Office Of Toxic Substances Research Articles

Perspectives of PHS Funding Agencies: Session Introduction

T oday we’re going to learn about the organizations that support our science. I’m honored and grateful that to­ day’s speakers took time away from their research, their students, their offices and their patients to travel to Bethesda to be part of this meeting. This morning’s session will be about the policies and philosophy of the Public Health Service organiza­ tions that support biomedical research. I’m going to introduce all the speakers in the order in which they will speak. First we will hear from my professional home, NIH, where Dr. Sally Rockey is Deputy Director for Extramural Research. She was recently confirmed in this position after serving as Act­ ing Deputy Director—congratulations, Sally. Dr. Rockey re­ ceived her PhD in entomology from the Ohio State University in 1985. She went to work for the USDA and quickly rose through the ranks to become Deputy Administrator for the Competitive Research Grants and Awards Management Unit in the Cooperative State Research, Education, and Extension Ser­ vice, and then she became Chief Information Offi cer. It is also my pleasure to welcome Dr. Tanja Popovic, Dep­ uty Associate Director for Science at the Centers for Disease Control and Prevention (CDC), where she previously served as Associate Director for Science and as Chief Science Offi ­ cer. She joined CDC as a Fulbright fellow in 1989. Since then she has served as the Chief of the Diphtheria Reference Unit, Chief of the Epidemiological Investigations Anthrax Labora­ tory, and Co-Director of the WHO Collaborating Center for Prevention and Control of Bacterial Meningitis. She has been a WHO consultant for bacterial meningitis and diphtheria in Russia and throughout Africa. She led the CDC laboratory during the 2000 anthrax events. Dr. Popovic is the CDC Insti­ tutional Official for both human and animal research subjects. She has many more awards and credentials, too many to list. And fi nally, we will hear from Dr. David Jacobson-Kram, who received his PhD in embryology from the University of Connecticut in 1976. He served as a senior staff fellow at the National Institute on Aging, on the faculty of the George Wash­ ington University School of Medicine, and at Johns Hopkins University Oncology Center. He has also served the Environ­ mental Protection Agency as a geneticist in the Offi ce of Toxic Substances and as acting Branch Chief in their Office of Re­ search and Development. Then Dr. Jacobsen-Kram entered the private sector, serving as Director of the Genetic Toxicology Division of Microbiological Associates. Microbiological As­ sociates changed its name to BioReliance and David’s respon­ sibilities expanded to include oversight of the Mammalian Toxicology Program and the Laboratory Animal Health Pro­ gram. He also served as Vice President of the Toxicology and Laboratory Animal Health Division. Dr. Jacobson-Kram is now Associate Director of Pharmacology and Toxicology at the FDA Office of New Drugs. We’re very lucky to have David here with us today—I understand he had a tremendous fall this weekend so don’t hug him or shake his hand too vigorously.

Registering Skepticism: Does the EPA’s Pesticide Review Protect Children?

When the EPA announced on 3 August 2006 that it had completed a 10-year review of U.S. pesticide safety, the agency issued a statement full of optimism from administrator Stephen L. Johnson: “By maintaining the highest ethical and scientific standards in its pesticide review, EPA and the Bush administration have planted the seeds to yield healthier lives for generations of American families.”

