Adverse Reactions

The Delicious World of Food Safety

April 07, 2022 Alexandria G. Lau, PhD, DABT, ToxStrategies Inc. Season 2 Episode 5
Adverse Reactions
The Delicious World of Food Safety
Show Notes Transcript Chapter Markers

Even chocolate companies and wineries need toxicologists. Alexandria G. Lau, ToxStrategies Inc., has worked for both and shares her experiences with co-hosts Anne Chappelle and David Faulkner. They also discuss the research and development that goes into new food products and how toxicologists play a role in food safety.

About the Guest
Alexandria G. Lau, PhD, DABT, ToxStrategies Inc., is a toxicologist with a decade of experience in the food and beverage industry. She has extensive knowledge of global regulations related to consumer products, including pesticides (US Environmental Protection Agency), food and packaging (US Food and Drug Administration, European Food Safety Authority), and alcoholic beverages (Alcohol and Tobacco Tax and Trade Bureau). 

 Working for a prominent vineyard/winery, Dr. Lau managed the company’s global quality and food safety efforts, decreasing pesticide use and overseeing growers and vintners to ensure global regulatory compliance and supply chain flexibility. For a major food product manufacturer, she managed a large portfolio of products and food safety initiatives, developing and maintaining global policies, standards, and programs for everything from contaminant/allergen management to labeling and stakeholder communication. Dr. Lau also served at a senior level for a global manufacturer of consumer products, working in safety assessment and regulatory toxicology to support development of pest control products, ensuring regulatory compliance that included California Proposition 65.

 Dr. Lau earned her PhD in toxicology and pharmacology from the University of Arizona, Tucson. She maintains a current and robust body of expertise through frequent continuing education and participation in professional associations and scientific conferences. She is often an invited speaker for association and industry events, and she has published extensively in the scientific literature. She also serves as an invited reviewer for the journals Toxicology Research and Application and Toxicological Sciences.

[00:00:00] Adverse Reactions “Decompose” Theme Music

[00:00:05] David Faulkner: Hello, and welcome to Adverse Reactions Season 2. My name is David Faulkner, and this is my co-host,

[00:00:11] Anne Chappelle: Anne Chappelle. 

[00:00:12] David Faulkner: As much fun as the first season of Adverse Reactions was, I think Season 2 is better.

[00:00:16] Anne Chappelle: Hidden.

[00:00:17] David Faulkner: Secretive.

[00:00:18] Anne Chappelle: Exactly.

[00:00:19] David Faulkner: The toxicology that happens when you’re not looking,

[00:00:22] Anne Chappelle: or toxicology that you forgot about. 

[00:00:24] David Faulkner: It’s still important, and we’re here to talk about it. Welcome to Season 2 of Adverse Reactions:

[00:00:28] Anne Chappelle: “Hidden Toxicology.”

[00:00:31] Adverse Reactions “Decompose” Theme Music

[00:00:37] Anne Chappelle: The delicious world of Alex Lau.

[00:00:41] Alex Lau: The R and D process can take up to two years for a new type of cereal or a new candy bar and you’re just thinking, wow, it’s the same chocolate, it’s the same peanuts, it’s the same caramel, it’s the same nougat, but just in different combinations. And so, how complicated can it really be?

[00:00:58] David Faulkner: Or, tox and treats: unconventional careers in food safety.

[00:01:03] Alex Lau: When I worked at the large chocolate and wine company, I was the only toxicologist. There was not an army of toxicologists.

[00:01:14] Anne Chappelle: Well, we want to welcome Alex Lau.

[00:01:16] David Faulkner: Who’s worked on food toxicology at both a winery and a chocolate maker. 

[00:01:22] Anne Chappelle: Tell me a little bit about yourself.

[00:01:24] Alex Lau: I am a food toxicologist, and what I do is ensure that the ingredients that are going into our foods by different companies are safe to consume for kids and adults and elderly and all the different types of populations. And so, we just make sure that everybody is happy and healthy and can count on our food supply for being safe.

[00:01:49] Anne Chappelle: How hard is that?

