Sci­en­tists are trained to express them­selves ratio­nal­ly. They avoid per­son­al attacks when they dis­agree. But some sci­en­tif­ic argu­ments become so polar­ized that tem­pers fray. There may even be shouting.

Scientists typically shy away from activism, but many now believe it’s what’s needed to punch through the machinations and inertia regarding chemical regulation.

Such is the cur­rent state of affairs between two camps of sci­en­tists: health effects researchers and reg­u­la­to­ry tox­i­col­o­gists. Both groups study the effects of chem­i­cal expo­sures in humans. Both groups have pub­licly used terms like ​“irrel­e­vant,” ​“arbi­trary,” ​“unfound­ed” and ​“con­trary to all accu­mu­lat­ed phys­i­o­log­i­cal under­stand­ing” to describe the other’s work. Pri­vate­ly, the lan­guage becomes even harsh­er, with phras­es such as ​“a pseu­do­science,” ​“a reli­gion” and ​“rigged.”

The rift cen­ters around the best way to mea­sure the health effects of chem­i­cal expo­sures. The reg­u­la­to­ry tox­i­col­o­gists typ­i­cal­ly rely on com­put­er sim­u­la­tions called ​“phys­i­o­log­i­cal­ly based phar­ma­co­ki­net­ic” (PBPK) mod­el­ing. The health effects researchers — endocri­nol­o­gists, devel­op­men­tal biol­o­gists and epi­demi­ol­o­gists, among oth­ers — draw their con­clu­sions from direct obser­va­tions of how chem­i­cals actu­al­ly affect liv­ing things.

The debate may sound arcane, but the out­come could direct­ly affect your health. It will shape how gov­ern­ment agen­cies reg­u­late chem­i­cals for decades to come: how tox­ic waste sites are cleaned up, how pes­ti­cides are reg­u­lat­ed, how work­ers are pro­tect­ed from tox­ic expo­sure and what chem­i­cals are per­mit­ted in house­hold items. Those deci­sions will pro­found­ly affect pub­lic health: the rates at which we suf­fer can­cer, dia­betes, obe­si­ty, infer­til­i­ty, and neu­ro­log­i­cal prob­lems like atten­tion dis­or­ders and low­ered IQ.

The link from cer­tain chem­i­cals to these health effects is real. In a paper pub­lished ear­li­er this year, a group of lead­ing endocri­nol­o­gists con­clud­ed with 99 per­cent cer­tain­ty that envi­ron­men­tal expo­sure to hor­mone-dis­rupt­ing chem­i­cals caus­es health prob­lems. They esti­mate that this costs the Euro­pean Union health­care sys­tem about $175 bil­lion a year.

Clos­er to home, Amer­i­cans are rou­tine­ly sick­ened by tox­ic chem­i­cals whose health effects have been long known. To cite one infa­mous exam­ple, peo­ple exposed to the known car­cino­gen formalde­hyde in FEMA trail­ers after Hur­ri­cane Kat­ri­na suf­fered headaches, nose­bleeds and dif­fi­cul­ty breath­ing. Dozens of can­cer cas­es were lat­er report­ed. Then there are work­place expo­sures, which fed­er­al gov­ern­ment esti­mates link to as many as 20,000 can­cer deaths a year and hun­dreds of thou­sands of illnesses.

“We are drown­ing our world in untest­ed and unsafe chem­i­cals, and the price we are pay­ing in terms of our repro­duc­tive health is of seri­ous con­cern,” wrote the Inter­na­tion­al Fed­er­a­tion of Gyne­col­o­gy and Obstet­rics in a state­ment released on Octo­ber 1.

Yet chem­i­cal reg­u­la­tion in the Unit­ed States has pro­ceed­ed at a glacial pace. And cor­po­rate prof­it is at the heart of the story.

That the chem­i­cal indus­try exerts polit­i­cal influ­ence is well doc­u­ment­ed. What our inves­ti­ga­tion reveals is that, 30 years ago, cor­po­rate inter­ests began to con­trol not just the polit­i­cal process but the sci­ence itself. Indus­try not only funds research to cast doubt on known envi­ron­men­tal health haz­ards; it has also shaped an entire field of sci­ence — reg­u­la­to­ry tox­i­col­o­gy — to down­play the risk of tox­ic chemicals.

Our inves­ti­ga­tion traces this web of influ­ence to a group of sci­en­tists work­ing for the Depart­ment of Defense (DOD) in the 1970s and 1980s — the pio­neers of PBPK mod­el­ing. It quick­ly became clear that this type of mod­el­ing could be manip­u­lat­ed to min­i­mize the appear­ance of chem­i­cal risk. PBPK method­ol­o­gy has sub­se­quent­ly been advanced by at least two gen­er­a­tions of researchers — includ­ing many from the orig­i­nal DOD group — who move between indus­try, gov­ern­ment agen­cies and indus­try-backed research groups, often with lit­tle or no transparency.

