Genetic Susceptibility to the Effects of Aromatic Solvents on Reproductive Health

EPA Grant Number: R825818
Title: Genetic Susceptibility to the Effects of Aromatic Solvents on Reproductive Health
Investigators: Xu, Xiping , Chen, Dafang , Christiani, David , Ryan, Louise , Smith, Thomas , Wang, Lihua
Institution: Harvard T.H. Chan School of Public Health , Beijing Medical University
Current Institution: Harvard T.H. Chan School of Public Health
EPA Project Officer: Hahn, Intaek
Project Period: February 1, 1998 through January 31, 2001
Project Amount: $792,308
RFA: Issues in Human Health Risk Assessment (1997) RFA Text |  Recipients Lists
Research Category: Health Effects , Human Health , Human Health Risk Assessment , Health


The objective of the proposed research is to assess the impact of gene-aromatic solvent interaction on adverse reproductive outcomes, including menstrual disturbance, infertility, spontaneous abortion, preterm delivery, and low birth weight. Specifically, using resources from a large, well-characterized cohort study, we will prospectively investigate whether the risk of adverse reproductive outcomes associated with aromatic solvent exposure is elevated in individuals with relevant variants of one of the following nine genes: GSTM1, GSTT1, GYPIAI, CYP2D6, CYP2E1, NAT2, NQO1, ALDH2, EPHX.


To assess gene-aromatic solvent interaction in the etiology of adverse reproductive outcomes, we will utilize a large extant population resource in Yanshan, Beijing, China, which has been assembled for an international collaborative study funded by NIOSH (RO1 OH03027; 2/94-2/98) to evaluate the effects of aromatic solvent exposure on reproductive outcomes. A total of 1,000 married women (approximately two-thirds are exposed to aromatic solvents and one-third are non-exposed) who obtain birth permission from the family planning administration between June 1994 and June 1997 have or will have been registered and invited to participate in the study. Upon enrollment, each woman and her husband are evaluated via questionnaire with regard to smoking, indoor pollution sources, diet, and physical activity at work/home (possible confounding factors) as well as occupational exposrue to benzene, toluene, styrene, and their derivatives (with special consideration given to chemicals relevant to the participant's job or work site). Later, environmental exposure is assessed through the collection of personal and area samples (e.g., for determination of benzene, toluene, and styrene concentrations in the air) and through detailed diary information. A 5-ml blood sample is drawn from each woman and from her husband for clinic testing, and the white-cell buffy coat is preserved for genetic analysis. In this proposed project, we will perform DNA extraction from the white-cell buffy coats, and genotype plymorphisms of nine genes (GSTM1, GSTT1, CYP1A1, CYP2D6, CYP2E1, NAT2, NQO1, ALDH2 and EPHX). After the initial visit, each woman is asked to provide a daily urine sample and to keep a diary of her menstrual periods, symptoms, sexual activity, general health status, medication, cigarette smoking, alcohol consumption, and physical activity. Time to conception as well as subclinical daily measurement of urinary human chorionic gonadotropin (Beta-hCG). When a woman develops early signs or symptoms of pregnancy, she is evaluated at her regular hospital (where she will also receive routine prenatal care, delivery services, and postnatal care) for reproductive end points, such as menstrual disturbances, time to conception, fertility, spontaneous abortion, preterm labor, preterm delivery, intrauterine growth retardation, malformations, and still birth. With these data, aromatic solvent exposure-response relationships will be established, and (in the proposed study) gene-aromatic solvent interactions will be assessed with adjustment for important confounders.

Expected Results:

Our calculations indicate that the proposed study will have 80% power to identify important gene-aromatioc solvent interactions.

Publications and Presentations:

Publications have been submitted on this project: View all 6 publications for this project

Journal Articles:

Journal Articles have been submitted on this project: View all 6 journal articles for this project

Supplemental Keywords:

Aromatic solvents, gene-aromatic solvent interaction, menstrual disturbance, infertility, spontaneous abortion, preterm delivery, and low birth weight., Health, Scientific Discipline, Air, Toxics, Geographic Area, air toxics, Genetics, Environmental Chemistry, Chemistry, HAPS, Risk Assessments, 33/50, International, exposure and effects, aromatic solvents, blood samples, China, Toluene, developmental effects, genetic analysis, benzene, human exposure, toxic environmental contaminants, reproductive health, Benzene (including benzene from gasoline), Styrene, biomarker

Progress and Final Reports:

  • 1998
  • 1999 Progress Report
  • Final Report