[00:01:51] Alex Lau: It is pretty hard. People conceptually think that food is food. Like, a banana a banana, right? But bananas, if you really look at it, there are a lot chemical compounds that make up banana or banana flavor. If you want to isolate that flavor and put it into, like, a pudding cup, it’s not just banana puree added to pudding; they have to chemically isolate those compounds and then add it back. So, now you’re eating banana compounds in a place that you don’t typically find it naturally. And so, as a toxicologist, you have look at whether or not those additional uses of that flavor or component or whatever ingredient they’re adding is going to be safe over a person’s life. And so, it’s hard in that you have to think about what people eat throughout their entire life, because you don’t eat just a banana pudding when you’re a kid—you may love it so much that you eat it until you die, hopefully not from banana pudding.

[00:02:53] David Faulkner: Death by banana pudding.

[00:02:57] Alex Lau: It is kind of hard, but I think when people think about it, or initially, they think, oh, it should be really easy; everything that we eat is safe. Not really. And then there’s chemical contaminants, too. Fruits and vegetables naturally have heavy metals or things that are in the environment that it can take up, and so as toxicologists, we try to help understand the levels that are naturally there and how can we mitigate that risk for food companies in order to meet those regulations and/or thresholds of safety and still make food widely available to everybody?

[00:03:35] David Faulkner: I’m thinking about trying to estimate over the course a lifetime how much somebody might eat of a certain thing or be exposed to a certain chemical. I think in the US, at least, it’s a pretty heterogeneous population; you’ve got people from many different food cultures that are going be eating a lot of types of things. How do you account for that, those different ways of eating? 

[00:03:55] Alex Lau: So, the US government actually does a survey on a regular basis. It’s Foods and What We Eat, and the dataset’s called NHANES, and they basically go out and do a diary of what people eat for two weeks. They follow a large population—10-to-20,000 people—and they basically collect all of that and use that data. And so, it’s been probably at least two decades of data. So, when you see salt intake or sugar intake changing or they’re going to change how much people can eat of those nutrients, they usually rely on that data to say how much do people typically eat? And so, we use that same dataset, at least for the US population, to calculate exposure. Now, the hard part is when you talk about adding a flavor into different foods. So, say a company wants to add banana flavor to beverages as well as yogurts, cheeses, sodas, breads. We have to go figure out from the recipes in that dataset how much of that recipe could be banana flavor or whatever flavor that we’re interested in. I think a really good example is when you think about cheese and how you eat cheese differently, right? In a sandwich, in mac and cheese. That’s really hard to calculate, even just for an individual, of how much cheese you’ve really eaten and all the different ways. It’s a little bit complicated and we have statisticians and people who are experts in those datasets to help us pull that data for companies.

[00:05:28] David Faulkner: Coming from the Midwest, I eat an enormous amount of cheese. So, I’m probably an outlier there, at least for the California population. So, when you talk about the daily allowances—so, this is when someone looks at the side of a box cereal or something and there’s that box, the nutrition facts, those are the values that are being derived from this NHANES data? That’s where that comes from? 

[00:05:49] Alex Lau: That’s where the nutritional data may be coming from, just to kind of understand where’s the population right now? And we usually, as toxicologists, take the 90th and 95th percentile of the population to say, so the outliers like you, David, who eat a lot of cheese are included in that distribution so that we’re capturing the high-end eaters because we want to be very conservative in those estimations or calculations.

[00:06:16] Anne Chappelle: I remember that I was doing a project with one of my companies that I was working with and we were talking about residual on an apple and, out of all the fruits, how hard you really have to look at apples in their own category because little kids eat so much apple—the apple sauce and the flavorings, the fructose syrup, you’ve got all these sugars and stuff from apples. And so, it seems that there should be some kind of regular update or even regional updates, potentially, for how people eat. Do you see the NHANES really changing over time? All of a sudden, everybody wants to have avocado toast. It may take five years for NHANES to catch up to the avocado toast trend. How do you stay relevant and predict, oh, we’ve got to care about avocados?

[00:07:11] Alex Lau: That’s a really good question. I don’t think we can predict that. And NHANES is obviously lagging, too; because they do the diary potentially in 2013, we may not see that data until 2017 or whenever they do the analysis. So, it is lagging. I worked for chocolate company, and we actually looked at NHANES data over a course 10 years. So, we looked at group of 10 years, and then we updated our data for the next 10 years, and chocolate consumption had not changed over the course of 20 years. I haven’t seen a lot of change from the food categories I looked at; it’s probably changed for different things like avocado toast, and I would think that the pandemic may throw a curve into the NHANES data because everyone’s eating comfort food. They went back to a store-bought, shelf-stable foods, and so that may change 2020.

