Pregnancy Loss and Maternal Methemoglobin Levels: An Indirect Explanation of the Association of Environmental Toxics and Their Adverse Effects on the Mother and the Fetus

The aim of this epidemiologic study was to point out a relationship between the exposure to products of coal combustion, and complications in pregnancy where one third of causes of stillbirth are still unknown. In the town of Labin (Croatia) a coal-powered thermoelectric power plant is the single major air polluter. We compared the records of miscarriages, premature births and stillbirths in two periods: the control and the exposure period. Data on reproductive loss was based on the records of pregnant women visiting for regular monthly pregnancy checkups. At the time of the epidemiological prospective study, 260 women (n = 138 in the clean period and n = 122 in the dirty period) were considered representative. The data were processed using Chi square and correlation tests. The frequencies of miscarriages and stillbirths were significantly lower in the control than in the exposure period (p < 0.05). Methemoglobinemia and stillbirths recorded over the “exposure” period are significantly higher than in the “control” period (p = 0.0205). The level of methemoglobin in the bloodstream is an worthy biomarker, predictor and precursor of environmental toxics’ adverse effects on the mother and fetus, and can indirectly explain the unrecognized level of fetal methemoglobin. Methemoglobin and heme, having prooxidant properties, also cause the early and late endothelial dysfunction of vital organs. Despite our retrospective epidemiological study findings, we emphasize that the rate of reproductive loss represents a hypothetical risk, which needs to be confirmed with further fetal clinical and anatomopatholgical researches about the effects of methemoglobin catabolism products on the fetal CNS

Brain iron accumulation in unexplained fetal and infant death victims with smoker mothers-The possible involvement of maternal methemoglobinemia

<p>Abstract</p> <p>Background</p> <p>Iron is involved in important vital functions as an essential component of the oxygen-transporting heme mechanism. In this study we aimed to evaluate whether oxidative metabolites from maternal cigarette smoke could affect iron homeostasis in the brain of victims of sudden unexplained fetal and infant death, maybe through the induction of maternal hemoglobin damage, such as in case of methemoglobinemia.</p> <p>Methods</p> <p>Histochemical investigations by Prussian blue reaction were made on brain nonheme ferric iron deposits, gaining detailed data on their localization in the brainstem and cerebellum of victims of sudden death and controls. The Gless and Marsland's modification of Bielschowsky's was used to identify neuronal cell bodies and neurofilaments.</p> <p>Results</p> <p>Our approach highlighted accumulations of blue granulations, indicative of iron positive reactions, in the brainstem and cerebellum of 33% of victims of sudden death and in none of the control group. The modified Bielschowsky's method confirmed that the cells with iron accumulations were neuronal cells.</p> <p>Conclusions</p> <p>We propose that the free iron deposition in the brain of sudden fetal and infant death victims could be a catabolic product of maternal methemoglobinemia, a biomarker of oxidative stress likely due to nicotine absorption.</p

The association between low level exposures to ambient air pollution and term low birth weight: a retrospective cohort study

BACKGROUND: Studies in areas with relatively high levels of air pollution have found some positive associations between exposures to ambient levels of air pollution and several birth outcomes including low birth weight (LBW). The purpose of this study was to examine the association between LBW among term infants and ambient air pollution, by trimester of exposure, in a region of lower level exposures. METHODS: The relationship between LBW and ambient levels of particulate matter up to 10 um in diameter (PM(10)), sulfur dioxide (SO(2)) and ground-level ozone (O(3)) was evaluated using the Nova Scotia Atlee Perinatal Database and ambient air monitoring data from the Environment Canada National Air Pollution Surveillance Network and the Nova Scotia Department of Environment. The cohort consisted of live singleton births (≥37 weeks of gestation) between January1,1988 and December31,2000. Maternal exposures to air pollution were assigned to women living within 25 km of a monitoring station at the time of birth. Air pollution was evaluated as a continuous and categorical variable (using quartile exposures) for each trimester and relative risks were estimated from logistic regression, adjusted for confounding variables. RESULTS: There were 74,284 women with a term, singleton birth during the study period and with exposure data. In the analyses unadjusted for year of birth, first trimester exposures in the highest quartile for SO(2 )and PM(10)suggested an increased risk of delivering a LBW infant (relative risk = 1.36, 95% confidence interval = 1.04 to 1.78 for SO(2 )exposure and relative risk = 1.33, 95% confidence interval = 1.02 to 1.74 for PM(10)). After adjustment for birth year, the relative risks were attenuated somewhat and not statistically significant. A dose-response relationship for SO(2 )was noted with increasing levels of exposure. No statistically significant effects were noted for ozone. CONCLUSION: Our results suggest that exposure during the first trimester to relatively low levels of some air pollutants may be associated with a reduction in birth weight in term-born infants. These findings have implications for the development of effective risk management strategies to minimize the public health impacts for pregnant women