The result is that chem­i­cals known to be harm­ful to human health remain large­ly unreg­u­lat­ed in the Unit­ed States — often with dead­ly results. For chem­i­cals whose haz­ards are just now being rec­og­nized, such as the com­mon plas­tics ingre­di­ent bisphe­nol A (BPA) and oth­er endocrine dis­rup­tors, this lack of reg­u­la­tion is like­ly to con­tin­ue unless the fed­er­al chem­i­cal review process becomes more trans­par­ent and relies less heav­i­ly on PBPK modeling.

Here we lay out the play­ers, the duel­ing par­a­digms and the high-stakes health con­se­quences of get­ting it wrong.

The dawn of PBPK simulation

The 1970s and 1980s saw a bliz­zard of envi­ron­men­tal reg­u­la­tion. The Clean Air Act, Clean Water Act and Tox­ic Sub­stances Con­trol Act, along with the laws that estab­lished Super­fund and Com­mu­ni­ty Right-to-Know Pro­grams, for the first time required com­pa­nies— and mil­i­tary bases — using and pro­duc­ing chem­i­cals to account for their envi­ron­men­tal and health impacts. This meant greater demand for chem­i­cal risk assess­ments as the Occu­pa­tion­al Safe­ty and Health Admin­is­tra­tion (OSHA) and the Envi­ron­men­tal Pro­tec­tion Agency (EPA) began to estab­lish safe­ty stan­dards for work­place expo­sures and envi­ron­men­tal cleanups.

In the 1980s, the now-defunct Tox­ic Haz­ards Research Unit at the Wright-Pat­ter­son Air Force Base in Day­ton, Ohio, was inves­ti­gat­ing the tox­i­c­i­ty and health effects of chem­i­cals used by the mil­i­tary. Of par­tic­u­lar con­cern to the DOD were the many com­pounds used by the mil­i­tary to build, ser­vice and main­tain air­craft, vehi­cles and oth­er machin­ery: fuels and fuel addi­tives, sol­vents, coat­ings and adhe­sives. The mil­i­tary is respon­si­ble for about 900 of the approx­i­mate­ly 1,300 cur­rent­ly list­ed Super­fund sites, many of which have been con­t­a­m­i­nat­ed by these chem­i­cals for decades.

In the mid-1980s, sci­en­tists at the Wright-Pat­ter­son Tox­ic Haz­ards Research Unit began using PBPK sim­u­la­tions to track how chem­i­cals move through the body. Known as in sil­i­co (in com­put­ers) mod­els, these are an alter­na­tive to test­ing chem­i­cals in vivo (in live ani­mals) or in vit­ro (in a test tube). They allow sci­en­tists to esti­mate what con­cen­tra­tions of a chem­i­cal (or its break­down prod­ucts) end up in a par­tic­u­lar organ or type of tis­sue, and how long they take to exit the body. The infor­ma­tion can then be cor­re­lat­ed with exper­i­men­tal data to set expo­sure lim­its — or not.

PBPK sim­u­la­tions made test­ing faster and cheap­er, some­thing attrac­tive to both indus­try and reg­u­la­tors. But the PBPK mod­el has draw­backs. ​“It tells you noth­ing about effects,” says Lin­da Birn­baum, direc­tor of both the Nation­al Insti­tute of Envi­ron­men­tal Health Sci­ences (NIEHS) and Nation­al Tox­i­col­o­gy Pro­gram (NTP). Obser­va­tion­al stud­ies and lab­o­ra­to­ry exper­i­ments, on the oth­er hand, are designed to dis­cov­er how a chem­i­cal affects bio­log­i­cal processes.

Even reg­u­la­to­ry tox­i­col­o­gists who sup­port PBPK acknowl­edge its lim­i­ta­tions: “[PBPK mod­els] are always going to be lim­it­ed by the qual­i­ty of the data that go into them,” says tox­i­col­o­gist James Lamb, who worked for the NTP and EPA in the 1980s and is now prin­ci­pal sci­en­tist at the con­sult­ing firm Exponent.

The late health effects researcher Louis Guil­lette, a pro­fes­sor at the Med­ical Uni­ver­si­ty of South Car­oli­na famous for stud­ies on DDT’s hor­monedis­rupt­ing effects in Flori­da alli­ga­tors, put it more blunt­ly: ​“PBPK? My imme­di­ate response: Junk in, junk out. The take-home is that most of the mod­els [are] only as good as your under­stand­ing of the com­plex­i­ty of the system.”

Many biol­o­gists say PBPK-based risk assess­ments begin with assump­tions that are too nar­row, and thus often fail to ful­ly cap­ture how a chem­i­cal expo­sure can affect health. For exam­ple, a series of PBPK stud­ies and reviews by tox­i­col­o­gist Justin Tee­guarden of the Pacif­ic North­west Nation­al Lab­o­ra­to­ry in Rich­land, Wash., and his col­leagues sug­gest­ed that BPA breaks down into less harm­ful com­pounds and exits the body so rapid­ly that it is essen­tial­ly harm­less. Their research began with cer­tain assump­tions: that BPA only mim­ics estro­gen weak­ly, that it affects only the body’s estro­gen sys­tem, and that 90 per­cent of BPA expo­sure is through diges­tion of food and bev­er­ages. How­ev­er, health effects research has shown that BPA mim­ics estro­gen close­ly, can affect the body’s andro­gen and thy­roid hor­mone sys­tems, and can enter the body via path­ways like the skin and the tis­sues of the mouth. When PBPK mod­els fail to include this evi­dence, they tend to under­es­ti­mate risk.

