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Introduction - Problems With Plastics

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In recent years the ability of certain compounds used in the manufacture of plastics such as Bisphenol A (BPA) to affect hormones such as oestrogen have come to prominence [1].

BPA appears to mimic/or increase the activity of oestrogens in a way that can lead to a whole host of problems including increased risk for certain types of cancer.

Some nations have enacted legislation to ban or reduce BPA in plastics as a means to reduce the risk to human health.

In an interesting parallel with legal highs vs illegal drugs, the substitutes being used are not necessarily harmless.

A new study in Nature Communications by Zhang et al [2] suggests that we may be substituting one toxic risk with another which may be just as harmful.

The study tests the effects of fluorene-9-bisphenol (BHPF), a BPA substitute, using a number of different methods.

You can read/download it here.

Due to the multitude of things tested in the study I will only cover the things that I feel are of most importance.

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Findings

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Oestrogen Receptor Activity

The first main finding is that BPHF has strong anti-oestrogenic activity.

In some cases the effect is comparable to specific oestrogen blocking drugs like Tamoxifen (commonly known as a treatment for breast cancer).

This is important because hormones are finicky things, for optimal function you need them to be in the right range.

Further some hormones act in opposition to each other.

Anything that manipulates them by increasing or reducing their activity can cause problems and ill health.

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Effects on Mice (Most Important)

The authors tested the effects of BHPF on mice and found:

1. It significantly reduced the uterine weights of female mice in a dose dependant manner.
2. It appeared to cause atrophy of the uterine tissues in a way that impaired normal pregnancy, increasing the risk of fetal death and reducing birth weights.
3. There also appeared to be some abnormalities in the reproductive systems of the males that would be consistent with reduced activity of oestrogens.
4. It seemed to trigger gene activation in the mice in a manner that is almost exactly the reverse of 17 beta-oestrodiol (an oestrogen).
5. A particular cluster of genes called SPRRs that are associated with oestrogen activity were being down-regulated.
6. There may also have been up-regulation of processes that accelerate the breakdown of oestrogens.

Though these findings are in mice they are worrying.

As the authors state:

"The incidence of adverse pregnancy outcomes, such as spontaneous abortion, preterm delivery, low birth weight and fetal death in humans, has increased in many countries, and it has been proposed that exposure to certain environmental pollutants may be linked with these adverse pregnancy outcomes."

Previous research has focused on pro-oestrogenic compounds, however, this study suggests we should also be looking closely at compounds which have anti-oestrogenic activity and indeed the interplay between them.

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Human levels of BHPF

For the final part of the experiment the authors tested 100 college students (50 Male and 50 Female) for BHPF in their blood.

These were individuals who drank bottled water but it was not known whether they were using bottles containing BHPF or not.

Of these students 7 (4 males, 3 females) had BHPF in their blood.

The levels were on average quite low at 0.7ng per ml of blood serum.

Levels in this sort of range did appear to affect uterine weight in mice but they did not reach statistical significance so we can't be certain about them.

It is possible that they are too small to have any significant effect but the only way to know for sure would be to do more research.

Some other questions also come up:

For example it would be interesting to know how many of the students were actually using BHPF containing bottles and also whether any of them were filling them with boiled water.

Also as regards the 93 that did not have BHPF in their blood was there something they were doing different?

One should also keep in mind that just because they don't have BHPF in their blood it does not mean that they do not have some other plastic related agent present.

This brings us back to the issue that we are still ignorant of the biological activity and toxicity of many of the agents we are exposed to in our environment.

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Problems

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The main problem with this study is that the bulk of the research was not carried out on humans.

The receptor activity was studied in yeast, computer simulations and then tested further in mice.

The human research was limited to simply testing blood serum levels in BPHF and this was in the absence of knowing the degree of actual exposure.

Though this implies effects in humans it is not the same as direct human research.

Also the low levels detected in humans may be so low as to not be problematic - we don't know for sure.

Another problem that I had here was that the sheer amount of material and different experiments carried out here made the study quite hard to follow.

Finally I cannot comment on the particular testing methodology used as it applies to particular aspects of the study e.g. testing levels of BHPF, receptor docking simulations and gene activity testing as I do not have the required expertise to do so.

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Conclusion

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The current study suggests that a commonly used BPA substitute called BHPF used in plastic water bottles has the ability to block the activity of oestrogen hormones and affect fertility/pregnancy in mice.

Whilst BHPF was found in the serum of 7 out of 100 human subjects tested, the levels were quite low.

It is not clear how representative these levels are in the general population or indeed if they are sufficient to have a significant effect on humans.

This study highlights the issues which may occur when a known toxic compound is simply substituted with another one which may not have been adequately tested for safety.

Further research is needed to clarify these issues and how they relate to human health.

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Thank you for reading

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References

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1. Seachrist, Darcie D., Kristen W. Bonk, Shuk-Mei Ho, Gail S. Prins, Ana M. Soto, and Ruth A. Keri. 2016. “A Review of the Carcinogenic Potential of Bisphenol A.” Reproductive Toxicology 59 (January): 167–82.

2. Zhang, Zhaobin, Ying Hu, Jilong Guo, Tong Yu, Libei Sun, Xuan Xiao, Desheng Zhu, et al. 2017. “Fluorene-9-Bisphenol Is Anti-Oestrogenic and May Cause Adverse Pregnancy Outcomes in Mice.” Nature Communications 8 (March): 14585.

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