[00:08:04] David Faulkner: One of my favorite subjects is shelf-stable foods.

[00:08:07] Anne Chappelle: Wait, I’m sorry. I have to say, one of your favorite subjects is shelf-stable food?

[00:08:13] Alex Lau: So, you’re a junk food addict?

[00:08:15] David Faulkner: No, no, no. I’m great at parties. It’s the trivia behind it. I think it’s fascinating, this idea that you can buy stuff to eat and you can have it sit there for, in some cases, years. And I don’t think people realize what kind of miracle of science that is, that you can store food for that long. There’s not a lot of foods that you can do that with. And so, I was wondering if you could talk a little bit about what is actually involved in making it such that food can sit on your shelf in all kinds of conditions? Because you’re not necessarily just storing it in, like, a cool, dry place; you could be storing it at any number of temperatures or humidities. What is the process? How complicated is it, basically?

[00:08:57] Alex Lau: It’s super complicated. And I think the R and D that goes into a candy bar or a bottle of wine or your cereal, there’s a large team of people behind that product. And it wasn’t just, I thought of it one day, and it was on the shelf the next day. Actually, the R and D process can take up to two years for a new type of cereal or a new candy bar, and you’re just thinking, wow, it’s the same chocolate, it’s the same peanuts, it’s the same caramel, it’s the same nougat, but just in different combinations. And so, how complicated can it really be? It is complicated because you have to be able to send it to Arizona in the summer at 110 degrees, and then you should be able to send it to Michigan at negative 20, and still everybody have it taste the same and be expected to find the same product and not be disappointed. It does rely heavily on science. As a toxicologist, we play a role in that as well; you have to make sure that the packaging that comes into contact to your food, there’s nothing that’s migrating into the food that would be harmful to people or at least the levels are acceptable. You have to look at the ingredients that are going in, whether or not they’ve been used in food previously and whether or not they have to be approved for food use. So, there’s a whole lot of toxicology that’s involved, too—whether or not a combination of things could cause a chemical reaction or cooking something could cause a heat-formed compound to form—that we have to be aware of and to minimize. So, there’s a lot of consideration, even for toxicologists, throughout the R and D process. 

[00:10:36] Anne Chappelle: So, I’m wondering, do you go to farmer’s markets and buy pies and cookies that have not necessarily undergone this kind of scrutiny? Because, I’m making fun, but there’s issues of food stability and transport, and I’ve seen enough on Shark Tank to know that it costs millions of dollars to actually get a new product into a market. But in thinking, we assume that there is such incredible food safety, and we are really lucky in this country to be able to have such incredible food safety and availability and variety of fresh foods. I’m very interested, how do you think about the whole fresh food and that preparation versus these very interesting shelf stable? 

[00:11:24] Alex Lau: Everyone assumes that the toxicologist eats a special food supply because we know what’s really in food, and I eat the same food everybody else does. I go to the same farmer’s market. Personally, I’m not opposed to farmer’s market or fresh food. To me, it’s the dose that makes the poison; we always come back that. And so, if you’re going to eat Martha’s pie once, you may not get the same contaminants. You still need that broad diet; don’t always eat rice three times a day for the only thing that you’re eating; you have to eat fruits and vegetables and meats and stuff. So, I would say, even for junk food like pies and donuts, you still want that variety.

[00:12:01] Anne Chappelle: I can’t just eat wine and chocolate. OK, I’ll take a note. You’ve just killed my weekend. There’s a lot of mixed messages out there about food, what’s in food, whether it’s GMOs, whether it’s eat eggs, don’t eat eggs; where should people be going to look for reasonable, reliable, accurate information?

[00:12:25] Alex Lau: That’s a really tough question, Anne, because I think that we struggle with that in the food industry because there’s really not one place of the truth other than the food companies themselves coming out and being transparent. I think consumers want it. They want to know what’s in their food. Now, consumers are like, well, we want to know if there’s those things in our food. But why do you want to know? Because we’re doing the assessment that it’s safe; if we tell you what’s in there, you’re just going to have a moment of fear-mongering in some ways, and people are capitalizing on that as well. We have bloggers that say, oh, my gosh, you shouldn’t buy this but you should buy this organic thing that’s better, but it’s no different; it’s just a field next door to the other field, different ways of farming that were used. It doesn’t necessarily mean that the contaminant levels may be any different.

