BPA-Affected Mating? Something's Fishy...

The hot scientific story this week comes courtesy of the University of Minnesota: fish exposed to bisphenol-A (BPA) exhibit diminished sex traits, which leads to aberrant mating behaviors (Check out the original paper by Ward and Blum, or for a more plain-English rundown, try Science Sushi over at SciAm Blogs).

Blacktail shiner, C. venusta
Source: Futurity.org

I've held off on writing about BPA for a long time; it's like a science journalism black hole, dense with conflicting data, politics, and social issues. But I had to weigh in here, because no other outlet seems to have shown proper skepticism, or asked the right questions.

1. Dose - The authors of a 2012 Endocrine Reviews article on low-dose endocrine disruptors point out (p. 18) that the EPA extrapolated reference dose for BPA in humans = 50 ug / kg body weight (Update, 7/12/12 - Check the comments for a more applicable animal toxicity value). That means, according to them, that you could eat a few specks of it with dinner every day for the rest of your life, and suffer no ill effects.

So what does this have to do with the fish paper? Note the dose (p.3): 1280 ug / L. Do the math: 1L of water = 1000 mL, density of water (room temp) = 1 g / mL, thus 1L = 1 kg. How much does a fish weigh, a few grams at most? This study overdoses them by at least a few orders of magnitude. Pardon the pun, but these little guys are literally swimming in BPA. Furthermore, the scientists change out the tank water every 24 hours, so the fish are certainly overexposed relative to their control brethren.

2. Cosolvent Effects - BPA has relatively low water solubility, so the authors dissolve it into their mixture with a cosolvent, triethylene glycol. Well, that's fine, as long as they run the control - water with triethylene glycol and no BPA - which they have. So, what happened? The female fish studied show no appreciable difference (Table 1) between straight H2O and cosolvent-H2O mixtures. Pity the poor blacktail shiner (C. venusta) males, though: they show marked dropoffs in all courtship metrics from cosolvent control water alone! (No BPA added). This data point does not merit discussion in the paper, however.


3. Standard Environment - Coloration and mating behavior definitely both suffer when we lock fish in tanks bombarded with BPA. But what about in the wild? How much BPA do these fish encounter in their native river habitats? Anywhere near these concentrations? Do wild fish caught on-site exhibit these same color losses? Is BPA exposure the sole factor influencing interspecies hybridization?

Readers, I'm no evolutionary biologist, so please set me straight on a few of these points. To clarify, I don't deny that xenobiotics (atrazine, estradiol) can affect marine life, but this particular study seems somewhat subject to interpretation - a scientific 'fish story.'

Sunscreen Chemophobia: Oxybenzone

(I wrote this for participation in the 2012 'Toxic Chemicals' Blog Carnival, over at ScienceGeist)

This 'suit' wants to sneak more chemicals into your sunscreen!
Source: EWG 'Hall of Shame'

Courtesy of Mother Jones and the Environmental Working Group (EWG), we can all breathe a bit easier. The eco-conscious nonprofit organizations have just released their recommendations for summer sunscreens. Unsurprisingly, the Top 20 are cut from the same cloth; words such as "natural," "clear," "garden," and "organic" abound. Ingredients, too: ~20% or so of 'micronized' (>100 nm) zinc oxide, some titanium dioxide for good measure . . .and just about every fruit oil, tea extract, or skin moisturizer you can think of.

Actually, I found myself much more drawn to the 'Hall of Shame.' These sunscreen outlaws represent all the nefarious tricks #BigChem might play on an unsuspecting public - sneaking in oxybenzone, "nano-zinc," and retinyl palmitate (synthetic Vitamin A) to make a buck off naive customers. I won't weigh in on the last two ingredients, but oxybenzone certainly caught my eye.

Oxybenzone, also called benzophenone-3, finds its way into sunscreen, lipstick, lotions, paints, and polymers. According to the Merck Index, it was first prepared over a century ago (1906), and patents from the 1950s show a simple one-step prep, Friedel-Crafts acylation of benzoyl chloride, which forms the new C-C bond between the "left" aromatic ring and the C=O group. Oxybenzone actually absorbs UV light over a wide swath of the spectrum, from 280-320 nm, meaning it offers sun protection from both UV-A and UV-B.

oxybenzone

The EWG calls oxybenzone a "hormone-disrupting chemical." Like bisphenol A (BPA), another well-reported and contentious molecule, oxybenzone contains a free phenol group, and two aromatic rings linked by a central carbon bridge. These atomic features tend to crop up in compounds that mimic estrogens in the body.

