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Benzene in Benzoyl Peroxide: How Worried Do We Need to Be? · The Science of Skin

• 0:09
  SPEAKER_00: Hello and welcome to Skincare Confidential.
• 0:11
  SPEAKER_00: My name is Dr.
• 0:12
  SPEAKER_00: Ted Lane.
• 0:13
  SPEAKER_00: I am a board-certified dermatologist and I am your host for today's episode.
• 0:17
  SPEAKER_00: Skincare Confidential is here to support the Science of Skincare Summit, an educational meeting held in Austin, Texas.
• 0:25
  SPEAKER_00: This year, 2024, will be November 8th through the 10th at the beautiful Fairmont Hotel.
• 0:30
  SPEAKER_00: But today I am so excited because I have got a pair of incredible guests, and we are discussing the benzene and benzoyl peroxide issue that was brought up by Vallister, which is an independent testing company, who on March the 5th, 2024, sent a citizen petition on benzene and benzyl peroxide drug products to the FDA.
• 0:56
  SPEAKER_00: Now, interestingly enough, March the 5th was the day before the annual American Academy of Dermatology meeting.
• 1:02
  SPEAKER_00: So it was an interesting date for that to drop.
• 1:05
  SPEAKER_00: Certainly had quite the effect on the American Academy of Dermatology meeting that we had recently.
• 1:12
  SPEAKER_00: And so, you know, we're here to really discuss, try and get some common sense answers and to understand how the dermatologist out in the community, as well as the consumer, can can really understand and translate this Valisher petition and how it translates to their use of benzyl peroxide products.
• 1:33
  SPEAKER_00: So let me go to my guests.
• 1:34
  SPEAKER_00: So first I've got Peter Fultis.
• 1:37
  SPEAKER_00: Dr.
• 1:37
  SPEAKER_00: Fultis is an expert formulator.
• 1:40
  SPEAKER_00: He is an independent consultant to the industry with over 30 years of formulating experience in both the drug and the OTC product space.
• 1:50
  SPEAKER_00: In addition, I've got Dr.
• 1:52
  SPEAKER_00: Tom Ree, who is an expert toxicologist with over 40 years of experience and is also an independent consultant to the industry.
• 2:00
  SPEAKER_00: Therefore, neither one of our guests is beholden to industry.
• 2:04
  SPEAKER_00: They do not have industry ties currently and can speak freely without consequence.
• 2:10
  SPEAKER_00: So it is uh such a great honor to have you both.
• 2:13
  SPEAKER_00: Thank you for being with us today.
• 2:15
  SPEAKER_00: Thank you.
• 2:16
  SPEAKER_01: Thank you for inviting us.
• 2:18
  SPEAKER_00: Absolutely.
• 2:19
  SPEAKER_00: So let's get into it, guys.
• 2:20
  SPEAKER_00: Uh I'm going to go ahead and just well, let's use first names, Peter and Tom.
• 2:24
  SPEAKER_00: Peter is our formulator.
• 2:26
  SPEAKER_00: So, Peter, you you and I have had some discussions regarding benzyl peroxide already.
• 2:30
  SPEAKER_00: And from what I understand, benzyl peroxide, in terms of its formulation, comes as crystals that need to be ground into a powder.
• 2:37
  SPEAKER_00: Is that right?
• 2:38
  SPEAKER_01: That's correct.
• 2:39
  SPEAKER_01: It comes as a crystal.
• 2:40
  SPEAKER_01: Um, the raw material manufacturers will grind it themselves and slurry it in water, usually.
• 2:47
  SPEAKER_01: And um, when I receive it as a raw material, it's a it's approximately a 20 to 40 percent slurry in water.
• 2:56
  SPEAKER_01: And that's how it's formulated.
• 2:57
  SPEAKER_01: It's usually micronized so that uh basically when it gets into the formula and into the patient's hands, actually, it's you really can't feel it.
• 3:07
  SPEAKER_01: It does um it doesn't agglomerate so forth if it's properly uh formulated.
• 3:12
  SPEAKER_01: Um the raw material itself, um as as you could remember from your chemistry classes, that peroxides can be explosive.
• 3:20
  SPEAKER_01: So handling it is um is tricky.
• 3:24
  SPEAKER_01: Uh anything over uh um if there's like less than 3% water, 4% water, you can easily have an explosion just from uh shocking it.
• 3:36
  SPEAKER_00: Okay.
• 3:37
  SPEAKER_00: So and and therefore, because of its explosive ability, you we were discussing that many manufacturers, I'm not sure how many, but many manufacturers will not necessarily produce their product in their own facilities.
• 3:50
  SPEAKER_00: They'll contract that out.
• 3:51
  SPEAKER_00: Is that right?
• 3:52
  SPEAKER_01: Typically, yeah, uh yes, we'll we'll contract it out, uh, making sure that that facility has uh the proper procedures in place uh for for uh handling such a material.
