American Chemistry Council Research Articles

Workshop Summary: Phosgene-Induced Pulmonary Toxicity Revisited: Appraisal of Early and Late Markers of Pulmonary Injury From Animal Models With Emphasis on Human Significance

A workshop was held February 14, 2007, in Arlington, VA, under the auspices of the Phosgene Panel of the American Chemistry Council. The objective of this workshop was to convene inhalation toxicologists and medical experts from academia, industry and regulatory authorities to critically discuss past and recent inhalation studies of phosgene in controlled animal models. This included presentations addressing the benefits and limitations of rodent (mice, rats) and nonrodent (dogs) species to study concentration × time (C × t) relationships of acute and chronic types of pulmonary changes. Toxicological endpoints focused on the primary pulmonary effects associated with the acute inhalation exposure to phosgene gas and responses secondary to injury. A consensus was reached that the phosgene-induced increased pulmonary extravasation of fluid and protein can suitably be probed by bronchoalveolar lavage (BAL) techniques. BAL fluid analyses rank among the most sensitive methods to detect phosgene-induced noncardiogenic, pulmonary high-permeability edema following acute inhalation exposure. Maximum protein concentrations in BAL fluid occurred within 1 day after exposure, typically followed by a latency period up to about 15 h, which is reciprocal to the C × t exposure relationship. The C × t relationship was constant over a wide range of concentrations and single exposure durations. Following intermittent, repeated exposures of fixed duration, increased tolerance to recurrent exposures occurred. For such exposure regimens, chronic effects appear to be clearly dependent on the concentration rather than the cumulative concentration × time relationship. The threshold C × t product based on an increased BAL fluid protein following single exposure was essentially identical to the respective C × t product following subchronic exposure of rats based on increased pulmonary collagen and influx of inflammatory cells. Thus, the chronic outcome appears to be contingent upon the acute pulmonary threshold dose. Exposure concentrations high enough to elicit an increased acute extravasation of plasma constituents into the alveolus may also be associated with surfactant dysfunction, intra-alveolar accumulation of fibrin and collagen, and increased recruitment and activation of inflammatory cells. Although the exact mechanisms of toxicity have not yet been completely elucidated, consensus was reached that the acute pulmonary toxicity of phosgene gas is consistent with a simple, irritant mode of action at the site of its initial deposition/retention. The acute concentration × time mortality relationship of phosgene gas in rats is extremely steep, which is typical for a local, directly acting pulmonary irritant gas. Due to the high lipophilicity of phosgene gas, it efficiently penetrates the lower respiratory tract. Indeed, more recent published evidence from animals or humans has not revealed appreciable irritant responses in central and upper airways, unless exposure was to almost lethal concentrations. The comparison of acute inhalation studies in rats and dogs with focus on changes in BAL fluid constituents demonstrates that dogs are approximately three to four times less susceptible to phosgene than rats under methodologically similar conditions. There are data to suggest that the dog may be useful particularly for the study of mechanisms associated with the acute extravasation of plasma constituents because of its size and general morphology and physiology of the lung as well as its oronasal breathing patterns. However, the study of the long-term sequelae of acute effects is experimentally markedly more demanding in dogs as compared to rats, precluding the dog model to be applied on a routine base. The striking similarity of threshold concentrations from single exposure (increased protein in BAL fluid) and repeated-exposure 3-mo inhalation studies (increased pulmonary collagen deposition) in rats supports the notion that chronic changes depend on acute threshold mechanisms.

American Chemistry Council v. Johnson : Community right to know, but about what? D.C. Circuit takes restrictive view of EPCRA

American Chemistry Council v. Johnson : Community right to know, but about what? D.C. Circuit takes restrictive view of EPCRA

Obstructing Authority: Does the EPA Have the Power to Ensure Commercial Chemicals Are Safe?