Pregnancy Loss and Maternal Methemoglobin Levels: An Indirect Explanation of the Association of Environmental Toxics and Their Adverse Effects on the Mother and the Fetus

The aim of this epidemiologic study was to point out a relationship between the exposure to products of coal combustion, and complications in pregnancy where one third of causes of stillbirth are still unknown. In the town of Labin (Croatia) a coal-powered thermoelectric power plant is the single major air polluter. We compared the records of miscarriages, premature births and stillbirths in two periods: the control and the exposure period. Data on reproductive loss was based on the records of pregnant women visiting for regular monthly pregnancy checkups. At the time of the epidemiological prospective study, 260 women (n = 138 in the clean period and n = 122 in the dirty period) were considered representative. The data were processed using Chi square and correlation tests. The frequencies of miscarriages and stillbirths were significantly lower in the control than in the exposure period (p < 0.05). Methemoglobinemia and stillbirths recorded over the “exposure” period are significantly higher than in the “control” period (p = 0.0205). The level of methemoglobin in the bloodstream is an worthy biomarker, predictor and precursor of environmental toxics’ adverse effects on the mother and fetus, and can indirectly explain the unrecognized level of fetal methemoglobin. Methemoglobin and heme, having prooxidant properties, also cause the early and late endothelial dysfunction of vital organs. Despite our retrospective epidemiological study findings, we emphasize that the rate of reproductive loss represents a hypothetical risk, which needs to be confirmed with further fetal clinical and anatomopatholgical researches about the effects of methemoglobin catabolism products on the fetal CNS