[00:13:16] David Faulkner: So, organic. This is an exciting label that everyone’s in a tizzy about. What is the difference? What does it mean for something to be organic?

[00:13:24] Alex Lau: The difference is that there’s a set of criteria for organic, and it usually has to do with farming practices that I’ve seen. It’s usually sometimes dealing with what pesticides you can and cannot use. There’s a long list of organic pesticides. But from a tox perspective, again, it goes back to the dose makes the poison. So, even an organic pesticide has toxicity to it; it just depends on how much is there. It goes through the same scrutiny that synthetic pesticides go through, and so, there’s some of that, farming practices. And whether or not you can use machines to till because machinery is going to add to the carbon footprint or unleaded gasoline could put some contaminants in, so it depends on what’s in the soil and how it’s grown predominantly. But there’s this perception that organic food is safer in some magical way, and it’s really hard to get people to understand that there is no difference between the nutritional value of an organic tomato versus a conventional tomato. And actually, pesticides are more effective when they’re synthetic in some ways because the residual’s much longer, they have to apply less of it because it lasts longer on the ground or on the plant, and there are regulations around safety that companies spend millions of dollars studying these materials to prove safety because the person who came up with it also has to eat the same food that everyone else is eating. Of course, they don’t to poison their own family and friends. There’s just a misconception about pesticides in general. It’s one of those personal beliefs that you can’t really convince people otherwise, even if you show them the science, and I’m sure there’s other topics that are the same way.

[00:15:11] Anne Chappelle: You call yourself a food toxicologist. How did you become a food toxicologist? Was it your graduate research? Was it, you always loved food? And if you can comment on lab food toxicology versus risk assessment–type stuff? I don’t know what a food toxicologist, if they were in a lab, would do. 

[00:15:31] Alex Lau: Food toxicology doesn’t really exist in school, I guess. I fell into this serendipitously. I went to the University of Arizona for my bachelor’s, and I was looking to see what I could do with a science degree, and it looked like the options were lab technician or running samples nonstop in some sort of industry. I thought I was going to go to medical school, and I did not get in, so it’s OK to not get into medical school. I tried twice, and so, I said, I need a backup plan, and I looked at just programs within my university. I looked at the College of Pharmacy, and they had a pharmacology and toxicology program that looked very intriguing because they combined some of the health care that I wanted so I could go into pharma and cure cancer, but it also had this appealing thing about toxicology. And I was like, what is that? And oh, it’s the study of poisons—that’s kind of cool. And so, I talked to several folks within the program and they seemed to love it, and I thought there were a lot of career options at the end. I did my PhD in pharmacology and toxicology at the University of Arizona, and then I graduated in 2012. I didn’t have a lot of pharmaceutical options. I had a friend that worked at a consumer goods company that makes household products—pesticides that you spray on your baseboards for spiders or cockroaches, and or sunscreen, or products used for mosquito repellant, and candles, and all kinds of cool things. I was like, well, I don’t really have any interest in consumer goods. And she said, think about how many people use our products a day; the impact that you can have on the lives of those people who may not know that you exist but you’re ensuring that those are safe for them to use in their house. I joined that company and then I was actually recruited to the chocolate company, and I was like, this is kind of weird that a food company wants a toxicologist. I never even thought about, what’s in our food that could possibly be dangerous?

[00:17:32] Anne Chappelle: Chocolate is bliss!

[00:17:33] Alex Lau: Right!

[00:17:34] Anne Chappelle: Chocolate is not poison!

[00:17:37] Alex Lau: Yes! I’m like, are we worried about the person who’s going to eat chocolate every meal? So, I started going that path and I had to do my own research on food toxicology. I went on LinkedIn to see who else is in food? And there weren’t a lot of people at that time. I applied for the job, and I just wanted to learn more of what they envisioned a toxicologist would do. They said, we have food safety plans that we’re starting to look at chemical contaminants, heavy metals, or even incidences within the plant, like, if an accident were to happen, like some chemical is added, we want to do a risk assessment on situations like that. It doesn’t happen often, but we need somebody with your education to help with that. So, I just kind of fell into it. I was like, I can’t go wrong with chocolate. This is so interesting. They pulled me away and I moved to the east coast and worked in chocolate for two and half years and then found the job for wine because husband said, “I’m sick of snow,” and I just happened to find a job posting. I contacted the person that I had met two years prior at a conference, and I said, “Hey, I saw this job posting. Tell me a little bit more about it. What are you looking for?” I was recruited to come to California.