Well, does oxybenzone pose endocrine risks? Where could you find that info, anyway?

I started where I usually do: TOXNET, the U.S. National Library of Medicine reference database. Oxybenzone triggers six references from the Developmental Toxin (DART) literature, which cover 18 years of studies on fish, mice, and cell cultures. I also checked PubMed, grabbed a 1992 National Toxicology Program (NTP) oxybenzone report, and the 2008 European Commission SCCP recommendations for consumer exposure.

What do the data show? At the highest doses - 50,000 ppm - all animals develop liver, kidney, and reproductive organ damage. But the dose makes the poison, and as you feed (oral) or rub on (dermal) less compound, the side effects fall off rapidly. No teratogenicity (fetal harm), no mutagenicity (DNA errors), and no unexplained deaths. The scientists did observe indications of "moderate reproductive toxicity," but, again, these showed up in the highest-dose groups. To replicate these effects in humans, you'd have to literally eat spoonfuls of the compound (For ongoing oxybenzone studies, see: NTP, CDC).

The European Union, exemplars for cautious chemical regulation, provide a convenient calculation for human exposure: for a standard 60 kg (132 lb) person, given skin absorption, sunscreen concentration (6% oxybenzone), and average application at 18 g (just over half an ounce), exposure = 1.78 mg / kg / body weight / day. That's ~2 ppm, fully 500 times less than the lowest doses currently testing at the NTP (see above). The 2008 EU panel assigns oxybenzone a Margin of Safety of 112; compounds above 100 generally meet their benchmark for safe use.

Delicious cup of low-dose,
 bioactive compounds
Source: Green Tea Health

But, hormones influence body chemistry at miniscule doses, right? And, these sunscreen compounds are ubiquitous! How can we be absolutely certain that they aren't toxic? Well, I'll counter with a simple observation: herbal, plant, and seed extracts - like the shea butter, aloe juice, camellia seed oil, jojoba, calendula, papaya, plantain leaf, starflower seed, linseed oil, green tea extract, olive oil, plankton, avocado oil, primrose oil, and bark extracts found in the "alternative" sunscreens - have just as many, if not more bioactive compounds!

For chemophobic consumers, the general (albeit, flawed) reasoning seems to go something like this:

Many small, aromatic, heteroatom-containing molecules may be endocrine disruptors.
Industrial companies produce many such chemical compounds.
Therefore, many "industrial" chemicals cause health problems.

Magically, however, this logical logjam clears if you mention "natural," "organic," or "chemical-free" formulations. I suspect the reasoning goes:

Many small, aromatic, heteroatom-containing molecules may be endocrine disruptors.
Natural product extracts contain dozens of compounds, some unknown, many untested.
But, since they're from plant extracts, they're probably safe.

Would consumer impressions of oxybenzone change if it were. . .a natural plant extract? Good news: it is.

That's right, the compound occurs naturally in various flower pigments, which chemically trained eyes might have detected in the "resorcinol-like" framework. To stretch the metaphor, given the eased FDA rules regarding dietary supplements, I wonder if one could employ this tactic to produce a "natural, plant-based sunscreen" that still contains oxybenzone!

Happy summer, everyone! Think clearly, ask questions, and challenge assumptions. And, wherever you buy it from, remember to always wear your sunscreen.

For a different perspective on EWG's sunscreen data, head over to Science-Based Medicine

Chemophobia Daily - NY Times (Again)

(This piece, by veteran Op-Ed columnist Nicholas Kristof of the New York Times, ran yesterday. It has been the focus of backlash and ire, from chemists on Twitter and other fora (#chemicalschangeus, #BigChem). Below, I've done some choice editing: to increase the alarmist hype, I've cut unnecessary interstitial words, focusing solely on inflammatory verbs and scary scientific terminology. Remember, this is only a 790-word column!)