Improving the Process of Making Rules at Independent Agencies

As a Commissioner of the U.S. Consumer Product Safety Commission (CPSC), I have found that we could greatly improve the Agency’s functioning by adopting several rulemaking procedures. Some of these procedures, like the publication of a regulatory agenda, are time-honored principles espoused by a long line of executive orders, while others, such as pay-go requirements that force agencies to consider the collective economic costs of their rules, are emerging practices used in other countries. Four key procedural steps could greatly improve rulemaking at CPSC and other independent agencies. First, independent agencies like CPSC should be expected to improve the accuracy and timeliness of their regulatory agendas. The regulatory agenda concept began with Executive Order 12,044, issued by President Jimmy Carter in 1978. Its plainly stated purpose was “to give the public adequate notice” of how agencies would be spending their time in the near term, which would allow for and encourage meaningful public participation in the regulatory process. The Regulatory Flexibility Act (RFA) extended the regulatory agenda requirement to all agencies, including independent agencies. President Ronald Reagan’s Executive Order 12,291 retained the agenda requirement and broadened it from significant rules to all rules. President Bill Clinton’s Executive Order 12,866 added a requirement for the issuance of a regulatory plan, which would highlight “the most important significant regulatory actions that the agency reasonably expects to issue in proposed or final form in that fiscal year.” Most recently, President Barack Obama’s Executive Order 13,563 expressly reaffirmed the principles and requirements of Executive Order 12866. Despite a 40-year history of presidents and Congress uniformly endorsing the principle behind regulatory agendas so interested parties can plan their participation in the regulatory process, CPSC appears not to have endorsed that principle. CPSC’s regulatory agenda contains regulatory projects that have been entirely stagnant for years—some that have been around for decades. It also includes proposals that have been described as not being among the Agency’s priorities, yet our attempts to align the agenda with the Agency’s actual work have too often been summarily rebuffed. As a result, stakeholders must piece together disparate, and sometimes conflicting, statements from a variety of sources, rather than simply relying on the Agency’s regulatory agenda to identify the Agency’s priorities. The Agency’s outdated agendas run the risk of not only under-informing the public, but also actively misleading them as to what projects the Agency will spend its time on in the coming year. Second, in addition to issuing more accurate regulatory agendas, independent agencies’ proposed rules should be subjected to external review. Executive orders have established that the White House Office of Information and Regulatory Affairs (OIRA) must review all of executive branch agencies’ significant regulatory proposals—which are generally those that have an annual economic impact of $100 million or more. This external review requirement currently does not extend to independent agencies. However, some legislative proposals would provide for independent agencies to submit some or all of their proposed rules to OIRA for review. Such legislation is needed because the principles that support external review of executive agencies’ proposed rules also apply to independent agencies. For example, CPSC’s proposed revisions to its Certificates of Compliance rule have been the target of substantial criticism in part because of assumptions surrounding the rule’s regulatory burden. If OIRA or another external reviewer had vetted the proposal, that reviewer might have identified problems with those assumptions and allowed us to present a sounder proposal. This is not to suggest that CPSC or any other agency is sloppy in its work. To the contrary, talented, dedicated public servants draft CPSC’s rules that staff believe are in citizens’ best interests. However, even experts with the best intentions can make mistakes. CPSC does not have a monopoly on good ideas, and we should seek wisdom wherever we can find it. Moreover, on occasion I have seen staff’s analysis function less as the objective opinion of experts and more as a post hoc justification of a decision that had already been made based on political considerations. Independent review will help ensure that CPSC’s decisions are based on career technical staff’s expertise, not on politics. Review by an outside entity can also provide a more holistic view of the regulatory landscape by incorporating views of other parts of government. As former OIRA Administrator Cass Sunstein has written, OIRA serves as “an information aggregator.” Particularly in an area like product importation—where CPSC shares the regulatory space with dozens of partner agencies that are led by U.S. Customs and Border Protection—OIRA’s administrative omniscience can ensure we neither duplicate nor contradict the messages stakeholders receive from other agencies. Third, CPSC and other independent agencies should do a better job implementing best practices for public participation in the rulemaking process. Too often, CPSC has failed to go beyond the minimum requirement for public participation established under the notice-and-comment structure in the Administrative Procedure Act (APA). As a result, CPSC has forsaken opportunities to obtain critical public input that could have greatly enhanced regulatory decision-making. For example, the advisory panel report underlying CPSC’s proposed rule on phthalates in some children’s products only underwent a closed, invitation-only peer review, rather than public peer review of the kind that for some instances is expressly recommended in the Office of Management and Budget’s (OMB) Final Information Quality Bulletin for Peer Review. OMB’s recommendations, of course, do not apply to independent agencies like CPSC, but their lack of legal or administrative force does not diminish their wisdom. In the phthalates rulemaking, the result was that the advisory panel’s failure to consider vital data was repeated in the Agency’s notice of proposed rulemaking, forcing the Chairman to direct staff to fill in that data gap and re-open the comment period. Thanks to the Chairman’s intervention, we were able to develop the record with public comment on all the data. However, earlier public participation—such as the kind of public peer review recommended by OMB—could have spared the Agency embarrassment and improved the quality of our work. Finally, in addition to deploying best practices for regulatory agendas, external review, and public participation, both executive and independent agencies should consider the use of an emerging regulatory practice known as “pay as you go.” Colloquially shortened to “pay-go,” this requirement would force agencies to view regulation-imposed economic costs as a finite resource and thoughtfully consider how they use that resource. A pay-go requirement would demand that agencies remove commensurate cost burdens from their books for each additional cost burden they create through a new rule. A related concept of a “regulatory budget” would set a maximum amount of economic costs that could be imposed through regulation. Pay-go and regulatory budgets could be applied either at an agency or government-wide level. For example, in an agency-level pay-go model, before promulgating a new rule, CPSC would have to repeal a current rule or rules that impose a comparable economic burden. A government-wide model would allow the repeal of a rule promulgated by another agency to offset the costs of a new CPSC mandate. Under either model, agencies—either individually or collectively—would have to prioritize their activities and decide where they want to allocate their finite burden resources. The pay-go model has been resoundingly successful in the United Kingdom. What began as a “One-in, One-out” program evolved to “One-in, Two-out,” which “meant that for every pound of cost that new domestic regulation imposed on business, two pounds of cost had to be removed through deregulation.” As a result of this program, “the Government has reduced the annual cost to business of domestic regulation by almost £2.2 billion.” Moreover, the reforms have improved not just the economic climate but the economic mood as well, as the percentage of businesses that find government regulation “fair and proportionate” has risen from under 40 to over 60 percent over the course of seven years. In fact, this program has been so successful, that the UK has now moved to “One-in, Three-out.” It remains to be seen whether the precise structure of “One-in, Two-out”—or any pay-go model—is appropriate for the American regulatory state. However, the United Kingdom’s experience demonstrates that when agencies face the same kinds of constraints their constituents face, they will do what their constituents must do: adapt and survive. Codifying the four reforms proposed here would go a long way toward improving the rulemaking process at independent agencies and helping ensure that the public can be better protected and the economy less burdened. However, as CPSC’s failure to use its Regulatory Agenda for its intended purpose underscores, the codification of new procedures will not be enough. The RFA already imposes a statutory obligation for CPSC to issue regulatory agendas, but this has not been enough to compel CPSC’s full obedience with the spirit of that requirement. Even if every reform I have described in this essay is enacted, they will remain paper reforms unless supported by the continued attention of a watchful Congress