Before 1976, the U.S. government had virtually no records of what chemicals were imported, manufactured, used, or released into the environment and no way of regulating these chemicals before they appeared on the market. That changed when Congress passed the Toxic Substances Control Act (TSCA), which required that chemical companies inform the EPA of the chemicals they currently used in American products and that they submit approval requests for any new chemical entering manufacture. Thirty years later, however, observers are asking how well TSCA has lived up to its initial promise and what powers the EPA actually has—questions Congress asked the U.S. Government Accountability Office (GAO) to investigate. A report released in June 2005 by the GAO titled Chemical Regulation: Options Exist to Improve EPA’s Ability to Assess Health Risks and Manage Its Chemical Review Program claims that the TSCA legislation failed to empower the EPA to ensure the safety of chemicals used in the United States. On 2 August 2006, John B. Stephenson, director of natural resources and environment at the GAO, testified on the report’s findings before the Senate Committee on Environment and Public Works. Several other environmental scientists also testified in support of the GAO’s position that TSCA is in need of a major reworking if it is to adequately protect the health of U.S. citizens and the environment. “Overhaul of TSCA is long overdue,” testified Lynn Goldman, former EPA assistant administrator for Prevention, Pesticides and Toxic Substances and now a professor of environmental health at the Johns Hopkins Bloomberg School of Public Health. “Minus congressional action on TSCA, we will continue to see the erosion of federal management of chemicals on many levels.” Several other experts, however, testified that TSCA has mostly accomplished what it was designed to do. James B. Gulliford, the current EPA assistant administrator for Prevention, Pesticides and Toxic Substances, stated, “TSCA provides the agency with the necessary authority to ensure that new chemicals are adequately reviewed, that EPA can require reporting or development of information needed to assess existing chemicals, and that those chemicals that pose an unreasonable risk can be effectively controlled.”

TAX BREAK Chemical makers call on Congress to restore federal R&D tax credit

Chemical manufacturers and other U.S. businesses are urging Congress to pass legislation before the end of the year to restore and expand the federal research and development tax which expired at the end of 2005. ACC strongly supports bipartisan efforts in Congress to extend and strengthen the R&D tax credit, says American Chemistry Council President Jack N. Gerard. An expired [credit] will impose financial consequences for American chemistry and may jeopardize research projects that are essential to the American economy. The 20% credit would again be available for certain R&D expenditures made only in the U.S., primarily spending on employees who perform qualified research activities. Originally enacted in 1981, the R&D tax credit has been extended 11 times by Congress. Nearly 16,000 companies have used the credit. The provision has wide support in Congress. But the tax break failed to advance before the elections when it was included in a controversial measure to ...

Setting a Baseline for Biomonitoring

Biomonitoring of tissues such as blood, urine, and breast milk is an extremely valuable tool for identifying population exposure to harmful chemicals. The data gathered through biomonitoring can provide guidance on how to prioritize toxicological research, and can result in measures to control and prevent exposure. Despite these benefits, however, “tremendous challenges” still surround the use of this technology, according to Human Biomonitoring for Environmental Chemicals, a report released 24 July 2006 by a committee of the National Research Council (NRC). The report noted, for instance, that there should be much more emphasis on communicating the results of studies in the design of the research. It also called for a “consistent rationale for selecting chemicals to be studied based on exposure and public health concerns.”

A New Model to Assess Incidental Ingestion Exposures to Residential Countertop Cleaning Products

MAB2-PD-04 Introduction: The Antimicrobials Division of the U.S. Environmental Protection Agency's Office of Pesticide Programs proposed a model to assess potential incidental ingestion exposures resulting from antimicrobial pesticide products used on residential countertops. The components of the Environmental Agency (EPA) model (which was modified from an FDA model to estimate dietary intake from sanitizing rinses regulated as indirect food additives) are an assumed product residue on countertops (1 mg/cm2), food contacting a countertop area (2000 cm2/day per person), and complete transfer of residues to food. Because the EPA model lacks a rigorous basis, the American Chemistry Council Biocides Panel initiated a program to develop an appropriate screening-level exposure model. Methods: A Generic Food Consumption Model has been developed in which foods were categorized based on physical form and likelihood of residential countertop contact (eg, liquid, solid, purees, pieces, and powders). Assumed residues on countertops (mg/cm2) are converted to estimated residues in food (mg/kg) with a “translation factor” for each food category derived from the contact area, weight of a single piece/serving and default residue transfer efficiency for a representative food. Incidental ingestion exposure is calculated as the product of the estimated residue and the quantity consumed of each food category. Initially, countertop residues are not reduced for potable water rinses even though such rinses are required for food contact surface uses, which increases the conservatism of the model. Results: The Generic Food Consumption Model relies on concepts of food consumption and preparation patterns, which represents a true paradigm shift from the EPA approach. The model takes advantage of data and assumptions that are not chemical-specific and that are therefore applicable to a broad range of situations. The model estimates an incidental ingestion exposure for the general population that is reduced more than 90% compared with the very conservative EPA model. Conclusions: The Generic Food Consumption Model results in a refined, yet still conservative, estimate of incidental ingestion exposure that may result when food contacts antimicrobial product residues on countertops. In the future, development of chemical-specific data for antimicrobial chemicals/families would allow further refinement of incidental ingestion exposure estimates. Additional research could improve characterization of residues on countertops and consumer behavior regarding food preparation practices.

