Progress 03/01/05 to 02/28/10
Outputs
OUTPUTS: Ecological and health risk of silver and titanium dioxide nanoparticles was conducted, based on their known physical, chemical, and biological features. A chain graph framework for extrapolation was proposed for assessing health risks of nanoparticles. I also participated in the planning of the Conference of Balancing Animal Agriculture and Communities, examined impacts of multiple policy issues on agriculture, community health, and the environment, examined the effect of hemochromatosis (HFE) gene mutation-associated changes in placenta transfer of lead (Pb), conducted risk assessment of phthalates on developmental health, and studied reproductive and developmental toxicity of chlorinated biphenyls, phytoestrogens, and pharmaceutical products in rats. PARTICIPANTS: Karen Chou, PI. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
The results of the toxicity assessment of nanomaterials indicate that nanoparticles tend to be more toxicity than their parent materials in the bulk forms and often induce different types of toxic effects . Health impacts of bulk material cannot be used to assess the risks of nanoparticles. Results from the lead study showed that maternal blood lead concentration (mpb) is a strong predictor of umbilical cord blood lead (cpb). Both maternal HFE C282Y/H63D and maternal HFE H63D negatively influence the relationship between cpb and mpb. On the average, each ug/dl of maternal blood Pb is associated with an increase in 0.54 ug/dl of Pb in umbilical blood Pb in the maternal C282Y/H63D carriers and 0.627 ug/dl in the maternal H63D carriers, comparing with the 0.76 ug/dl in the maternal non-C282Y/H63D and non-H63D carriers. The mean concentration of mpb (8.53 ug/dl), the maternal C282Y/H63D carriers is associated with a decrease of 1.04 ug/dl in cord blood Pb, while the maternal H63D carriers is associated with a decrease of 0.14 ug/dl. On the other hand, there is no effect of infant genotype on the relationship between cpb and mpb. Linear regression analysis also showed that maternal dietary Ca intake negatively influences the relationship between cpb and mpb. Each 1000 mg of Ca intake is associated with a decrease in 0.45 ug/dl cord blood Pb. Furthermore, the influence of HFE variants on the relationship between cpb and mpb is independent from Ca intake. The exposure assessment of phthalates indicates that food processing equipment and packaging material are the major sources of phthalate in human diet. Heating food in the ready-to-eat packages greatly facilitates phthalate migration from packaging materials to food. In dairy products, greater than 80% of total concentrations originated from milking equipment. For preterm babies and dialysis patients, the amounts of phthalates leaching from medical devices can exceed the recommended limits.
Publications
- Chou, K. 2009. Target Sites: Endocrine. In Information Resources in Toxicology, Fourth edition, Ed. P. Wexler, Academic Press, pp. 435-442 Steel, D. and K. Chou (2008) Bayes Net and Nanotech: a Chain Graph Framework for Extrapolation. Philosophy of Science Association Biennial Meeting, Nov. 6-8, Pittsburgh, U.S.
- Chou, K., H. Hu, A. Ettinger, M. Tellez-Rojo, J. Schwartz, M. Hernandez-Avila, R. Wright. 2006. Hemochromatosis Gene Variants Modify Placental Transfer of Lead. Joint ISEE/ISEA International Conference, Paris
- Chou, K. and R. Wright. 2006. Phthalates in food and medical devices, Journal of Medical Toxicology 2(3):126-135
- Vadnais, M.L., R.N. Kirkwood, R.J. Tempelman, D.J. Sprecher, and K, Chou. 2005. Effects of extender, incubation temperature, and addition of seminal plasma on capacitation of frozen-thawed boar spermatozoa determined using chlortetracycline assay. Animal Reproduction Science 90(3-4): 347-354
- Chou, K. 2005. Endocrine System. In: Encyclopedia of Toxicology, Second Edition, Elsevier, Oxford, UK, pp. 170-174
- Vadnais, M.L., R.N. Kirkwood R.J. Tempelman, D.J. Sprecher, and K, Chou. 2005. Effect of cooling and seminal plasma on the capacitation status of fresh boar sperm as determined using chlortetracycline assay. Animal Reproductive Science 87(1-2): 121-132
- Cui, W., L. Flores del Pino, T.C. Voice, K. Chou, and D. P. Kamdem. 2005. Speciation of arsenic and chromium in the leachate from chromated copper arsenate (CCA) type C treated southern pine. Holzforschung, 59(2):199-204
- Niagolova, N., S.P.McElmurry, T.C. Voice, D.T. Long, E.A. Petropoulos, I. Vavezov, K. Chou, and V. Ganev. 2005. Nitrogen species in drinking water indicate potential exposure pathway for Balkan Endemic Nephropathy. Environmental Pollution, 134(2):229-237
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Progress 01/01/09 to 12/31/09
Outputs
OUTPUTS: (1) The interview survey, initiated in 2008, on the perception of risks associated with large scale animal agriculture in Michigan, continued in 2009. Since the project started in October 2008, we have completed the interviews in Clinton County. We have contacted 48 individuals this year and performed a total of 28 interviews. A progress report was presented to the Ag AOE Team on January 12, 2009. Currently, the tape-recorded interviews are being transcribed and we will use the software package Nvivo to analyze the findings. (2) A publication in the February, 2009 issue of American Journal of agricultural Economics, by Sneeringer, on pollution caused by animal feeding operation has stirred up the public concerns over the health impacts of animal agriculture on human health, specifically increases in infant mortality associated with a doubling of number of livestock in the U.S. counties. After examining the methods of the study and known risk factors of infant mortality, I concluded that this study was designed based on many erroneous assumptions. Misuse of variables and lack of considerations of known confounders of birth outcomes in the regression analysis may have lead to an overestimation of the effects. These insidious maneuvering of the analysis could even lead to a wrong direction of the observations. (3) For the environmental and health concerns of nanoparticles, I have assessed the ecological and health risk of silver and titanium dioxide nanoparticles. The biological impacts of each of the nanoparticles are considerably higher than their respective bulk materials. (4) I have also examined the potential applications of mathematical modeling, spatial analysis and geographic information science (GISc) in toxicological and epidemiological studies. The usage of GISc and its associated computational methods can be transferred beyond the management of spatial data and mapping. For the problems stated in Item (2) and (3), the synthesis of the computational technology can be used to enhance the studies that are related to complex environmental issues coupled with social and political factors. PARTICIPANTS: Karen Chou (PI) designed and conducted the studies and supervised the progress and the quality of the project. Lisa Szymecko (research assistant, Department of Community, Ag, Recreation, and Resource studies, Michigan State University (MSU)) conducted, transcribed and summarized the interviews. Partner Organizations include Michigan Field Office, USDA National Agricultural Statistic Service, and Michigan Department of Community Health. Collaborators at MSU include Dale Rozeboom and Windy Powers of Animal Science, Craig Harris of Sociology, Geoffrey Habron of Fisheries and Wildlife, Roy Black of Agricultural, Food and Resource Economics, and Melissa Millerick-May of Occupational and Environmental Medicine. Three MSU extension educators, Dave Ivan, Marilyn Thelen and Faith Cullens also collaborated with us on the interview study. TARGET AUDIENCES: Results of the survey study were presented to extension educators. Outcomes of the study were also included in the teaching material for ANS 427 "Environmental Toxicology and society" and ESP 803 "Human and Ecological Health Assessment and Management." PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
(1) Preliminary findings of the agriculture community survey study show that there is a wide array of support for large scale animal agriculture in Clinton County. A final summary of the study and a publication are planned. (2) As for nanoparticles, they exhibit unique biokenetic, physiobiochemical, and toxicological properties, different from the bulk materials. The differences between nano- and bulk- materials are substance specific. Therefore, the design of toxicity studies needs to be chemically specific and structurally/dimensionally well defined. Because of the lack of effective study designs, sufficient toxicity data, and appropriate nano-specific -risk models, currently no regulatory exposure limits can be determined with acceptable amounts of confidence. In the absence of regulatory limits in the near future, and with the increasing amounts of nanomaterials being commercialized and released into the environment, it is imperative that the baselines and the time-course changes of environmental concentrations being monitored closely, especially for those which exposure are mostly like to cause undesirable ecological or health impacts. This understanding provides practical directions for current environmental management approaches. I have recently been asked by US EPA to evaluate grant proposals. While more than 15% of the applications are nanotoxicity related studies, very few could produce the urgently needed information for regulatory purposes. (3) A scale and space relevant quantitative approach to study the association between environmental factors and health effects is proposed. This approach, being highly automated, is most helpful in studying rare health events using a large data set which observations are heterogeneously distributed.