• 4:04
  SPEAKER_00: Okay.
• 4:05
  SPEAKER_00: And the contract manufacturers will still have to adhere to good manufacturing processes, correct?
• 4:11
  SPEAKER_00: Absolutely.
• 4:11
  SPEAKER_00: Absolutely.
• 4:12
  SPEAKER_00: They're all FDA facilities.
• 4:14
  SPEAKER_00: Okay.
• 4:14
  SPEAKER_00: And when we talk about good manufacturing uh practices, that means there has to be testing, right?
• 4:21
  SPEAKER_00: Can you can you just kind of overview?
• 4:23
  SPEAKER_00: Give us an overview.
• 4:24
  SPEAKER_01: Um the raw material will be tested uh upon receipt.
• 4:28
  SPEAKER_01: Um and uh once it's cleared and and uh uh passes all all the incoming specifications, it could be um used for manufacture.
• 4:39
  SPEAKER_01: Once it goes into manufacture, uh there could be um in-process specs, and then certainly um finished once the formulas finish their specifications, and then certainly after packaging their specifications.
• 4:54
  SPEAKER_01: Um usually that there the specifications are uh the color odor appearance, perhaps pH, and certainly the drug activity.
• 5:04
  SPEAKER_01: There's gonna be have to be measured at each step of the way.
• 5:07
  SPEAKER_01: Stability as well, right?
• 5:09
  SPEAKER_01: Stability is done prior to launching.
• 5:12
  SPEAKER_01: Okay.
• 5:13
  SPEAKER_01: Uh that will give you the expiration date.
• 5:15
  SPEAKER_01: Okay.
• 5:15
  SPEAKER_01: And it's usually excel, it's not it is accelerated testing at higher temperatures.
• 5:22
  SPEAKER_01: Um it ranges, it depends on uh the the raw material you're you're uh testing for.
• 5:30
  SPEAKER_01: But typically it's 30 degrees, maybe 35, 37 degrees for an extended period of time.
• 5:37
  SPEAKER_01: And um uh there's a calculation that goes through to determine uh the expiration date.
• 5:45
  SPEAKER_00: Okay.
• 5:46
  SPEAKER_00: So in other words, if you want to get a two-year expiration date, you may elevate the temperature, uh kind of heat the product up, and then use that for a certain amount of time.
• 5:55
  SPEAKER_00: And based on a mathematical equation, you will then determine, okay, based on 37 degrees for I'm making this up in nine months, would be equivalent to two years at room temperature.
• 6:07
  SPEAKER_01: Some yeah, exactly.
• 6:08
  SPEAKER_01: Exactly.
• 6:09
  SPEAKER_00: Now in the Valisher petition, they mentioned that they had essentially cooked benzoyl peroxide, right?
• 6:14
  SPEAKER_00: Uh in 30 degrees.
• 6:17
  SPEAKER_00: And what are your thoughts on that?
• 6:19
  SPEAKER_00: I mean, you know, they talk about at such high temperatures.
• 6:22
  SPEAKER_01: Yeah, so they did they did several.
• 6:24
  SPEAKER_01: They did, I believe, 50 and 70.
• 6:28
  SPEAKER_01: Um, and they they're claiming that perhaps during transit of the ramen of the um uh transit of the finished product to warehouses and to the stores, that it could easily reach that.
• 6:41
  SPEAKER_01: Perhaps.
• 6:42
  SPEAKER_01: I I don't know.
• 6:43
  SPEAKER_01: I I you could you could mitigate that by control temperature um transit and warehousing.
• 6:52
  SPEAKER_01: Um it uh and then I think they did 50 degrees saying that if you keep it in your car for four days, uh I'm not sure people do that.
• 7:04
  SPEAKER_01: I uh I think practically you could tell your patients that when you buy the product, check the expiration date, don't leave it in your car, bring it into the house, you know, in in a cool, dry place.
• 7:16
  SPEAKER_00: So essentially adhere to the storage and handling instructions that are on the box anyway.
• 7:20
  SPEAKER_00: Absolutely.
• 7:21
  SPEAKER_00: Which is keep at room temperature in a cool, dry place.
• 7:24
  SPEAKER_00: Yes.
• 7:24
  SPEAKER_00: Okay.
• 7:25
  SPEAKER_00: Uh now let's focusing on benzene, Peter.
• 7:29
  SPEAKER_00: Is benzene tested for in either the raw material or the finished product?
• 7:34
  SPEAKER_01: Uh I I look back at some uh raw material suppliers uh um and I did not see benzene as a uh listed as an um contaminant or an impurity, we'll say.
• 7:46
  SPEAKER_01: Um and my experience is that it was not tested for uh as um during any stability studies.
• 7:58
  SPEAKER_00: Mm-hmm.
• 7:58
  SPEAKER_00: Right.
