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Benzene and Benzoyl Peroxide: An Update · The Science of Skin

• 0:09
  SPEAKER_02: Hello and welcome to Skincare Confidential, the podcast supporting the Science of Skincare Summit, an annual educational event occurring September 5th through the 7th, 2025, in Austin, Texas.
• 0:21
  SPEAKER_02: My name is Dr.
• 0:22
  SPEAKER_02: Ted Lane.
• 0:23
  SPEAKER_02: I'm a board certified dermatologist and your host for today.
• 0:26
  SPEAKER_02: It is my extraordinary pleasure to invite back to our podcast Tom Ree and Peter Fultis.
• 0:34
  SPEAKER_02: So Tom is our toxicologist in residence and Peter is our formulation expert in residence.
• 0:39
  SPEAKER_02: And if you remember, they helped us uh a few months ago with our initial benzoyl peroxide podcast where we talked about the uh benzene issue and benzyl peroxide products.
• 0:51
  SPEAKER_02: And we are back for number two in our series on benzoyl peroxide, where we discuss the latest issues and publications and try and put some common sense to all of this data so that we can really understand how it affects our families, our patients, and just the use of benzoyl peroxide moving forward.
• 1:12
  SPEAKER_02: So, Tom, Peter, thank you so much for being with us.
• 1:16
  SPEAKER_02: It's a pleasure to be back.
• 1:18
  SPEAKER_01: Pleasure.
• 1:19
  SPEAKER_02: All right.
• 1:20
  SPEAKER_02: Well, Tom, let's start with you, our resident toxicologist.
• 1:24
  SPEAKER_02: Uh, you know, I just think it's worthwhile for us to back up, just like we did in the first one, and talk about hazard, exposure, and risk and how those three are related.
• 1:34
  SPEAKER_02: So if you wouldn't mind, could you just kind of go over with our audience the idea of exposure to a carcinogen, which we understand benzene is, the risk of that exposure and uh how that can relate to real life?
• 1:51
  SPEAKER_01: Sure.
• 1:51
  SPEAKER_01: Um I was just saying benzene is a known carcinogen.
• 1:55
  SPEAKER_01: Um it became a known carcinogen through workplace exposure and uh um animal studies and so forth.
• 2:03
  SPEAKER_01: So the carcinomas that uh are produced by benzene are well known.
• 2:08
  SPEAKER_01: Um they're mostly um they're mostly hematological um carcinomas.
• 2:16
  SPEAKER_01: Um so that's the hazard, okay?
• 2:20
  SPEAKER_01: The risk is uh being exposed to benzene.
• 2:23
  SPEAKER_01: Um just because you are exposed to a given amount of benzene doesn't mean that there is a great risk of developing a carcinoma.
• 2:33
  SPEAKER_01: So there's uh such a thing as a dust response curve.
• 2:37
  SPEAKER_01: Uh hazard doesn't equal risk necessarily.
• 2:40
  SPEAKER_01: Um there are a lot of a lot of things that we're exposed to on a daily basis that are hazardous, but they aren't risky because the exposure isn't there at a significant level.
• 2:54
  SPEAKER_02: Yeah, so so Tom, how do you respond?
• 2:57
  SPEAKER_02: And and this is what I hear a lot of my peers talking about in that any exposure per the FDA, uh any exposure to benzene is hazardous.
• 3:07
  SPEAKER_02: Uh even one particle per million of benzene is hazardous.
• 3:11
  SPEAKER_02: Uh how how do we respond to that?
• 3:12
  SPEAKER_02: How do I understand that in in a kind of real life way?
• 3:17
  SPEAKER_01: Does that come directly from the FDA?
• 3:19
  SPEAKER_01: Because I know that I'm not sure where that came from.
• 3:23
  SPEAKER_01: I mean, their FDA recognizes the fact that um uh the risk of cancer from chemicals is dependent upon a upon the exposure.
• 3:34
  SPEAKER_01: Um certainly we don't want people to be exposed to benzene if they don't have to be exposed to benzene.
• 3:42
  SPEAKER_01: Um, but you know, every time you walk past a uh a gas station, you're exposed to you're exposed to benzene because it's a component of gasoline.
• 3:50
  SPEAKER_01: And when the gasoline is pumped, benzene is one of the things that's off gas.
• 3:54
  SPEAKER_01: So um again for me it's it's a matter of um how much you're exposed to.
• 4:02
  SPEAKER_01: If you're in the workplace, um you're at a high risk because you're not high volume benzene area.
• 4:12
  SPEAKER_01: Um applying a product that may contain benzene is probably not a risk because the the the quant the quantity just isn't there.
• 4:22
  SPEAKER_02: Right.