Because of its reliance on what­ev­er data are includ­ed, PBPK mod­el­ing can be delib­er­ate­ly manip­u­lat­ed to pro­duce desired out­comes. Or, as Uni­ver­si­ty of Notre Dame biol­o­gist Kristin Shrad­er-Frechette, who spe­cial­izes in human health risk assess­ment, says: ​“Mod­els can offer a means of avoid­ing the con­clu­sions derived from actu­al exper­i­ments.” In oth­er words, PBPK mod­els can be cus­tomized to pro­vide results that work to industry’s advantage.

That’s not to say PBPK itself is to blame. ​“Let’s not throw the baby out com­plete­ly with the bath­wa­ter,” says New York Uni­ver­si­ty asso­ciate pro­fes­sor of envi­ron­men­tal med­i­cine and health pol­i­cy Leo Trasande. ​“How­ev­er, when you have biol­o­gy telling you there are basic flaws in the mod­el, that’s a com­pelling rea­son that it’s time for a par­a­digm shift.”

A handy tool for industry

That PBPK stud­ies could be used to make chem­i­cals appear safer was as clear in the 1980s as it is now. In a 1988 paper tout­ing the new tech­nique, Wright-Pat­ter­son sci­en­tists explained how their mod­el­ing had prompt­ed the EPA to stop its reg­u­la­tion process for a chem­i­cal of great con­cern to the mil­i­tary: meth­yl­ene chloride.

Meth­yl­ene chlo­ride is wide­ly used as a sol­vent and as an ingre­di­ent in mak­ing plas­tics, phar­ma­ceu­ti­cals, pes­ti­cides and oth­er indus­tri­al prod­ucts. By the 1990s, the U.S. mil­i­tary would be the country’s sec­ond great­est user. Meth­yl­ene chlo­ride was — and remains — reg­u­lat­ed under the Clean Air Act as a haz­ardous air pol­lu­tant because of its car­cino­genic and neu­ro­tox­ic effects.

Between 1985 and 1986, the Nation­al Insti­tute for Occu­pa­tion­al Safe­ty and Health esti­mat­ed that about 1 mil­lion work­ers a year were exposed to meth­yl­ene chlo­ride, and the EPA clas­si­fied the com­pound as a ​“prob­a­ble human car­cino­gen.” A num­ber of unions, includ­ing Unit­ed Auto Work­ers and Unit­ed Steel­work­ers, also peti­tioned OSHA to lim­it on-the-job expo­sure to meth­yl­ene chloride.

In 1986, OSHA began the process of set­ting occu­pa­tion­al expo­sure lim­its. Stake­hold­ers were invit­ed to sub­mit pub­lic comments.

Among the mate­ri­als sub­mit­ted was a PBPK study by Melvin Ander­sen, Har­vey Clewell — both then work­ing at Wright-Pat­ter­son — and sev­er­al oth­er sci­en­tists, includ­ing two employed by meth­yl­ene chlo­ride prod­uct man­u­fac­tur­er Dow Chem­i­cal. Pub­lished in 1987, this study con­clud­ed, ​“Con­ven­tion­al risk analy­ses great­ly over­es­ti­mate the risk in humans exposed to low con­cen­tra­tions [of meth­yl­ene chloride].”

Lat­er that year, the EPA revised its pre­vi­ous health assess­ment of meth­yl­ene chlo­ride, cit­ing the Wright-Pat­ter­son study to con­clude that the chem­i­cal was nine times less risky than pre­vi­ous­ly esti­mat­ed. The EPA ​“has halt­ed its rule­mak­ing on meth­yl­ene chlo­ride [based on our stud­ies],” wrote Wright-Pat­ter­son sci­en­tists in 1988.

OSHA, too, con­sid­ered the Wright-Pat­ter­son study in its meth­yl­ene chlo­ride assess­ment — and its rule­mak­ing dragged on anoth­er 10 years before the agency final­ly lim­it­ed expo­sure to the chemical.

The use­ful­ness of PBPK mod­el­ing to indus­try did not escape the Wright-Pat­ter­son researchers. ​“The poten­tial impact,” wrote Ander­sen, Clewell and their col­leagues in 1988, ​“is far reach­ing and not lim­it­ed to meth­yl­ene chlo­ride.” Using PBPK mod­els to set expo­sure lim­its could help avoid set­ting ​“exces­sive­ly con­ser­v­a­tive” — i.e., pro­tec­tive— lim­its that could lead to ​“unnec­es­sary expen­sive con­trols” and place ​“con­straints on impor­tant indus­tri­al process­es.” In oth­er words, PBPK mod­els could be used to set less-strin­gent envi­ron­men­tal and health stan­dards, and save indus­try money.