Determination of the aquatic PNEC 0.05 for boron

Several weight of the evidence approaches for the effects assessment of boron to aquatic organisms have been conducted. The focal point for all of these assessments is the appropriate interpretation of the LC1 for rainbow trout ( Oncorhynchus mykiss) from W.J. Birge, J.A. Black, Report No. EPA5601176408. Environmental Protection Agency, Office of Toxic Substances, Washington, DC, 1977, as the LC1 from their studies provided the lowest chronic toxicity values for boron. Other studies by these investigators (W.J. Birge, J.A. Black, Completion Report prepared for the Procter & Gamble Company, Cincinnati, USA, 1981; W.J. Birge, J.A. Black, A.G. Westermann, T.M. Short, S.B. Taylor, M.C. Parekh. Completion Report prepared for the Procter & Gamble Company, Cincinnati, USA, 1984; J.A. Black, J.B. Barnum, W.J. Birge, Chemosphere 26 (1993) 1383–1413) further indicate this species to be particularly sensitive to boron. While weight of the evidence approaches have been necessary for diverse risk assessment needs, they each suffer from potential bias via professional judgment. In order to allay these issues and to update the effects assessment for boron, a probabilistic approach was used. Raw data from the Birge and Black studies were reanalyzed to generate chronic values representative of the adverse effects threshold (e.g., LC10) for several species. A comprehensive list of chronic data from these studies and other studies were combined into a cumulative probability term, allowing for the determination of the fifth percentile protection value, or PNEC 0.05. The PNEC 0.05 for boron was determined to be at least 1.3 mg B/l.

081051 (E10) Determination of a tolerable daily intake of DDT for consumers of DDT contaminated fish from the Lower Yakima River, Washington: Mariën K., Laflamme D.M., State of Washington, Department of Health, Office of Toxic Substances, Olympia, Washington, Risk Analysis, Vol., 15, Number 6, pp. 709–717

081051 (E10) Determination of a tolerable daily intake of DDT for consumers of DDT contaminated fish from the Lower Yakima River, Washington: Mariën K., Laflamme D.M., State of Washington, Department of Health, Office of Toxic Substances, Olympia, Washington, Risk Analysis, Vol., 15, Number 6, pp. 709–717

Permeation of Multifunctional Acrylates through Selected Protective Glove Materials

In support of the Premanufacture Notification (PMN) program of the Environmental Protection Agency's Office of Toxic Substances, the resistance of three glove materials to permeation by multifunctional acrylate compounds was evaluated through a program for the Office of Research and Development. Several recent PMN submissions relate to multifunctional acrylates and essentially no permeation data are available for this class of compounds. To better understand permeation behavior, tests were conducted with trimethylolpropane triacrylate (TMPTA), 1,6-hexanediol diacrylate (HDDA), and two mixtures of HDDA with 2-ethylhexyl acrylate (EHA). Because of the low vapor pressure and low water solubility of these compounds, the tests were conducted by using ASTM Method F739-85 with a silicone rubber sheeting material as the collection medium. Tests were performed at 20°C with butyl, natural, and nitrile rubber glove materials. None of the acrylate compounds nor mixtures was found to permeate the butyl or nitrile rubber under the test conditions. Permeation through the natural rubber was observed in tests with pure HDDA, a 50% HDDA/50% EHA mixture, and a 25% HDDA/75% EHA mixture. TMPTA permeation through the natural rubber was also detected, but only in one of the triplicate tests after the 360–480 min sampling interval. For pure HDDA, the breakthrough detection time was 30–60 min and the steady-state permeation rate was 0.92 µg/cm2-min. For the HDDA/EHA mixtures, permeation of both mixture components was detected during the same sampling interval in each test. The breakthrough detection time was 30–60 min for the 50/50 mixture and from 15–30 to 30–60 min for the 25/75 mixture. The HDDA steady-state permeation rates from the mixtures were somewhat higher than that measured for pure HDDA: 1.02 µg/cm2-min from the 50/50 mixture and 1.35 µg/cm2-min from the 25/75 mixture. The slight increase in permeation rate is attributed to the presence of the more rapidly permeating EHA carrier solvent, which had a permeation rate of 11.7 µg/cm2-min from the 50/50 mixture and 20.0 µg/cm2-min from the 25/75 mixture.