• 4:23
  SPEAKER_02: And so if we go back to the initial paper published um from Valisher, essentially, uh, which is the company that did the initial testing, they showed that there was uh degradation to benzene in these benzoyl peroxide products, especially when they are exposed to high heat levels, right?
• 4:42
  SPEAKER_02: And then and and then I remember from our first podcast episode, Tom, we talked about how there may have been some issues with the testing and how those tests, those tests were done in closed chambers and didn't take into account any airflow uh and the the rapidity of application and the fact that somebody that does apply in the bathroom probably walks out of the bathroom quite quickly as well.
• 5:06
  SPEAKER_02: There are all these different factors that could be related to exposure of the benzene in the product that would really mitigate that that that exposure and therefore the risk, right?
• 5:17
  SPEAKER_02: Has anything changed in your mind about that after reading these latest papers that have been published?
• 5:22
  SPEAKER_01: No.
• 5:23
  SPEAKER_01: No, not at all.
• 5:25
  SPEAKER_01: Um I think what we discussed in the um last podcast, um in my mind anyway, nothing nothing has changed.
• 5:34
  SPEAKER_01: There's no subsequent uh studies that uh for me would mimic real life situations.
• 5:40
  SPEAKER_02: Okay, got it.
• 5:41
  SPEAKER_02: Now, Peter, you know, as a formulation specialist, there there is a paper that that we are going to review.
• 5:48
  SPEAKER_02: It's it's entitled The Role of Formulation uh in benzene formation in benzoyl peroxide products.
• 5:56
  SPEAKER_02: It was a letter, it was a research letter to the editor in JAMA dermatology.
• 6:01
  SPEAKER_02: It was published online in February 12th, 2025, uh by Dr.
• 6:05
  SPEAKER_02: John Barbieri et al.
• 6:07
  SPEAKER_02: Um and and it's it's interesting, Peter, because he really does focus on the presence of heat in the uh production process of these benzoyl peroxide products.
• 6:18
  SPEAKER_02: And and much like we saw in the testing that was done by Valisher, it's heat seems to be the major issue, right?
• 6:25
  SPEAKER_02: Correct.
• 6:25
  SPEAKER_00: Uh heat is certainly one of them.
• 6:28
  SPEAKER_00: Um uh UV, which I don't think is going to be an issue in package or or in typical use.
• 6:35
  SPEAKER_00: Um so I think just looking at heat and processing, um, I think most uh processors, when they when they're making this product, are going to add the benzoyl peroxide towards the cooling down phase.
• 6:52
  SPEAKER_00: In other words, if you're making emulsion, typically you would heat the batch up to about maybe 60 to 70 degrees centigrade, uh, melt all your waxes or or whatever, form your emulsion, start cooling it down, and uh somewhere under maybe 30 degrees centigrade, you would add uh your your benzoyl peroxide and continue cooling it down to say 25.
• 7:17
  SPEAKER_00: Uh that period of time, depends on your batch size, would be probably less than a couple hours at most.
• 7:24
  SPEAKER_00: At most, uh these batches typically aren't made in large quantities, I would imagine.
• 7:30
  SPEAKER_00: So uh I think care in processing is is um a mainstay.
• 7:36
  SPEAKER_00: I I would I would hazard a guess that I would think most manufacturers of this know that automatically.
• 7:44
  SPEAKER_00: It's it's a typical thing we would do on any heat-sensitive active, even fragrance, Dr.
• 7:50
  SPEAKER_00: Lane, we would you know, we would add that at the end of the batch because it's very labile to heat.
• 7:54
  SPEAKER_00: So any any kind of uh heat-sensitive materials would always be added at the end of the batch.
• 8:00
  SPEAKER_00: So, yeah, processing certainly plays a huge role in this.
• 8:04
  SPEAKER_00: Um, the the other thing I think uh manufacturers could look at is incoming, the quality of their incoming raw material to make sure that uh there is uh minimal or no benzene in the raw material before they put it in the batch.
• 8:21
  SPEAKER_00: Yeah.
• 8:22
  SPEAKER_00: And that that would be something that manufacturers or um uh could ask the suppliers of of benzoyl peroxide, the raw material itself, to add that to their incoming specifications as an option.
• 8:38
  SPEAKER_02: So, you know, Peter, recently the FDA performed its own testing on multiple batches of different benzoyl peroxide containing products, and they issued a a voluntary recall notice to uh a couple of manufacturers on on specific lots of specific products.
• 8:55
  SPEAKER_02: Yeah, which call that yeah, which tells me that that specific lots of very specific products it can't be related, and please correct me if I'm wrong, it can't be related to the formulation if we're just looking at one lot of a multiple, multiple lots, right?
