Saturday, November 26, 2016

Effect of Dioxin (TCDD) on Sex Ratio After Occupational Exposure

Persistent organic pollutants (POPs) are chemical substances that persist in the environment, bio-accumulate through the food chain, and are deleterious to the environment and to human health (1).  The Stockholm Convention, an international treaty signed in 2001, established a list of the 12 most serious POPs in order to enforce proper management/disposal, at the very least (1).  This “dirty dozen” includes dioxins, a family of industrial byproduct chemicals, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (2).  TCDD, previously linked to reproductive health issues (among other things), is found more abundantly as it moves up the food chain (2).

In August of this year, a study was published in Occupational & Environmental Medicine that studies the effect of TCDD exposure on the ratio of male-to-female offspring of those exposed (3).  The study back-calculated serum TCDD concentration of 244 voluntary participants who worked in an herbicide production plant between 1969 and 1984 (3).  The data ultimately analyzed included 355 births from 127 biological fathers and only 21 biological mothers (3).

While the results of the study found no statistically significant effect of serum TCDD concentration in women, they do indicate that a serum TCDD level above 20 pg/g in men was associated with the birth of fewer boys relative to girls (3).  However, limited studies on the endocrine/reproductive effects of TCDD, an overall scarcity of research in this area, and severe methodological drawbacks (e.g. model estimations of serum TCDD at time of conception), should be considered.

A month later, the Huffington Post published an article entitled “Men Exposed to This Herbicide Chemical May Be Less Likely to Have Sons” (4).  Despite the obvious click-bait nature of the title, the article is reasonably well-written.  The author, Lisa Rapaport, simplifies the science for a non-scientific audience, and includes caveats about sample sizes, contradictory studies, and an overall lack of available research (4).  For example, she concisely defines dose-dependence as, “the higher the dioxin exposure, the bigger the effect” (4).  Fruther, she is critical of the sample size of women in the study, mentions that few studies of this nature have been done, and that some of the others do not observe the same effects.

Rapaport is a member of the Center for Health Journalism, an organization that extensively trains journalists how to approach science in the news. She presents the information effectively while being critical of the underlying science.  As a result, despite HuffPo’s sensationalist nature and several missed opportunities to be even more critical, I give this article an 8/10 for Rapaport’s reasonably critical and efficient approach to the study.

Works Cited
1.    "Persistent Organic Pollutants (POPs)." UNEP. United Nations Environment Programme, n.d. Web. 25 Nov. 2016. <http://www.unep.org/chemicalsandwaste/POPsold/tabid/1059787/Default.aspx>.
2.    "Dioxins and Their Effects on Human Health." World Health Organization. World Health Organization, n.d. Web. 25 Nov. 2016. <http://www.who.int/mediacentre/factsheets/fs225/en/>.
3.    Mannetje, Andrea รข€˜T, Amanda Eng, Chris Walls, Evan Dryson, Manolis Kogevinas, Collin Brooks, Dave Mclean, Soo Cheng, Allan H. Smith, and Neil Pearce. "Sex Ratio of the Offspring of New Zealand Phenoxy Herbicide Producers Exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin." Occup Environ Med Occupational and Environmental Medicine (2016): 1-6. Web.

4.    Rapaport, Lisa. "Men Exposed To This Herbicide Chemical May Be Less Likely To Have Sons." Huffington Post. Huffington Post, 30 Sept. 2016. Web. 25 Sept. 2016. <http://www.huffingtonpost.com/entry/men-exposed-to-this-herbicide-chemical-may-have-fewer-sons_us_57eea9d7e4b024a52d2ec72a>.

38 comments:

  1. I thought it was interesting that the researchers back calculated the concentration of serum TCDD. That makes me curious as to how accurate the study was in general as a back calculation seems like it requires a lot of speculation on previous exposure. Obivously they can't go back in time to take measurements but I wonder about the accuracy of all studies that rely on back-calculations. I'm also curious as to how TCDD acts in the body; does it promote the effects of estrogens or antagonize the effects of androgens? Just some thoughts, nice post!

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    1. Many of the notable studies in this area back calculate to a known TCDD exposure event, unfortunately. The TCDD back-calculations definitely undermine the results. The model includes the half-life, but what if some of the participants had been exposed again in recent years? Even with a perfect model, their current serum TCDD would then yield a higher result.