NTP Draft Brief on DEHP

Questions about the safety of the plasticizer di(2-ethylhexyl) phthalate (DEHP), particularly in regards to exposure during medical procedures such as transfusions, have swirled for decades, but especially in the last several years, given growing concerns about endocrine disruption. In October 2005, an independent panel of experts convened by the National Toxicology Program Center for the Evaluation of Risks to Human Reproduction (NTP-CERHR) sought to take stock of what is known and identify critical research needs regarding human exposure to DEHP, in particular its potential reproductive and developmental toxicity. Now that the independent experts have had their say, the NTP is weighing in with its interpretation. Based on the expert panel’s report, comments from stakeholders and peer reviewers, and new information published since the experts’ meeting, the NTP released a draft brief in May 2006 about DEHP exposure and toxicity. With peer review completed in late August, the brief is now being finalized and will be added to the forthcoming NTP-CERHR monograph The Potential Human Reproductive and Developmental Effects of DEHP. This monograph will comprise the CERHR expert panel report, a list of the panel experts, all public comments made about the report, and the NTP brief on DEHP. Although the brief summarizes what the expert report says, it is more than just an executive summary—it represents the NTP’s view of the various public and peer-review comments and additional research studies received since the report was prepared. The 2005 expert panel meeting marks the first time the CERHR has had a compound re-evaluated; a previous evaluation was published in 2000. The need for another just five years later underscores the intensity with which DEHP is being investigated. “[Assessing] DEHP again shows that the CERHR process is evergreen,” says Paul Foster, deputy director of the NTP-CERHR. “This is the first time that CERHR has gone back and said there’s now been a significant amount of water that’s gone under the bridge, and we should go back and re-evaluate to see whether or not any of our original conclusions have changed.” According to Foster, the brief distills the intricate and detailed scientific knowledge of the monograph into information that educated laypeople can use to put concerns about the potential for DEHP toxicity into perspective.

JACK GERARD SHAKES UP ACC

WHEN JACK N. GERARD took the reins as president and chief executive officer of the American Chemistry Council (ACC) in July 2005, he found that the chemical industry's largest trade association was having a difficult time advancing its agenda on Capitol Hill. A little over a year later, Gerard is being praised by industry leaders and outside observers alike for moving swiftly to coordinate the group's message on natural gas and security issues and for strengthening the organization's role in advocating public policy. He has pledged to make ACC the gold standard of trade associations. For an organization representing a $550 billion industry, we were punching below our weight, says Gerard, who was hired away from the National Mining Association (NMA) to reinvigorate ACC, which had been struggling from internal disputes following the absorption of the American Plastics Council (APC) in 2002. Gerard replaced Thomas E. Reilly Jr., the former chairman of Reilly Industries, who ...

HOUSE PASSES BILL TO END DRILLING BAN

CHEMICAL INDUSTRY OFFICIALS are hailing House passage of legislation that would lift a quarter-century federal ban on most offshore drilling for oil and natural gas. The bill (H.R. 4761), which passed on a vote of 232 to 187 on June 29, would open waters off the East and West Coasts and in the eastern Gulf of Mexico, where trillions of cubic feet of natural gas and billions of barrels of oil have been off-limits since 1981. Jack N. Gerard, president of the American Chemistry Council, described the vote as one of the most important of the past two decades. Affordable energy is inextricably linked to America's economy, jobs, competitiveness, and security, he remarks. Now it's up to the Senate to act to put America on a path toward a stronger, more secure future. Robert Slaughter, president of the National Petrochemical & Refiners Association, notes that the chemical industry has been particularly hard-hit as plants and ...