So far, they’ve been proven right. The work done at Wright-Pat­ter­son set the stage for the next 30-plus years. Results obtained using PBPK mod­el­ing — espe­cial­ly in indus­try-fund­ed research, often con­duct­ed by for­mer Wright-Pat­ter­son sci­en­tists — have down­played the risk and delayed the reg­u­la­tion of numer­ous wide­ly used and com­mer­cial­ly lucra­tive chem­i­cals. These include formalde­hyde, styrene, tri­choloreth­yl­ene, BPA and the pes­ti­cide chlor­pyri­fos. For many such chem­i­cals, PBPK stud­ies con­tra­dict what actu­al bio­log­i­cal exper­i­ments con­clude. Reg­u­la­tors often defer to the PBPK stud­ies anyway.

A web of influence

Click to zoom infographic

At the time that PBPK mod­el­ling was being devel­oped, the chem­i­cal indus­try was strug­gling with its pub­lic image. The Bhopal, India, dis­as­ter—the methyl iso­cyanate release that killed and injured thou­sands — hap­pened in 1984. The fol­low­ing year, a tox­ic gas release at a West Vir­ginia Union Car­bide plant sent about 135 peo­ple to hospitals.

In response to these inci­dents, new fed­er­al reg­u­la­tions required com­pa­nies to account for the stor­age, use and release of haz­ardous chem­i­cals. The min­utes from a May 1988 Chem­i­cal Man­u­fac­tur­ers Asso­ci­a­tion (CMA) meet­ing show indus­try was feel­ing the pres­sure. Not­ing the fed­er­al scruti­ny and the grow­ing test­ing require­ments, the CMA rec­om­mend­ed that indus­try help ​“devel­op expo­sure data” and ​“explore inno­v­a­tive ways to lim­it required test­ing to that which is needed.”

Indus­try had already begun to do this by found­ing a num­ber of research insti­tutes such as the Chem­i­cal Indus­try Insti­tute of Tox­i­col­o­gy (CIIT), a non­prof­it tox­i­col­o­gy research insti­tute (renamed the Ham­n­er Insti­tutes in an act of lin­guis­tic detox­i­fi­ca­tion in 2007). This peri­od also saw the rise of for-prof­it con­sult­ing firms like Env­i­ron (1982), Gra­di­ent (1985), Chem­Risk (1985) and K.S. Crump and Com­pa­ny (1986), with which indus­try would col­lab­o­rate advan­ta­geous­ly in the fol­low­ing decades.

“Our goal was to do the sci­ence that would help the EPA and oth­er reg­u­la­to­ry bod­ies make the poli­cies,” explained William Green­lee, Ham­n­er pres­i­dent and CEO, in an inter­view for a busi­ness web­site. Indeed, over the past 30 years, Ham­n­er and these con­sul­tan­cies have pro­duced hun­dreds of PBPK stud­ies, often with the sup­port of chem­i­cal com­pa­nies or trade groups. Over­whelm­ing­ly, these stud­ies down­play or cast doubt on chem­i­cals’ health effects — and delay regulation.

“I have seen how sci­en­tists from the Ham­n­er Insti­tutes can present infor­ma­tion in a way that care­ful­ly shapes or con­trols a nar­ra­tive,” says Lau­ra Van­den­berg, an assis­tant pro­fes­sor of envi­ron­men­tal health sci­ences at Uni­ver­si­ty of Mass­a­chu­setts Amherst. She explains that Ham­n­er sci­en­tists often use nar­row time win­dows or present data in a lim­it­ed con­text, reject­ing infor­ma­tion that does not con­form to their mod­els. ​“These are the kinds of tac­tics used to man­u­fac­ture doubt,” she says.

A close look at the authors of stud­ies pro­duced by these indus­try-linked research groups reveals a web of influ­ence trace­able to Wright-Pat­ter­son (see chart on fol­low­ing page). At least 10 researchers employed at or con­tract­ed by Wright-Pat­ter­son in the 1980s went on to careers in tox­i­col­o­gy at CIIT/​Hamner, for-prof­it con­sult­ing firms or the EPA. About half have held senior posi­tions at Ham­n­er, includ­ing the co-authors of many of the ear­ly Wright-Pat­ter­son PBPK stud­ies: Melvin Ander­son, now a chief sci­en­tif­ic offi­cer at Ham­n­er, and Har­vey Clewell, now a senior inves­ti­ga­tor at Ham­n­er and prin­ci­pal sci­en­tist at the con­sult­ing firm ENV­I­RON. ​“I’m prob­a­bly giv­en cred­it as the per­son who brought PBPK into tox­i­col­o­gy and risk assess­ment,” Ander­sen told In These Times.