      As for the mechanism of TCDD, there's really nothing concrete. The authors of this study suggest that TCDD causes Y-bearing sperm to become less fertile, as the Y-bearing:X-bearing sperm ratio is unaffected across various studies. Perhaps there's some effect like you suggest, but the increased sex ratio from exposed women has only been found at a significant level in one study, to my knowledge.

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  2. This was a nice complement to Stacey's post last week, Chris! Shannon bought up some interesting points - I am also curious about the accuracy of back-calculation studies. I'd like to see what a study on another population using the same methods would look like.

    I agree with your rating, it's refreshing to see the writer have some background in science journalism, and by criticizing the study herself, Rapaport brings more depth into the article.

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    2. Personally, I'd like to see studies that have contemporaneous TCDD measurements! But if you'd like to see a study on another population using these methods, check out this Seveso, Italy-based study, which serves as the background for this study. It can be accessed through lib.umich.edu: https://www.ncbi.nlm.nih.gov/pubmed/8709758

      As far as the writing goes, I agree! She does a much better job than I was expecting given the title, and the lazy way that most of these articles are written.

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  3. I agree, I though the Huffington Post did a nice representing the peer-reviewed article. The title is quite “click-bait”-like, but the contents of the article seem accurate, while also simplified for the general audience. I wonder if Rapaport gave the article this title herself. Coming from a scientific background, I am curious what she thinks of these flashy news titles. Those in scientific communities may overlook an article titled like this, when in reality, it is actually quite informative.

    One thing that stood out to me was a sentence at the beginning of the article. She says, “studies have been done on people exposed to dioxin; some found a similar effect on the gender of children but others did not.” Immediately, I wanted to know more about these results. One other study in Italy is mentioned, but no others. It would have been nice if she would have at least linked some of the other sources. Overall though, I thought that the Huffington Post and Rapaport did a very good job.

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    1. Rapaport writes for a newswire service, so I doubt she gave the article this title (nor do I think she'd like it haha). I do think that plenty of people would overlook this article because of its title, which is so uninformative compared to the article itself.

      As far as the other studies, I agree that it would be nice to see some of those! Unfortunately, the study that Rapaport focuses on doesn't really give much information about them, nor do there appear to be very many in the first place.

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  4. It would be interesting to see if these correlations are true among other populations as well. Are there any studies that the authors of the article elude to for further studies? What else do they suggest needs to be done? I also find it a strange sample size for women vs men...we'll need to see what comes of later studies. More importantly, what is the by mechanism which men are more affected than women?

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    1. The discussion section of the paper doesn't allude to much with regard to future studies. It mentions that some small yet statistically significant proportion of the offspring have thyroid problems, and suggest that further studies be done in this area (specific papers referenced can be found here [https://www.ncbi.nlm.nih.gov/pubmed/16217675] and here [http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0050161].

      As far as what else they suggest needs to be done, they seem to be well aware of the study's shortcomings, particularly with regard to sample size. The issue of small sample size might actually be the confounding variable to your last question. Evidence from this study and others weakly suggest that both men and women are affected, but in different ways. The relatively small amount of affected females simply renders those results not significant.

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  5. Nice post Christopher! For a long time it has been considered that this type of substances in particular herbicides can affect other species on the ecosystem. However, its impact on human health is undeniable. One case in particular occurred in Ecuador in which high doses of these compounds in the blood of mothers were associated with premature births and a shorter duration of lactation. This evidence points to greater effects than just the likelihood of sons from men who have been exposed.

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    1. Certainly the effects of these POPs is variable and can be more dangerous than offspring sex ratio. In any case, the most important piece of the puzzle here is beginning to explain this sort of thing mechanistically, particularly as some evidence exists to suggest that effects can vary by sex.

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  6. I think Rory brings up a lot of interesting points that I would not mind having more information on. I am curious as to why they chose to study people who worked at a plant between 1969 and 1984? Also DDT, a chemical commonly used in agriculture, was massed produced and used during the early portion of this time frame until it was banned in 1972 due to its carcinogenic characteristics. I am curious if the authors of the Occupational & Environmental Medicine article took DDT into consideration when they analyzed the data?