CHEMICAL SHIPPERS DECRY RAIL MONOPOLIES

UNRELIABLE SERVICE AND HIGH shipping rates charged by the nation's dwindling number of freight railroads are contributing to the increasing cost of chemicals, electricity, and agricultural commodities, critics told a Senate panel last month. The system is broken, and Congress needs to fix it, said J o hn L. Mcintosh, president of chlor-alkali products for Olin Corp. Railroad monopolies are driving a golden spike through the heart of American competitiveness. Testifying before the Surface Transportation & Merchant Marine Subcommittee of the Senate Commerce, Science & Transportation Committee on June 21, Mcintosh said captive shippers—those served by only one railroad—are completely at the mercy of the carrier, and free and fair market forces no longer ride American rails. Without competition, rail carriers have no incentive to deliver efficient, predictable service, said Mcintosh, who testified on behalf of the American Chemistry Council. For a captive shipper, regardless of its size or location, ...

INDUSTRY CALLS FOR ACTION ON ENERGY

ABROAD COALITION OF INdustrial consumers of natural gas launched a campaign last week to win congressional approval of legislation that would open new areas of offshore waters to energy exploration and development. At a Washington, D.C., news conference, representatives of the recently formed Consumer Alliance for Energy Security said rapidly rising domestic gas prices are damaging the U.S. industrial base, citing a loss of more than 3.1 million manufacturing jobs since the price surge began in 2000. America is suffering an energy crisis, which is hurting our economy and threatening our jobs, said John M. Engler, president of the National Association of Manufacturers. With our manufacturing base and our communities at risk, it's time to reduce costs and expand supplies. Every single American is feeling the pain of high energy prices, added American Chemistry Council President and CEO Jack N. Gerard. After the warmest winter on record, he said, consumers' heating bills are ...

CHERTOFF CALLS FOR LEGISLATION

AFTER HINTING NEARLY A ago that the Bush Administration might heed the call of security experts and support chemical plant security legislation, Department of Homeland Security Secretary Michael Chertoff now says the time is ripe for give his department the authority to create a sensible regulatory structure for the nation's chemical infrastructure. Chertoff defines a sensible scheme as one that manages the most significant risks, doesn't micromanage the chemical industry, and rewards those companies that voluntarily have taken steps secure their facilities against terrorist attacks. Speaking at a March 21 forum sponsored by George Washington University and the American Chemistry Council, Chertoff said he thinks Congress can pass a balanced, risk-based security measure for the chemical industry this year that relies ultimately on the expertise and knowledge of the chemical sector itself. Chertoff proposed that chemical plants be ranked or tiered into four groups, with the ...

The Hidden Cost Of Coal

WHEN I OPENED OUR HOME HEATING bill last week, it was a shock to find that Washington Gas had doubled the amount it expects us to pay each month on its budget plan. The company blamed the increase on soaring natural gas costs. If we don't increase your monthly payment it explained, you'll owe a huge amount at the end of the winter. Our monster heating bill should not have been a surprise. For some time now, C&EN has been reporting on the effects of escalating energy costs on the chemical enterprise. The chemical industry is the biggest consumer of energy among U.S. manufacturing sectors, and in the past months, the pain of high prices and concern about shortages of natural gas—used by the chemical industry both for power and as a raw material—have reached panic levels. The American Chemistry Council has been pushing vigorously for Congress to open ...