Controlling Microbes Versus Disinfection By‐products

Jennifer Orme, who coordinates development of the US Environmental Protection Agency's (USEPA's) maximum contaminant level goals for drinking water disinfectants and their by‐products, talked with Journal Editor Nancy Zeilig in Orlando, Fla., Nov. 11, 1991, about the toxicologic aspects of the upcoming Disinfection—Disinfection By‐products (D—DBP) Rule as well as the tradeoffs inherent in trying to control microbial risks and the risks posed by DBPs. Currently chief of the drinking water health assessment section in the human risk assessment branch of the Health and Ecological Criteria Division in USEPA's recently formed Office of Science and Technology, Orme has been with the agency for 10 years and has worked in the area of drinking water for six and a half years. She joined USEPA's Health Effects Research Laboratory in Cincinnati, Ohio, then moved to the agency's Office of Toxic Substances in Washington, D.C. She received her bachelor's degree from Ohio Wesleyan University (Delaware, Ohio) and her master's degree from Miami University (Oxford, Ohio).

Permeation of multifunctional acrylates through selected protective glove materials.

In support of the Premanufacture Notification (PMN) program of the Environmental Protection Agency's Office of Toxic Substances, the resistance of three glove materials to permeation by multifunctional acrylate compounds was evaluated through a program for the Office of Research and Development. Several recent PMN submissions relate to multifunctional acrylates and essentially no permeation data are available for this class of compounds. To better understand permeation behavior, tests were conducted with trimethylolpropane triacrylate (TMPTA), 1,6-hexanediol diacrylate (HDDA), and two mixtures of HDDA with 2-ethylhexyl acrylate (EHA). Because of the low vapor pressure and low water solubility of these compounds, the tests were conducted by using ASTM Method F739-85 with a silicone rubber sheeting material as the collection medium. Tests were performed at 20 degrees C with butyl, natural, and nitrile rubber glove materials. None of the acrylate compounds nor mixtures was found to permeate the butyl or nitrile rubber under the test conditions. Permeation through the natural rubber was observed in tests with pure HDDA, a 50% HDDA/50% EHA mixture, and a 25% HDDA/75% EHA mixture. TMPTA permeation through the natural rubber was also detected, but only in one of the triplicate tests after the 360-480 min sampling interval. For pure HDDA, the breakthrough detection time was 30-60 min and the steady-state permeation rate was 0.92 micrograms/cm2-min. For the HDDA/EHA mixtures, permeation of both mixture components was detected during the same sampling interval in each test. The breakthrough detection time was 30-60 min for the 50/50 mixture and from 15-30 to 30-60 min for the 25/75 mixture.(ABSTRACT TRUNCATED AT 250 WORDS)

EPA use of in vivo germ cell mutagenicity data

The Toxic Substances Control Act (TSCA) provides the U.S. Environmental Protection Agency, Office of Toxic Substances (EPA, OTS) with the authority to regulate chemical use by requiring testing and use restrictions as appropriate to protect human health. Regulation on the basis of heritable mutation induction is specifically mentioned in the Test Rule section of the law and has also been pursued for new chemical substances. A tiered scheme of mutagenicity testing has been employed and recently revised to assess mutagenicity hazard. In vivo assay systems play key roles at all three levels in the scheme, beginning with the first level of determining intrinsic mutagenicity hazard. Once intrinsic mutagenicity has been identified, the revised scheme requires an assay or assays to assess chemical interaction with gonadal DNA. Finally, the scheme contains tests that permit risk assessment for a chemical. The recently-revised Office of Pesticide Programs (OPP) mutagenicity testing requirements closely parallel those of OTS.

EPA Develops Product Stewardship, Hazard Communication Regulations

In an effort to revitalize its activity under the Toxic Substances Control Act, the Environmental Protection Agency is developing regulations on hazard communication and product stewardship. EPA says initial regulations calling for inclusion of environmental data on existing material safety data sheets could be proposed as early as next summer. According to Lin Moos, deputy director of the chemical control division in EPA's Office of Toxic Substances, the agency is using its authority under Section 6 of TSCA to issue the regulations. Section 6 is a broad article that gives EPA power to control or ban specific chemicals that it believes pose or could pose an unreasonable risk to health or the environment. Controls can range from public warnings, to notification of the agency before a chemical is used in certain ways, to record-keeping requirements, or any combination of these. It is under this rubric that the agency is moving forward with its two-part rule-making ...

