Chapter 30 — Exercises

No answers are provided here. Several of these have no single correct answer; the ones that do have one will reward you more if you find it yourself.

† marks an extension exercise — longer, harder, or requiring you to go outside the chapter. Ten of the thirty-two are marked. If you are working through the 💄 Cosmetic path, the daggered items are the ones worth the extra hour.

A standing rule for this chapter: never write "it works" or "it doesn't work." Write a claim, with a population and an endpoint, and then a rating. If you cannot state the claim precisely enough to rate it, that is the exercise.

Part 1 — The barrier

A. In your own words, in three sentences and without using the word "barrier," explain what the stratum corneum is and why its structure makes topical delivery of a peptide difficult.

B. The 500-dalton rule of thumb is described in §30.2 as a heuristic rather than a law. List three molecular or formulation properties, other than mass, that affect whether a compound penetrates intact skin, and explain how each one could make the rule misleading in a specific case.

C. Rank these by approximate molecular mass, smallest to largest: acetyl hexapeptide-8, botulinum toxin type A, GHK, palmitoyl pentapeptide-4, palmitoyl tripeptide-1. Then state which of them has the best evidence of clinical effect, and explain why that ordering is not a paradox.

D. A product's marketing states that its peptide has been "shown by independent laboratory testing to penetrate the skin." Write the three follow-up questions you would ask, in the order you would ask them, and say what answer to each would satisfy you.

E. † Find a real product — one you own, or one on a retailer's website — whose marketing makes a penetration claim. Write down the exact wording. Then write the strongest honest version of that claim (the version that is most likely to be true) and the weakest (the version a reader is likely to hear). Assess how far apart they are, and whether the gap looks accidental.

F. §30.2 argues that a molecule "detected in the skin" may have been detected in a layer that is about to be shed. Explain why this distinction is not pedantic, using the difference between a signal peptide's target and where tape stripping samples.

G. † Penetration enhancers work partly by disrupting the stratum corneum lipid matrix. Construct the strongest possible argument that this trade-off is acceptable for a cosmetic product, then the strongest argument that it is not. Do not conclude — just make both arguments as well as you can.

Part 2 — Mechanism versus evidence

H. Explain, in a paragraph a non-scientist could follow, why palmitoylation is described in §30.3 as a delivery modification rather than an activity modification.

I. Chapter 33 describes fatty-acid attachment as a half-life strategy for injected peptide drugs. §30.3 describes it as a barrier-crossing strategy for topical peptides. Write two sentences identifying what is the same about the two uses at the level of chemistry, and what is different at the level of the problem being solved.

J. The signal-peptide mechanism proposes that a collagen fragment is a damage announcement. Identify one prediction this mechanism makes that could be tested in living human skin, and describe the study that would test it.

K. §30.4 says the GHK-Cu literature "is not fabricated science." Write a paragraph explaining what that literature does establish, then a second paragraph explaining precisely what it does not — and make sure the second paragraph does not contradict the first.

L. † Chapter 6 §6.8 and Chapter 30 §30.4 give GHK-Cu the same split rating. Reread both, then write a short memo (300 words) to an editor arguing either that the split rating is the right call or that it should be collapsed into one. Whichever side you take, address the strongest point against you.

M. Draw or write out, in your own format, the five-step obstacle course an acetyl hexapeptide-8 molecule must complete (§30.5). For each step, note whether the chapter says the step is known to be crossed, assumed to be crossed, or unmeasured.

N. §30.5 argues that step 3 (crossing the dermis) works against step 4 (reaching muscle). Explain this in your own words, and then name one other route of administration anywhere in this book where the same tension appears.

O. Botulinum toxin is roughly 170 times the mass of acetyl hexapeptide-8 and works far better. Write three sentences explaining to a skeptical friend why this is not evidence that molecular size is irrelevant to topical delivery.

P. † Botulinum toxin type A cleaves SNAP-25 enzymatically. Acetyl hexapeptide-8 is proposed to compete with SNAP-25 stoichiometrically. Explain why an enzymatic mechanism and a competitive one have very different concentration requirements at the target, and why that difference compounds the delivery problem rather than merely adding to it.

Part 3 — Regulation and language

Q. For each of the following, state whether it is a permissible cosmetic claim or a drug claim, and give your reason in one sentence: (i) "visibly firms"; (ii) "stimulates fibroblast collagen synthesis"; (iii) "helps skin look more youthful"; (iv) "reduces the depth of wrinkles"; (v) "treats sun damage"; (vi) "supports the skin's moisture barrier."

