title: A novel model to characterize postnatal exposure to lipophilic environmental toxicants and application in the study of hexachlorobenzene and infant growth.
abstract: BACKGROUND
  Infants are exposed to persistent environmental contaminants through breast milk, yet studies assessing the health effects of postnatal exposure are lacking. Existing postnatal exposure assessment is either too simple (lactation exposure model, LEM) or requires complex physiologically-based pharmacokinetic (PBPK) models.
  
  
  OBJECTIVE
  We present equations for postnatal exposure calculations. We applied these equations to study the effect of hexachlorobenzene (HCB) on infant growth in the two first years of life.
  
  
  METHODS
  HCB was measured in breast milk samples in 449 mother-child pairs participating in the Norwegian birth cohort study HUMIS. We used these concentrations, mother's weight, height and age, together with child's weight at 8 age points, and proportion of milk consumed each month, to calculate HCB concentrations in the infant over age. We then estimated the association between HCB and infant growth using a linear mixed model.
  
  
  RESULTS
  Children exposed to HCB via mother's milk reached concentrations 1-5 times higher than the mother. HCB was associated with lower weight gain in the first 2years (-33g per unit HCB and month, 95% CI: -38, -27 at 6months). Associations were stronger during the first 3months (-57g per unit HCB and month, 95% CI: -67, -49 at 1month), indicating a critical window of effect. Our equations gave more precise estimates than the LEM.
  
  
  CONCLUSIONS
  Our equations for postnatal exposure of lipophilic environmental toxicants give better results than the LEM and are easier to implement than the complex PBPK models. HCB exposure, especially during the first three months of life, has a negative effect on infant growth up to 2years.
authors.affiliation: Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, NO-0403 Oslo, Norway. Electronic address: hein.stigum@fhi.no.
authors.forename: Hein
authors.initials: H
authors.lastname: Stigum
authors.affiliation: Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, NO-0403 Oslo, Norway.
authors.forename: Nina
authors.initials: N
authors.lastname: Iszatt
authors.affiliation: Norwegian School of Veterinary Science, Oslo, Norway; National Veterinary Institute, Oslo, Norway.
authors.forename: Anuschka
authors.initials: A
authors.lastname: Polder
authors.affiliation: Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, NO-0403 Oslo, Norway.
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Mandal
authors.affiliation: Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, NO-0403 Oslo, Norway.
authors.forename: Merete
authors.initials: M
authors.lastname: Eggesbø
mesh_terms: D000818:Animals; D002648:Child; D002657:Child Development / Q000187:drug effects*; D002675:Child, Preschool; D015331:Cohort Studies; D004785:Environmental Pollutants / Q000032:analysis* / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D015386:Hazardous Substances / Q000032:analysis* / Q000493:pharmacokinetics / Q000633:toxicity; D006581:Hexachlorobenzene / Q000032:analysis* / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D007223:Infant; D016014:Linear Models; D008297:Male; D018811:Maternal Exposure; D008895:Milk, Human / Q000737:chemistry; D008962:Models, Theoretical; D009664:Norway; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D004785:Environmental Pollutants; D015386:Hazardous Substances; D006581:Hexachlorobenzene
keywords: HCB; Infant growth; Linear mixed model; Modeling; Postnatal exposure