• 9:10
  SPEAKER_00: So I I thought the same thing.
• 9:12
  SPEAKER_00: So I I just don't know how many lots they looked at.
• 9:15
  SPEAKER_00: So I I saw that one brand they they recalled maybe three or four lots.
• 9:20
  SPEAKER_02: Uh-huh.
• 9:20
  SPEAKER_00: Did they look at 10 lots?
• 9:22
  SPEAKER_00: Did they is that did they only look at those three lots?
• 9:25
  SPEAKER_00: So is there a product um issue there, you know?
• 9:30
  SPEAKER_00: Um that the Valley Shore, the second Valley Shore paper, and again, I'll leave the toxicology to Tom.
• 9:37
  SPEAKER_00: Um the uh the the it it confirmed some of the data they presented in the first paper, and they went into a little bit more detail.
• 9:47
  SPEAKER_00: Yes, there's benzene present in the product that is being sold on the market.
• 9:52
  SPEAKER_00: Is it a problem?
• 9:53
  SPEAKER_00: Again, I'll let the toxicologists deal with that.
• 9:57
  SPEAKER_00: Um but knowing um knowing knowing how uh the bad it's just bad press to have your product recalled.
• 10:05
  SPEAKER_00: So my position or would be to reformulate the products, um, be proactive in reformulating for a few reasons.
• 10:15
  SPEAKER_00: One is um we we know that we can fix it because there's some products that were well below the two ppm threshold consistently.
• 10:24
  SPEAKER_00: Um so there are methods to to reformulate.
• 10:29
  SPEAKER_00: Um nobody wants their product recall, it's just bad press to have your product recalled.
• 10:34
  SPEAKER_00: Uh what I'd be afraid of is that the FDA will declassify BPO out of the OTC category uh and and make it category two or three.
• 10:46
  SPEAKER_00: And there's really no good alternative, if I'm not mistaken, to BPO.
• 10:49
  SPEAKER_00: That's a mainstay for for you to use uh in in acne treatment.
• 10:55
  SPEAKER_00: Well, and I would hate for that to go away.
• 10:57
  SPEAKER_02: You're 100% right.
• 10:58
  SPEAKER_02: Benzyl peroxide is known as an antimicrobial, so it it is not only just antibacterial, it kills it's as an oxidant, it kills all the the organisms on the skin.
• 11:09
  SPEAKER_02: It kind of carpet bombs the microbiome, which for acne can be very helpful.
• 11:14
  SPEAKER_02: It also has some um keratolytic effects as well.
• 11:17
  SPEAKER_02: So so it it is a foundational OTC monograph product for us, monographed ingredient for us.
• 11:24
  SPEAKER_02: And and I would hate to see it go away.
• 11:26
  SPEAKER_02: And so I I see what you're saying.
• 11:28
  SPEAKER_02: It and better part of Valor on on behalf of these companies to reformulate just to make sure that we have, and and this is something that we should talk about as well, Peter.
• 11:39
  SPEAKER_02: The the the opportunities within reformulation are are available, right?
• 11:44
  SPEAKER_02: There's there's antioxidants.
• 11:46
  SPEAKER_02: If you add those, it looks like that's helpful.
• 11:48
  SPEAKER_02: And I believe there was obviously using cold is you know, making sure that you don't apply, you add the benzo peroxide in with high heat, like you just referred to.
• 11:57
  SPEAKER_02: And there was also uh the antioxidant, and there was also something else, making sure the excipients are are small in number because apparently inactive ingredients require higher temperature during formulation.
• 12:09
  SPEAKER_00: Right.
• 12:09
  SPEAKER_00: So there's a few things.
• 12:11
  SPEAKER_00: Uh pH was important.
• 12:12
  SPEAKER_00: Uh it appears uh three between pH three to four was optimum.
• 12:17
  SPEAKER_00: Avoid metal uh uh ions because as you know, they can they can uh catalyze oxidations.
• 12:23
  SPEAKER_00: Um it looks like there's some solvent effects as well between water and ethanol.
• 12:29
  SPEAKER_00: And if you looked at that second Valishore paper, they they were very good.
• 12:33
  SPEAKER_00: And they had a nice big chart at the end of the paper where they listed the the uh benzene uh you know that they found, and they had the formulation, they had the ingredient list.
• 12:45
  SPEAKER_00: And it what was very striking to me was especially for the non-cleansers, in other words, the gels, the the leave on products, they were very simple for the most stable ones, were very, very simple formulas.
• 12:58
  SPEAKER_00: There were maybe five ingredients.
• 13:00
  SPEAKER_00: Yeah, and um, I I know this uh from my own experiences trying to take a nice base that I had that was very stable and very uh well appreciated by by uh consumers and try to incorporate uh BPO into it.