A revolv­ing door between these indus­try-affil­i­at­ed groups and fed­er­al reg­u­la­tors was also set in motion. More than a dozen researchers have moved from the EPA to these for-prof­it con­sul­tan­cies; a sim­i­lar num­ber have gone in the oth­er direc­tion, end­ing up at the EPA or oth­er fed­er­al agencies.

Fur­ther blur­ring the pub­lic-pri­vate line, CIIT/​Hamner has received mil­lions of dol­lars in both indus­try and tax­pay­er mon­ey. The group stat­ed on its web­site in 2007 that $18 mil­lion of its $21.5 mil­lion annu­al oper­at­ing bud­get came from the ​“chem­i­cal and phar­ma­ceu­ti­cal indus­try.” Infor­ma­tion about its cor­po­rate fun­ders is no longer detailed there, but Ham­n­er has pre­vi­ous­ly list­ed as clients and sup­port­ers the Amer­i­can Chem­istry Coun­cil (for­mer­ly the CMA, and one of the most pow­er­ful lob­by­ists against chem­i­cal reg­u­la­tion), Amer­i­can Petro­le­um Insti­tute, BASF, Bay­er Crop­Science, Dow, Exxon­Mo­bil, Chevron and the Formalde­hyde Coun­cil. At the same time, over the past 30 years, CIIT/​Hamner has received near­ly $160 mil­lion in grants and con­tracts from the EPA, DOD and Depart­ment of Health and Human Ser­vices. In sum, since the 1980s, these fed­er­al agen­cies have award­ed hun­dreds of mil­lions of dol­lars to indus­try-affil­i­at­ed research insti­tutes like Hamner.

But the fed­er­al reliance on indus­try-linked researchers extends fur­ther. Since 2000, the EPA has signed a num­ber of coop­er­a­tive research agree­ments with the ACC and CIIT/ Ham­n­er. All involve chem­i­cal tox­i­c­i­ty research that includes PBPK mod­el­ing. And in 2014, Ham­n­er out­lined addi­tion­al research it will be con­duct­ing for the EPA’s next gen­er­a­tion of chem­i­cal test­ing — the Tox­Cast and Tox21 pro­grams. Over the past five years, Ham­n­er has received fund­ing for this same research from the ACC and Dow.

Mean­while, the EPA reg­u­lar­ly con­tracts with for-prof­it con­sul­tan­cies to per­form risk assess­ments, assem­ble peer review pan­els and select the sci­en­tif­ic lit­er­a­ture used in chem­i­cal eval­u­a­tions. This gives these pri­vate orga­ni­za­tions con­sid­er­able sway in the deci­sion-mak­ing process, often with lit­tle trans­paren­cy about ties to chem­i­cal man­u­fac­tur­ers. The upshot: Experts select­ed to over­see chem­i­cal reg­u­la­tion often over­rep­re­sent the indus­try perspective.

These cozy rela­tion­ships have not gone unno­ticed; the EPA has been called to task by both its own Office of Inspec­tor Gen­er­al and by the U.S. Gov­ern­ment Account­abil­i­ty Office. ​“These arrange­ments have raised con­cerns that ACC or its mem­bers could poten­tial­ly influ­ence, or appear to influ­ence, the sci­en­tif­ic results that may be used to make future reg­u­la­to­ry deci­sions,” wrote the GAO in a 2005 report.

Asked for com­ment by In These Times, the EPA said these arrange­ments do not present con­flicts of interest.

Decades of dead­ly delay

PBPK stud­ies have stalled the reg­u­la­tion of numer­ous chem­i­cals. In each case, nar­row­ly focused mod­els devel­oped by indus­try-sup­port­ed research con­clud­ed that risks were low­er than pre­vi­ous­ly esti­mat­ed or were not of con­cern at like­ly expo­sure levels.

Take, for exam­ple, meth­yl­ene chlo­ride, the sub­ject of the 1987 paper Wright-Pat­ter­son sci­en­tists bragged had halt­ed the EPA’s reg­u­la­to­ry process. Despite the chem­i­cal being iden­ti­fied as ​“prob­a­bly car­cino­genic to humans” by the U.N. Inter­na­tion­al Agency for Research on Can­cer, a ​“rea­son­ably antic­i­pat­ed” human car­cino­gen by the U.S. Nation­al Tox­i­col­o­gy Pro­gram, and an ​“occu­pa­tion­al car­cino­gen” by OSHA, the EPA has yet to lim­it its use. EPA researchers not­ed this year that the 1987 PBPK mod­el by the Wright-Pat­ter­son sci­en­tists remains the basis for the agency’s risk assessment.

Today, meth­yl­ene chlo­ride remains in use — to pro­duce elec­tron­ics, pes­ti­cides, plas­tics and syn­thet­ic fab­rics, and in paint and var­nish strip­pers. The Con­sumer Prod­uct Safe­ty Com­mis­sion, OSHA and NIOSH have issued health warn­ings, and the FDA bars meth­yl­ene chlo­ride from cos­met­ics— but no U.S. agency has total­ly banned the chem­i­cal. The EPA esti­mates that some 230,000 work­ers are exposed direct­ly each year. Accord­ing to OSHA, between 2000 and 2012, at least 14 peo­ple died in the Unit­ed States of asphyx­i­a­tion or heart fail­ure after using meth­yl­ene chlo­ride-con­tain­ing prod­ucts to refin­ish bath­tubs. The Cen­ter for Pub­lic Integri­ty reports that meth­yl­ene chlo­ride expo­sure prompt­ed more than 2,700 calls to U.S. poi­son con­trol cen­ters between 2008 and 2013.

