresh sterile cartridge every time, single use, no exceptions.
• Skip active acne, cold sores, eczema, psoriasis or any broken skin.
• Do not treat over keloid scarring or moles.
• Stop if you are on isotretinoin, pregnant, or under treatment for a skin condition.
• Use sunscreen daily in the days after a session.
• Hold retinol on either side of a session. See microneedling and retinol.

Read who should not microneedle and microneedling side effects before your first session.

How re:tones uses acetyl hexapeptide-8

None of the studies above tested a re:tones product. We have not run that study, and we carry no finding across from theirs. What follows is a description of two objects.

One ampoule, one concentration, released as the tip meets skin.

re:firm-8 holds acetyl hexapeptide-8 at 500 ppm in a 50 mL glass vial. The vial is crimp-sealed medical glass, sealed until you open it. A pump meets air and fingers every day.

The same vial carries adenosine at 400 ppm, an active with its own separate literature. We cover it in adenosine in skincare. Two peptides appear at trace levels on the ingredient list, and we build no claims on either.

The Tap Pen is the other half. An 8 micrometer tip. A depth collar with no clicks. Six intensity settings. The ampoule releases at the moment the needle meets skin. We describe the mechanism on our science page. We promise you no result, and the ampoule finder will tell you if another vial suits your priority.

Questions people ask about acetyl hexapeptide-8

Is Argireline the same as acetyl hexapeptide-8?

Yes. Argireline is a trade name for the peptide whose INCI name is acetyl hexapeptide-8. The CIR assessment lists acetyl hexapeptide-3, acetyl hexapeptide-24 and acetyl hexapeptide-8 amide as the same material. All share CAS number 616204-22-9. Different suppliers, different marketing, one molecule.

Is acetyl hexapeptide-8 a topical Botox?

No. Both interact with SNAP-25, and that is where the similarity ends. Botulinum toxin is an enzyme that cleaves the protein after a clinician injects it. The peptide competes for a binding site and must cross skin first. The developers' own 2002 paper reported much lower efficacy than the toxin.

What concentration of acetyl hexapeptide-8 should a product have?

Read the units before the number. A label saying 10 percent may mean 10 percent of a supplier solution. That solution holds 0.5 grams per liter, so that reading gives about 50 ppm. Undiluted, the same solution is 500 ppm. The CIR record does not settle which figure marketed labels quote. The panel recorded a product purported to hold 10 to 30 percent. It did not say whether that product is a drug or a cosmetic. Ask any brand which figure they quote.

How long does acetyl hexapeptide-8 take to work?

The published trials ran 4 weeks and 30 days. Blanes-Mira measured at day 15 and day 30. Wang measured at 4 weeks. Blanes-Mira reported an emulsion containing 10 percent of the hexapeptide. The paper does not say whether that is by weight or by volume. Wang did not publish a concentration we could verify. Neither trial tells you what your face will do. Judge on months, not days.

Can you use acetyl hexapeptide-8 with retinol or vitamin C?

On ordinary days, yes. Peptides and retinoids sit in different pathways, and we are not aware of a published interaction. Around a needle session the answer changes, and both should pause. See vitamin C after microneedling and how to layer serums.

Does acetyl hexapeptide-8 work on static wrinkles?

Its proposed mechanism targets movement, so lines from expression are the logical target. Lines that sit on your face at rest come from collagen and elastin loss. That is a different problem. Our pieces on what causes wrinkles and under eye wrinkles separate the two.

Is acetyl hexapeptide-8 safe in pregnancy?

No published data answers that question for this peptide, so we will not guess. Ask your clinician. The same answer applies to any ingredient with no pregnancy data behind it. Device cautions are a separate matter and live on the product page.

Why does molecular weight matter so much here?

The outer skin layer sorts molecules by size. Bos and Meinardi put the working limit near 500 daltons in 2000. At 889 daltons this peptide is over it, so delivery dominates every honest discussion of it. The same logic drives hyaluronic acid molecular weight.

Last updated 2026-08-21. Not intended to diagnose, treat, cure or prevent any disease.