• 7:59
  SPEAKER_00: And it okay, so and as we know, benzyl peroxide, benzene is not a contaminant, it is it is a byproduct of the the degradation of benzyl peroxide.
• 8:07
  SPEAKER_01: Yes, and and let me just go back is during the manufacture, um, we typically would add it towards the end of the uh typically when you're making a batch, you'll heat uh heat the temperature, get the temperature up high to dissolve maybe uh some oils, fats, and waxes, uh if you're making emulsion or to dissolve some uh preservatives and so forth.
• 8:29
  SPEAKER_01: But the the benzoyl peroxide was added towards the end of the batch as you were cooling it down.
• 8:34
  SPEAKER_01: So if there was any exposure to high temperature, um it would flash off and um it would be incumbent upon the chemical operators who are manufacturing it to wear the proper PPE um to avoid any exposure there.
• 8:51
  SPEAKER_01: Um and it it would be minimal because uh the batch cycles aren't that long.
• 8:57
  SPEAKER_01: You wouldn't be making it wouldn't be holding it at a high temperature for hours upon hours.
• 9:01
  SPEAKER_01: It would be more like a half an hour or less as you're cooling the batch down.
• 9:06
  SPEAKER_01: So any any uh benzene produced during production, I think would be very minimal.
• 9:12
  SPEAKER_00: Okay.
• 9:12
  SPEAKER_00: And the reason we are talking about benzene in production versus benzene that could have occurred because uh post-production and the handling and transportation is because there, you know, when Valisher bought these products either from wholesalers or they bought them off the shelf, they did note that even at baseline, prior to their heating or their testing of their products, many of these products contained benzene.
• 9:36
  SPEAKER_00: And so that's why we are talking about benzene, you know, what could have happened during the manufacturing process that may have led to benzene being present in the product even prior to the testing occurring.
• 9:48
  SPEAKER_00: And I think, Peter, not to put words in your mouth, but what I glean from all of this is adherence to good manufacturing processes plus what you as an expert formulator know about how the formulation works, the process, there really isn't exposure to these high temperatures specifically.
• 10:06
  SPEAKER_00: If there is, it's very low, small number of minutes.
• 10:10
  SPEAKER_00: Uh, and and therefore we don't, we're not necessarily looking at an issue with the manufacturing process in terms of that being culpable for benzene uh accumulation within the product.
• 10:21
  SPEAKER_01: Correct.
• 10:23
  SPEAKER_01: So that would lead me to believe perhaps transit and warehousing.
• 10:27
  SPEAKER_00: Okay.
• 10:28
  SPEAKER_01: Perhaps uh we didn't talk about methods yet, but we will soon.
• 10:32
  SPEAKER_00: Well, let's talk about that.
• 10:33
  SPEAKER_00: Okay.
• 10:33
  SPEAKER_01: Okay, so I think um uh the first thing I I look at is is methodology.
• 10:38
  SPEAKER_01: I I'm not an analytical chemist, but one thing that I did note that um from various trade organizations and and I believe even the USP themselves had questioned the validity of the method.
• 10:51
  SPEAKER_01: So before everybody gets worried about um is there benzene or not, is the method needs to be validated.
• 10:58
  SPEAKER_01: Uh, I I I tried to go through the analytical methods, but again, I'm not an analytical chemist.
• 11:03
  SPEAKER_01: So for me to pass judgment on their methods, I'm gonna wait for the FDA and and the powers to be to decide whether those methods were real or not.
• 11:14
  SPEAKER_01: Um and if they are, then I think appropriate steps need to be taken.
• 11:19
  SPEAKER_01: If they're not, then um I think there has to be some kind of uh um assurance to the public that we're not uh uh we're we're we're producing safe products for them.
• 11:32
  SPEAKER_00: And by method, you're referring to the methods of testing that Balisher used in the analytical method now themselves.
• 11:39
  SPEAKER_00: Yes.
• 11:40
  SPEAKER_00: Yeah.
• 11:40
  SPEAKER_00: Okay.
• 11:40
  SPEAKER_00: Yeah.
• 11:41
  SPEAKER_00: Okay.
• 11:42
  SPEAKER_00: Is there anything that is out of the ordinary, just on in terms of what you do, kind of what you are aware of?
• 11:48
  SPEAKER_01: No, no, I I really don't know.
• 11:50
  SPEAKER_01: The the um the temperatures I think were the ones that struck me as is uh yeah, uh can it reach uh that temperature uh during trucking and so forth in the in August in the southwest?
• 12:04
  SPEAKER_01: Probably, yeah, absolutely.
• 12:06
  SPEAKER_01: Um uh warehousing, I think um companies can easily adjust for that at a cost if there's any issue if they think that uh that will help uh is getting um temperature control shipping and warehousing.
• 12:24
  SPEAKER_01: Okay.
• 12:24
  SPEAKER_01: I know of one manufacturer that does that already.
• 12:27
  SPEAKER_00: Okay.