Publications
- Chou, K. 2009. Target Sites: Endocrine, In P. Wexler (ed.),Information Resources in Toxicology. Academic Press. London, UK, p. 435-442.
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Progress 01/01/08 to 12/31/08
Outputs
OUTPUTS: I assessed the literature on nanotechnology and public health data for constructing mathematical models that can be used to examine potential health risks of environmental contaminants, with focuses on potential impacts on endocrine and neurological functions. A chain graph framework approach for toxicity extrapolation between nano and bulk materiel is presented at the Meeting of the Philosophy of Science Association. I am a member of the planning committee for the conference "Balancing Animal Agriculture and Communities," held at MSU on February 29, 2008. A research proposal "Framing Impacts of Multiple Policy Issues on Animal Agriculture, Communities and the Environment" was prepared and submitted to Michigan Applied Public Policy Research; I was the principal investigator of a team of 18 researchers. An interview survey was conducted to examine the perception of risks associated with large scale animal agriculture in Michigan. I spoke at the conference "Pharmaceuticals in the Environment: Current Trends and Research Priorities", as an invited panelist for discussion and reaction on Veterinary and Human-used Medicines in the Environment. I taught two courses, ANS 827 "Integrated Approaches to Risk Assessment of Environmental Hazards" and ESP 803 "Human and Ecological Health Assessment and Management." I also taught a one-week module on Metal and Trace Mineral Toxicity in the course of VM 812 "Food Safety Toxicology". PARTICIPANTS: The participating faculty members include Daniel Steel (Dept. of Philosophy, MSU), Dale Rozeboom (Dept. of Animal Science, MSU), Wendy Powers (Dept. of Animal Science, MSU), Geoffrey Habron (Dept. of Fisheries & Wildlife and Dept. of Sociology, MSU), and Craig Harris (Dept. of Sociology, MSU). The participating graduate students include Chidozie Amuzie (Dept. of Food Science & Human Nutrition, MSU), Leila Desotelle (Dept. of Zoology, MSU), Rich Grogan (Dept. of Community, Agriculture, Recreation, and Resource studies, MSU), Rebecca Hullman (Dept. of Civial & Environmental Engineering, MSU), Emily Norton (Dept. of Fisheries & Wildlife, MSU), Matt Grisko (Dept. of Philosophy, MSU), Shauna Hanisch (Dept. of Fisheries & Wildlife, MSU), Jason Karl (Dept. of Fisheries & Wildlife, MSU), Zarraz Lee (Dept. of Microbiology & Molecular Genetics, MSU), Norbismi Nordin (Dept. of Packaging), and Leilei Ruan (Dept. of Soil Science, MSU). The participation provides publication and future funding opportunities for all individuals. The graduate students gained the knowledge and skill to integrate chemical/physical, biological, and social factors in assessing the risks of environmental factors. TARGET AUDIENCES: A chain graph framework for extrapolation was presented at the "Symposium: Extrapolation and Public Policy" in the 21st Biennial Meeting of the Philosophy of Science Association, Pittsburgh, Pennsylvania, to demonstrate a new approach to assess the health risk of a set of substances which toxicity is mostly unknown. We are also in communication with the scientists at US EPA as an effort to provide effective and timely inputs for future regulatory decisions on the methods of assessing the risk of nanoparticles. On January 12, 2009, the preliminary results of the interview survey on community's perception of the risk of large scale animal operations will be presented to the Animal Ag and Environment Team, which members including university researchers and extension educators. The role of animal agriculture in life quality and the comparative impacts of the size of livestock operations on environment and the society are added to the teaching curriculum of the course ESP 803 "Human and Ecological Health Assessment and Management." Students in the course were invited to participate in the preliminary survey study. PROJECT MODIFICATIONS: The overall objective of the project remains the same: effects of environmental contaminants on human and animal health. Nano material as a new type of environmental contaminants was described in the "2007/01 to 2007/12" report. In addition to the lack of toxicological data, people also disagree how nano materiel should be regulated. In environmental disagreements there are many competing stakeholders with incompatible views and values. Conflicts could generate misperceptions and hostile attitudes, but may also have valuable functions for societal adaptability (Simonsi and Allen, 1998). A secondary objective is therefore added to the project: Assessing public perception of risk and risk management in environmental controversies. For these objectives, additional approaches are implemented: (1) mathematical modeling and extrapolation of toxicological data and (2) community survey on environmental health and risk perceptions.
Impacts
To understand the biological behavior of nanoparticles and associated health effects, a database is constructed to estimate the toxicity of nanoparticles. A set of automated tools for searching and integrating the contents of the database has been examined. Two newly developed mathematical approaches have been identified to be potentially useful for computing probability distribution in estimating the uncertainties in the nanotoxicity assessment. One of the methods is a mechanism-based information extrapolation framework that relies on comparative process tracing, a strategy for justifying a model as a basis for extrapolation when available information about the target mechanism is limited. Two strategies for minimizing the required information about the mechanism in the target are proposed. First, it is not necessary to compare the model and target mechanisms at points where, given background knowledge, similarities are very probable. Secondly, it may be possible to restrict attention to later, or downstream, stages of the mechanism upon which any relevant upstream differences must leave their mark. The other is the application of a Spatial Autoregression Model. In this approach, one may explored the relationship between a vector Y and a weight matrix W, where Y represents an (nx1) set of observed nanoparticle properties and W, an (nxn) set of weights, represents the degree of association between the properties. As for the risk of potential impacts of pharmaceutical products in the environment, the amounts of antimicrobial agents present in drinking water, in general, is less than one hundredth of the known effective doses in humans. Further analysis of the risk of antimicrobial agents in surface water are needed to estimate recreational exposure, sensitive of the intestinal microbial population in children, and potential impacts on the population of critical microorganisms in soil and sediments. As for the public's perception of impacts of the animal agriculture operations, results from the preliminary survey suggested a tendency to identify positive and negative aspects of large scale animal agriculture similar to what was provided in media outlets. The interview survey is, in part, supported by funding obtain by the Animal Ag and Environment Team and the Environmental Science and Policy Program.