• 13:17
  SPEAKER_00: And that just does not work, Dr.
• 13:19
  SPEAKER_00: Lane.
• 13:20
  SPEAKER_00: You really need to start from scratch and build these formulas up.
• 13:22
  SPEAKER_00: You just can't um take an existing formula, um, a nice cream or a lotion that you maybe use for another product and expect BPO to fit into that.
• 13:32
  SPEAKER_00: These are very, very simple formulas that seem to be the most stable.
• 13:37
  SPEAKER_00: The ones, and just on the corollary, the most unstable ones appear to be very ingredientless that were very long and had a lot of excipient products in there.
• 13:48
  SPEAKER_00: Remember, um uh a lot of um metal cations, they could be hiding in a lot of those raw materials.
• 13:56
  SPEAKER_00: Um, and and maybe they're at small enough levels in one or two of them, but when you put three or four or five of them in there, it it adds it adds up.
• 14:05
  SPEAKER_00: So that that to me would be is to look at the formula and take out a lot of those, say, marketing ingredients that people want in there and just base it, base it um on a very, you know, uh if you look at prescription product, uh prescription ointments and and creams and so forth, if you look at them, they're very bare bones.
• 14:27
  SPEAKER_00: And I think that's the approach companies should look at that um when when they're doing it.
• 14:31
  SPEAKER_00: Now, all of what we discussed, mine and whenever they launch a new product, there's I know there's a lot of uh patent applications.
• 14:38
  SPEAKER_00: I don't know if they've been granted surrounding this um uh this intellectual property.
• 14:44
  SPEAKER_00: So it behoove the companies to look at what uh are available.
• 14:49
  SPEAKER_00: But you're right, antioxidants will pay a potential role.
• 14:53
  SPEAKER_00: Um buffering between three to four uh pH three and four will play a role.
• 14:58
  SPEAKER_00: Look at your solvent effects, uh especially alcohol, I believe, has a negative um effect as well.
• 15:05
  SPEAKER_00: Um in the meantime, um if we could jump the gun, is is uh consumers maybe would want to refrigerate the product that they have, um, but not freeze.
• 15:17
  SPEAKER_00: You don't want to freeze, do any freeze claws on them because it could split the product, but refrigerate them, normal refrigerator temperatures, um be mindful of expiration dates, and uh maybe for now uh avoid mail order so that, especially during the summer months, where the product might be sitting in a uh mail truck or or a vehicle and um or a um you know warehouse that's not uh temperature controlled.
• 15:45
  SPEAKER_02: Okay, great points.
• 15:47
  SPEAKER_02: And and Peter, your thoughts on encapsulation of BPO.
• 15:50
  SPEAKER_00: Oh, yes, that's another one, absolutely good point.
• 15:52
  SPEAKER_00: Yes, absolutely encapsulation definitely works because basically what you're doing is you're really protecting it from oxygen.
• 15:58
  SPEAKER_00: Okay, yeah, okay, great.
• 15:59
  SPEAKER_00: And and maybe even metals too.
• 16:01
  SPEAKER_00: It depends on the the uh encapsulation method.
• 16:04
  SPEAKER_00: But they they there are commercially available products out there.
• 16:08
  SPEAKER_00: Um uh raw materials uh with encapsulated BPO.
• 16:13
  SPEAKER_02: Okay, okay, great, thank you.
• 16:14
  SPEAKER_02: So it's so it's readily available.
• 16:16
  SPEAKER_02: I mean, uh in other words, if if I can summarize what what your thoughts are, and and please correct me if I'm wrong again.
• 16:21
  SPEAKER_02: The idea is reformulation is probably the best way to go.
• 16:24
  SPEAKER_02: Don't just take your current formula and try and tweak it, start from the ground up.
• 16:29
  SPEAKER_02: Ensure your raw material does not is not contaminated, uh, and then from there keep it keep it simple, keep it cold, and uh and look at these other opportunities, including the addition, the the buffering to a certain pH, as you an acidic pH, the addition of antioxidants, and then possibly encapsulation as well.
• 16:50
  SPEAKER_02: Those seem to be all um uh uh strategies for ensuring that that your product has the least risk possible of of degrading into some benzene.
• 17:01
  SPEAKER_00: Absolutely.
• 17:02
  SPEAKER_00: And um, and uh maybe even packaging, some packaging aspects.
• 17:06
  SPEAKER_00: Um make sure it's a uh uh maybe metal tubes to prevent uh any uh gas transferring through the uh any kind of plastic.
• 17:15
  SPEAKER_00: Uh again, these might add some costs, but it the the downside, the the upside would be preventing um the product being removed, you know, uh from category one.