• 12:28
  SPEAKER_01: Okay, great.
• 12:29
  SPEAKER_00: Now, I you know, Dr.
• 12:31
  SPEAKER_00: Ree as a toxicologist, you you and I have have spoken about benzene, and certainly in the petition, it talks about how there is no safe level of benzene.
• 12:42
  SPEAKER_00: Uh, but you uh have really enlightened me about the difference between hazard and risk and and dose and exposure time.
• 12:51
  SPEAKER_00: Yeah, and there's so much to really consider there.
• 12:55
  SPEAKER_00: I mean, looking at it just there's no safe limit is really taking a kindergarten approach to this.
• 13:00
  SPEAKER_00: And if if you just dig a little deeper, we can really understand the true risk to health for these products.
• 13:07
  SPEAKER_00: Would you mind just giving us a little toxicology 101?
• 13:10
  SPEAKER_02: Sure, but for uh first of all, uh the FDA does have a limit, uh a lower limit, for which materials are are no longer considered to be questionogenic.
• 13:25
  SPEAKER_02: So even the FDA says that there are doses that are safe.
• 13:30
  SPEAKER_02: Um there are two aspects of benzene toxicity.
• 13:38
  SPEAKER_02: Um one is the acute toxicity if you're exposed to it uh at a high concentration.
• 13:46
  SPEAKER_02: Um it could become drowsy, it could become easy to sort of um as you would with any logical solid after.
• 14:00
  SPEAKER_02: And then there's high toxicity, which is long-term, and um case of density we're talking about uh a variety of blood cases.
• 14:12
  SPEAKER_02: Like specifically in industrial settings where uh workers were exposed to high levels of density over entire work work days over months or years.
• 14:28
  SPEAKER_02: Um those high levels of exposures just are uh the same thing about uh the first thing to understand about high technology is hazard is not the same thing as risk.
• 14:46
  SPEAKER_02: So the hazard of NZ, the clinic hazard of enzyme can be a very hazard.
• 14:56
  SPEAKER_02: Um hazard because I said to the disorientation.
• 15:04
  SPEAKER_02: Um the risk of either one of those depends on the exposure.
• 15:11
  SPEAKER_02: If I have a jar of benzene on the shelf in the seal, I have no exposure and my risk is uh close to zero, right?
• 15:21
  SPEAKER_02: If I open that jar, I may have some exposure to benzene, but it's not likely to be enough to have to cause any of the acute effects.
• 15:33
  SPEAKER_02: If I drop that jar of benzene on the floor and we release it all into the atmosphere, then I have a good chance of getting dizzy, nauseous, etc.
• 15:41
  SPEAKER_02: etc.
• 15:42
  SPEAKER_02: So the exposure it is really determining the risk and not not and not the hazard.
• 15:49
  SPEAKER_00: Right.
• 15:50
  SPEAKER_00: So so there's a there's this equation that I was reading in some of the material you sent over where risk is is equivalent to hazard times exposure, right?
• 15:58
  SPEAKER_00: And so that equation really is telling for us because if we're talking about a benzyl peroxide product, and and I'm not talking about the benzyl peroxide that's aerosolized, just that that which is actually in the product, and you apply it on your face, it and it probably, Peter, I might be wrong about this, but from my understanding, it's it kind of a lot of it will flash off, right?
• 16:19
  SPEAKER_01: I I believe uh in a when you put it on a thin layer, you have such a large surface area, some of it's gonna flash off.
• 16:26
  SPEAKER_01: Absolutely.
• 16:27
  SPEAKER_00: So we have the flash-off effect in terms of decreasing the concentration right away.
• 16:31
  SPEAKER_00: And then the amount that actually gets absorbed, uh, Thomas, you you you found some data to show that the absorption is actually quite low.
• 16:40
  SPEAKER_02: Um yeah, the problem, the problem is a lot of absorption data is not expressed as percentage.
• 16:47
  SPEAKER_02: But I did I did find a paper that expressed the skin absorption of benzene, not benzyl peroxide, uh, benzene to be about 0.3%.
• 16:56
  SPEAKER_00: Okay.
• 16:57
  SPEAKER_02: So that's extremely low.
• 16:58
  SPEAKER_00: Extremely low.
• 16:59
  SPEAKER_00: So in terms of topical application, then uh just leading to systemic adverse events, you know, carcinogenesis, for example, if that exposure is very low, the hazard is there, but the exposure is very low.
• 17:14
  SPEAKER_00: Therefore, the risk would be very low, right?
• 17:16
  SPEAKER_02: Correct.
• 17:17
  SPEAKER_00: Okay.
• 17:17
  SPEAKER_00: So that's that's one common sense answer to me is if we're looking at risk equals hazard times exposure, okay, got it.
• 17:24
  SPEAKER_00: The exposure is very low.