Publications
- Steel, D. and Chou, K. 2008. Bayes nets and nanotech: A chain graph framework for extrapolation, Symposium: Extrapolation and Public Policy, Proc. 21st Biennial Meeting of the Philosophy of Science Association, Pittsburgh, Pennsylvania
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Progress 01/01/07 to 12/31/07
Outputs
OUTPUTS: The overall objective of the project, Effects of environmental contaminants on human animal health, remains the same. Nonetheless, while monitoring changes to the human and ecological environment I observed a new challenge to environmental toxicology: the increasing use of both organic and inorganic nanomaterials in commercial, pharmaceutical and household products and a lack of toxicological understanding of the impact of "size" on a substance's biological and ecological behaviors. The scope of the activity in 2007 focused on two aspects of nanotoxicology (1) examining the physical, chemical and biological features of nanomaterials, and (2) constructing new approaches of assessing the health risk of nanomaterials. Evolutionary nanotechnology has produced numerous types of nanomaterials at the 1-100 nanometer scales. Nano products are already on the market and generating billions of dollars in industry profits. They possess unique quantum and surface properties, which not
only allow improved exiting processes, materials and applications by scaling down to the nano scale, but also enhance the performance of each element, all at a low cost. Worldwide funding for nanotech innovation reached $12.4 billion by 2004 (LuxResearch 2007). Current applications of nanomaterials include nanoclays for structure composites and packaging, ZnO and TiO2 UV absorbers in cosmetics and coatings, CeO for fuel catalysts, and Li nanomaterials in batteries. Other fields supported by nanotechnology are memory chips, sensors, solar cell components, thermal management, material coatings, insulation, separation media, drug delivery, therapeutics, catalysis, antioxidants, and medical diagnostic agents. The market of Nanomaterials has exceeded $200 million and more than $32 billion in products incorporating nanomaterials were sold in 2005. The NSF predicts a $1 trillion revenue level of nanotechnology products by 2015 (Roco 2005), while other predictions for the same timetable are
as high as $2.9 trillion (LuxResearch 2007). The understanding of the environmental, health and safety consequences, however, has not kept up with the steep pace of innovation and product development. Nanomaterials do not behave the same, physically, chemically, and biologically as the same material in larger particles. Some nanomaterials and products have the potential to cause harm, depending not only on the type of chemical elements, but also their sizes, shapes, and functional surface groups. Regulatory agencies and toxicologists recognize that the conventional approach of testing health effects one substance, one shape, and one size at a time is unable to keep up with the numerous nanomaterials entering the market each year. I have co-hosted a seminar on inference modeling of nanomaterial properties, with the intention of recruiting a research collaborator from Carnegie Mellon, held weekly meetings with Dr. Dan Steel of the MSU Department of Philosophy for data extrapolation, and
have been invited to served as an expert and advisor for a NRI grant proposal titled "Public Perceptions Of Agrifood Nanotechnologies: Using Extension To Assess And Link Stakeholder Knowledge with Public Policies."
PARTICIPANTS: David M. Danks, Department of Philosophy, Carnegie Mellon, will work on the interpretation part Bayesian network and Daniel P. Steel, Department of Philosophy, Michigan State University, is an expert of extrapolation in buidling a theoretical framework for presenting claims about cause and effect and thier relation to statistical data.
TARGET AUDIENCES: The target audiences include nanotechnology Industry, FDA, EPA, other regulatory agencies, Environmental NGOs, toxicologists, general public, and health and environmental risk assessors. New topics on toxicity and risk of nanomaterials have been introduced to two graduate level courses. A manuscript on toxicity assessment of nanomaterials is in preparation.
Impacts
I analyzed existing data and identified key toxicity mechanisms and the strength and weakness of current nanotoxicology. We now propose a new risk assessment approach for health effects of nanoparticles based on existing data of nanotoxicity and are in the process of establishing an inferential model what would permit the introduction of prior knowledge and future data, as they become available, into the extrapolation and interpretation networks of nanotoxicity across different nano structures and sizes. In addition, I have introduced two new group studies in my graduate courses, "Current EPA Regulatory Approach to Nanoparticles" and "Current FDA Regulatory Approach to Nanoparticles".
Publications
- No publications reported this period
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Progress 01/01/06 to 12/31/06
Outputs
For the reporting period, hemochromatosis (HFE) gene mutation-associated changes in placenta transfer of Pb is mainly focused. This study was nested within a randomized controlled trial of calcium supplementation in breastfeeding mothers in and around Mexico City. Mothers were recruited during pregnancy and followed longitudinally from three hospitals in Mexico City, Mexican Social Security Institute, Manuel Gea Gonzalez Hospital, and National Institute of Perinatology. Baseline information on health status and social and demographic characteristics was extracted from all eligible participants. Interviewers explained the study to the women and the cohort included those who gave a live birth of vaginal delivery, were willing to participate, and provided written consent. Each mother completed a set of questionnaires, including a dietary survey. The exclusion criteria include Apgar missing at both 1 and 5 min and score 4-6 at 5 min, maternal mental alteration, maternal
postpartum infection, cardiopathies, nephropathies, urinary infection, kidney stones, gestational diabetes, anticonvulsive drug usage, and living outside of study area. Peripheral maternal and infant umbilical cord blood samples were collected at delivery and used to measure lead concentration and for HFE genotyping. Two HFE polymorphisms, C282Y and H63D, were genotyped in 580 mothers and 416 infants. Baseline characteristics of the study population are similar to that of the total cohort. So are frequency of the marital status, sex of newborn stored or prepared salsa in lead ceramic containers (11.0%), and smoked during pregnancy (4.2%). One mother and infant pair was excluded from the analysis, because the mpb concentration (35.4 ug/dl) is considerably outside the range of the other data points. Person correlation analysis revealed a positive correlation between cord blood lead (cpb) and maternal blood lead (mpb) (r, 0.861; p less than.0001). Multiple linear regression analysis
showed that mpb is a strong predictor of cpb. Furthermore, the regression models suggest that both maternal HFE C282Y/H63D and maternal HFE H63D negatively influence the relationship between cpb and mpb. On the average, each ug/dl of maternal blood Pb is associated with an increase in 0.54 ug/dl of Pb in umbilical blood Pb in the maternal C282Y/H63D carriers and 0.627 ug/dl in the maternal H63D carriers, comparing with the 0.76 ug/dl in the maternal non-C282Y/H63D and non-H63D carriers. The mean concentration of mpb (8.53 ug/dl), the maternal C282Y/H63D carriers is associated with a decrease of 1.04 ug/dl in cord blood Pb, while the maternal H63D carriers is associated with a decrease of 0.14 ug/dl. On the other hand, there is no effect of infant genotype on the relationship between cpb and mpb. Linear regression analysis also showed that maternal dietary Ca intake negatively influences the relationship between cpb and mpb. Each 1000 mg of Ca intake is associated with a decrease in
0.45 ug/dl cord blood Pb. Furthermore, the influence of HFE variants on the relationship between cpb and mpb is independent from Ca intake.
