Grantee Research Project Results

2006 Progress Report: Latent Effects of Gestational Exposure to Heptachlor

EPA Grant Number: R829439
Title: Latent Effects of Gestational Exposure to Heptachlor
Investigators: Baker, Dean , Yang, Haiou , Kesner, James , Gollapudi, Sastry , Luderer, Ulrike
Institution: University of California - Irvine , National Institute for Occupational Safety and Health
EPA Project Officer: Aja, Hayley
Project Period: March 1, 2002 through February 28, 2005 (Extended to August 31, 2006)
Project Period Covered by this Report: March 1, 2006 through February 28, 2007
Project Amount: $1,931,310
RFA: Endocrine Disruptors: Epidemiologic Approaches (2001) RFA Text |  Recipients Lists
Research Category: Endocrine Disruptors , Human Health , Safer Chemicals

Objective:

The objective is to determine whether gestational exposure to the cyclodiene insecticide heptachlor permanently alters reproductive and immune function. The study is based on a unique, well-characterized episode in which the entire commercial milk supply on the Hawaiian island of Oahu was contaminated with heptachlor epoxide during a 15-month period (1981–1982), resulting in gestational exposure to offspring of women who drank cows’ milk during that period. The study used a population of 1,891 young adults, born between July 1981 and June 1982, who participated in an earlier study of the neurobehavioral effects of this exposure. The target for the study population is 400 young adults who were born on Oahu and 200 comparison participants who were not born on Oahu. This target study population was supplemented by recruitment of additional age-eligible young adults using school records from the State of Hawaii Department of Education.

The study has assessed sensitive biological indicators of reproductive and immune function, including: serum reproductive hormone concentrations—testosterone in men, estradiol and progesterone in women, and luteinizing hormone and follicle-stimulating hormone in both men and women; semen samples in men; and one menstrual cycle of daily urine specimens in women to measure levels of luteinizing hormone, estrone-3-glucuronide (EG), and pregnanediol 3-alpha-glucuronide (PG). Indicators of immune function include measurement of cutaneous delayed hypersensitivity reaction to recall antigens, antibody titer response to immunization with tetanus and multivalent pneumcooccal vaccine, and the proportion of Th₁ and Th₂ type CD4+ cell subsets in the peripheral blood.

The analysis will compare reproductive and immune function measures between the Oahu-born and non-Oahu born participants, controlling for relevant confounders. Estimates of gestational heptachlor epoxide exposure during the milk contamination will be modeled based on exposure data obtained in earlier studies and on historical data of pesticide concentration in the contaminated milk.

Progress Summary:

During year 5, we completed data collection for participants who had entered the study prior to the end of recruitment, conducted data verification for field office data, closed the project office, and worked with collaborating laboratories to obtain and verify their final analyses.

To summarize the recruitment efforts, we attempted to trace and recruit all 1,891 persons in the recruitment database. We were able to contact 1,123 potential participants. Of the contacted persons, we were able to recruit and enroll 351 participants, 354 were not willing to take part in the study, 367 were not eligible, and 51 were lost to recruitment after being contacted. After attempting to contact all persons in the recruitment database, we developed several strategies to expand participant recruitment, including mailing special outreach letters and using school databases to contact eligible students who did not participate in the previous study. We recruited an additional 106 participants through these other recruitment strategies.

At the end of data collection, the number of participants enrolled in the study was 457, of whom 249 were male and 208 were female. We collected 457 participant questionnaires and 409 parent questionnaires. To evaluate the integrity of cell-mediated immunity in vivo, we administered 406 skin tests with 2 standard recall antigens (tetanus and Candida), 324 tetanus vaccines, and 388 pneumococcal vaccines, along with the collection of pre/post blood samples to measure antibody response and 430 blood samples for complete blood count (CBC) laboratory testing. To evaluate lymphocyte cell subtypes and cytokine expression following activation of peripheral blood T cells, the staff collected fresh blood samples for 263 participants, which were express mailed to the University of California at Irvine (UCI) for delivery and analysis within 24 hours of the blood draw. To measure luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E), and progesterone (P), we collected 152 female and 245 male blood specimens, which were processed, frozen, and subsequently sent in batches to the National Institute for Occupational Safety and Health (NIOSH) for analysis. To determine whether the women are ovulating normally, we collected a month of daily urine samples for 162 female participants. In addition, we collected 197 semen specimens at a licensed medical laboratory to assess semen quality among male participants.

Because of the complexities of the data collection procedures and coordination of the two project offices, we devoted substantial effort toward verifying the tracking data, the hard copies of the data forms, and the data entered into the databases for future analyses. After going through the final data collection followup and data verification, we closed the Hawaii project office on April 30, 2006. The major project equipment and the original charts were sent to the project office at UCI. Employment of the last field office project staff member was terminated on April 30, 2006. Another major activity was working with the collaborating laboratories, the UCI Immunology Laboratory and the NIOSH Reproductive Function Laboratory, to verify the consistency of participant IDs and dates for the specimens. The project could not be completed because of ongoing efforts to verify the Immunology Laboratory analysis results and because the Reproductive Function Laboratory reported multiple delays and was not able to provide the final laboratory analysis results.

Future Activities:

We plan to focus on data analysis for future activities. As of now, we do not have a firm date for the endocrine analysis in serum and urine samples to be delivered, although the NIOSH Reproductive Function Laboratory has indicated that they will now proceed with the analyses.

Supplemental Keywords:

epidemiology, heptachlor, pesticide, reproductive function, immune function,, RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Geographic Area, Toxics, International, Health Risk Assessment, Physical Processes, pesticides, Risk Assessments, Chemistry, Environmental Chemistry, Endocrine Disruptors - Human Health, Children's Health, endocrine disruptors, Endocrine Disruptors - Environmental Exposure & Risk, Genetics, health effects, toxicity, particle exposure models, toxic environmental contaminants, environmental mutagens, environmental stressors, harmful environmental agents, embryonic development, biological markers, age-related differences, growth & development, risk assessment, developmental biology, pesticide exposure, human exposure, estrogen metabloism, susceptibility, cumulative environmental exposure, exposure studies, diet, insecticides, endometriosis, fertility, endocrine disrupting chemicals, reproductive processes, exposure, Oahu, Hawaii, epidemiologic studies, gestational exposure, lactational exposure, latent effects, environmental toxicant, gene-environment interaction, human health risk, Heptachlor, exposure assessment, human malformation, vulnerability, childhood development, puberty, developmental disorders

Progress and Final Reports:

Original Abstract

2002 Progress Report

2003 Progress Report

2004 Progress Report

2005 Progress Report

Final