Improving Regulatory Analysis at Independent Agencies

When conducting the analysis needed to inform sound regulatory decision-making, independent agencies could benefit from following key analytical standards that over the years have been imposed on executive branch agencies by executive orders. As a Commissioner of the U.S. Consumer Product Safety Commission (CPSC), too often I have seen my Agency depart from these analytical best practices, which then can lead to misinformed and even unnecessary regulations. Regulatory decision-making at independent agencies like CPSC would benefit from adherence to four main analytic requirements contained in executive orders. First, independent agencies should be required to identify a market failure before promulgating a new regulation. Currently, Executive Order 12,866, which applies to executive but not independent agencies, provides that regulation can be justified on the basis of “material failures of private markets to protect or improve the health and safety of the public.” CPSC’s authorizing legislation does state that the Agency can only issue mandatory product safety standards if either no voluntary standard addresses a detected risk or if industry fails to comply with an existing standard. However, this legislation does not expressly limit the Agency to stepping in only where private markets have failed. Too often, CPSC focuses on regulation in the absence of a demonstrated market failure. For example, many have called on CPSC to address the significant number of hand and finger injuries among users of table saws. Those advocates want us to mandate the use of Active Injury Mitigation (AIM) technology to prevent many of these serious injuries. This technology, they argue, is already on the market, with versions from two different manufacturers, so compliance with a future mandate would be feasible. However, the fact that two companies already make AIM-equipped saws actually suggests that we do not need a rule: The market has not failed. Consumers are well aware of the risk that a spinning blade poses, and they can already choose an AIM-equipped saw to mitigate that risk. If they do not choose such a saw—whether because they do not like the technology or because they do not believe that the benefits justify the added cost—their informed choice is part of a functioning market, not a failed one. If CPSC were to require AIM technology on all saws, we would not be repairing the market but rather impairing it. We would be favoring two firms over their competitors, imposing a cost that informed consumers can presently choose to avoid. If the “market failure” language of Executive Order 12,866 applied to CPSC by statute, we would have to demonstrate that the consumers were being harmed because they lacked the information to make a choice, not just that consumers are making choices we do not like. Second, the kind of cost-benefit analysis required of executive branch agencies would lead to better rules at CPSC and other independent agencies. For example, starting in 1981, Executive Order 12,291 called for executive agencies “to maximize the net benefits to society.” Although this order was subsequently replaced by Executive Order 12,866, which was later supplemented with Executive Order 13,563, these more current orders also state that agencies should choose regulations that “maximize net benefits.” A similar concept is Executive Order 12866’s principle that “each agency . . . tailor its regulations to impose the least burden on society,” a principle that Executive Order 13,563 retains. When developing product-specific safety standards, CPSC already operates under even clearer mandates than these executive orders provide. Under Section 9 of the Consumer Product Safety Act (CPSA), in order to mandate a safety standard for a particular product or product category, CPSC must analyze the costs and benefits of the proposed standard, must explore any alternatives, must ensure the costs bear a reasonable relationship to the benefits, and must select the least burdensome option. The value of Section 9 is not just that it provides an analytical framework, but also that it allows for judicial review, as we saw recently in the 10th Circuit’s decision to strike our magnet rule because of uncertainty in our cost-benefit analysis. Although having a rule thrown out is not pleasant for the agency, if we take to heart this reminder of the importance of the Section 9 analysis, our future rules will be better and sounder for the effort. For any of our rules that are not product safety standards, however, no similar requirement for cost-benefit analysis applies. As a result, CPSC fell short of standard cost-benefit principles in developing its rule detailing the testing that children’s product manufacturers must undertake to certify that their products comply with applicable safety standards. The Consumer Product Safety Improvement Act (CPSIA) required such testing and certification, and it required the Agency to issue a rule setting forth the “protocols and standards” for the testing. The Agency dutifully issued a testing rule, but it pointedly did not undertake a full cost-benefit analysis. Indeed, in response to comments suggesting cost-benefit