[00:18:50] Anne Chappelle: So, was your degree, your training, then, in risk assessment, or was it more chemical based? I’m just curious as to the classes, or even your dissertation.

[00:19:00] Alex Lau: I was traditional toxicology. Casarett & Doull’s was the toxicology Bible, right? Nothing specific in food. I think there’s a very small chapter in food toxicology. 

[00:19:11] Anne Chappelle: Exactly.

[00:19:12] Alex Lau: And so, you don’t really get exposed to it a lot in school. And my research was in arsenic and the antioxidant pathway Nrf2, and so it was very traditional laboratory signaling pathway and mechanisms. I never tied it to food or any consumer goods of any kind. It really didn’t prepare me. Fortunately, I had a really good mentor and boss and teachers at my first job, so if anyone’s looking for a career, I would look at the company and how many toxicologists are there to help train you, because I think that’s the limiting step. Without those two and a half years at the consumer goods company, with eight to 10 great toxicologists who had been doing it for several years, I would have not learned risk assessment. That’s not something that’s taught in class. I think it should be taught more, and I think I’m seeing more pharm-tox programs pick up risk assessment, or SOT offering it for graduate students who may be entering workforce. It’s great to see.

[00:20:15] David Faulkner: Yeah, I took one risk assessment class in my public health degree, just because I liked the professor who was teaching it, and was like, oh, that sounds kind of cool; it’s not really something I’m interested in. It’s been the most valuable class in terms of my career.

[00:20:29] Alex Lau: I would say a risk assessment class and if you have time to take a business course like Econ 101 or any type of class business related, because regardless if you’re in academia, industry, or nonprofit, everybody runs like a business, and so you should have that mentality a little bit as a scientist of, how do I turn this into the audience of who’s running the organization? 

[00:20:55] Anne Chappelle: So, if you don’t have a huge network, you said you have a good network of peers and colleagues that you could go to. Are the other people, then, that you work with that are not toxicologists, are those mostly chemists or food science? Is there food science, too, that isn’t tox? 

[00:21:13] Alex Lau: So, I do work with a lot of food scientists. I work with a lot of chemists because the analytical methods that go behind detecting some of these contaminants can be complicated. The other large population I work with within an organization is usually the food safety team or quality team. And there’s a lot of food safety programs out there. When I worked at the large chocolate and wine company, I was the only toxicologist; there was not an army of toxicologists. So, I was the sole toxicologist that did look at chemical contaminants, and any risk assessments that needed to be done, it was through me. That’s hard as a person coming out, and so that’s why I emphasized, the first job I had there eight to 10 other toxicologists you can bounce ideas off of. I really credit that training and those toxicologists to really being the people who brought me where I am today.

[00:22:05] David Faulkner: Well, we’re getting close to the end of scheduled time. There’s a couple of questions we try to ask everybody. The podcast is called Adverse Reactions. What was the most significant adverse reaction that you’ve experienced in your life?

[00:22:16] Alex Lau: I think it would have to be, not getting into medical school was detrimental at the time because it’s like, oh, my gosh, what am I going to do? I can’t apply to graduate school right now because the timing is relatively the same. And I didn’t have a backup plan, and I freaked out for probably a good six months before graduating from my bachelor’s degree. And it’s like, what am I going to do? I think that was the biggest turning point in my career. And I’m very grateful that it happened, now looking back, because I would not be in food toxicology. I have two brothers that are doctors that have told me the horrors of how medicine is now, and I’m so grateful that I ended up where I ended up.

[00:22:55] Anne Chappelle: I love how this connects back to what you said earlier of how many people you really touch and influence and make sure that they’re safe. Medicine is a noble profession and such, but really, you touch everyone. For several years, you did that. I mean, Halloween, thank you: my kids and their sugar high, it was a safe sugar high because of you. And I want to say thank you. 

[00:23:20] Alex Lau: And then, the wine you enjoy to cope with their sugar high.