Proceedings of the workshop on the acceptability and interpretation of dermal developmental toxicity studies

The workshop on The Acceptability and Interpretation of Dermal Developmental Toxicity Studies, held April 13–14, 1988, was organized by the U.S. EPA's Office of Research and Development and Office of Toxic Substances and was supported by the Agency's Risk Assessment Forum. The purpose of the workshop was to review the current state of knowledge on the use of the dermal route of exposure in developmental toxicity studies. In evaluating this area, three major issues were considered by the participants: (1) the evaluation of maternal toxicity in dermal developmental toxicity studies, (2) what types of pharmacokinetic data are necessary or desirable for the appropriate design and interpretation of these studies, and (3) what factors are important to consider in the design of dermal developmental toxicity studies. The participants concluded: (1) dermal developmental toxicity studies without any indication of maternal or developmental toxicity are inadequate for risk assessment unless accompanied by absorption data, (2) absorption data and limited pharmacokinetic data should be collected in every dermal developmental toxicity study, and (3) dermal developmental toxicity studies in which skin irritation is too marked should be considered inadequate for risk assessment. General recommendations made for all developmental toxicity studies regardless of the route of exposure were: signs of local irritation should be examined, and absorption/pharmacokinetic data should be developed. Areas in which additional research is needed to permit more complete assessment of dermal developmental toxicity studies were also identified.

EPA Plans Health, Environmental Safety Review of CFC Substitutes

As the chlorofluorocarbon (CFC) industry races to develop alternatives to ozone-depleting CFCs and halons, the Environmental Protection Agency is forming its own strategy for reviewing the effects of the chemical substitutes on human health and the environment. We clearly do not want to blunder along and unwittingly create new health and environmental problems while solving the one we've targeted/' says Charles L. Elkins, director of EPA's office of toxic substances. With a little foresight and advance work, we can either avoid the use of any toxic substitutes or control exposure to them to an acceptable level. ...

Adoption of new guidelines and data requirements for more extensive neurotoxicity testing under FIFRA.

In 1987 the Center for Science in the Public Interest (CSPI) and others petitioned EPA to, "issue testing methods necessary to fully assess the neurotoxic and neurobehavioral effects of pesticide active and inert ingredients." In response OPP convened a meeting of an expert subpanel on neurotoxicity of the Scientific Advisory Panel to review its proposed response. The petitioners proposed specifically that OPP use the neurotoxicity guidelines developed by EPA's own Office of Toxic Substances. They asserted that the scope of potential neurotoxic hazards is broad and that current guidelines will neither adequately identify nor characterize these effects. A series of expert panels have endorsed the use of more extensive neuropathological evaluations, better clinical examinations, explicit unconditioned and conditioned behavioral testing, testing of prenatally exposed animals for neurological deficits, and development of a means for evaluation of the broad range of potential neurotoxic effects. In response to this petition the following additions to the assessment of pesticides were proposed by OPP and approved by the SAP: expanded functional observation neuropathology, and motor activity into an acute and subchronic screening battery; addition of tests of operant behavior or other tests of sensory or cognitive function as conditional data requirements; and addition of a conditional requirement of postnatal neurofunctional and neuropathological evaluation of offspring.

Toxic chemicals monitoring program threatened

A program that determines the level and prevalence of toxic chemicals in human tissues may be forced to end this year. Because of the current budget squeeze, the Environmental Protection Agency is providing no funds for that program in its fiscal 1988 budget. However, program staffers in EPA's Office of Toxic Substances are trying to save it. Called the National Human Monitoring Program, it consists of the National Human Adipose Tissue Survey, the National Blood Network, and special studies. The adipose tissue survey is more than 20 years old. The blood network was begun because some chemicals accumulate in blood but not in body fat. Martin P. Halper, director of the exposure evaluation division, says budget constraints alone led to the decision to end the program. If fully operational, the effort would cost less than $2 million a year. It has been funded at about $1.1 million in each of the past two fiscal years. ...

