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Will Your Lipstick cause Early Menopause?

I was going to avoid blogging on this topic, but seeing as the story made the Australian with the headline “Chemicals in lipstick and cleaning products linked to early menopause”, I feel I have to weigh in a bit to avoid undue panic and the inevitable dangers of people hurling their lipsticks out the window at great speed. Also, there are issues of science communication and “the dose makes the poison”

To set the scene, there are a number of chemicals that are persistent pollutants in the environment such as polychlorinated biphenyl’s (PCB’s) and phthalates. These can weakly mimic estrogen or testosterone. As they are (relatively) easily absorbed and can accumulate in the body (Phthalates much less than PCBs), these chemicals may accumulate to levels that have adverse effects on human health (although there is no strong evidence they actually do).

Against this background the Australians' headline (and others like it) were generated by this paper just published in PLOS 1, “Persistent Organic Pollutants and Early Menopause in U.S. Women

This study looks at the occurrence of early menopause in a sample of US women with levels of a variety of persistent organic pollutants that can mimic estrogens’ effects. The study found that women who had high levels of PCB’s or phthalates in their urine, higher than 90% of women in the general community, went through menopause between 6 months to four years earlier than women in the general community (not 2-4 years as reported).

The amount menopause was shifted by, and the statistical strength of the association, varied quite a bit even in the same chemical class.

There are a couple of limitations to the paper. One is that I could not find if they had adjusted their statistical analysis for multiple comparisons, which will exaggerate the strength of the association. As well, it is not clear that for different chemicals were found in different urine samples, or if say, people with high PCB levels also had high Phthalates, which could cause spurious associations. Another is that the urine samples may not accurately reflect exposure when the women were going through menopause. The levels of the chemical were in many cases measured years after menopause occurred.

When the researchers tried to control for the length of time the women had been exposed to these chemicals, the association disappeared for phthalates and some pesticides, and remained for PCB’s. While the associations for PCBs are suggestive, correlation studies suffer from the problem that other factors may be involved.

For example, during the 1952 polio outbreaks in the US, there was a strong correlation between polio and icecream sales, leading some to suggest the banning of icecream. In fact it was simply that in summer more people were outside interacting.

In this case, there is some reasonable evidence that high exposure to PCBs could have a an effect on menopause, so an actual link is plausible. For phthalates, the link is less likely given the concentrations that cause estrogen mimicking effects are relatively high, and that the link goes away when you control for length of exposure.

However, the headlines and stories concentrated on things like lipstick and makeup, cleaning products and food containers. Things that contribute to phthalate exposure, not PCB exposure. Remember that the association with phthalates went away when corrected for length of exposure to the compounds.

Also remember that the associations were seen in people who had concentrations higher than 90% of the US populations.

So what does this mean for Australians, should we be hurling away our lipstick and eye liner with great force? Not eating food wrapped in cling film?

Food Standards Australia and New Zealand surveyed foods for a variety of contaminants, and did not detect phthalates (or a number of other persistent organic pollutants). So food contributions to Phthalate exposure in Australia will be low.

What about make up? There are a variety of phthalates at low levels in makeup. Different phthalates are used as plasticizers in nail polish and hair sprays, and as a solvent in perfumes and such. Studies looking at typical make up and cosmetic product use show that these phthalates are absorbed and excreted, but that the levels of exposure to these compounds is around 10 fold lower than the recommended total daily intake of the compounds.

The amount absorbed depends on how much you use, but even using 11-12 personal care products (lotion, perfumes, lipstick etc.) only doubles the amount of metabolites excreted, suggesting exposure is still well under the recommended levels.

Now, there is a LOT of variability in how people absorb and break down phthalates, but all the data we have suggests that standard use of cosmetics and food consumption is not the source of the phthalates for that 10% of women with the highest phthalate levels. And again remember that the phthalate association went away when length of exposure was corrected for.

Yet this is the angle most newspaper went after, and the PCBs, which were the chemicals with the most consistent association after correcting for exposure, were largely ignored. PCB’s are banned in Australia, but people may still be exposed to PCBs through contaminated land sites, industrial exposure (working with old electrical equipment that contains PCBs, and through food that has been contaminated though bioaccumulation. Fish is the most likely source of PCB exposure, although in Australia the levels are generally low.

Given the association of PCBs with early menopause these results should be carefully considered with a view to reducing PCB exposure in people with the highest levels of PCB’s. This is already occurring to some extent, the latest US National Health and Nutrition Examination Survey shows that exposures to a variety of persistent organic pollutants have fallen (see,-265,378 WARNING big file).