• 17:26
  SPEAKER_00: Um and then we've got, you know, as part of their as part of their testing, they talk about this bathroom effect, right?
• 17:34
  SPEAKER_00: Where they they simulated a bathroom, which is obviously where most of the the benzoyl perox hybrids are gonna be, uh, either as a wash in the shower or as a leave on, probably close to the sink.
• 17:44
  SPEAKER_00: And then they look at an eight by eight by eight foot space, they heat it up to 40 degrees centigrade, which given may actually occur.
• 17:52
  SPEAKER_00: We could get up to 40 degrees centigrade.
• 17:54
  SPEAKER_00: It's not gonna stay that way.
• 17:55
  SPEAKER_00: We're not in a hot yoga studio.
• 17:56
  SPEAKER_00: No, so um, it kind of goes up to that temperature and then goes down, and they heat it up for 16.7 hours and they get you know the concentration of benzene of 1.5 parts per billion per billion, which they claim is four times the EPA threshold for an increased cancer risk for long-term exposure.
• 18:14
  SPEAKER_00: But if we put that into common sense terms, Dr.
• 18:17
  SPEAKER_00: Ree, can you can you help us with that?
• 18:20
  SPEAKER_02: Um the way I write it, they extrapolate it from 16 hours at 40 degrees in a simulated bathroom.
• 18:31
  SPEAKER_02: Um but we don't spend sixteen hours at 40 degrees in the bathroom.
• 18:39
  SPEAKER_02: So the the correct way of doing that is to um is to have someone uh have subjects actually use the product in a standardized bathroom, uh measure the air concentrations of of benzene as they're using it, um measure the concentration beforehand, measure the air concentrations as they're using it, and then air concentration afterwards.
• 19:04
  SPEAKER_02: Uh you know, and that uh that's the correct way to do it.
• 19:08
  SPEAKER_02: You can't you can't extrapolate from 60, 16 hours at 40 degrees to 15 or 20 minutes at uh at 40 degrees.
• 19:17
  SPEAKER_01: Uh the other thing is um, of course, when they're doing those experiments, they have to control it.
• 19:22
  SPEAKER_01: So they have uh, I believe they have uh a closed encounter um container with a fan to circulate so they're getting uniform measurements in that space.
• 19:33
  SPEAKER_01: But most people have a um a vent uh some kind of ventilation in their bathroom, number one, um, and the time 16 out 16 hours over the course of the lifetime of the product.
• 19:45
  SPEAKER_01: I think people are going to use it up if they kept it only in their bathroom.
• 19:50
  SPEAKER_01: Um, and not only that, um, it's also a uh measure of the the barrier of the package that it's in.
• 19:59
  SPEAKER_01: If it was in a metal container, I don't think there'd be any benzene in the air.
• 20:05
  SPEAKER_01: Uh if there was a metal tube, for instance.
• 20:08
  SPEAKER_01: Um the the the plastics that are used are they're very good vapor barriers, they're very good air barriers.
• 20:15
  SPEAKER_01: I don't know about organic solvents.
• 20:18
  SPEAKER_01: I off the top of my head, um, I don't think it'd be benzene, would be something we would typically measure for.
• 20:24
  SPEAKER_01: Um, but even if the if it did um escape, um two things.
• 20:29
  SPEAKER_01: One is the ventilation in the bathroom.
• 20:31
  SPEAKER_01: You're not in a closed situation.
• 20:33
  SPEAKER_01: You're gonna have people in and out, you're gonna have ventilations on.
• 20:37
  SPEAKER_01: Also, the vapor density of benzene is almost three times that of air.
• 20:42
  SPEAKER_01: So it's gonna be settling on the ground.
• 20:45
  SPEAKER_00: Gotcha.
• 20:46
  SPEAKER_01: Okay, so uh it coming up to your face for in uh inhalation.
• 20:52
  SPEAKER_01: Perhaps you have to worry about your pets in the bathroom.
• 20:56
  SPEAKER_01: Okay.
• 20:56
  SPEAKER_01: Um, but uh certainly uh with it uh being heavier than air, it's gonna be sitting closer to the ground.
• 21:03
  SPEAKER_01: If you're in a static situation, doors closed in a sealed system, it would be closer to the ground.
• 21:10
  SPEAKER_01: So you're the by the time it gets up to your nose, I think it's gonna be further diluted.
• 21:15
  SPEAKER_00: Okay.
• 21:16
  SPEAKER_00: And again, for a short amount of time.
• 21:18
  SPEAKER_01: For sure, absolutely, yeah.
• 21:20
  SPEAKER_01: That other part of that equation that Tom mentioned.
• 21:22
  SPEAKER_00: Yeah.
• 21:22
  SPEAKER_00: And so and so therefore the risk would be low.
• 21:25
  SPEAKER_00: Uh for a short amount of time at a low exposure, it the risk we would imagine would be low.