Implications of the consensus workshop on the evaluation of maternal and developmental toxicity.

Teratogenesis, Carcinogenesis, and MutagenesisVolume 7, Issue 3 p. 329-338 Article Implications of the consensus workshop on the evaluation of maternal and developmental toxicity† G. L. Kimmel, G. L. Kimmel U.S. Environmental Protection Agency, Reproductive Effects Assessment Group, Office of Health and Environmental Assessment, Office of Research and Development; and Toxic Effects Branch, Health and Environmental Review Division, Office of Toxic Substances, Office of Pesticides and Toxic Substances, Washington, DCSearch for more papers by this authorC. A. Kimmel, C. A. Kimmel U.S. Environmental Protection Agency, Reproductive Effects Assessment Group, Office of Health and Environmental Assessment, Office of Research and Development; and Toxic Effects Branch, Health and Environmental Review Division, Office of Toxic Substances, Office of Pesticides and Toxic Substances, Washington, DCSearch for more papers by this authorE. Z. Francis, E. Z. Francis U.S. Environmental Protection Agency, Reproductive Effects Assessment Group, Office of Health and Environmental Assessment, Office of Research and Development; and Toxic Effects Branch, Health and Environmental Review Division, Office of Toxic Substances, Office of Pesticides and Toxic Substances, Washington, DCSearch for more papers by this author G. L. Kimmel, G. L. Kimmel U.S. Environmental Protection Agency, Reproductive Effects Assessment Group, Office of Health and Environmental Assessment, Office of Research and Development; and Toxic Effects Branch, Health and Environmental Review Division, Office of Toxic Substances, Office of Pesticides and Toxic Substances, Washington, DCSearch for more papers by this authorC. A. Kimmel, C. A. Kimmel U.S. Environmental Protection Agency, Reproductive Effects Assessment Group, Office of Health and Environmental Assessment, Office of Research and Development; and Toxic Effects Branch, Health and Environmental Review Division, Office of Toxic Substances, Office of Pesticides and Toxic Substances, Washington, DCSearch for more papers by this authorE. Z. Francis, E. Z. Francis U.S. Environmental Protection Agency, Reproductive Effects Assessment Group, Office of Health and Environmental Assessment, Office of Research and Development; and Toxic Effects Branch, Health and Environmental Review Division, Office of Toxic Substances, Office of Pesticides and Toxic Substances, Washington, DCSearch for more papers by this author First published: 1987 https://doi.org/10.1002/tcm.1770070314Citations: 11 † The views expressed in this document are those of the authros and do not necessarily represent those of the U.S. Environmental Protection Agency. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume7, Issue3Special Issue: Evaluation of Maternal and Developmental Toxicity1987Pages 329-338 RelatedInformation

Application of the preliminary developmental toxicity screen for chemical hazard identification under the Toxic Substances Control Act.

The Office of Toxic Substances (OTS) within the U.S. Environmental Protection Agency (EPA) is authorized to carry forth the mandates of the Toxic Substances Control Act (TSCA). Included among the provisions of TSCA are the development of requirements for testing of "new" and "existing" chemicals that may present an unreasonable risk of injury to health or the environment. There are over 63,000 "existing" chemicals on the TSCA inventory, and EPA in recent years has been receiving an average of over 1,300 submissions for "new" chemicals a year. Since it is illogical and unrealistic to expect that all of these chemicals should be subjected to detailed testing for all potential adverse health and environmental effects, OTS views screening assays as highly useful tools to assign priorities to chemicals for further testing according to standard methodologies. The Chernoff/Kavlock assay (preliminary developmental toxicity screen) was specifically developed to address the need for a developmental toxicity assay to prioritize for further testing the large number of "new" and "existing" chemicals. OTS has been involved in seeking the development of data through the preliminary developmental toxicity screen for purposes of validating the screen and to obtain critical data necessary for evaluating chemicals. OTS believes that the screen has a role in the risk assessment process and has developed a testing protocol, which is included along with other OTS test guidelines; has provided internal guidance on when the screen may be recommended; and has discussed how the data may be applied in prioritizing chemicals for further study.