Including phthalates, levels of phthalates have fallen by around 45% from the levels examined in this study (they looked at menopause and urinary chemical levels from 1999-2008, levels of phthalates have dropped dramatically since then).

So what about lipstick then? While the newspaper articles gave the impression that ordinary personal care product use may put you at risk, the earlier menopause was seen only in women with the highest levels of personal care products, and the association for phthalates, the ones that actually occur in personal care products, went away when corrected for exposure puts a different complexion on things.

Obviously you do not need to hurl your lipstick (or other personal care products) away with great force. But still, you may wish to consider using fewer (12 is probably a bit much). And eating fresh food, especially fresh fruit and vegetables, is always a good idea.

A fishy story: zebra fish, Bisphenol A and hyperactivity

A paper has just been released that will raise health concerns about Bisphenol A again. The paper, “Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypothalamic neurogenesis in embryonic zebrafish” was published in the Proceedings of the National Academy of Sciences. This is a very interesting paper, but in terms of implications for human health everything hinges on what “low dose” means.

Bisphenol A (BPA) is a chemical widely used in the manufacture of plastics, is present as a developer in thermal printing paper and is present in trace amounts in the environment (I have written about BPA before here, here, here and here). Bisphenol S (BPS) is a replacement for BPA that is thought to be less estrogenic and more resistant to leaching into foods and the enviroment.

Because BPA has weak sex-hormone effects, being 1/10,000th as potent as estrogen, there has been concern that it may have adverse effects on human health. To date, no convincing evidence has been presented that the trace levels present in the environment represent a human health hazard.

The present paper looks in some detail at the ability of BPA to alter the brain development of zebra fish. Why zebra fish you ask? Zebra fish are a widely used model of vertebrate development that has been used in toxicological screening.

One of my friends and colleagues works extensively with them (I have two co-authored papers on zebra fish with him). They don’t take long to grow from embryo to adult, have well established neuronal developmental pathways, they are easy to test behaviours on and their genes can be easily modified.

However, as with all models, you have to be careful about how you extrapolate your data to humans.

The paper finds evidence that there is an effect of BPA and BPS on zebra fish behaviour and that nerve growth in specific brain regions are affected. The result that has drawn most attention is that fish embryos exposed to BPA become hyperactive as they develop (possibly due to the accelerated nerve growth).

Excitingly, the authors find that these effects are probably not due to an effect on estrogen receptors (or estrogen-like receptors) but may be working by affecting the levels of a key enzyme in steroid hormone synthesis (aromatase B).

However, despite these interesting results, this study is not applicable to human environmental exposures. There are two reasons, how much they were exposed to (relating to the “low” in low dose) and how and when they were exposed.

The concentrations of BPA in this study, while low, are still much higher than humans would be exposed to. It is a bit difficult to relate the exposures of the fish to those of humans, as humans typically do not swim immersed in solutions of BPA day in and day out, but let us look at it from a variety of perspectives.

The human exposure limit is between 25-50 microgram BPA per kilogram body weight per day (depending on which country you are in).

The fish were in water containing either 100 nanomole BPA per litre or 6.8 nanomole BPA per litre. Let’s take the lowest dose, 6.8 nanomole BPA per litre. This is 1.5 microgram per litre. This looks a lot less than the permitted human exposures, until you realise that a zebra fish embryo weighs on the order of 80 microgram. This means that their exposure is around 1,900 microgram BPA per kilogram per day (while the regulatory limit is 50 microgram per kilogram per day, humans typically consume less than 0.1 microgram per kilogram body weight per day).

Again, the fish are constantly soaking in the BPA laced water, so the BPA per kilogram body weight per day comparison may be misleading. What about looking at the intakes of the food we eat? Some canned soups will have on the order of 1.5 microgram BPA per litre (or even more), but you would have to be continuously drinking soup 24 hours a day to get the same exposure the zebra fish embryos had.

What about blood levels? Maybe that is a good comparison? The water contained 6.8 nanomole BPA per litre, human blood typically contains 0.0002 nanomole BPA per litre. Even newborns in intensive care units who are highly exposed to BPA through plastic tubing have around a thousand fold less BPA in their blood.

So, even though the concentrations the zebra fish were exposed to were “low” they are still very much higher than human exposures (see also here).

Furthermore, the zebra fish embryos were directly exposed to the BPA and BPS at times when the major degradation pathway of BPA has not yet developed.

Human embryos at a similar developmental stage are protected by the placental barrier and the mother’s enzymes that remove BPA from the circulation. Human embryos would never be exposed to the kinds of BPA levels in this experiment.