• 21:31
  SPEAKER_00: And and Tom, you actually mentioned a personal story of you back in the day when you were in the military.
• 21:36
  SPEAKER_00: Could you share that with us?
• 21:38
  SPEAKER_02: Uh back in uh nineteen seventy, seventy-six, I was um in the Army National Guard.
• 21:46
  SPEAKER_02: Um, I was in a unit that rebuilt one of the beal parts.
• 21:51
  SPEAKER_02: Um and we used benzene as a solvent to clean the parts.
• 21:56
  SPEAKER_02: So I had we didn't have gloves.
• 21:59
  SPEAKER_02: Um There was nineteen seventy the cancer risk wasn't recognized.
• 22:03
  SPEAKER_02: We didn't use respiratory.
• 22:05
  SPEAKER_02: Uh we had our hands in benzene two, three, four hours a day for two weeks.
• 22:10
  SPEAKER_02: And uh I don't have leukemia, so yeah.
• 22:19
  SPEAKER_02: A lot of people in 19 and then in the 70s had extreme exposures to uh to benzene.
• 22:26
  SPEAKER_02: Um not worth place exposures, but they had exposures to it.
• 22:33
  SPEAKER_02: Um so again, you know, it goes then it goes to the dose response.
• 22:40
  SPEAKER_02: You know, if we were exposed to high levels of benzene for long periods of time, that's a high dose, um, we might see effects.
• 22:47
  SPEAKER_02: But if we're exposed to negligible amounts, and I consider what's here, negligible amounts, um, then we're not gonna have an effect.
• 22:55
  SPEAKER_00: Okay.
• 22:55
  SPEAKER_00: So so let's go into that real quick, uh, Tom.
• 22:58
  SPEAKER_00: The dose response curve, which we talk about in in pharmacology quite a bit, uh, and and essentially this is the the body's response to a certain concentration of the drug, right?
• 23:09
  SPEAKER_00: Right.
• 23:09
  SPEAKER_00: Uh can you can you explain that further in in regards to toxicology?
• 23:14
  SPEAKER_02: Um in pharmacology, you're looking at the dose response for an effect.
• 23:20
  SPEAKER_02: Yes.
• 23:20
  SPEAKER_02: In toxicology for a positive effect.
• 23:24
  SPEAKER_02: In toxicology, we look at the dose response in terms of a negative response.
• 23:29
  SPEAKER_02: Um I like to use these I like to use an example of alcohol.
• 23:34
  SPEAKER_02: Um if you have if you have one drink, um, you probably don't have much of an effect unless you've never been sourced alcohol in your life.
• 23:43
  SPEAKER_02: But um if you have three or four drinks, then you're going to have some kind of an effect.
• 23:49
  SPEAKER_02: Um the idea is whatever.
• 23:54
  SPEAKER_00: Yeah.
• 23:54
  SPEAKER_02: And you can get up to a you can get up to a point where you can die from drinking too much alcohol.
• 24:01
  SPEAKER_00: Yeah.
• 24:01
  SPEAKER_00: So that's the top of that S curve of the dose response, right?
• 24:05
  SPEAKER_00: High dose, high response, right?
• 24:07
  SPEAKER_00: Low dose, low response, and there's usually a middle curve where there's it's somewhat linear.
• 24:12
  SPEAKER_00: Right.
• 24:12
  SPEAKER_00: Yeah.
• 24:13
  SPEAKER_00: Okay.
• 24:13
  SPEAKER_00: So if we're talking about at the kind of lower left of the graph, you're right if it's a if it's an S curve and you're at the lower left, low dose, very low response.
• 24:22
  SPEAKER_00: And and that would apply to benzene.
• 24:24
  SPEAKER_00: Right.
• 24:25
  SPEAKER_02: And and in this case, I think it would be negle a negligible response.
• 24:28
  SPEAKER_00: Negligible response.
• 24:30
  SPEAKER_00: Okay, thank you.
• 24:31
  SPEAKER_00: Um the other test that was done, uh, which they claim is similar to being in a in a locked car or hot car, is that 520 plus liter closed container where they they heated up the uh the benzene and they found an elevated level in the in the air, which is fine, but but that doesn't really, again, if we're trying to apply this to real life, it doesn't apply in in effect if you're talking about a car where we have the air conditioning going, where we have you know in and people in and out, they're not in the car for that much time, they have doors opening and closing.
• 25:03
  SPEAKER_00: I mean, if you you really have to take into account all the variables that can be put into play here that could affect the concentration, right?
• 25:12
  SPEAKER_00: Right.
• 25:12
  SPEAKER_00: Yeah.
• 25:13
  SPEAKER_00: Okay.
• 25:13
  SPEAKER_00: Yeah.
• 25:13
  SPEAKER_00: And Peter, anything else to add to that?
