Authors
Lawson, C., Schnorr, T., Whelan, E., Deddens, J., Dankovic, D, Piacitelli, L., Sweeney, M., and Connally, L.

Title:
Paternal occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and birth outcomes of offspring: birth weight, preterm delivery, and birth defects

Source:
Environmental Health Perspectives. 112(14):1403-1408

Summary:
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been noted as highly toxic, with both carcinogenic (cancer-causing) and developmental affects. TCDD is lipophilic, persistent and ubiquitous in the environment at low levels and the general population is exposed to small quantities of this compound, primarily through dietary intake of animal fats and dairy products. TCDD is also present as a contaminant in some chemicals including the phenoxy herbicide Agent Orange used in Vietnam with several studies attempting to evaluate the effects of TCDD exposure using groups occupationally exposed during chemical manufacture and U.S veterans exposed during Vietnam. Given that most of the individuals highly exposed to TCDD are men, there has been increasing interest in investigating the potential male reproductive health outcomes associated with exposure. Previous analysis of male workers exposed to chemicals contaminated with TCDD revealed small alterations in reproductive gonadotrophin and testosterone levels in male workers. Fetal development has been shown to be sensitive to TCDD and other chemical exposures, and thus, may represent yet another endpoint adversely affected by paternal exposure to TCDD. It has been suggested that paternal exposures may be related to adverse reproductive outcomes through genetic damage to the male germ cell or transfer of chemicals via seminal fluid.

Lawson et al. examined pregnancy outcomes among wives of male chemical workers who were highly exposed to chemicals contaminated with TCDD compared to wives of age-matched non-exposed neighbourhood controls. Pregnancies conceived after the father's first date of exposure (date of employment) were considered exposed, whereas control pregnancies and pregnancies conceived before the fathers' exposure at the plants were considered unexposed. The serum TCDD concentration at the time of conception of exposed pregnancies was estimated using a pharmacokinetic model. TCDD serum measurements were obtained from a random sample of controls, and the median level was assigned as the exposure estimate to all control pregnancies and pregnancies fathered by workers before employment exposure. The median estimated TCDD concentration for exposed births was 254pg/g and the median for control births and pre-exposure births was 6pg/g.

A total of 1,117 full-term live births were included in the birth weight analysis. Mean birth weight was similar among controls, pre-exposure workers' babies, and exposed workers' babies. Analysis of birth weight, limited only to exposed births, revealed a statistically significant increase in birth weight of 38 g with each increase in the log TCCD concentration. A crude analysis of pre-term births showed a somewhat protective association with TCDD concentration. The data was insufficient to present a statistical analysis of reported birth defects and paternal TCDD exposure. However, there was one reported case of spina bifida in the highest exposure category.

The results of this study do not support a causal relationship between low birth weight and high paternal TCDD exposure, and indeed, a positive association between dioxin exposure and the birth weight of offspring was noted. One limitation of this study is that serum TCDD concentrations were measured several years after the pregnancies, and therefore this biological measurement of internal dose only provides an estimate of the actual concentration at the period of interest. However, the investigators used a pharmacokinetic model to estimate exposure which allowed for changes in individual body burden over time. Other strengths of this study include a large sample size, verification of outcome data by birth certificates and medical records, and adjustment for confounding variables. The evidence obtained from this well designed study suggests that it is unlikely exposure to TCDD increases the risk of low birth weight or preterm delivery through a paternal mechanism. hould be followed by studies to elucidate the mechanisms of action.