analysis, the Agency flatly refused, noting that because the rule was not a safety standard under Section 9 of the CPSA the Agency was not required to complete a cost-benefit analysis. Even if a law does not require cost-benefit analysis, it is still prudent for an agency to undertake one. CPSC’s testing rule would have been better informed by analyzing manufacturers’ compliance costs and the benefits consumers would get in exchange. We owe it to consumers to ensure that regulations will maximize their best interests. Even if a full cost-benefit analysis would have only supported the Agency’s testing rule, we would still have had the benefit of added confidence in our decision. Third, agencies—whether executive or independent—should be expected to assemble the best available scientific evidence to inform their regulatory decisions. Executive Orders 13563 and 12866 recognize this principle, observing that “our regulatory system . . . must be based on the best available science.” Executive Order 12866 calls upon agencies to ground their decisions on the “best reasonably obtainable scientific, technical, economic, and other information.” During his first term, President Barack Obama also issued a memorandum requiring that executive agencies put in place rules and procedures that ensure the use of the highest quality science in regulatory development. At CPSC, the Chronic Hazard Advisory Panel (CHAP) report on phthalate exposure is an example of the desire for new regulations that do not reflect current science. Despite the availability of data on the current state of phthalate usage by manufacturers, the CHAP chose to use data that were nearly a decade old. An outside review found that “the CHAP report is not a systematic review of the available scientific evidence and, as such, is of questionable reliability and validity, lacking in the objectivity and transparency generally recognized as critical by the scientific community.” CPSC staff, at the Chairman’s direction, have accepted this criticism and undertaken an internal review using more recent data; however, other problems remain. The final rule may go beyond our statutory mandate by using a novel, unproven cumulative risk assessment as a way to justify banning certain phthalates. Mere novelty is, of course, not a reason to disregard an analytical method or its conclusions. However, when novel concepts form the core of a regulatory effort, agencies should take extra care to ensure those methods bear the hallmarks of scientific validity. Unfortunately, the sound science requirements contained in the Information Quality Act do not “explicitly provide for judicial review.” Codifying the best sound science practices found in executive orders and in President Obama’s memorandum on scientific integrity, along with providing for more robust judicial review of agencies’ scientific analysis, would help ensure independent agencies like CPSC use the best available data and methods when crafting new rules. Finally, President Obama’s Executive Order 13,610 calls for executive agencies to engage in retrospective review of existing regulations and report on their progress to the White House Office of Information and Regulatory Affairs. No matter how thoughtful an agency’s promulgation of a rule may be, there will always be potential for improvements. Agencies’ vision can be obscured by market complexities, unquantifiable forces, or emerging trends. Although human beings may be naturally inclined both to resist change and to prefer the allure of solving a new problem instead of revisiting their solution to an old problem, agencies need to set those inclinations aside if they wish to ensure their regulations function properly as a whole. CPSC has had a mixed history with retrospective review. Even prior to the issuance of President Barack Obama’s call for retrospective review, CPSC had conducted its own retrospective examinations. However, the resource demands of the myriad rules required under the CPSIA diverted the Agency’s focus, and its retrospective review program was dormant for several years. Spurred by the Obama Administration’s emphasis on retrospective review, the Agency sought to revive its retrospective review efforts, but the Commissioners were initially unable to reach consensus on how to proceed. Recently, CPSC unanimously adopted an important plan that does comply with the spirit of Executive Order 13,610. That plan includes additional elements of an institutional culture of review, such as calling for the Agency to incorporate “retrospective review provisions in new rulemakings.” I hope CPSC can become a leader in this regard as it puts its retrospective review plan into action. Overall, independent agencies would do well to adopt all four requirements currently applicable to executive branch agencies. They should be expected to make a threshold finding of market failure before proposing new regulations, conduct robust cost-benefit analysis of new rules, take steps to rely only on the best available science, and put in place plans to undertake serious retrospective review of existing regulations. In these ways, agencies like CPSC can better ensure that their regulations are truly working to serve the public’s best interests