Anoth­er telling exam­ple of indus­try-fund­ed PBPK stud­ies’ influ­ence is formalde­hyde. This chem­i­cal remains large­ly unre­strict­ed in the Unit­ed States, despite being a well-rec­og­nized res­pi­ra­to­ry and neu­ro­log­i­cal tox­i­cant linked to nasal can­cer and leukemia, as well as to aller­gic reac­tions and skin irri­ta­tion. The EPA’s tox­i­co­log­i­cal review of formalde­hyde, begun in 1990, remains incom­plete, in no small part because of delays prompt­ed by the intro­duc­tion of stud­ies — includ­ing PBPK mod­els con­duct­ed by CIIT/​Hamner — ques­tion­ing its link to leukemia.

If that link is con­sid­ered weak or uncer­tain, that means formalde­hyde — or the com­pa­nies that employ the sick­ened work­ers — won’t be held respon­si­ble for the dis­ease. The chem­i­cal indus­try is well aware that ​“more peo­ple have leukemia … than have nasal tumors,” says recent­ly retired NIEHS tox­i­col­o­gist James Huff.

Some of this CIIT/​Hamner research was con­duct­ed between 2000 and 2005 with fund­ing from an $18,750,000 EPA grant. In 2010, Ham­n­er received $5 mil­lion from Dow, a formalde­hy­de­prod­uct man­u­fac­tur­er, for tox­i­c­i­ty test­ing, includ­ing PBPK mod­el­ing. The ACC, which oppos­es formalde­hyde restric­tion, also sup­port­ed this research.

Con­se­quent­ly, apart from a few state reg­u­la­tions and a pend­ing EPA pro­pos­al to lim­it formalde­hyde emis­sions from com­pos­ite wood prod­ucts like ply­wood, com­pa­nies can still use the chem­i­cal — as in the FEMA trailers.

Cos­met­ics and per­son­al-care prod­ucts can also be sources of formalde­hyde expo­sure. This made head­lines in 2011 after hair salon work­ers using a smooth­ing prod­uct called Brazil­ian Blowout report­ed nau­sea, sore throats, rash­es, chron­ic sinus infec­tions, asth­ma-like symp­toms, bloody noses, dizzi­ness and oth­er neu­ro­log­i­cal effects. ​“You can’t see it … but you feel it in your eyes and it gives you a high,” salon own­er and hair styl­ist Cort­ney Tan­ner tells In These Times. ​“They don’t teach this stuff in beau­ty school,” she says, and no one warns styl­ists about these prod­ucts or even sug­gests using a ventilator.

OSHA has issued a haz­ard alert for these prod­ucts and the FDA has issued mul­ti­ple warn­ings, most recent­ly in Sep­tem­ber, but reg­u­la­tions pre­vent fed­er­al agen­cies from pulling the prod­ucts from store shelves. So, for formalde­hyde, as in the case of the paint strip­pers con­tain­ing meth­yl­ene chlo­ride, expo­sures continue.

BPA rings alarm bells

The chem­i­cal cur­rent­ly at the cen­ter of the most heat­ed debates about con­sumer expo­sure is BPA. The build­ing block of poly­car­bon­ate plas­tics, BPA is used in count­less prod­ucts, includ­ing the resins that line food cans and coat the ther­mal receipt paper at cash reg­is­ters and ATMs. While sci­en­tif­ic evi­dence of adverse health effects from envi­ron­men­tal­ly typ­i­cal lev­els of BPA mounts, and many man­u­fac­tur­ers and retail­ers have respond­ed to pub­lic con­cern by chang­ing their prod­ucts, fed­er­al reg­u­la­to­ry author­i­ties still resist restrict­ing the chemical’s use.

BPA does not pro­duce imme­di­ate, acute effects, like those expe­ri­enced by salon work­ers exposed to formalde­hyde or machin­ists work­ing with meth­yl­ene chlo­ride. But in lab­o­ra­to­ry tests on ani­mals, BPA is a known endocrine dis­rup­tor. Struc­tural­ly sim­i­lar to nat­ur­al hor­mones, endocrine dis­rup­tors can inter­fere with nor­mal cel­lu­lar process­es and trig­ger abnor­mal bio­chem­i­cal respons­es. These can prompt numer­ous health prob­lems, includ­ing can­cer, infer­til­i­ty, and meta­bol­ic and neu­ro­log­i­cal dis­or­ders. BPA has also been linked to increased risk of car­dio­vas­cu­lar dis­ease, dia­betes and obesity.

