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Most U.S. water plants, including Toledo's, use the World Health Organization's globally accepted guideline for drinking water when deciding how much microcystin - a highly potent algal toxin in western Lake Erie - can safely exist in the public's water supply.
But the science behind the WHO's guideline is more than 16 years old, applies to only one of 80 known forms of microcystin toxin, and has been considered subject to change since it was developed in 1998.
The WHO guideline of 1.0 parts per billion was based on the best available science at the time. It applies to only one specific type of microcystin, called microcystin-LR.
The WHO, which is based in Geneva, is one of the world's leading authorities on major health threats, including the emerging Ebola epidemic. It does work mostly for countries that belong to the United Nations.
It has stated in its own literature that its guideline for microcystin-LR should be used as just that - a guideline and not a firm standard.
The WHO also has said its guideline for microcystin-LR should not be universally applied to all forms of microcystin, and has called for more research.
The United States often develops standards that equal or surpass the WHO's guidelines, but the U.S. Environmental Protection Agency could still be years away from establishing a national standard for microcystin, despite pleas to move faster by western Lake Erie water plant operators, state regulators, and members of Congress.
About 50 variations of microcystin were known to exist when the WHO established its guideline in 1998.
Today, scientists know of 80.
Microcystin-LR was the first to be identified. It is the most prevalent form of microcystin and, as far as anybody knows, the most potent.
Not all 80 variations act the same.
While many are believed to attack the liver, at least one - microcystin-LA - attacks the brain and has been linked to Alzheimer's disease, according to Fernando Rubio, president and chief executive officer of Abraxis LLC, a Pennsylvania company that has developed many of the microcystin test kits used by water treatment plants.
Microcystin-LR is more potent than cyanide and saxitoxin, and only slightly less toxic that dioxin, one of the most deadly.
'We don't know how toxic they all are,' Mr. Rubio said. 'There could be others that are more toxic.'
The U.S. EPA's ongoing assessment of microcystin has been expanded beyond microcystin-LR to include three other variations - microcystin-LA, microcystin-RR, and microcystin-YR, Mr. Rubio said.
All four were found in Toledo water during the state of emergency the first weekend of August, when the city's Collins Park Water Treatment Plant became so overwhelmed by algal toxins that the system's 500,000 customers were told to avoid drinking the city's tap water for three days.
Research published in 2013 by a team of Chinese scientists showed that humans are the most susceptible mammal for at least two of those, microcystin-LR and microcystin-RR.
In its 2003 assessment, the WHO said its 1998 guideline for microcystin-LR was still 'provisional, as the database is limited.'
'Nothing's been done since then. Absolutely nothing. I can guarantee that,' according to Wayne Carmichael, a retired Wright State University professor and one of the global pioneers in toxic-algae research. He also said there were no substantial changes in the most recent WHO assessment for microcystin, done in 2011.
Microcystin-LR 'is the best studied cyanobacterial toxin, whereas information for the other toxins is largely lacking,' according to a peer-reviewed paper out of Germany's University of Konstanz in 1999.
'The presence of cyanobacterial toxins in drinking water supplies poses a serious problem to water treatment facilities, since not all technical procedures are able to effectively remove these toxins to below acceptable levels,' the paper stated.
The foundation for the WHO's 1998 guideline was a 13-week study of laboratory mice in Great Britain. It was followed up by a 44-week study of pigs in Australia, as well as subsequent studies of monkeys and rats.
By taking into account the differences in body mass between mice and humans, the WHO came up with its guideline of 1.0 ppb for humans.
One part per billion is the rough equivalent of a single drop of water in an Olympic-sized swimming pool.
The U.S. EPA has never determined if the WHO guideline is conservative enough or too restrictive.
Standards vary
Canada has a limit of 1.5 ppb, although its formula is based on an assumption that the average Canadian weighs 22 pounds less than the average American and drinks a half-liter less water per day.
Minnesota has adopted a state standard that is far more restrictive than the WHO guideline. Minnesota allows no more than 0.04 ppb microcystin in its drinking water.
Laura Allen, U.S. EPA deputy press secretary, declined requests to interview agency scientists for this story.
In a prepared statement, she said the WHO guideline 'is a tool that states can use when developing procedures for ensuring safe drinking water for their residents' and said the U.S. EPA is continuing to evaluate information about the health effects of algal toxins in general.
She said a health advisory is expected to be issued in the spring for microcystin-LR and another toxin generated by harmful blue-green algae, cylindrospermopsin. In 2016, the agency plans to publish federal Clean Water Act criteria for those two toxins, Ms. Allen said.