Workshop: Predicting Workplace Exposure to New Chemicals

Abstract Abstract EPA's Office of Toxic Substances (OTS) recently held a Workshop entitled “Predicting Workplace Exposure to New Chemicals.” EPA and industry representatives divided into four cooperative “brainstorming” workgroups, which addressed the topics of inhalation exposure, engineering controls, respiratory protection, and dermal exposure, as these pertain to the Agency's risk assessment and risk management processes for new chemical substances. All four groups emphasized the need for better characterizations of workplace environments in order to strengthen the predictive power of many of the tools that are already used. The inhalation workgroup made specific suggestions regarding fugitive emission estimations and OTS's current volatilization model, and emphasized their preference for engineering controls in lieu of personal protective equipment. The engineering control group suggested categorizing process facilities and operations by degree of containment, by ventilation system, and by range of concentration, in order to standardize the consideration of additional control measures. Participants in the respiratory protection session recommended that a target exposure level be established to facilitate the choice of an appropriate respirator or engineering control, and discussed which breathing apparatus is most suitable for certain use scenarios, including scenarios involving carcinogens. Finally, the dermal exposure workgroup encouraged more quantitative assessment techniques. They commented on the use of deposition rate versus absorption rate to calculate absorbed dose, and on both the physical state of a PMN chemical, and the function of carrier solvents in mixtures, as factors influencing absorption rate.

Reproductive Toxicity Testing: Evaluating and Developing New Testing Systems

Reproductive toxicity testing systems are used by national and international regulatory agencies. Protocols have not been standardized between agencies or even within certain agencies. Although there have been efforts at standardization, a certain amount of the differences between testing protocols is a reflection of the needs of the particular agency. New developments in in vitro techniques might lead to new test systems, but reproductive function is dependent upon the interaction of various cells and organs that cannot presently be copied in the test tube; this makes whole-animal testing systems a necessity. The present whole-animal models used by the Food and Drug Administration include the 3 segment reproduction studies used for testing drug safety and the multigeneration studies used for food additives. The Environmental Protection Agency has adopted 2 similar versions of a 2-generation study for the Office of Pesticide Programs and the Office of Toxic Substances. The National Toxicology Program, although not a regulatory agency, has taken a prominent role in reproductive toxicity testing, test system development, and test system evaluation. A new testing system, Fertility Assessment by Continuous Breeding (FACB), is currently being studied as a cost-effective and reliable alternative test system. The FACB protocol houses male and female mice as breeding pairs and removes offspring as soon as they are born during the first 14 weeks to allow continuous mating. Each breeding pair normally has up to 5 litters, and the last litter is saved to evaluate the second generation. The efficiency, reliability, and expense of the protocol are being compared to the existing testing systems.

Information Resource Guide to Chemical Hazardous Wastes in the Environment

According to the Environmental Protection Agency Office of Toxic Substances, there are some 70,000 chemical compounds manufactured or processed at approximately 115,000 sites across the U.S. About 1,000 new chemical compounds are introduced every year and many of these are unquestionably toxic to human, animal, or plant life.

Office of Toxic Substances' Spot on the Learning Curve Influenced by EPA's Origins and Subsequent Experience

Office of Toxic Substances' Spot on the Learning Curve Influenced by EPA's Origins and Subsequent Experience