In Katrina’s Wake

Hurricane Katrina has been called the most devastating natural environmental calamity in U.S. history. Visitors to the scene say the destruction is worse than anyone can imagine. Scientists also say that some perceived health threats have been overblown and others understated. Months after Katrina roared into the Gulf Coast, the environmental health implications of the storm are still being assessed. Katrina presented residents of the Gulf Coast with a bewildering array of environmental health hazards. Aside from standing floodwater, hazards included a lack of potable water, sewage treatment, and electricity; chemical spills; swarms of insects (with anecodotal accounts of vermin and hungry domestic dogs); food contamination; disrupted transportation; mountains of debris; buildings damaged and destroyed; rampant mold growth; tainted fish and shellfish populations; and many potential sources of hazardous waste. Some impacts, such as deaths from drowning and injuries from cleaning up debris, have been relatively easy to determine. Others, such as post-traumatic stress disorder from the loss of homes and loved ones, may never be fully quantified. In the weeks following the storm, federal agencies such as the NIEHS, the Centers for Disease Control and Prevention (CDC), and the Environmental Protection Agency (EPA), as well as state environmental and public health agencies, sent scientists to the region to begin assessing the environmental and human health impact of the disaster. Much of what they found was presented on October 20 at a meeting of the National Academies Institute of Medicine’s Roundtable on Environmental Health Sciences, Research, and Medicine (commonly known as the EHSRT), supported by the NIEHS, the CDC, the EPA, Exxon-Mobile Corporation, the American Chemistry Council, and the Brita Water Research Institute. Still more information continues to emerge today. And much simply remains to be seen.

New Jersey Mandates Chemical Plant Security

On Nov. 29, Acting Gov. Richard J. Codey announced an order making New Jersey the first state in the nation to have mandatory standards for chemical plant security. There are no equivalent national standards. The state's 140 chemical facilities now are explicitly required to implement existing best security practices guidelines. These were largely crafted by the chemical industry and roughly based on the American Chemistry Council's Responsible Care security code. They were approved in 2003 by New Jersey's Domestic Security Preparedness Task Force to protect communities against catastrophic chemical releases caused by terrorist attacks. The standards continue the site-specific security assessments of the best practices. Although the 72 member companies of the Chemistry Council of New Jersey (CCNJ) have implemented this requirement, all 140 chemical facilities now must evaluate potential vulnerabilities and likely consequences of a chemical release. All 140 facilities also must prepare an incident preventi...

GAO Sounds Off on Chemical Regulation

Since 1976 the Toxic Substances Control Act (TSCA) has given the federal government the power to require that chemicals are properly tested and regulated before they reach the market, and that they don’t pose unreasonable risks to human and environmental health. TSCA is the key piece of legislation governing the way the U.S. Environmental Protection Agency (EPA) reviews and regulates chemicals including solvents and constituents of paints, fuels, and plastics. Yet, concerns persist about chemical safety and the adequacy of regulation. Now, in a June 2005 report titled Chemical Regulation: Options Exist to Improve EPA’s Ability to Assess Health Risks and Manage Its Chemical Review Program, the Government Accountability Office (GAO) has reviewed the EPA’s efforts to control the risks of new chemicals not yet in commerce, to assess the risks of existing chemicals used in commerce, and to publicly disclose information provided by chemical companies under TSCA. The report points out shortcomings in TSCA and its implementation, and suggests ways to strengthen the law.