"Chemicals Affect Us increasing alarm very common hormone-mimicking chemicals grotesque effects widely used herbicide female hormone feminizes male animals male frogs female organs male fish produce eggs contaminated chemicals male alligators tiny penises

growing evidence linking class chemicals problems humans breast cancer infertility low sperm counts genital deformities early menstruation diabetes and obesity congenital defect hypospadias misplacement urethra suspects endocrine disruptors wreak havoc endocrine system

Endocrine disruptors everywhere thermal receipts canned foods, cosmetics plastics food packaging Test blood urine human breast milk cord blood newborn babies

failure tackle Big Chem regulate endocrine disruptors

scolded Food Drug Administration failure ban bisphenol-A common endocrine disruptor

government vigilant threats grocery stores mountains Afghanistan

Researchers warn endocrine disruptors trigger hormonal changes DES synthetic estrogen cause vaginal cancer breast cancer decades later daughters now banned.

Scientists tiniest variations hormone levels influence fetal development female twin masculinized exposed hormones. Studies aggressive sensation-seeking eating disorders

worry endocrine disruptors hormones swamping fetuses analysis Endocrine Reviews

Fundamental changes chemical testing safety determination protect human health analysis declares chief environmental scientist toxicologist

nation’s safety system endocrine disruptors broken

endocrine disruptors data conclude chemicals not safe human populations developmental biologist

Worrying research long-term effects chemicals higher levels common endocrine disruptor, PFOA overweight PFOA unavoidable everything solutions.

Big Chem sensationalist science blocked strict regulation adopted tighter controls endocrine disruptors

Uncertainties scientists endocrine disruptors overwhelmingly protect families

microwave plastic pesticides refuse receipts"

~Fin~

*RECAP: That's 229 words there (29% of the article), including negatively-connoted words like "grotesque," "broken," and "aggressive," and even a bonus allusion to the U.S. military campaign in Afghanistan. Seven mentions of "chemical" (all negative), and a record 12 mentions of "disruptor."

And we wonder why there's so much extant public fear of chemicals?

Orange Juice: Full of Vitamin C, Fiber, and....Carbendazim?

NPR reports that the US FDA recently detained several shipments of orange juice imported from Brazil. The agency received a December 2011 tip-off from a juice company (Minute Maid, via parent company Coca-Cola) that the imports contained low concentrations of the fungicide carbendazim. While this amount is unlikely to harm anyone, FDA indicated in its letter that the EPA hasn’t established safe levels for the compound in juice, and thus considers it an unlawful additive.

Carbendazim, a benzimidazole (a two-ringed aromatic structure with two nitrogens) metabolite of benomyl, was first prepared as a discrete compound by DuPont in the early 1960’s. It’s approved in several other countries to treat black spot, Dutch elm disease, powdery mildew, and a host of other fungal diseases. The fantastic NIH resource Toxnet tells us that carbendazim is a “Group C Possible Human Carcinogen,” but given how many different standards exist for this metric, what does that mean?

Diving deeper into the data, carbendazim appears to be both a teratogen (meaning it impairs fertility or embryonic development), and causes chromosomal aberrations; both effects appear at relatively high doses that you wouldn’t drink in a single glass of OJ.

The unspoken fear here may be long-term exposure. Consider other recent reports on the ability of PFC’s (perfluorinated compounds, like the long-chain PFOS found in Scotchgard) to decrease vaccine response. Or, read the never-ending list of maladies brought on by exposure to phthalates, omnipresent plasticizers known to cause endocrine disruption. Health risks from accumulated compound may prompt the FDA’s proactive stance towards even tiny amounts of this fungicide in imported juice.

Surly Chemist Soapbox Moment – Both NPR reports refer to their subjects as “chemicals” sometimes as early on as the article’s title! The connotation for this word is overwhelmingly negative, which should be apparent from the “chemical-free” movement and the interchangeable use of “chemical” with toxin, poison, or contaminant. Doesn’t chemistry already have image problems?

Here are a few chemical synonyms for the next go-around: compound, moiety, substance, entity, additive, species, or molecule. None of these are perfect for every situation, but any would be preferable over the catch-all, “chemical.”