Impacts
Results of this study provides information for clinical intervention to decrease placenta transfer of lead from maternal body burden to fetal circulation.
Publications
- Chou, K., Hu, H., Ettinger, A. Tellez-Rojo, M., Schwartz, J., Hernandez-Avila, M. and Wrigh, R. 2006. Hemochromatosis Gene Variants Modify Placental Transfer of Lead. Joint ISEE/ISEA International Conference, Paris
- Chou, K. and Wright, R. 2006 Phthalates in food and medical devices. Journal of Medical Toxicology 2(3) September
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Progress 01/01/05 to 12/31/05
Outputs
Efforts were made to identify current and emerging problems in environmental health. The topics examined included developmental toxicity of lead and phthalates. Existing publications suggest that, while maternal blood lead at delivery predicts 30% of infant blood lead, placenta transfer is strongly associated with the average of all antenatal maternal blood lead and only weakly associated with maternal blood lead at delivery. A model has been built to examine factors that influence the lead transfer from mother to fetus. A comprehensive review was conducted to examine potential health problems associated with phthalates in the modern world. In commercial products, phthalates are the most frequently used plasticizers. They function as intermolecular lubricants, which allow polymer molecules to slide against each other and confer pliability and elasticity to plastics. Results from animal studies demonstrate developmental and reproductive effects of some of the commonly
used phthalates in commercial products, at dosages close to the potential exposure levels. Other effects observed in laboratory animals are allergic reactions of the respiratory system and tumor formation. However, there is a ongoing debate on whether phthalates could also induce tumors in human. In the modern living environment, humans and animals are constantly exposed to phthalates through numerous pathways, including food, air, drinking water, soil, toys, aerosol sprays, cosmetics, automobile interior, pharmaceutical products, and medical devices. For the general, non-occupationally and non-medical device exposed population, ingestion of contaminated food and inhalation of household aerosol sprays and fragranced personal care products are the major routes of exposure. Raw agricultural products contain minimum amount of phthalates. Phthalates typically are unintentionally added to food during processing and packaging. Total phthalates in the muscle of livestock and raw milk (120 -
280 microg/kg) rarely exceed 500 microg/kg. However, elevated concentrations of phthalates, up to 53,000 microg/kg, have been detected in food items on the market likely contaminated by processing and packaging. Direct contact with phthalate containing surfaces of processing equipment and packaging material is a major source of phthalates in human diet. For example, an increase in diethylhexyl phthalate (DEHP) in chicken, from 80 microg/kg precooking to 13,100 microg/kg after frying in a Teflon coated pan, and further to 16,900 microg/kg after packing. Printing ink on wrapping films is another source of phthalates in confectionary and snack products. Heating food in the ready-to-eat packages greatly facilitates phthalate migration from packaging materials to food. In dairy products, greater than 80% of total concentrations, ranging from 50 to 200 microg/kg in commercial milk, may be originated from milking equipment. Additional processing, packaging, and condensation can lead to 5
-100 fold increases in DEHP concentrations in cream and cheese products. Up to 11,100 microg/kg of DEHP in food can be attributed to leaching from PVC gloves used during food preparation.
Impacts
Knowledge generated from the lead model can be used to prevent or minimize fetal exposure to lead. The effects of lead on physical and mental development at extremely low exposure levels are well documented. I have been invited by the medical community to write an article to assess potential health effects of phthalates, with major focuses on phthalates in food and medical devices. Information will be used by health professional for advising patients and minimizing patient exposure from medical procedures, such as blood transfusions, hemodialysis, and Total Parenteral Nutrition administration. The work is funded by Center for Diseases and Prevention (CDC).
Publications
- Chou, K. 2005. Endocrine system and disruptors. In: Encyclopedia of Toxicology, Second Edition, Elsevier, Oxford, UK, pp.170-174
- Vadnais, M.L., Kirkwood, R.N., Specher, D.J., Chou, K. 2005. Effects of extender, incubation temperature, and added seminal plasma on capacitation of cryopreserved, thawed boar sperm as determined by chlortetracycline staining. Anim. Reprod. Sci. 90(3-4):347-354
- Vadnaisa, M.L., Kirkwooda, R.N., Tempelmanb, R.J., Sprechera, D.J. and Chou, K. 2005. Effect of cooling and seminal plasma on the capacitation status of fresh boar sperm as determined using chlortetracycline assay. Anim. Reprod. Sci. 87(1-2):121-132
- Cui, W., Flores del Pino, L., Voice, T.C., Chou, K. and Kamdem, D. P. 2005. Speciation of arsenic and chromium in the leachate from chromated copper arsenate (CCA) type C treated southern pine. Holzforschung, 59(2)199-204
- Niagolova, N., McElmurry, S.P., Voice, T.C., Long, D.T., Petropoulos, E.A., Vavezov, I., Chou, K. and Ganev, V. 2005. Nitrogen species in drinking water indicate potential exposure pathway for Balkan Endemic Nephropathy. Environmental Pollution, 134(2):229-237
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Progress 01/01/04 to 12/31/04
Outputs
Dr. Chou examined reproductive toxicity of several environmental factors, including chlorinated biphenyls, phytoestrogens, and pharmaceutical products that could potentially alter reproductive capacity of mammalian species. After high doses of exposure, decreases in offspring survival and low gamete production and fertilizing ability were observed in both male and female mice. However, significant increases in the number of ovulated eggs and egg fertilizing ability were observed after in-utero exposure to low doses of exogenous estrogenic chemicals. Chou and colleagues also studied the biochemical mechanism of sperm capacitation and the effect of cryopreservation on the viability of boar sperm cells. Seminal plasma not only protected sperm membrane against frozen-thaw induced membrane changes when it is added to semen extender before cooling, but also appeared to reverse the membrane changes when it was added during thawing. Using the chlortetracycline fluorescent
assay, Chou et al. demonstrated that sperm membrane changes caused by frozen and thaw are similar to that of sperm capacitation. The protective effect by seminal plasma, however, was nullified in the present of egg yolk.
Impacts
There have been increasing concerns over potential human and animal health effects caused by exposure to environmental estrogenic compounds, such as phytoestrogens in soybeans and corn, pharmaceutical products and persistent organochlorines in the environment. Our observations indicate that the amount of activity of estrogenic compounds in human food and animal feed are unlikely to cause any adverse effects on reproduction. Soybeans and corn remain to be the major crops for animal feed. They are also valuable sources of protein and antioxidants in human diets. Furthermore, the basic scientific knowledge generated from this project has generated two patents on methods for enhancing semen preservation and sperm fertilizing ability.