• 17:27
  SPEAKER_02: Yeah.
• 17:28
  SPEAKER_02: Um, Tom, a thought that I've had is look, you know, there there may be some exposure to benzene in some products that people may have at home just because they've kept them in a hot environment, or when they bought them, there was already some benzene uh uh in the product.
• 17:42
  SPEAKER_02: But, you know, again, uh exposure, right?
• 17:45
  SPEAKER_02: Um hazard times exposure equals risk.
• 17:48
  SPEAKER_02: It if this is for someone that is not using it their entire life.
• 17:53
  SPEAKER_02: In fact, most people don't even use these products on a daily basis forever and ever.
• 17:56
  SPEAKER_02: They may use it for on the period in the period of months, right?
• 18:00
  SPEAKER_02: And so again, just to put everything into perspective, and uh understanding that exposure is cumulative, especially with with uh carcinogen, but are do you have any concern about uh a teenager using this versus an adult using this?
• 18:15
  SPEAKER_02: Uh and and for the amount of time they're using it, especially if it's a cleanser that they use in the shower, which most benzyl peroxide products are cleansers, right?
• 18:23
  SPEAKER_02: Um can you just speak to that?
• 18:26
  SPEAKER_02: But you know, age of the use, the the type of formula that's being applied, the type of glenic that's being applied, if it's a cleanser versus an emulsion, for example.
• 18:35
  SPEAKER_02: Uh do all of those play into the the risk that that people may have with these drug with these products?
• 18:44
  SPEAKER_01: Age can be a factor, but it would really be more at the lower age lower ages.
• 18:50
  SPEAKER_01: Um you know um babies are different than children, but children are different um then once you get into the teenage years, um there's no really no appreciable difference in the skin, um, certainly.
• 19:05
  SPEAKER_01: Um organ systems have all been developed.
• 19:09
  SPEAKER_01: Um so you know, for me there's no no real difference between uh a teenager using this product and and somebody using it, um, an adult later in life using it.
• 19:23
  SPEAKER_01: Okay, that's great.
• 19:25
  SPEAKER_01: You know, age can be a factor for some things, but um I don't think it's a factor here.
• 19:32
  SPEAKER_01: Okay.
• 19:32
  SPEAKER_01: I think I think exposure is the biggest factor.
• 19:35
  SPEAKER_02: Okay.
• 19:36
  SPEAKER_02: And so the exposure, if we could just focus on that for a second, um, Tom, and and the idea of this, especially if if as a dermatologist, I'm thinking about this benzyl proxide that I'm recommending to my patients, uh, because most benzyl peroxide products, as I mentioned, are over the counter.
• 19:50
  SPEAKER_02: If I focus on a cleanser versus a leave-on, am I reducing exposure?
• 19:56
  SPEAKER_01: Yeah, definitely.
• 19:58
  SPEAKER_01: Okay.
• 20:00
  SPEAKER_01: Um when we look at a at a shower product, um we reduce the exposure by at least uh uh by le by about 90% because it's washed off.
• 20:15
  SPEAKER_01: So all you're really looking at is the residual.
• 20:18
  SPEAKER_02: Okay.
• 20:19
  SPEAKER_02: All right.
• 20:19
  SPEAKER_02: Well, so there you go.
• 20:20
  SPEAKER_02: I mean, and and and that's not difficult for dermatologists really to focus on these cleansers versus the leave-on products.
• 20:26
  SPEAKER_02: But but even if we did use a leave-on, so for example, uh many of our patients have trunchal acne, acne on their shoulders, their chests, their back, and and the the the truncal skin is very different than the facial skin.
• 20:38
  SPEAKER_02: There's fewer follicles, they're there's more spread apart.
• 20:41
  SPEAKER_02: We tend to have to use a higher concentration and more of active ingredients.
• 20:46
  SPEAKER_02: Uh, and so if I wanted to use a leave-on benzyl peroxide product at night, uh, it'd say I have them apply it to their chest and back.
• 20:53
  SPEAKER_02: If I have them put a t-shirt over it, do you think that that would reduce exposure?
• 20:59
  SPEAKER_01: Um yeah, I think I definitely think so.
• 21:02
  SPEAKER_01: I mean, anything that's going to um we're talking the exposure that we're talking to, as I remember from our last our last uh uh podcast, um there isn't a great deal of absorption through the skin.
• 21:17
  SPEAKER_01: Right.
• 21:18
  SPEAKER_01: So most of the exposure would be um through the respiratory system.
• 21:22
  SPEAKER_01: Exactly.
• 21:23
  SPEAKER_01: So if you're you know if you have clothing on, it's not gonna um vaporize as much as as it would without without the clothing.
