Paternal Occupational Exposure to 2,3,7,8-Tetrachlorodibenzo- p -dioxin and Birth Outcomes of Offspring: Birth Weight, Preterm Delivery, and Birth Defects

Abstract

Agent Orange is a phenoxy herbicide that was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We studied pregnancy outcomes among wives of male chemical workers who were highly exposed to chemicals contaminated with TCDD and among wives of nonexposed neighborhood referents. For exposed pregnancies, we estimated serum TCDD concentration at the time of conception using a pharmacokinetic model. The mean TCDD concentration for workers’ births was 254 pg/g lipid (range, 3–16,340 pg/g). The mean referent concentration of 6 pg/g was assigned to pregnancies fathered by workers before exposure. A total of 1,117 live singleton births of 217 referent wives and 176 worker wives were included. Only full-term births were included in the birth weight analysis (≥37 weeks of gestation). Mean birth weight among full-term babies was similar among referents’ babies (n = 604), preexposure workers’ babies (n = 221), and exposed workers’ babies (n = 292) (3,420, 3,347, and 3,442 g, respectively). Neither continuous nor categorical TCDD concentration had an effect on birth weight for term infants after adjustment for infant sex, mother’s education, parity, prenatal cigarette smoking, and gestation length. An analysis to estimate potential direct exposure of the wives during periods of workers’ exposure yielded a nonstatistically significant increase in infant birth weight of 130 g in the highest exposure group (TCDD concentration > 254 pg/g) compared with referents (p = 0.09). Mothers’ reports of preterm delivery showed a somewhat protective association with paternal TCDD (log) concentration (odds ratio = 0.8; 95% confidence interval, 0.6–1.1). We also include descriptive information on reported birth defects. Because the estimated TCDD concentrations in this population were much higher than in other studies, the results indicate that TCDD is unlikely to increase the risk of low birth weight or preterm delivery through a paternal mechanism.

Developmental dioxin exposure of either parent is associated with an increased risk of preterm birth in adult mice

“…Although to date these studies have failed to identify a significant increase in risk of PTB correlating to TCDD exposure, a non-significant increase in risk was noted in the most heavily exposed individuals [47,48]. With regard to paternal exposure, at least two studies have examined birth outcomes in women whose partners were exposed to TCDD via the herbicide known as Agent Orange [49,50]. As with the Seveso cohort, neither of these studies revealed a significant increase in PTB in the wives of men occupationally exposed to TCDD [49,50]; however, these studies examined the impact of an adult exposure on subsequent pregnancy outcomes.…”

Estimating perchlorate exposure from food and tap water based on US biomonitoring and occurrence data

“…Dioxin and other organochlorine chemicals have been shown to interfere with male and female reproductive development in experimental and wild animals, particularly during gestational exposure (Gao et al, 1999;Grey and Ostby, 1995;Roman et al, 1998;Sonne et al, 2006;Theobald et al, 1997). In studies of women with environmental or accidental exposures, associations between dioxin-like chemical exposures and various reproductive endpoints (Eskenazi et al, 2003;Lawson et al, 2004;Schnorr et al, 2001;Warner et al, 2004 and and endometriosis (Eskenazi et al, 2002;Fierens et al, 2003;Heilier et al, 2005;Hoffman et al, 2007) have been either absent or of unknown significance, though animal studies have demonstrated reproductive effects at high doses (Arisawa et al, 2005;U.S. EPA, 2004).…”

Possible constraints on adaptive variation in sex ratio at birth in humans and other primates

“…At first, the results of Mocarelli et al (2000) seemed to confirm the prediction (as did those of and Del Rio Gomez et al (2002)). But other workers (Schnorr et al, 2001;Karmaus et al, 2002;Lawson et al, 2004) reported failures to confirm, perhaps as a result of contamination with androgenic or estrogenic congeners . (Mocarelli et al (2000) emphasized that the dioxin to which their subjects had been exposed in Seveso was pure).…”