The Administrative State Has Run Amok

Recently, this publication was gracious enough to publish a two-part essay I wrote on the issue of regulatory reform from the perspective of a Commissioner at the U.S. Consumer Product Safety Commission (CPSC). My ever-attentive, ever-thoughtful colleague, Commissioner Robert S. Adler, was inspired to pen a retort, and, in the spirit of the stimulating intellectual exchange we regularly enjoy, I would like to offer a reply. In my original essay, I encouraged the use of four regulatory best practices that, among others, could improve the regulatory work product from CPSC and agencies across the federal government. These included: The central thrust of Commissioner Adler’s response is that the analytical tools I endorsed, despite having been advocated by presidents, both Democratic and Republican, as far back as President Jimmy Carter and reflected in some—though not enough—agency statutes, somehow constitute “paralysis by analysis.” That is, these tools inconvenience regulators who would much rather govern by whim and impulse than by facts, science, data, and a recognition that Washington elitists do not, in fact, always know what is best. My colleague apparently did not hear President Bill Clinton more than 20 years ago when he proclaimed that the era (error?) of big government was over. Many unelected, unaccountable bureaucrats fail to recognize that Americans have grown weary of hearing that more regulation is the answer to all that ails us. Even some of the most ardent consumerists recognize that “regulation” has effectively become a pejorative term in Washington. In a recent hearing, Senator Richard Blumenthal (D-Conn.) couldn’t even bring himself to say it, admitting—perhaps in a Freudian slip—that “nobody likes the word regulation these days.” For over a decade, Gallup polling has consistently found that Americans believe regulations are placing too great a burden on our economy. This sentiment resulted late last year in the largest electoral upheaval the country has seen in generations—a fact that my colleague does not appear to have yet come to grips with. In the absence of some badly needed regulatory reforms, the administrative state has run amok, with the total annual cost of regulation now nearly two trillion dollars. That is 11 percent of total Gross Domestic Product. If U.S. regulation were a country, it would have the world’s ninth largest economy, right between Russia and India. This has real consequences for our country: the World Economic Forum currently ranks the United States 51st in the world for the compliance burden imposed by regulation, sandwiching us between Bhutan and Guatemala. When both American citizens and global indices have awoken to the realization that regulation in our country is out of control, it is worth asking: why hasn’t the bureaucratic establishment? They want agencies to be able to continue doing what they have always done, no matter how great a competitive disadvantage our country is placed at or how many good government reforms have been put forward. Professor Adler, accustomed to the luxury of tenure, no doubt instinctively seeks to protect agencies from the inconvenience of change. Fortunately, a change is coming regardless of whether he chooses to accept it. The last few months have seen progress from both the White House and Congress in holding agencies accountable for overly burdensome regulation. An executive order from President Donald Trump directed agencies to repeal two existing regulations for every new one promulgated. Such “pay-go” schemes have worked remarkably well in Canada and the United Kingdom, the latter of which has now expanded to a one-in, three-out requirement. Another executive order requires each agency to designate individuals and task forces with the responsibility of ensuring their agency is following the President’s regulatory reform mandates. While these executive orders do not apply to independent agencies, CPSC is fortunate to have a new acting chairman inclined to voluntarily comply with the spirit of them. Congressional momentum is similarly moving toward regulatory reform, with numerous examples of good government legislation proceeding quickly through both chambers. I hope CPSC engages proactively, looking for any opportunity to improve its own regulatory product. If, instead, we dig our heels in and insist that a 1970s approach to product safety regulation makes sense in the 21st century, I predict we will have more drastic measures imposed upon us. There is no doubt that change is inevitable—the only question is whether or not we will forfeit our opportunity to be in control of at least some of that change. The longer we play the victim, the more likely we will become one