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    1. The authors never say why they chose those 15 years. Google search results seem to suggest that by 1987, the production plant in question had curbed its production of dioxin, so perhaps those 15 years were the peak of exposure? Wish I had an answer to that one.

      As far as taking into consideration other chemicals, they did... Kind of. They said that other chemicals may be at play, but since their results matched up with previous studies (which also may have been confounded by the presence of other chemicals), the results really don't mean much. I believe that other chemicals may have played a role in these health effects, and shrugging them off because the previous studies seemed to do the same doesn't exactly strike me as sound science.

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  7. I wonder if age of conception had any significance. I assume that the males and females in this study did not all have there children at the same age. They were more than likely a range of ages from 20 to 40? I agree more studies like this one would need to be performed to get a better understanding of the subject. That being said, this study is a good stepping stone that can be used for futures studies for sure.

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    1. While true that the ages of the parents in the study varied, there was no statistical significance between age and sex ratio.

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  8. Thanks Chris! Interesting post and comments. These types of chemicals are so persistent and common in our environment and yet we were learning last week in exposure science class about how water treatment systems are not designed to remove them. I wonder what adjustments to municipal water treatment will be made (and how soon!) to protect our communities from real changes.

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    1. That's a great question, but I'd guess that we won't see anything incredibly soon. The Stockholm Convention, the treaty that banned certain POPs in 2001, has been ratified by more than 170 countries - notably, though, it has not been ratified in the United States.

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  9. I really think this area does need more research. I have definitely heard around chemistry that male chemists are more likely to have female children. I have never seen any studies to support this but it is something I have heard. It will be interesting to see what further studies come after this and what we can do to prevent this. Research in this area also faces a number of ethical issues. If scientist reported that some other drug could lead to more male children this could become a problem for cultures that prize male offspring.

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    1. The fact that you've heard this about male chemists in general suggests to me that this study is even less significant, though still perfectly suggestive, given their assumption that chemicals other than TCDD had no effect on this result. Definitely true that more research should be done, as well as the challenges that await.

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  10. I find it interesting that the Huffington Post author was actually critical of the scientific journal. Most of the time they will be the exact opposite of that and make the conclusions of the journal article more dramatic or conclusive than they actually are.
    I agree with everyone above that this is a very interesting topic. It's something that a lot of people would think is important and would want to make sure is not happening to them. I think people in different industries should be studied in a similar manner to see who else may be affected by this.

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    1. I was surprised too, given the title. In most popular news articles, they'll summarize the findings without including any sort of caveat, so this was a refreshing read. Beyond different industries, I believe they should be testing different regions, durations of exposure, etc., but with a more solid methodology.

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  11. As many other have already said, I think this article compliments Stacey's post from last week very well. However, I think the data conveyed in both these studies demonstrate how little we actually know about the specific effects of POPs as it seems that every new study raises many more questions than it answers. It will be very interesting to see how research in this area progresses over the next few years, and if scientists can determine exactly how these chemicals act on the endochrine system. Hopefully, once the mechanism of action is determined we can better explain the effects these POPs have on human reproduction and development.

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    1. Certainly agreed. Scientists do know a fair amount about some of the more prominent and/or toxic effects of some of these chemicals, but studies like this compound just how widespread the effects might be. For that reason, more studies and more regulation are critical.

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  12. Hi Chris, great post. In your first paragraph, you said that TCDD is bioaccumulative. I was wondering why the authors of the study chose a group of people to study that had been exposed in a herbicide factory over 30 years ago. Like you pointed out, modeling the level of exposure at this point in time must be difficult. I wonder why the researchers chose that particular population. Are there no incidents of more modern exposure, perhaps in areas that TCDD may be found in food sources, or was the Stockholm Convention that effective at preventing these compounds from entering the environment? I wouldn't immediately expect so in such a short period of time. I definitely think the authors of the study should have selected a larger (or more reliable) sample group, especially if there have been studies with contradictory findings.

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    1. Even prior to the Stockholm Convention, the risks of chemicals like TCDD caused a decline in production and some regulation. Its peak usage in industrialized nations seems to have come several decades ago, so a more modern exposure would likely be difficult to yield the volume of subjects necessary for relevant conclusions. There have been several rodent models in recent years, though.

      As far as the sample size of this study, they originally contacted more than 1,000 individuals, but due to the self-reporting and voluntary nature of the study, less than one-fifth of that population participated.