• 25:15
  SPEAKER_01: Yeah, no, I mean, if uh, like I said, is if if it does reach that temperature, if you if they leave it in their car, I think the uh the thing to stress to the patients is is when as soon as you buy it, bring it into the house, keep it in a in a cool, dry place, and don't leave it in your car, certainly uh um for for those periods of time.
• 25:37
  SPEAKER_02: Okay.
• 25:37
  SPEAKER_02: No, if you if you buy a frozen food, you can transfer it to your home and it'll still be frozen when you put it in your freezer.
• 25:44
  SPEAKER_00: Yeah.
• 25:45
  SPEAKER_02: But if you leave it in your car in the sun for an hour, two hours, whatever, um, I wouldn't eat that food.
• 25:52
  SPEAKER_02: Yeah.
• 25:53
  SPEAKER_02: Right, exactly.
• 25:54
  SPEAKER_01: Yeah.
• 25:54
  unknown: Yeah.
• 25:55
  SPEAKER_00: So probably should have started with this, quite frankly, Peter, but uh benzoyl peroxide for the consumers out there is is considered a grass ingredient, which is generally recognized as safe.
• 26:06
  SPEAKER_00: It's it's got an FDA monograph.
• 26:08
  SPEAKER_00: Correct.
• 26:08
  SPEAKER_00: Which could you could you just quickly go over what that means?
• 26:13
  SPEAKER_01: Yeah, so so basically the FDA monograph uh for acne includes benzoyl peroxide.
• 26:19
  SPEAKER_01: I believe it was reviewed again.
• 26:21
  SPEAKER_01: Uh I want to say 2018, 2019.
• 26:26
  SPEAKER_01: Yeah.
• 26:26
  SPEAKER_01: And it was it was approved as category one, which means it's safe and effective uh between the levels of 2.5% and 10%.
• 26:35
  SPEAKER_01: And if I my memory uh serves me well, it it can only be used um alone.
• 26:41
  SPEAKER_01: It can't be combined with another anti-acne ingredient.
• 26:44
  SPEAKER_01: Um now their prescription products, as you know, contain BPO and say antibiotics.
• 26:50
  SPEAKER_01: That's that's a different story now.
• 26:51
  SPEAKER_01: Uh but for the OTC monograph, um, yes, it's it's there with salicylic acid and sulfur.
• 26:58
  SPEAKER_00: Yeah.
• 26:59
  SPEAKER_00: And we were looking at the the monograph and and how the FDA required some actually additional testing in order to kind of reapprove the benzyl peroxide as a monographed ingredient.
• 27:10
  SPEAKER_00: Uh, and I believe it was extra carcinogenic carcinogenicity testing.
• 27:15
  SPEAKER_00: Is that is that right, Peter?
• 27:17
  SPEAKER_00: Um they would I'm sure they would have to look at that.
• 27:20
  SPEAKER_01: Tom, maybe you remember?
• 27:21
  SPEAKER_01: Um, I'm not sure.
• 27:23
  unknown: Okay.
• 27:24
  SPEAKER_02: I know that they've done tumor promotion studies.
• 27:27
  SPEAKER_02: Yes.
• 27:28
  SPEAKER_02: But that's that's um I I I think that would be more of the irrit irritating uh action of benzoyl peroxide than the actual benzyl peroxide itself.
• 27:41
  SPEAKER_00: Okay.
• 27:42
  SPEAKER_00: Um it's it's mentioned in the Balisher petition.
• 27:45
  SPEAKER_02: Yeah, I'm not I'm not overly familiar with the studies, but okay uh my guess would be that it's it is irritating, and irritating substances just uh applied to the skin of a hairless mouse over long periods of time.
• 28:00
  SPEAKER_02: Um can promote tumors.
• 28:03
  SPEAKER_00: Okay.
• 28:04
  SPEAKER_02: As can sunlight, by the way.
• 28:06
  SPEAKER_00: Sure, sure.
• 28:07
  SPEAKER_00: So so again, not necessarily related to the compound itself, but perhaps just to its mechanism of action.
• 28:15
  SPEAKER_00: Right.
• 28:15
  SPEAKER_00: Okay.
• 28:16
  SPEAKER_00: All right, gotcha.
• 28:17
  SPEAKER_00: Um, you know, uh I look, I just wanted to come up with some common sense approaches here to interpret the data, and I think we've done that today.
• 28:26
  SPEAKER_00: So, so I thank you both very, very much.
• 28:29
  SPEAKER_00: Um, I think what we learned is that the testing that was done may be not applicable to real life.
• 28:37
  SPEAKER_00: Uh, and therefore the amount that was found in these tests, we're probably going to be much higher than we would be exposed to in real life conditions.
• 28:48
  SPEAKER_00: And I learned that today from from Peter and Tom.
• 28:51
  SPEAKER_00: So thank you very much.
• 28:52
  SPEAKER_00: In addition, Tom, you really focused on the hazard versus the risk and how we we mitigate that risk by having such a low time of exposure as well as low level of exposure.