Publications
- No publications reported this period
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Progress 01/01/03 to 12/31/03
Outputs
The project is designed to examine potential reproductive toxicity of environmental estrogenic compounds, including phytoestrogens in food/feed and synthetic estrogens in human and animal waste. Previously, we reported decreases in sperm production and fertilizing ability in mice after utero and lactational exposure to high doses (1 and 10 ug/kg of maternal BW) of diethylstilbestrol (DES) and increases in fertilizing ability after low dose exposure. In contrast, genistein increased sperm production and fertilizing ability up to the maternal dose of 10 mg/kg of BW. The study reported here examined the effect of ethynylestradiol (EE2), the major estrogenic component of oral contraceptives, on sperm production and fertilizing ability in male offspring. Pregnant C57BL/6 mice (F-0), bred with DBA/2 male, were gavaged with 0, 0.1, 1, or 10 ug EE2/kg of BW per day from gestational day 12 to postnatal day (PND) 20. The male offspring (F-1), at 15-17 or 45-48 weeks of age,
were examined for sperm quality by using sperm motion analysis and in vitro fertilization (IVF) assay. The anogenital distance (AGD) of the male offspring in the 1 and 10 ug dose groups was shorter than that of the control animals on PND21. Sperm concentration from 45-48 week-old male offspring was lower in the 10 ug dose group than that in the control (P<.05), but not at 15-17 weeks of age. However, when equal sperm concentrations were used in IVF assay, no treatment effect on fertilization in either age group was observed. Results from this study suggest that exposure to high doses of EE2 during gestation could decrease sperm production, body weight, and AGD, while there is no apparent effect on sperm fertilizing ability. Similar to the observation in our DES study, low dose exposure, 0.1 ug/kg of maternal body weight, had no detrimental effect on sperm production of the offspring. The median dose tested, 1 ug/kg, is about 1.5 to 2 times of the dosage used in oral contraceptives.
United States Patent 6,596,310, July 22, 2003
Impacts
There have been concerns over potential human and animal health effects of exposure to environmental estrogenic compounds, including phytoestrogens in soybean and soybean products and estrogens released to the environment from human and animal waste. Results from this project indicate that at low doses, such as the concentrations observed in food, feed, and environment, are unlikely to be harmful for reproductive development in human and animals. There is no evidence for the need of replacing soybeen products in animal feed or installing additional treatments to decrease estrogenic compounds in animal and human waste.
Publications
- Fielden, M.R., Samy, S.M., Chou, K., and Zacharewski, T.R. 2003. Effect of human dietary exposure levels of genistein during gestation and lactation on long-term reproductive development and sperm quality in mice. Food and Chemical Toxicology, 41(4):447-454.
- Fielden, M.R., Halgren,R.G., Fong, C.J., Staub, C., Johnson, L., Chou, K. and Zacharewski, T.R. 2002. Gestational and lactational exposure of male mice to diethylstilbestrol causes long-term effects on testes, sperm fertilizing ability in vitro, and testicular gene expression. Endocrinology, 143(8):3044-3059.
- Chou, K., Lin,C.Y., Huang, A., Inglis, R. and Lin, S. 2002. Great Lakes contaminants reduce sperm production and fertilizing ability in mice. Lakes & Reservoirs: Research & Management, 7:231-239.
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Progress 01/01/02 to 12/31/02
Outputs
The long-term reproductive effects of gestational and lactational exposure to genistein on male mice at levels comparable to or greater than dietary exposure have been studied. No significant effects on male offspring body weight, anogenital distance, seminal vesicle weight or testis weight were observed. There were no significant effects on sperm concentration or sperm motility. Sperm fertilizing ability in mouse received 10 mg/kg/day genistein was 17% higher than that received phytoestrogen free diet.
Impacts
The results indicate that the amount of genistein in soy bean and soy bean products are unlikely to be harmful for male reproductive development in humans and animals.
Publications
- Fielden, M.R., Halgren, R.G., Fong, C.J., Staub, C., Johnson, L., Chou,K., and Zacharewski, T.R. 2002. Gestational and lactational exposure of male mice to diethylstilbestrol causes long-term effects on the testis, sperm fertilizing ability in vitro, and testicular gene expression. Endocrinology, 143(8):3044-59.
- Chou, K., Lin, C.Y., Huang, A., Rochelle, I., and Lin, S.L. 2002. Great Lakes' Contaminants Reduce Sperm Production and Fertilization Ability in Mice, Lakes & Reservoirs: Research and Management 7:231-239.
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Progress 01/01/01 to 12/31/01
Outputs
A mouse cDNA microarray containing 1948 genes was used to profile the testicular gene expression of the offspring from DES exposed dams. Pregnant C57BL/6 female mice bred with DBA/2 males were gavaged with 10 ug of DES/kg of b.w./day from gestational day 12 to postnatal day 21. The fluorescence measurements were analyzed using two interconnected mixed models, a "normalization" model and a "gene" model. The normalization model accounted for experiment-wide systematic effects that could bias inferences made on the data from individual genes. The residuals from this model represent "normalized" values, and were the input for the gene model. The gene model was fitted separately to the normalized data for each gene, allowing inferences to be made using separate estimates of variability. Differences between Least Squares Means for treatment groups were estimated using Scheffe adjustments. At 15 weeks of age, the expression of 20 genes in the exposed males were four times or
higher of the levels in the controls. Additional 39 genes were expressed at least twice of that in the controls. Among the suppressed genes, 31 genes were expressed less than one fourth of that in the controls and another 31 were expressed at less than half of the control levels. Over expression of prolactin receptor, serine/threonine kinase 10, and tyrosine phosphatase and under expression of prostaglandin E receptor 1 are among the several prominent changes observed in the testes of DES exposed offspring.
Impacts
This study identified the genes which expression are susceptible to estrogenic compounds during early development. The information can be used to maximize reproductive performance in male animals.
Publications
- Fielden, M.R., R. G. Halgren, C. H.M. Tashiro, B. R. Yeo, B., K. Chou, and T. R. Zacharewski, 2001 Effects of gestational and lactational exposure to Aroclor 1242 on testicular size and sperm quality in early adult and middle-age mice. Reproductive Toxicology,15:281-292.
- Long, D., G. Icopini, V. Ganev, E. Petropoulos, I. Havezov, T. Voice, and K. Chou, A. Spassov, A. Stein, 2001 Geochemistry of Bulgarian Soils in Villages Affected and Not Affected by Balkan Endemic Nephropathy: A Pilot Study, J. of Occupational Medicine and Environmental Health. V. 14: 193-196.