While the ability of BPA and BPS to modulate changes in steroid hormone processing in zebra fish is intriguing, there is little evidence to suggest this pathway existing in mammals, let alone humans.

Finally, in the largest multigenerational study of exposure to low levels of BPA (from 2.5 micrograms per kilogram body weight per day and higher conducted in rats), no effects were seen until levels were achieved that could activate estrogen receptors (that is much more than seen in the zebra fish experiments.

Overall, a nicely done and very interesting paper, which identifies a new pathway that may be involved in embryonic neurogenesis. However, the concentrations used were many times what humans would be exposed to, and the fish were exposed at a time when the BPA degradation enzymes were not present. Thus it is of little relevance to human exposures and should be no cause for anxiety.

And, as always, the best way to avoid BPA is to eat plenty of fresh food, especially fresh fruit and vegetables. This in itself has enormous health benefits beyond avoiding BPA.

Comet C/2014 Q2 Lovejoy, the Christmas Comet, is Brightest this Sunday.

Comet C/2014 Q2 Lovejoy, the Christmas Comet, is brightest this Sunday, January 11. Not that it will be obvious, at a predicted magnitude 4.5 it will be quite dim and be only marginally brighter than the days before or after. However, it is bright enough to be seen with the unaided eye in dark sky locations during the next two weeks, and people with good eyesight may glimpse it with the unaided eye from relatively unpolluted suburban locations.

What follows is a simple guide to finding the comet, with printable star charts. The comet is very easy to see in binoculars or a small telescope, so if you have them, this guide will help you too.

Printable black and white horizon chart facing north an hour and a half after sunset showing the location of comet C/2014 Q2 Lovejoy as seen from Adelaide. Similar views will be seen from Southern Hemisphere locations at the equivalent local time. Click to embiggen and print Animation showing the path of the comet an hour and a half after sunset. simulated in Stellarium. Click to embiggen

Over the next few days the Moon leaves the evening sky, and once again comet  C/2014 Q2 Lovejoy has a chance to shine again. Even with full Moon, comet Lovejoy has been easy to see in binoculars.

Sketch of comet Lovejoy near the globular cluster M79 on 29 December made using 10x50 binoculars Ian Musgrave

With the Moon waning and rising later the comet, which is brightening as it heads towards maximum brightness on January 11, should now be easily seen as a dimmish fuzzy star with the unaided eye. In binoculars it looks like a large ball of cotton wool and in even small telescopes a thin faint tail can be seen.

For the next 7-8 days the obvious constellations of Orion and Taurus are your guide to finding the comet. The comet is currently around magnitude 4.8, and may get as bright as 4.5 or  hopefully even brighter.

Printable black and white binocular chart an hour and a half after sunset showing the location of comet C/2014 Q2 Lovejoy. The circle is approximately the field of view of 10x50 binoculars. Click to embiggen Comet Lovejoy on 29 December 2014, before the rising Moon made it too hard to see. The comet is above Orion and Canis Major. This is a stack of 10x15 second images taken with my Canon IXUS, ASA 400. Click to embiggen.

If you go out when the sky is dark (a little after 10:20 pm daylight saving time in most of Australia), and look north-east you will see the distinctive shape of the “saucepan” almost dead ahead of you.

Just above this is a bright-blue white star, Rigel.

For the next few days if you sweep your eyes (or binoculars) north you will follow a trail of brightish stars, these form the celestial river Eridanus.  After you have passed the fifth star and before the sixth is the space where the comet will pass. There are no bright globular clusters in this area so the comet is distinctive as a fuzzy star to the unaided eye, and a large fuzzy ball in binoculars or telescopes. You may need to locate it in binoculars before you are confident of a visual sighting. If you watch on consecutive days you can see the comet move.

From around the 8th start your sweep at the saucepan it self,  then from the 10th the comet is nestled between the legs of Taurus the Bull. Start your sweep at blue-white Bellatrix, the bright star below and to the north of the  saucepan (not the bright red Betelgeuse below and to the south),  towards the like of stars that marks Orion’s shield  and then on further to a U shaped group of faintish stars, just above the obvious inverted “V” that is the head of Taurus. The “U” shape is where the comet will be at its brightest.

Once again, the printable charts above can help you with your quest. For telescope users, the image will be upside down compared to the charts. Remember, when looking for the comet allow at least 5 minutes for your eyes to adjust and become dark adapted. Here’s some hints on dark adaption of your eyes. If using the charts above, cover your torch with red cellophane so as to not destroy your night vision.

Good comet hunting!

Comet Lovejoy imaged with a remote telescope at Siding Springs Observatory on January 3, 2015 Ian Musgrave