• 21:34
  SPEAKER_02: Okay, so that's a technique that we could use to reduce exposure as well.
• 21:38
  SPEAKER_02: And um thank you.
• 21:40
  SPEAKER_02: So I I'd like to now just kind of shift to the idea of the risk of malignancy, the risk of developing malignancies with ben the use of benzyl peroxide products, uh, Tom, because there have been a couple of papers that have been uh released over the last you know 12 to 18 months related to this.
• 21:59
  SPEAKER_02: And and You know, they're they're really um contradictory.
• 22:04
  SPEAKER_02: There's one, let's let's focus on the one that showed that there may be an increased risk.
• 22:08
  SPEAKER_02: Okay.
• 22:08
  SPEAKER_02: And that's the one that really relied on the the FAIRS database from the FDA, which is that voluntary reporting of adverse events from consumers, for example, or or uh medical providers to to or practitioners, I should say, um, related to any adverse event that could be you caused by our product.
• 22:31
  SPEAKER_02: And that in and of itself, Tom, I mean, using that database to me is it's it's difficult to really believe in any kind of broad-based claim because it's there's so much bias related to the reporting.
• 22:45
  SPEAKER_01: Right.
• 22:46
  SPEAKER_01: And I uh I don't think that database is meant to be used that way to begin with.
• 22:50
  SPEAKER_01: Um I think that database is meant to um alert the agency to serious adverse effects, effects that may be related to a product, um, hospitalization or death.
• 23:04
  SPEAKER_01: Um the agency itself says that uh uh there's no certainty that the reported event um was due to the product.
• 23:16
  SPEAKER_01: Um as I said, healthcare professionals can report it, you can report an adverse event to me uh to this database.
• 23:25
  SPEAKER_01: The consumer itself can, the manufacturer can.
• 23:28
  SPEAKER_01: Um there's a possibility of multiple uh reports on the same same event.
• 23:35
  SPEAKER_01: Um so it and and there's no uh unless there's a serious death or a serious injury, the FDA is not gonna go back to whoever reported it to do any further investigation.
• 23:51
  SPEAKER_01: Um so the the the study that that you talked about they found that um that there may be a signal for uh BPL products to cause skin and breast cancers, which has never been reported in any other studies.
• 24:13
  SPEAKER_01: Um there's no indication in this paper that it causes the carcinoma that we know that it causes.
• 24:21
  SPEAKER_01: So um, you know, for me this is um yeah, I'm not gonna say it's not a valid study, but it's it's not something that I would rely on.
• 24:32
  SPEAKER_02: Yeah, and and so this is this is a letter to the editor that was published in the GID uh in 2025, uh February 2025.
• 24:42
  SPEAKER_02: And it reports, it's looking at this um Fayers database, F-A-E-R-S database, uh, which is the FDA adverse event reporting system, which is a public database containing adverse event reports.
• 24:58
  SPEAKER_02: And they looked at those reports of BPO and malignancy, and then they compared it to adapene and malignancy, adaplene being another OTC product that is um used for acne.
• 25:09
  SPEAKER_02: And they showed a slight increased risk of breast, as you said, um skin cancer, and and maybe some hematologic malignancies as well.
• 25:18
  SPEAKER_02: But but you're right, they, you know, in the paper themselves, they say could possibly uh and very much hedge on the language that they're using.
• 25:28
  SPEAKER_02: And they they do admit that there are limitations with the data.
• 25:32
  SPEAKER_02: Uh the information in the in this database has not been verified.
• 25:36
  SPEAKER_02: Um causation cannot be established.
• 25:40
  SPEAKER_02: Essentially what they're saying is look, there may be a signal here, more data needs to be generated.
• 25:45
  SPEAKER_02: And I appreciate that, that they are very much kind of opting to say, we think there may be something based on this kind of somewhat flawed database, but it's definitely worthwhile for for us to investigate in a in a larger database, which which brings us to larger databases.
• 26:02
  SPEAKER_02: And and there was one that I'd like to uh to talk about, which was uh which is this is JAD, Journal of American Academy of Dermatology, November of 2024.
• 26:16
  SPEAKER_02: This is Dr.
• 26:16
  SPEAKER_02: Barbieri at all as again.
• 26:19
  SPEAKER_02: Uh, and this is looking at the uh if I remember correctly, yeah, this is looking at the Trinetics US Collaborative Network.
• 26:26
  SPEAKER_02: So this is where looking at just an enormous amount of data uh that has de-identified charts uh from 63 healthcare organizations where they can use these electronic EMR charts to assess the risk of for those patients who are diagnosed with acne and prescribed something with benzyl peroxide, if that led to an increased risk of any kind of any kind of cancer.