- Fielden, M.R., R.G. Halgren, C.J. Fong, K. Chou, P.M. Saama, and T.R. Zacharewski, 2001, Male Reproductive and Genomic Effects of Developmental Exposure to Diethylstilbestrol in Mice, Toxicological Sciences, Supplement, 60(1) 247
- Han, J., M. Fielden, R. Halgren, T. Zacharewski, P.M. Saama, and K. Chou, 2001, Effect of Gestational and Postnatal Exposure of Diethylstilbestrol on Female Reproduction, Toxicological Sciences, Supplement, 60(1) 387
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Progress 01/01/00 to 12/31/00
Outputs
Effects of maternal exposure to diethylstilbestrol (DES) on the reproductive function in the offspring were examined. Pregnant C57BL/6 mice (F-0), bred with DBA/2 male, were gavaged daily with 0.1cc corn oil containing DES at a nominal dose of 0, 0.1, 1, or 10ug/kg from gestational day 12 to postnatal day 21. No statistically significant effects on gestational index or 4 day pup survival were observed. Litter size was significantly decreased in the 10ug/kg treatment group. Sex ratio (male/female) was significantly higher in the 1ug/kg treatment group and lower in the 10ug/kg treatment group. In the high does group, aneogenital distance (AGD) in the male offspring, recored on day 21 postpartum, was shorter, while the AGD in female offspring was longer, than that in the controls. To assess sperm quality in male offspring, epididymal sperm count, sperm motility, and sperm fertilizing ability was examined at 15 weeks of age. Decreases in testes weight, sperm count and
sperm fertilizing ability was observed in all treatment groups. These effects occurred without apparent histological abnormalities in the testes. Testicular gene expression was examined in weanling mice using a custom cDNA microarray containing 2300 genes known to be expressed in the testis. A number of small, but consistent, decreases in the expression of genes involved in the ubiquination pathway, cell differentiation, meiosis, and cell-cell communication were observed. On the hand, the expression of genes involved in protection from oxidative and heat shock were induced. Transcriptonal repressors were also induced. At 3 weeks of age, anogenital distance in the female offspring was longer in the 1 ug/kg treatment group that in the control group. At 3 and 8 weeks of age, eggs from the F-1 females were collected and examined for fertilizing ability in vitro. At 8 weeks of age, the number of eggs ovulated in responding to PMSG and HCG injections was significantly lower in the 10 ug/kg
treatment group than that in the controls. The numbers of egg ovulated were not different among 3 weeks of age treatment groups. DES did not have any effect on the fertilizing ability of eggs. At 8 weeks of age, the degeneration rate was lower in the 10 ug/kg treatment group than in the control group. No relationship between body weight and the number of egg ovulated was observed. Results from this study indicated that high dose treatment of DES could compromise female offspring's ovulatory function in adulthood.
Impacts
Results of this study provide information for understanding the potential effects of estrogenic chemicals on reproduction in male and female offspring. The data are important in the decision making process when regulating endocrine disruptors in the environment.
Publications
- Chou, K., Haug, A. and Shi, B. 2000. Arsenic and Aluminum Speciation in Environmental Toxicicology -- a Minireview in Metal Spceciation in the Environment, The Global Network of Environmental Science and Technology, pp. 9-19.
- Fielden M.R., Halgren, R.G., Chou, K., and Zacharewski, T.R. 2000. Developmental effects of Aroclor 1242 on male offspring after gestational and lactational exposure. Toxicological Sciences (Suppl 1-S) 54:288
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Progress 01/01/99 to 12/31/99
Outputs
Developmental effects of PCBs on male reproduction in rodents have been reported previously, however, with inconsistent results. The effects on testicular weights and fertility depend on the test congener or mixture, the dosage, the developmental stage during exposure, and the age of the animals when examined. We have previously reported an increase in testes weight and a decrease in sperm fertilizing ability in 3,3',4,4'-tetrachlorobiphenyl treated young males. The effect of Aroclor 1254 on sperm fertilizing ability after neonatal exposure, however, was not observed until 45 weeks of age. In this study effects of gestational and lactational exposure of Aroclor 1242 (0, 10, 25, 50 and 100 mg/kg/2 days) on testicular development and sperm quality in 16-week and 45 week old male mice were examined. Sperm concentration and quality were examined using in vitro fertilization and computer-assisted sperm motion analysis. There was no effect on maternal body weight,
fecundity, litter size, litter weight, sex ratio or the 21-day survival index. There were no differences in liver weights and thymus weights at 3 and 16 weeks of age. Nor were any detectable changes in sperm quality or testicular gene expression at 16 weeks of age. There was, however, an increase in anogenital distance in the male offspring in the 25 mg/kg treatment group, observed on post natal day 21. A trend of increases in testes weights was observed in the 25 and 50 mg/kg treatment groups. At 45 weeks of age, sperm concentration decreased signifcantly, a 31% decrease, in the 25 mg/kg treatment group, but not in 16 mg/kg, 50 mg/kg and 100 mg/kg treatment groups. This result suggest that the effects of Great Lakes pollutants on sperm quality in post-maturity male mice observed in our previous studies is, at least in part, cuased by PCBs. The testicular gene express experiments are in progress.
Impacts
The effect of PCBs on sperm production is non-linear. An apparent effect on sperm production observed at 25mg/kg B.W. exposure level, is not obsvervable in animals that had higher exposures. This knowledge, a non-linear dose-response effect, which has also been reported in other studies where low-dose effects of environmental contaminants were examined, should have an impact on how laboratory data should be used in environmental risk assessment for regulatory purposes.
Publications
- Chou, K. 1999. Disruption of sperm production and puberty in mice by Great Lakes contaminants. Proceedings of The 6th CEST Conference. B:147-153.
- Chou, K., Haug, A. and Shi, B. 2000(accepted) Arsenic and Aluminum Speciation in Environmental Toxcicology -- a minireview. J. Global Network of Environmental Science and Technology.
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Progress 01/01/98 to 12/31/98
Outputs
The effects of Great Lakes contaminants on the growth and maturation of female mice were investigated. Female C57BL/6J mice (F-O) were mated with DBA/2J male mice producing B6D2-F2 offspring. Dams (F-O) were fed one of three treatment diets following parturition. The offspring (F-1) were continued on their respective parental treatment diets from weaning through the termination of the study. The three treatment diets were as follows: diet C contained lab chow and fish oil, diet I contained 60 percent Iowa carp and 40 percent lab chow, and diet G contained 60 percent Great Lakes carp and 40 percent lab chow. Diet C was the lab chow control treatment, while diet I served as a fish-diet control treatment. Diet G contained 2500 ppb polychlorinated biphenyls (PCBs) and 300 ppb 1,1-dichloro-2,2,bis-[p-chlorophenyl]ethylene (4,4'-DDE), while neither was detected in diets C and I. A delay in vaginal opening was observed in F-1 mice on diet G. These mice also had lower body
weights than control mice from three to eight weeks of age. Patent/Invention No: 5834225. DATE: November 10, 1998.
Impacts
(N/A)
Publications
- Huang, A., Powell, D., Chou, K. 1998. Pre- and post-natal exposure to 3,3',4,4'-TCB: I. Effects on breeding ability and sperm fertilizing ability in male mice. Arch. Environ. Contam. Toxicol. 34:204-208.
- Huang, A., Powell, D., Chou, K. 1998. Pre and post-natal exposure to 3,3', 4,4'-TCB: II. Effects on the reproductive capacity and fertilizing ability of eggs in female mice. Arch. Environ. Contam. Toxicol. 34:209-214.
- Mousa, M., Ganey, P.E., Quensen, J.F., Madhukar, B.V., Chou, K., Giesy, J.P., Fischer, L.J., Boyd, S.A. 1997. Altered biological activity of commercial PCB mixtures after microbial reductive dechlorination. Environ. Health Persp. (Accepted).