Joe Cotruvo, a Toledo native who ran the U.S. EPA's national drinking water program from 1976 to 1990 and served on the WHO committee that developed that organization's 1998 guideline, said he believes most states will use the upcoming U.S. EPA advisory as their new guideline when it comes out, even though it is not a binding standard.
That's because the science will be more current and specific to the United States, he said.
He said he considers the WHO's 1998 guideline 'very reasonable' and one that uses 'standard toxicological principles.'
Mr. Cotruvo earned his undergraduate and doctoral degrees in chemistry from the University of Toledo and Ohio State University, respectively, before embarking on a career that made him an internationally known water consultant after he left the U.S. EPA.
He said there appears to be confusion over how states should interpret the WHO guideline.
According to Mr. Cotruvo, the recommendation was intended more for chronic, long-term exposure.
A fact sheet he created quotes WHO literature as stating its 1.0 ppb guideline represents 'a tolerable intake for a lifetime' and is 'not so precise that [it] cannot be exceeded for short periods of time.'
'You shouldn't treat these numbers as biblical,' Mr. Cotruvo said. 'They are just benchmarks.'
But where does a water plant operator or state regulatory agency draw the line in the absence of a U.S. EPA standard?
Best science
Mr. Carmichael, a co-member of the same WHO committee, sharply disagrees with Mr. Cotruvo's recollection of how the organization wants the guideline used.
He said there is no question the WHO developed it to guard against short-term, acute exposure.
'That number is based on toxicology of acute exposure, not chronic or long-term exposure,' according to Mr. Carmichael, who headed a U.S. Centers for Disease Control and Prevention investigation into 75 microcystin-related deaths at a kidney dialysis center in Brazil in 1996.
Regulatory agencies want certainty, something they can more definitively use to protect public health.
'We haven't been dealing with microcystin that long,' Ohio EPA Director Craig Butler said. 'You have to use the best science of the day. For the foreseeable future, that's still the WHO [guideline]. It's not perfect. We are anxious for the U.S. EPA to get some more work done.'
Ottawa County Sanitary Engineer Kelly Frey, who manages Port Clinton's regional water-treatment plant, said he wants more direction than he's getting from the WHO guideline. He said he often gathers technical information about microcystin from other countries because he's not finding what he needs from the U.S. EPA.
A critical question to him is not just what works against microcystin - but why.
'My concern is with the process. I don't want to get blindsided like this again,' Mr. Frey said. 'Who do we listen to? It's confusing. What else is sitting out there that we have to be prepared for that will catch us in a similar situation?'
Research
Brenda Snyder, chief chemist of Toledo's Collins Park Water Treatment Plant, said she's aware the U.S. EPA is studying four variations of microcystin.
'The only thing that caught us off guard was that this bloom moved over the top of our intake and just stood there,' she said, referring to the concentrated algae that led to the city's state of emergency in early August.
To Mr. Carmichael, the whole situation is frustrating.
Records of the first livestock sickened by algae date back to 1878.
The field of research around harmful, blue-green algae began to emerge in the 1950s. But Mr. Carmichael said there was virtually no testing funded until he and some of his graduate students began gathering data in 1975.
The United States didn't invest much in algal research until about 20 years ago - and its commitment to the issue has been spotty, he said.
'I spent much of my career at Wright State going to other countries. It wasn't until the early 1990s we started doing routine tests of blooms in the United States,' Mr. Carmichael said.
Microcystis has been the dominant form of algae in western Lake Erie since 1995. It is the chief producer of the toxin, microcystin.
But there are other forms of harmful algal blooms that also produce some varieties of microcystin, such as planktothrix, which is common to Lake Erie's Sandusky Bay, and anabaena, another one of Earth's most ancient forms of cyanobacteria, or blue-green algae.
Algal blooms are not unique to western Lake Erie. In a 2007 assessment of 1,100 lakes across America, the U.S. EPA found microcystin in about a third of them, Mr. Rubio said.
The problem is expected to get worse under climate change as the planet continues to warm, with more frequent and more intense storms causing more nutrients to flow off land into streams and lakes.
By 2025, half of the world's population will be living in water-stressed areas, according to the WHO.
Mr. Carmichael said he fully supports efforts for more research into microcystin, but doubts there will be the commitment to study all 80 variations of it anytime soon.
'If you can't even get an adequate database funded for one, how are you going to do it for 80?' he asked. 'I get frustrated because I've got 40 years of hindsight.'
Contact Tom Henry at: thenry@theblade.com, 419-724-6079, or via Twitter @ecowriterohio.
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