• 26:52
  SPEAKER_02: And what they did is they looked at patients aged 12 to 40 years of age, diagnosed with either a nevus, a sebury keratosis, or acne, uh, with the acne being exposed to benzoyl peroxide and those with the other um diagnosis codes not being exposed.
• 27:07
  SPEAKER_02: So, in other words, they're looking at controls.
• 27:09
  SPEAKER_02: Uh and and they they found no increased risk with I believe it was 60 million uh patient lives worth of charts, like just an enormous number of charts.
• 27:20
  SPEAKER_02: I don't have the number of charts here, but yeah, it was just incredible.
• 27:25
  SPEAKER_02: And and Tom, to me, like this this kind of data is is is it's much more telling to me just you know, because of the number of data points that they have available to them.
• 27:36
  SPEAKER_01: Right.
• 27:37
  SPEAKER_01: The only negative the only negative thing with retrospective studies is that they're retrospective, right?
• 27:43
  SPEAKER_01: So you know, so it depends on things like patient memory and so forth.
• 27:48
  SPEAKER_01: Um, but just as sheer size overcomes um that concern.
• 27:54
  SPEAKER_01: Yeah.
• 27:55
  SPEAKER_01: Certainly the best way to do it is is prospective.
• 27:58
  SPEAKER_01: Prospective, yeah.
• 27:59
  SPEAKER_01: Yeah, but um these are certainly two this study and the subsequent study, um as you said, you there's a huge number of patients.
• 28:10
  SPEAKER_01: Um the they're matched uh in in the study we're discussing now, they're matched um by uh age based on demographics and um other co-founding comorbidities.
• 28:24
  SPEAKER_01: So there's a the real balance in in uh and how the data is analyzed.
• 28:30
  SPEAKER_02: You know, there was uh another uh study that looked at benzyl peroxide for acne treatment shows no significant association with benzene-related cancers.
• 28:41
  SPEAKER_02: And this was using data from EPIC Cosmos, which is a data set of 261 million patients, over 1,500 hospitals, 36,000 clinics.
• 28:51
  SPEAKER_02: And Tom, they they looked at very specific cancers, didn't they?
• 28:55
  SPEAKER_02: Um they looked at hematologic malignancies, lung cancer, and um bone main malignancies as well.
• 29:01
  SPEAKER_01: Yeah, AML, MDS, non-hosh lymphoma, and other hematologic malignancies as well as lung cancer.
• 29:09
  SPEAKER_02: Yeah.
• 29:10
  SPEAKER_01: And they compared prescription products to, I guess, over-the-counter products, um, and they compared um prescription products to non-acne products as well.
• 29:23
  SPEAKER_02: Yeah.
• 29:24
  SPEAKER_02: And they just didn't see with a 115,000 plus benzyl peroxide patients 12 to 40 at the time of their first benzyl peroxide prescription, they just didn't see an increased risk.
• 29:34
  SPEAKER_02: And and they do it, they do admit that there's a dose-dependent nature of benzene link cancers, right?
• 29:39
  SPEAKER_02: Greater exposure, cumulative over lifetime may increase the risk of cancer.
• 29:43
  SPEAKER_02: And they said maybe we should look at a longer time period, but for the follow-up of over 10 years.
• 29:48
  SPEAKER_02: But it's just unusual for someone to use benzyl peroxide daily for 10 years.
• 29:52
  SPEAKER_02: Again, it's usually used for a very finite period of time in one's life to treat acne.
• 29:57
  SPEAKER_02: Yes.
• 29:57
  SPEAKER_02: Um, and so I'm not sure if that would even be very helpful because it doesn't mimic real life use.
• 30:02
  SPEAKER_02: Uh, it does.
• 30:04
  SPEAKER_02: But I think overall, gentlemen, you know, I think what we found in this, you know, thank you again for being with us.
• 30:09
  SPEAKER_02: But I think what we found is look, probably worthwhile to reformulate, as per Peter's you know, recommendation, there are opportunities to reformulate so that this this kind of risk or this kind of exposure is minimized.
• 30:23
  SPEAKER_02: But to Tom's point and to the data, the propensity of data that we have available to us, it just doesn't look like exposure to benzyl peroxide for the majority of us leads to an increased risk of malignancy.
• 30:36
  SPEAKER_02: Uh, and and perhaps we need more data over a longer period of time.
• 30:40
  SPEAKER_02: But gosh, you would think with the amount of time that benzoyl peroxide has been out, that if there were a signal, we would have gotten that already, wouldn't we?
• 30:49
  SPEAKER_01: Yeah, yes, we should, especially something like skin cancer or breast cancer.