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Progress 01/01/97 to 12/31/97
Outputs
This study investigated the effects of 3,3',4,4'-tetrachlorobiphenyl (TCB) on the reproductive capacity of female mice. Female C57BL/6J mice (F-0) were fed diets containing 0, 3, or 30 ppm TCB for 2 weeks before pairing with nontreated C57BL/6J males for a 10-day breeding period. Females were continued on their treatment diet throughout mating, gestation, and lactation. Offspring (F-1) were fed the same diet as their dams throughout the study. The reproductive capacity of F-1 females was examined by mating with non-treated B6D2-F1 males. The fertilizing ability of eggs from F-1 females was examined in vitro by insemination with sperm from nontreated B6D2-F1 males. Fecundity in F-0 females after mating was 80%, 71% and 47% in the 0, 3, and 30 ppm treatment groups, respectively. Four-day and 21-day survival indices were lower for offspring of 30 ppm TCB-treated F-0 females than for offspring of the control females. Fecundity in F-1 females was the same among all
treatment groups, however, all offspring born to 3- and 30-ppm TCB-treated F-1 females died before 4 days of age. Although the litter size at birth was not affected, the in vitro fertilizing ability of eggs in the 3- and 30-ppm treatment groups was lower than in the control group. At 5 and 6 weeks, liver enlargement and thymus atrophy were apparent in F-1 females exposed to 30 ppm TCB. This study demonstrated impaired reproductive capacity and decreased egg fertilizing ability in TCB-treated female mice. F-1 males at 7 and 17 weeks of age were mated to nontreated B6D2-F1 female mice. Body weight, litter size, and survival indices of offspring sired by F-1 males were recorded. Sperm fertilizing ability of F-1 males at 9 and 19 weeks of age was examined in vitro using eggs collected from nontreated B6D2-F1 females. Sperm motion analysis was performed at the same time. When 7- and 17-week-old F-1 males were mated to nontreated females, no differences in fecundity, litter size, sex ratio,
or survival indices among any of the treatments were observed. However, sperm fertilizing ability of 30 ppm-treated F-1 males at 19 weeks of age was less than that of the control mice. Testes weights were greater in 3-week-old, 30 ppm-treated mice.
Impacts
(N/A)
Publications
- ENGLIS, R., LIN, C.Y., CHOU, K. 1997. Effects of lactational and neonatal exposure to Aroclor 1254 on vaginal opening and gamete fertilizing ability in mice. Biology of Reprod., Vol 56, Supplement 1.
- HUANG, A., POWELL, D., CHOU, K. 1998. Pre- and post-natal exposure to 3,3',4,4'-TCB: I. Effects on breeding ability and sperm fertilizing ability in male mice. Arch. Environ. Contam. Toxicol. (in press).
- HUANG, A., POWELL, D., CHOU, K. 1998. Pre and post-natal exposure to 3,3', 4,4'-TCB: II. Effects on the reproductive capacity and fertilizing ability of eggs in female mice. Arch. Environ. Contam. Toxicol. (in press)
- BRIESKE, J.A., MOUSA, M., MADHUKAR, B.V., BOYD, S.A., CHOU, K. 1997. Anti-androgenic potential of endosulfan and its microbial transformation products. Dioxin'97, Indianapolis, IN.
- MOUSA, M., GANEY, P.E., QUENSEN, J.F., MADHUKAR, B.V., CHOU, K., GIESY, J.P., FISCHER, L.J., BOYD, S.A. 1997. Altered biological activity of commercial PCB mixtures due to microbial reductive dechlorination. Dioxin `97, Indianapolis, IN.
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Progress 01/01/96 to 12/30/96
Outputs
Aroclor 1242 and Aroclor 1254 were dechlorinated by microorganisms eluted from PCB-contaminated Silver Lake (SL) and River Raisin (RR) sediments. Toxicities of the parent Aroclor mixtures and their dechlorinated products were evaluated using in vitro fertilization of mouse gametes, as PCBs have previously been demonstrated to inhibit this process. The gametes were exposed to 0, 10, and 20 ppm of Aroclor 1242 and Aroclor 1254 and to equal total molar concentrations of the RR and SL dechlorinated products of each Aroclor. Exposure of gametes to the non-dechlorinated Aroclors resulted in two adverse effects: a high percentage of degenerated eggs and a low percentage of fertilized eggs (0-35%). In the absence of PCBs, few eggs (1-7%) degenerated and most eggs (83-86%) were fertilized. At high doses, dechlorination of Aroclor 1242 and 1254, by both sources of organisms, markedly reduced the inhibitory effect on fertilization. At low doses, dechlorination by RR organisms
eliminated the adverse effects.
Impacts
(N/A)
Publications
- Mousa, M.S., J.F. Quensen, K. Chou, S. Boyd. 1996. Microbial dechlorination alleviates inhibitory effects of PCBs on mouse gamete fertilization in vitro. Environ. Sci. & Technol. 30(6): 2087-2092.
- Lin, S.C., B. Salem, K. Chou. 1996. The relationship between glucose and the requirement for reactive oxygen species in mouse sperm fertilizing ability. Biology of Reprod, Vol. 54, Supplement 1.
- Lin, S.C., B. Salem, K. Chou. 1996. The requirement and Toxicity of Reactive Oxygen Species in Mouse Gamete Fertilization. Fundamental and Applied Toxicology, Supplement, 30(1): 122.
- Huang, A.J. and K. Chou. 1996. Effect of perinatal and continuous exposure to 3,31, 4, 41 -tetrachlorobiphenyl on reproductive performance and sperm fertilizing ability in mice. Fundamental and Applied Toxicology, Supplement, 30(1): 291.
- C. Lin and K. Chou. 1996. Long-term effects of Great Lakes carp containing diet on reproduction in mice. Fundamental and Applied Toxicology, Supplement, 30(1): 144.
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Progress 01/01/95 to 12/30/95
Outputs
The necessity for reactive oxygen species in fertilization was examined. Glucose, as the sole carbohydrate source, supports capacitation and fertilization of mouse gametes in vitro. In the presence of glucose alone, 78.6 +/- 7.6% of the eggs were fertilized. Without glucose, despite the presence of other carbohydrates, no eggs were fertilized. When glucose was substituted with fructose or fructose-6-phosphate, along with xanthine, xanthine oxidase, and catalase (the xanthine oxidase system), maximum fertilization was obtained. The results indicated that the xanthine oxidase system, providing the exogenous reactive oxygen species for sperm fertilizing ability, could also be toxic to gametes in the absence of catalase. When catalase was eliminated, the substitution supported only 13.5 +/- 3.3% fertilization. Results from this study support the hypothesis that reactive oxygen species are essential for the normal progress of sperm capacitation while excess hydrogen
peroxide is detrimental to fertilization. Therefore, xenobiotics may decrease sperm fertilizing ability by either increasing or decreasing the production of reactive oxygen species.
Impacts
(N/A)
Publications
- Chou, K.C., Cook, R.M. 1995. Acetylcholine prevents toxic effects of paraoxon on mouse sperm. Bull. Environ. Contam. Toxicol. Bull. Envrion. Contam. Toxicol. 54:251-257.
- Yang, H.H., Aulerich, R.J., Helferich, W., Yamini, B., Chou, K.C., Miller, E.R., and Bursian, S.J. 1995. Effects of Zearalenone and/or Tamoxifen on Swine and Mink Reproduction. J. of Applied Tox. 15(3):223-232.