• 29:03
  SPEAKER_00: We can't mitigate the hazard.
• 29:05
  SPEAKER_00: The hazard of benzene is what it is.
• 29:07
  SPEAKER_02: Hazardous hazard.
• 29:08
  SPEAKER_00: Hazardous hazard, but we can mitigate the risk by decreasing exposure.
• 29:12
  SPEAKER_00: And even as we looked at this data and and kind of put it into real life, contextualized it in real life, we realized that really the exposure is so small that perhaps the risk is something that we don't really need to worry about.
• 29:26
  SPEAKER_00: But for those who are still nervous and and want to mitigate as much as possible their risk associated with benzene exposure, you know, as Dr.
• 29:35
  SPEAKER_00: Fultus mentioned, glycerin seems to be uh an ingredient that you may want to look for in the formulation, although uh more testing needs to be done on that for sure.
• 29:45
  SPEAKER_00: It was an observation that needs to be validated.
• 29:49
  SPEAKER_00: Um otherwise, keeping it again according to the storage and handling on the box at room temperature, making sure you don't keep it past its expiration.
• 29:58
  SPEAKER_00: Um, not even sure that I would recommend keeping it in the refrigerator, Peter.
• 30:02
  SPEAKER_00: Is there would you say that that would help much at all?
• 30:06
  SPEAKER_01: It could.
• 30:07
  SPEAKER_01: Um I it just uh um when we do stabilities, typically we would put it at a lower temperature for a few reasons.
• 30:16
  SPEAKER_01: One is just because it could be exposed to that temperature during shipping uh as well.
• 30:22
  SPEAKER_01: Um, and we want to know the fit at least the physical stability.
• 30:25
  SPEAKER_01: But um uh we I I don't want to say automatically put in a refrigerator because uh the formula may not survive very well.
• 30:36
  SPEAKER_01: And you know, you could run into problems in that situation, certainly not freezer.
• 30:41
  SPEAKER_01: I mean, you wouldn't want to freeze it.
• 30:43
  SPEAKER_01: Uh but uh I th I I saw one website where they actually recommended putting it in a refrigerator.
• 30:48
  SPEAKER_01: I think if you have a keep it in a cool place in your house, you know, uh uh uh I think it would be uh adequate.
• 30:57
  SPEAKER_00: Okay.
• 30:57
  SPEAKER_00: All right.
• 30:57
  SPEAKER_00: So again, keeping it according to the storage and handling instructions.
• 31:01
  SPEAKER_00: Wouldn't it follow the indirections, wouldn't worry too much about the transient increase in temperature in the bathroom, especially with a well-ventilated bathroom.
• 31:10
  SPEAKER_00: Uh obviously, if you are concerned about transportation, you'd want to, instead of relying on a third party to transport it to your house, you may want to go pick it up yourself from the from the drugstore or the grocery store and keep it in your air-conditioned car and transport it that way to avoid as much as you can, the consumer, as much as you can keep, you know, exposing it to higher temperatures.
• 31:32
  SPEAKER_00: Uh and and, you know, listen, I'm in Austin, Texas, and and certainly uh, you know, a car left in the in the parking lot of a grocery store can get very, very hot.
• 31:40
  SPEAKER_00: So, you know, even allowing the car to cool down, there's different ways of doing it.
• 31:46
  SPEAKER_00: But I do think the hysteria that this has caused, uh I don't want to downplay it, but I do think we need to reframe it in terms of real life conditions, and those do not mimic what is in this petition.
• 32:02
  SPEAKER_00: And so for those of you uh who have any other questions, you are are welcome to to send us an email at inquiry at scienceofskincare summit.com.
• 32:12
  SPEAKER_00: I I'm hoping Dr.
• 32:13
  SPEAKER_00: Fultis and Dr.
• 32:14
  SPEAKER_00: Ree wouldn't mind if I came back to them with questions if we do get any.
• 32:17
  SPEAKER_00: Absolutely.
• 32:18
  SPEAKER_00: Um you you both have been so generous with your time and and teaching uh me a true neophyte uh in in toxicology in particular, Dr.
• 32:26
  SPEAKER_00: Ree and Peter really kind of setting me straight in terms of formulation-wise uh how benzyl peroxide is used in products.
• 32:33
  SPEAKER_00: I I appreciate you both so much.
• 32:35
  SPEAKER_00: Um this is Dr.
• 32:36
  SPEAKER_00: Tedlane, this is Skincare Confidential.
• 32:38
  SPEAKER_00: Thank you so much for listening.
• 32:40
  SPEAKER_00: Uh, again, if you have questions, inquiry at Science of Skincare Summit.com.
• 32:44
  SPEAKER_00: Uh please like the episode, subscribe it, refer us to a friend.
• 32:48
  SPEAKER_00: Uh, we appreciate all your support.
• 32:51
  SPEAKER_00: Uh, and thank you.