[00:23:23] Anne Chappelle: Yes, exactly.

[00:23:21] Alex Lau: The chief marketing officer of the wine company I worked for, and she always said, one thing that always rang true to me is we create of joy, moments that matter. And so, when you’re sitting around that dinner table and you’re sharing a glass of wine, those are the moments that you’re incorporating safety into that product so that people can sit around a dinner table and enjoy it with their family and friends. So, that always rung true to me that it’s not just medicine or pharmacy or the pharmaceutical industry that’s really impacting lives; it’s also the toxicologists who sit at these food companies.

[00:24:00] Anne Chappelle: That is an awesome tagline. You’re going to have this massive influx of people wanting to study food toxicology.

[00:24:08] David Faulkner: I’m curious: you’ve said that medicine probably wasn’t, in hindsight, as good of a choice for you as what you’re doing. But what would you be doing if you weren’t doing what you are doing now?

[00:24:18] Alex Lau: Oh, my gosh. So, my husband and I have the same conversation all the time, and I told him yacht captain. I’ve never been on a yacht, I’ve never sailed or anything, I don’t swim very well. And he’s like, why yacht captain? And I said, “I want to travel the world on else’s dime.” So, if someone hires me to drive their yacht around the Mediterranean, why not?

[00:24:40] David Faulkner: This is the best answer we’ve gotten so far. 

[00:24:42] Anne Chappelle: Actually, my favorite genre of music is yacht rock.

[00:24:46] David Faulkner: Yacht rock.

[00:24:47] Alex Lau: Perfect. See? I think you and I are kindred spirits and that we think just go run tox yacht.

[00:24:52] Anne Chappelle: Tox yacht.

[00:24:53] David Faulkner: Tox yacht! Tox yacht!

[00:24:56] Anne Chappelle: This has been really fun. I could talk to you all day long.

[00:25:01] David Faulkner: Absolutely, absolutely. Oh, man, so many things about food industry. It’s fascinating. Thank you so much for talking with us. This was a lot of fun.

[00:25:08] Anne Chappelle: And next time, on Adverse Reactions

[00:25:15] David Faulkner: The wild the side of toxicology.

[00:25:19] Anne Chappelle: Or lions and vultures and tox, oh my! With Caroline Moore.

[00:25:24] Caroline Moore: This is why I’m in toxicology, because I want to know why. I want to know the mechanism. And so, the next step after that is, what’s a safe level of mercury in a sloth? What’s a safe level of mercury in a sloth who is a juvenile? I don’t know.

[00:25:36] Anne Chappelle: Thank you, all, for joining us for this episode of Adverse Reactions, presented by the Society of Toxicology. 

[00:25:46] David Faulkner: And thank you to Dave Leve at Ma3stro Studios.

[00:25:49] Anne Chappelle: That’s Ma3stro with a three, not an E.

[00:25:52] David Faulkner: Who created and produced all the music for Adverse Reactions, including the theme song, “Decompose.”

[00:25:59] Anne Chappelle: The viewpoints and information presented in Adverse Reactions represent those of the participating individuals. Although the Society of Toxicology holds the copyright to this production, it has, 

[00:26:10] David Faulkner: definitely,

[00:26:11] Anne Chappelle: not vetted or reviewed the information presented herein,

[00:26:15] David Faulkner: nor does presenting and distributing this podcast represent any proposal or endorsement of any position by the Society.

[00:26:22] Anne Chappelle: You can find out more information about the show at AdverseReactionsPodcast.com,

[00:26:27] David Faulkner: and more information about the Society of Toxicology on Facebook, Instagram, LinkedIn, and Twitter. 

[00:26:33] Anne Chappelle: I’m Anne Chappelle.

[00:26:35] David Faulkner: And I’m David Faulkner. 

[00:26:36] Anne Chappelle: This podcast was approved by Anne’s mom.

Introduction to the Episode
The Complexity of Determining Food Safety for Flavor Additives
Estimating the Amount of a Food Someone Eats throughout a Lifetime
The R&D for Shelf-Stable Foods
Transparency in Food Production
What Does It Mean If Something Is Organic?
How Do You Become a Food Toxicologist?
What Other Scientific Disciplines Are Involved in Food Safety?
What Was a Significant Adverse Reaction in Your Life?
If You Weren't a Scientist...
Next Time on Adverse Reactions