Autoimmune Disease: Phthalate Linked to Lupus in Mice

No one knows to what degree genetics or environmental agents cause lupus, an autoimmune disorder that affects the skin, joints, and internal organs including the kidneys. However, researchers at Indiana State University may have strengthened the environmental evidence by discovering that phthalates trigger lupus antibodies in a mouse model. Phthalates are found in adhesives, cosmetics, fragrances, vinyl flooring, polyvinyl chloride pipe, and certain toys and medical supplies. According to a report out of the Centers for Disease Control and Prevention and the National Toxicology Program, published in the October 2000 issue of EHP, phthalate exposure is more extensive than previously suspected, especially in women aged 20–40 years. Other studies have pointed to possible links with asthma, rhinitis, and eczema in children as well as altered genital development in male infants. The new lupus findings add to a growing list of potential health effects caused by these chemicals. In lupus, the immune system loses its ability to tell the difference between foreign substances (antigens) and the body’s own cells and tissues. The immune system makes antibodies against the body itself, causing inflammation, tissue injury, and pain. Up to 1.5 million Americans have been diagnosed with lupus, and another 16,000 develop the disease each year, according to the Lupus Foundation of America. While investigating the gene sequence of a monoclonal antibody used as a marker for tumor growth, biochemist Swapan Ghosh, interim chair of the Life Sciences Department at Indiana State University, noticed that it shared 98% similarity with an antibody protein component (light chain) made by NZB mice, a popular model for autoimmune diseases. In lupus, such antibodies attack DNA in the kidneys, heart, and lungs. The finding, published in the December 2003 issue of Immunology, was a surprise: “I was not studying lupus or autoimmune diseases at all,” says Ghosh. But he took advantage of the unexpected turn and has launched a series of experiments to further explore the phthalate–lupus connection. In the latest study, Ghosh and graduate student So-Yon Lim injected four types of mice, including NZB mice, with di-(2-ethylhexyl) phthalate, or DEHP. Initially, all the mice generated antiphthalate antibodies, but only the lupus-prone NZB mice developed nephritis, which led to kidney failure and early death. The other mice initially produced antiphthalate antibodies, but the antibodies were counteracted by CD8+ suppressor T cells, which prevented kidney damage. “There’s something different about the immune systems of NZB mice [that makes them more susceptible to phthalates],” says Ghosh. The details of the investigation are reported in the August 2005 issue of the Journal of Autoimmunity. Although the phthalate–lupus connection has been observed only in mice, “many things found in the mouse immune system have proven to be true in humans,” says Ghosh. On the other hand, “not everything seen in a mouse model reflects what happens in humans,” cautions Betty Diamond, chief of rheumatology at Columbia University. Although Ghosh’s results are far from applicable to humans, they do raise several questions for future studies on the potential phthalate–lupus link in people. Do lupus patients have high levels of antiphthalate antibodies? Ghosh plans to screen lupus patients and healthy people in the future to find out. Does exposure to phthalates increase the risk for lupus? He plans to explore this, too, by measuring blood levels in workers exposed to phthalates in the plastics manufacturing industry. Lupus is five times more common in women than men. Might this be because women use more phthalate-containing cosmetics and perfumes than men do? The American Chemistry Council (ACC), an industry trade group, has criticized Ghosh’s study because he combined DEHP to proteins like bovine serum albumin. “The attached proteins may cause autoimmune and allergic responses,” says Marian Stanley, director of the ACC’s Phthalate Esters Panel. Ghosh counters, “We also studied DEHP not complexed to a protein, and it evoked an anti-DNA response.” He explains that he attached a main metabolite of DEHP to proteins because some studies have suggested that phthalate metabolites show an affinity for albumin in the body. So far, exposure to ultraviolet light is the only environmental factor that has been clearly linked to lupus in genetically susceptible patients. As lupus researchers continue to investigate other environmental causes, “we need to be open-minded, but not jump to conclusions,” Diamond says.

CHEMICAL MAKERS SEEK RELIEF

A TOP CHEMICAL INDUSTRY official urged Congress on Nov. 17 to lift the generation-old moratorium on natural gas production along the U.S.'s outer continental shelf, warning that the consequences of insufficient supplies will soon become painfully clear to all U.S. consumers. If U.S. natural gas prices do not return to their historically affordable levels, American Chemistry Council President Jack I Gerard told a panel of the House Resources Committee, the nation's key manufacturing industries will accelerate the transfer of operations and jobs overseas, where the cost of energy is much cheaper. Paying the highest natural gas prices in the world puts Americabased manufacturing at a severe competitive disadvantage, and this is a largely self-inflicted wound, Gerard testified. What I can't predict is how Congress will respond to this crisis. There has never been a better or more critical time to pass natural gas supply legislation. The committee is considering ...

HURRICANES REVIVE FIGHT OVER DRILLING

WITH HURRICANE-RElated shortages pushing energy prices to record highs, Congress appears to be headed toward a showdown over politically charged proposals to expand offshore drilling for natural gas and oil and to open an Alaskan wildlife refuge to development. Chemical industry officials are pushing for quick action on a bill crafted by House Resources Committee Chairman Richard W. Pombo (R-Calif.) that would maintain a quarter-century-old moratorium on new oil and natural gas leasing on the outer continental shelf (OCS) but allow individual states to petition the federal government to lift the ban off their coasts. We are calling on Congress to immediately approve legislation by Congressman Pombo to increase the nation's gas supply, says Owen A. Kean, senior policy adviser at the American Chemistry Council (ACC). This would send a strong signal to the futures market that a correction to our long-standing supply/demand imbalance is in sight, and help bring prices down. Kean says the ...

Vinyl Chloride: Sass et al. Respond

Vinyl Chloride: Sass et al. Respond