To pro­mote the idea that BPA is safe, the chem­i­cal indus­try rou­tine­ly lob­bies pol­i­cy­mak­ers and ​“edu­cates” con­sumers. What has not been wide­ly dis­cussed, how­ev­er, is how indus­try has backed PBPK stud­ies that mar­gin­al­ized research show­ing risks from envi­ron­men­tal­ly typ­i­cal lev­els of BPA. Many of these doubt-induc­ing stud­ies have been con­duct­ed by researchers whose careers can be linked to the PBPK work done at Wright-Pat­ter­son. In pub­lished cri­tiques, health effects researchers — among them Gail Prins and Wade Welshons — have detailed the many ways in which these PBPK mod­els fail to accu­rate­ly reflect BPA exposure.

PBPK and endocrine disruption

Over the past sev­er­al decades, our evolv­ing under­stand­ing of our bod­ies’ respons­es to chem­i­cals has chal­lenged pre­vi­ous tox­i­co­log­i­cal assump­tions— includ­ing those that are fed into PBPK mod­els. This is par­tic­u­lar­ly true of endocrine disruptors.

Cause-and-effect rela­tion­ships between endocrine dis­rup­tors and health prob­lems can be hard to pin­point. We now know that ear­ly — even pre­na­tal— expo­sure to endocrine dis­rup­tors can set the stage for adult dis­ease. In addi­tion, a preg­nant woman’s expo­sures may affect not only her chil­dren but also her grand­chil­dren. These trans­gen­er­a­tional effects have been doc­u­ment­ed in ani­mal exper­i­ments. The clas­sic human evi­dence came from vic­tims of DES, a drug pre­scribed in the 1940s, 1950s and 1960s to pre­vent mis­car­riages. Daugh­ters of women who took the endocrine dis­rup­tor devel­oped repro­duc­tive can­cers, and pre­lim­i­nary research sug­gests their daugh­ters may be at greater risk for can­cer and oth­er repro­duc­tive problems.

“The trans­gen­er­a­tional work rais­es an incred­i­ble specter,” says Andrea Gore, who holds the Vacek Chair in Phar­ma­col­o­gy at the Uni­ver­si­ty of Texas at Austin and edits the influ­en­tial jour­nal Endocrinol­o­gy. ​“It’s not just what you’re exposed to now, it’s what your ances­tors were exposed to.”

Com­pli­cat­ing PBPK mod­el­ing fur­ther, hor­mone-mim­ic­k­ing chem­i­cals, just like hor­mones, can have bio­log­i­cal effects at con­cen­tra­tions as low as parts per tril­lion. In addi­tion, envi­ron­men­tal expo­sures most often occur as mix­tures, rather than in iso­la­tion. And each indi­vid­ual may respond differently.

“PBPK doesn’t come close” to cap­tur­ing the real­i­ty of endocrine dis­rup­tion, the late devel­op­men­tal biol­o­gist Louis Guil­lette told In These Times, in part because mod­el­ers are ​“still ask­ing ques­tions about one chem­i­cal expo­sure with one route of expo­sure.” Even for health effects researchers, under­stand­ing of mix­tures’ effects is in its infancy.

The debate over how endocrine dis­rup­tion can be rep­re­sent­ed in PBPK mod­els has inten­si­fied the unease between reg­u­la­to­ry tox­i­col­o­gists and health effects researchers. That ten­sion is par­tic­u­lar­ly well-illus­trat­ed by a recent series of events that also reveal how some jour­nal edi­tors priv­i­lege the industry’s point of view.

A life-and-death debate

In Feb­ru­ary 2012 the World Health Orga­ni­za­tion (WHO) and the U.N. Envi­ron­ment Pro­gramme (UNEP) pub­lished a report intend­ed to inform reg­u­la­tion world­wide. The authors were an inter­na­tion­al group of health effects researchers with long expe­ri­ence study­ing endocrine disruption.

“There is an increas­ing bur­den of dis­ease across the globe in which [endocrine dis­rup­tors] are like­ly play­ing an impor­tant role, and future gen­er­a­tions may also be affect­ed,” said the report. These dis­eases, it con­tin­ued, are being seen in humans and wildlife, and include male and female repro­duc­tive dis­or­ders, changes in the num­bers of male and female babies born, thy­roid and adren­al gland dis­or­ders, hor­mone-relat­ed can­cers and neu­rode­vel­op­men­tal diseases.

The back­lash from tox­i­col­o­gists was imme­di­ate. Over the next few months — as the EU pre­pared to begin its reg­u­la­to­ry deci­sion-mak­ing on endocrine dis­rup­tors — the edi­tors of 14 tox­i­col­o­gy jour­nals each pub­lished an iden­ti­cal com­men­tary harsh­ly crit­i­ciz­ing the WHO/UNEP conclusions.

The com­men­tary includ­ed a let­ter from more than 70 tox­i­col­o­gists urg­ing the EU not to adopt the endocrinedis­rup­tion frame­work. The let­ter said that the WHO/UNEP report could not be allowed to inform pol­i­cy because its sci­ence is ​“con­trary to all accu­mu­lat­ed phys­i­o­log­i­cal understanding.”