• 30:53
  SPEAKER_01: I mean, it it it would have shown up in the um in the in the st in the industrial studies as well as the animal studies if it was if it was there.
• 31:05
  SPEAKER_01: Um you know, I'm not I'm not saying that benzene should be in these products at all.
• 31:10
  SPEAKER_01: It shouldn't be.
• 31:11
  SPEAKER_01: We should do everything we can to avoid it being in there either by putting it in there or having it um uh having it uh having produced in CETO.
• 31:24
  SPEAKER_01: It doesn't belong there.
• 31:25
  SPEAKER_01: And uh, you know, I I agree with Peter, we should do everything we can to not have it there.
• 31:31
  SPEAKER_01: And if it is if it is there to um to minimize the product's ability to form it to form it as a so refrigeration of the product or whatever.
• 31:45
  SPEAKER_02: Yeah.
• 31:46
  SPEAKER_02: Peter, what are your last thoughts?
• 31:48
  SPEAKER_00: That that's exactly right.
• 31:50
  SPEAKER_00: I mean, as many times uh uh whether there's a risk or not, the cosmetic and uh cosmosceutical uh manufacturers kind of uh react to public pressure in a way.
• 32:04
  SPEAKER_00: I think uh the Tom can attest to this.
• 32:07
  SPEAKER_00: Um the power bin issue, for instance.
• 32:10
  SPEAKER_00: Uh we you know uh once it became clear that the consumers didn't want power bins in their product, the whole industry started removing power bins, you know, very systematically, product by product, and and so forth.
• 32:26
  SPEAKER_00: And yeah, there's still some products with power band in it, but it's very very few these days uh with power bins in in there.
• 32:34
  SPEAKER_00: So we react to it, and and I think um, you know, the the again, the public perception, the recalls, our ability to reformulate, um, and then the fear of having it removed from the market.
• 32:48
  SPEAKER_00: I mean, why wouldn't we do this?
• 32:50
  SPEAKER_00: You know, um, and and it's just uh regardless of how you know whatever information was that you you're gonna come across on social media, um, regardless of whatever assurances that BPO products are safe, it's just it's not gonna work.
• 33:07
  SPEAKER_00: You know, I think you need to uh um you need to assure the public that we're gonna take it out, we're gonna minimize the risk and and so forth um the best we can.
• 33:16
  SPEAKER_00: And methods exist, so let's do it.
• 33:19
  SPEAKER_00: It might take a while.
• 33:21
  SPEAKER_00: You know, it takes a while to do these to run through the stability studies and so forth, but um I think it's well worth it for these companies to do it.
• 33:30
  SPEAKER_02: In the meantime, we have other uh monographed ingredients to use for those of us who are who are very concerned about this.
• 33:36
  SPEAKER_02: You certainly can substitute you know, you just your beta hydroxy acids, your alpha hydroxy acids, and and other ingredients that are available to us.
• 33:44
  SPEAKER_02: Certainly they don't have the exact same effect as benzoyl peroxide, but there are thankfully other ingredients that we can focus on.
• 33:51
  SPEAKER_02: And I would assume some of these companies might, uh, as they work on reformulation to your point, Peter, they'll just kind of focus more on the products that they have in their in their portfolio that that use different ingredients, uh push those forward as they work on reformulating the BPO ingredient, uh BPO containing products as well.
• 34:09
  SPEAKER_02: Gentlemen, thank you so much.
• 34:11
  SPEAKER_02: Uh, this was great.
• 34:12
  SPEAKER_02: I I really enjoy these discussions.
• 34:14
  SPEAKER_02: And, you know, I'll continue to monitor the the data as it's published, and and once we have a good amount of new data to discuss, I'll reach out again and we can continue this series.
• 34:25
  SPEAKER_02: But as of now, I think what we've done is is reviewed the the latest data.
• 34:29
  SPEAKER_02: We've come up with some ideas for both industry, for for um clinicians as well as for consumers to limit risk and exposure.
• 34:38
  SPEAKER_02: And I think that was the goal.
• 34:40
  SPEAKER_02: So uh my name is Dr.
• 34:41
  SPEAKER_02: Ted Lane, and uh with me I've had uh Tom Ree, a toxicologist, Peter Fultis, a uh formulation expert.
• 34:48
  SPEAKER_02: And uh this has been the second uh in our series on benzene and benzoyl peroxide.
• 34:54
  SPEAKER_02: Uh again, thank you all for listening.
• 34:56
  SPEAKER_02: Uh if if you have enjoyed the podcast, please subscribe, uh, give us a five star rating, and and also refer us to your friends.
• 35:03
  SPEAKER_02: And other than that, gentlemen, uh, thank you very much.
• 35:05
  SPEAKER_02: Have a good evening.