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  13. Really nice post, Chris. It was interesting to see a study like this with a possible connection to birth-dependence and exposure to TCDD. I think your article did a good job with pointing out some of the major flaws associated with the study as well as claiming the contradictory evidence that is available. Its odd, though, that the article's authors didn't seem to comment as strongly on these issues, like the Huffington Post did. It also seemed an interesting choice to go into a study with a relatively small population of participants, unless they initial goal was for a much larger pool, and only the 244 participants consented to have their information taken?

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    1. The initial participant pool was over 1,000, but due to the voluntary nature of the study, most people contacted did not respond. And the fact that the authors didn't comment so strongly on a few criticisms of the study probably just shows that they didn't want to totally undermine their results, though the authors are certainly more critical of their own methodology than the HuffPo article is.

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  14. Great post. It would be interesting to learn more about this topic. Hopefully more studies will be done with better methods. It makes sense to me that the men would have a higher percentage of female children because the default pathway for a fetus is female. There's a lot that needs to happen for a fetus to become male. Perhaps TCDD keeps the male pathways from happening especially if this chemical has estrogenic or anti-androgenic properties.

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    1. That could be how this works mechanistically, though that wouldn't necessarily explain the rise in sex ratio (more male offspring) across some studies with affected women. Definitely need more research in this area.

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  15. Well done, Christopher! It is such a short but worth reading report on the topic of sex ratio after occupational exposure. We all know that occupational exposure nowadays has aroused public's attention and it indeed needs more consideration and scientific exploration. Unbalanced sex ratio can exert influential effects on the stability of the whole society, thus I find the report is of great significance. However, just as you mentioned, limited studies on the endocrine/reproductive effects of TCDD in this area will block the further development, we should continuously pay more efforts in this specific field in the future. Thanks again for your refreshing topic!

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  16. Interesting post and topic. It was interesting that they could back-calculate the serum level of TCDD in the participants. Im curious how accurate these measurements are and how they were taken. I do agree with you that there needs to be more research in this area but I also agree with Dan when he says that this could raise some ethical issues with gender in the community.

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    1. They back-calculated the serum TCDD levels using a model that was heavily influenced by the half-life of the chemical. Because TCDD can accumulate in fat, I believe that BMI was also taken into consideration. Other than that, I'd guess that the measurements of TCDD levels from 25-40 years ago are far from perfect.

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  17. Nice post Chris! I also agree that the study would have benefited from a larger sample size of women. Perhaps the minimal effects (with regard to sex ratio) observed in the women in the study indicate that TCDDs aren't as detrimental towards male embryos? Of course, more studies would need to be performed to better understand how TCDDs affect women. Additionally, I was curious if the authors also investigated other potential (and more serious) reproductive effects in the women exposed to TCDD (ex: problems associated with conception, fetal health/chance of birth defects).

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    1. On the contrary, the effects seen in women were just as striking as they were in men. The sample size was simply not large enough to make the observed effects significant. Absolutely, though, more studies must be done to investigate these weakly suggestive results.

      As far as the authors investigating other effects, there really isn't much they focused on aside from sex ratio, and the sample size of women is so small that there is nothing that can really be ascertained regardless.

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  18. A really interesting post. Personally I do not know of many persistent organic pollutants and their potential effects on human health. It is a bit unclear on the authors technique and their relatively small population that they studied. I think there is much more research needed to develop a firm understanding of this topic and its effect on baby sexes. Do they comment on how they came about studying this in the first place because the connection was not immediately clear to me? But overall a neat article although it doesnt seem to applicable to the general public.

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    1. They came to study this because of a related study a few years prior... Not positive why they decided specifically to perform a similar study this year. It seemed to be a statistical analysis of new data. Definitely much more research should be done on this area to validate these conclusions.

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  19. This is a very interesting study! I've heard of similar effects from other POPs that effect the health of the reproductive system. I'd be curious to know if there have been similar effects found in wildlife as there is a bioaccumulation effect. I hope that this research will go towards informing more appropriate public policy to protect populations.

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  20. I would be curious to see more work look into this effect in terms of the mother. Gender is of course determined by the genes in the sperm, however would the mother's exposure to such a toxin have a similar effect as is being seen in men. Unfortunately the sample size in this study is simply too small for that to be determined.

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