This com­men­tary was fol­lowed by fur­ther attacks. One cri­tique, pub­lished in the jour­nal Crit­i­cal Reviews in Tox­i­col­o­gy, was fund­ed and vet­ted by the ACC.

These com­men­taries infu­ri­at­ed health effects researchers. Twen­ty endocrine jour­nal edi­tors, 28 asso­ciate edi­tors and 56 oth­er sci­en­tists — includ­ing sev­er­al WHO/UNEP report authors — signed a state­ment in Endocrinol­o­gy, say­ing in part:

The dis­mis­sive approach to endocrine dis­rup­tion sci­ence put forth … is unfound­ed, as it is [not] based on the fun­da­men­tal prin­ci­ples of how the endocrine sys­tem works and how chem­i­cals can inter­fere with its nor­mal function.

Endocrinol­o­gy edi­tor Andrea Gore tells In These Times that she and oth­er health effects researchers don’t think the sci­en­tif­i­cal­ly demon­strat­ed dan­gers of endocrine dis­rup­tors are sub­ject to debate. ​“There are fun­da­men­tal dif­fer­ences between reg­u­la­to­ry tox­i­col­o­gists and what I refer to as ​‘peo­ple who under­stand the endocrine science.’ ”

The out­come of this debate and the struc­ture of future reg­u­la­to­ry tox­i­c­i­ty test­ing in the Unit­ed States and Europe is not yet clear. The EPA appears to be attempt­ing to incor­po­rate endocrine dis­rup­tion into PBPK mod­els, but many sci­en­tists are skep­ti­cal the process will pro­duce reli­able results, giv­en the mod­els’ lim­i­ta­tions and the com­plex­i­ty of endocrine effects.

From sci­ence to activism

Although couched in com­plex lan­guage, these argu­ments are not aca­d­e­m­ic, but have pro­found impli­ca­tions for pub­lic health. Dis­or­ders and dis­eases, increas­ing­ly linked to expo­sure to endocrine dis­rup­tors— includ­ing meta­bol­ic, repro­duc­tive, devel­op­men­tal and neu­ro­log­i­cal prob­lems — are wide­spread and increas­ing. About 20 per­cent of U.S. adults show at least three of the five indi­ca­tors of meta­bol­ic syn­drome: obe­si­ty, dia­betes, high blood pres­sure, high cho­les­terol and heart dis­ease. Neu­ro­log­i­cal prob­lems, includ­ing behav­ioral and learn­ing dis­abil­i­ties in chil­dren as well as Parkinson’s dis­ease, are increas­ing rapid­ly. Fer­til­i­ty rates in both men and women are declin­ing. Glob­al­ly, the aver­age sperm count has dropped 50 per­cent in the last 50 years.

Sci­en­tists typ­i­cal­ly shy away from activism, but many now believe it’s what’s need­ed to punch through the machi­na­tions and iner­tia regard­ing chem­i­cal reg­u­la­tion. Shan­na Swan, Mount Sinai pro­fes­sor of pre­ven­tive med­i­cine, obstet­rics, gyne­col­o­gy and repro­duc­tive med­i­cine, notes that some of the biggest reduc­tions in chem­i­cal expo­sures have hap­pened in response to con­sumer pres­sure on both indus­try and pol­i­cy­mak­ers. Or, as the Uni­ver­si­ty of California’s Bruce Blum­berg says, ​“I think we need to take the fight to the people.”

The Endocrine Soci­ety stressed the urgency of address­ing these pub­lic health impacts in a state­ment released Sep­tem­ber 28. Not sur­pris­ing­ly, indus­try dis­agreed, call­ing this sci­ence ​“unsup­port­ed” and ​“still-unproven.”

Mean­while, PBPK stud­ies con­tin­ue to suc­ceed in sow­ing doubt about adverse health effects of endocrine dis­or­ders. Their extreme­ly nar­row focus leads to nar­row con­clu­sions that often result in calls for more research before reg­u­la­tion. In reg­u­la­to­ry deci­sions, ​“the assump­tion is that if we don’t know some­thing, it won’t hurt us,” says Uni­ver­si­ty of Mass­a­chu­setts, Amherst pro­fes­sor of biol­o­gy R. Thomas Zoeller. In oth­er words, the bur­den of proof remains on health effects researchers to prove harm, not on indus­try to prove safe­ty — and prov­ing harm is dif­fi­cult, espe­cial­ly when oth­er sci­en­tists are seed­ing doubt.

But the clock is tick­ing. As Wash­ing­ton State Uni­ver­si­ty geneti­cist Pat Hunt told In These Times, ​“If we wait [to make reg­u­la­to­ry deci­sions] for ​‘proof’ in the form of com­pelling human data, it may be too late for us as a species.”

This inves­ti­ga­tion was sup­port­ed by the Leonard C. Good­man Insti­tute for Inves­tiga­tive Reporting.