R. §30.7 argues that the category of a product is decided by the sentence on the box rather than the chemistry in the bottle. Explain the consequence of this for a consumer trying to infer efficacy from packaging.

S. † Collect the marketing copy from five peptide products (photographs of packaging or retailer web pages are fine). Tabulate every efficacy-adjacent phrase. Then sort your table into three columns: phrases that make a testable claim, phrases that make an untestable claim, and phrases that make no claim at all while sounding like they do. Report the proportions.

T. "Clinically proven," "dermatologist tested," and "data on file" are discussed in §30.7. For each, write the sentence you would say to a friend who cited it as a reason to buy something — warm, not smug, and under twenty-five words.

U. Sunscreen is a drug in one jurisdiction and a cosmetic in another. Explain what this reveals about the nature of the drug/cosmetic distinction, and whether it undermines the argument of §30.7 or supports it.

V. † The 2022 modernization of United States cosmetic regulation added safety obligations but not efficacy ones. Draft the outline of a hypothetical efficacy requirement for cosmetic claims: what would have to be proven, to what standard, and by whom. Then identify the two strongest practical objections to your own proposal.

Part 4 — Read this cosmetic study

Each of the following is a [constructed teaching example] — an abstract assembled from the recurring features of the genre. None describes a real study. Use the §30.8 checklist on each.

W. "In a 12-week, split-face, vehicle-controlled study, 60 women aged 40–65 applied a serum containing a signal peptide to one side of the face and the identical vehicle to the other. Assessment was by silicone-replica profilometry and by two dermatologists blinded to treatment allocation, grading standardized photographs. Wrinkle depth decreased on both sides; the difference between sides did not reach statistical significance. Subjects reported no preference between sides." List everything this study did right. Then state what its result actually tells you, and explain why a company that funded it might not publish it.

X. "Twenty-four subjects applied a copper peptide cream to the forearm twice daily for six weeks. Punch biopsies at baseline and week 6 showed increased dermal procollagen staining (p < 0.01). The product is therefore proven to rebuild collagen." Identify the study's genuine strength — it has one that most of this literature lacks — and then identify the two largest problems with the concluding sentence.

Y. "Forty subjects used a peptide eye cream for 28 days. Corneometry showed a significant increase in hydration and cutometry showed a significant increase in elasticity, both versus baseline. 92% of subjects said their under-eye area looked smoother." Explain what almost certainly produced these results, and design the single additional arm that would settle the question.

Z. † "A randomized, double-blind, vehicle-controlled trial enrolled 180 adults for 24 weeks. Primary endpoint was change in a validated wrinkle severity scale assessed by independent evaluators blinded to allocation, from standardized photographs. The active arm showed a small but statistically significant improvement over vehicle. The trial was funded by the ingredient manufacturer; two authors were employees." This is a much better study than the others. State what rating you would provisionally attach to the claim it supports, and what three additional pieces of information would move you up or down a tier.

AA. Take exercises W through Z and rank the four studies from most to least informative. Then write one sentence explaining why sample size is not the variable that determines your ranking.

AB. † Find a real cosmetic efficacy study — a published paper, a manufacturer's technical document, or a poster. Run the full seven-item §30.8 checklist on it and write a one-page assessment. End with a single sentence stating the claim the study actually supports, phrased so that it could be printed on a box without being misleading.

Part 5 — Rating, dossier, and advising

AC. Write a complete four-line 📊 Evidence Rating block for the following claim: topical acetyl hexapeptide-8 improves skin hydration. Note that this is a different claim from the one rated in §30.5. Decide what rating it deserves and be prepared to defend the difference.

AD. §30.10 gives a category-level rating and then argues that category-level ratings are the weakest kind. Explain the apparent contradiction, and say what work the category rating is legitimately doing.

AE. Complete Field 4 (Route and Delivery) for every peptide in your Evidence Dossier. For each topical entry, add the required sentence: what is the evidence that this arrives, as distinct from the evidence that it would work if it did?

AF. † A friend shows you a serum that cost more than their weekly grocery budget and asks whether they wasted their money. Write what you would actually say — out loud, in conversation, in under two minutes of speech. It must be honest, it must be useful, and it must not be condescending. Then write down which of those three constraints was hardest, and why.