- Chou, K., Mousa, M., Quensen, J. 1995. Reductive dechlorination reduced negative impact of PCBs on In Vitro Fertilization. Soc of Environ Tox & Chemistry. 2nd SETAC World Congress, Vancouver, British Columbia, Canada. (Abstr.).
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Progress 01/01/94 to 12/30/94
Outputs
Effects of microbial dechlorination on PCB toxicity was examined using in vitro fertilization (IVF) of mouse gametes as the testing methods. Aroclor 1242 & Aroclor 1254 were incubated with microorganisms collected from either River Raisin (RR) or Silver Lake (SL). Before dechlorination, 20 ppm Aroclor 1242 or 1254 completely inhibited fertilization of mouse gametes in vitro. At 10 ppm, 35% of eggs were fertilized in Aroclor 1242 & 21% fertilized in Aroclor 1254. A substantial reduction in PCB toxicity was observed by anaerobic dechlorination with microorganisms of both sources, as demonstrated by IVF. After dechlorination by RR microorganisms, 63 % & 8% of the eggs fertilized in the presence of 20 ppm Aroclor 1242 and Aroclor 1254, respectively. At 10 ppm, no inhibition of IVF was observed. After dechlorination by SL microorganisms, 21% & 31% of the eggs were fertilized in 20 ppm, & 41% and 49% of the eggs were fertilized in 10 ppm, of Aroclor 1242 & Aroclor 1254,
respectively. The anaerobic incubation & the identification of PCB congeners were performed by the laboratory of Dr. S. Boyd in the Depart. of Crop & Soil Science.
Impacts
(N/A)
Publications
- NO PUBLICATIONS REPORTED THIS PERIOD.
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Progress 01/01/93 to 12/30/93
Outputs
Ethylene Bisdithiocarbamates (EBDCs) are a group of widely-used fungicides for fruits and vegetables. The common metabolite of EBDCs, ethylene thiourea (ETU), has been found in exposed animals and plants, as well as in commercial EBDC formulations. It has been hypothesized that ETU toxicity is related to a highly reactive form of atomic sulfur released during the metabolic formation of ethyleneurea from ETU. The objectives of this study were to examine the ETU effects on fertilization in vitro and free radical production in ETU treated spermatozoa. Sperm were collected from epididymides of mature B6D2-F1 males. Eggs ere obtained from 4 to 12 week-old females. Sperm lipid-peroxyl radicals were examined by an Varian E-4 ESR spectrometer, using spin Trap alpha-(4- pyridyl-1-oxide) N-t-butylnitrone. No inhibitory effects of 1 ppm ETU on fertilization in vitro were observed. At 5, 10, 25 and 50 ppm, fertilization was inhibited to about 80% of that seen in the controls. At
800 ppm, no eggs were fertilized. In the controls, 80 to 90% of the eggs were fertilized. In the control spermatozoa, the production of lipid peroxyl radicals surged at two sampling points: one at the first hr and the other at the fourth hr. Spermatozoa incubated in the 1000 ppm ETU produced more lipid peroxyl radicals than the controls at all sampling points. Instead of two surges, ETU-treated spermatozoa showed only one peak production of peroxyl radicals at 2 hr.
Impacts
(N/A)
Publications
- SHI, B., CHOU, K., HAUG, A. 1993. Aluminum impacts elements in inositolphosphotide signaling pathway in neuroblastoma cells. J. Molec. Cell Biol. 121:109-118.
- KUO, J., OSWALT, M.D., CHEN, L., GRIGNOLA, F.E., CHOU, K. 1993. Reproductive performance of mice fed Great Lakes carp and fish farm-raised carp. Toxicologist, 13(1):202 (Abstr.).
- CHEN, L., GRIGNOLA, F.E., KUO, J., KING, L.E., CHOU, K. 1993. Effects of mancozeb on sperm variables in second generation of mice. Toxicologist, 13(1):202 (Abstr.).
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Progress 01/01/92 to 12/30/92
Outputs
Long-term effects of mancozeb on sperm Ca(superscript 2+)(subscript int), concentration and motility of the second generation were evaluated. Twenty-five male mice (CBA/CAJ), at 3 weeks of age, were treated with mancozeb (0, 5, 30, 300 or 3000 ppm) in the diet for 14 weeks, and then housed with mature, previously non-treated females. Female mice received the respective mancozeb-containing diet from the beginning of breeding throughout gestation and lactation. The offspring continuously received the treatment diet until termination. At 6 weeks of age, male offspring of the 30, 300 and 3000 ppm treatments had body weights 8% lower (p=0.17), and sperm concentrations 64, 53, and 25% lower (p=0.12), respectively, than the controls. The percentage of motile sperm, however, was the same among all treatment groups. At 8 weeks of age, no differences in body weights, sperm concentration or sperm motility among treatment groups were observed. Similar to that observed in the
previous single generation study, sperm Ca(superscript 2+)(subscript int) of the 30, 300 and 3000 ppm-treated mice were 26, 23, and 46% higher, respectively, than control values. This study demonstrated the effect of mancozeb exposure on sperm Ca(superscript 2+)(subscript int) and its transient effects on mouse body weights and sperm concentration of the second generation at 6 weeks of age.
Impacts
(N/A)
Publications
- SHI, B., L. CHEN, K. CHOU, and A. HAUG. 1992. Elevation of Intracellular Free Calcium Levels in Sperm in Response to Long-Term Feeding of Fungicides to Mice. J. Environ. Sci. Health B27(1):1-8.
- SHI, B., M.D. OSWALT, K. CHOU, and A. HAUG. 1992. Loss of Inositol Phospholipids in Epididymal Sperm Following Exposure of Mice to Long-Term Feeding of Organophosphates. Pharmacology & Toxicology 70:75-76.
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Progress 01/01/91 to 12/30/91
Outputs
Eighty five male mice (C57BL/6J), at 3 weeks old, were treated with mancozeb (0,5, 30, 300 or 3,000 ppm) and later housed individually with a mature, previously non-treated C57BL/6J female during week 10, 14 or 30 of the feeding. After 14 weeks of treatment, intracellular calcium, hydrogen peroxide concentration and free radical production of epididymal sperm were examined. The pregnancy rate and litter size of the treatment groups were not lower than that of the controls. The sperm intracellular calcium concentration from 30, 300 and 3,000 ppm treated mice were 45-60 % higher than that of the controls. Sperm hydrogen peroxide concentration, initiated by NADPH, was lower in mancozeb treated groups than that of the controls. Sperm lipid peroxyl radicals were examined by Varian E-4 EPR spectrometer, using spin trap ?(alpha)-(4-pyridyl-1-oxide) N-t-butylnitrone), A(superscript N)=15.8 G and A(superscript H)=2.6 G. The production of lipid peroxyl radicals in the sperm
appears to be correlated with sperm hydrogen peroxide concentration. Although free radical production and intracellular calcium concentration in the sperm from long-term, low-dose mancozeb treated mice were different from that of the controls, natural breeding was not affected under the conditions tested in this study.
Impacts
(N/A)
Publications
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