Appendix B:  Other studies that have found associations of postnatal PCB exposures with adverse neurological effects:

*Studies marked with * showed not only adverse postnatal effects of PCBs but also no effects or only insignificant effects of prenatal exposures to PCBs.

 

According to the EPA's web page on health effects of PCBs, "Effects of PCBs on nervous system development have been studied in monkeys and a variety of other animal species. Newborn monkeys exposed to PCBs showed persistent and significant deficits in neurological development, including visual recognition, short-term memory and learning. Some of these studies were conducted using the types of PCBs most commonly found in human breast milk." (EPA web page on health effects of PCBs at http://www.epa.gov/osw/hazard/tsd/pcbs/pubs/effects.htm) 

 

*-- A Dutch study (Patandin et al.) found a strong association of exposure to PCBs specifically via breastfeeding with problems of inattention and hyperactivity in children at 42 months of age. The study distinguished between effects of prenatal and lactational exposure, and found that only the lactational exposure was associated with “less sustained attention” as well as slower reaction time. (S Patandin et al.,  Effects Of Environmental Exposure To  Polychlorinated Biphenyls And Dioxins On Growth And Development In Young Children:  A Prospective Follow-Up Study Of Breast-Fed And Formula-Fed Infants From Birth Until 42 Months Of Age  Table 7.5 and accompanying text.  at   http://Repub.Eur.Nl/Res/Pub/19721)

 *-- When effects of both prenatal and breast milk exposures to PCBs were considered, only “breast milk exposure to PCB 153 appears to be associated with decrements in motor development.” (Lynch et al., The effect of prenatal and postnatal exposure to polychlorinated biphenyls and child neurodevelopment at age twenty four months, Reprod Toxicol. 2012 Nov;34(3):451-6. doi: 10.1016/j.reprotox.2012.04.013. Epub 2012 May 5.  at http://www.ncbi.nlm.nih.gov/pubmed/22569275)  

 

*-- Boucher et al. found effects of postnatal exposures to PCBs to be significant whereas effects of prenatal exposures were mixed, small, and did not reach statistical significance. (Boucher et al., Response Inhibition and Error Monitoring during a Visual Go/No-Go Task in Inuit Children Exposed to Lead, Polychlorinated Biphenyls, and Methylmercury,   Environ Health Perspect. Apr 2012; 120(4): 608–615 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339450)    

In a 1995 study of over 400 Dutch infants, PCB levels that represented prenatal exposure were not related to neurological function. But higher levels of PCBs and dioxins in breast milk (as determined in the second week after delivery) were related to reduced neonatal neurological optimality. (Huisman et al., Perinatal exposure to polychlorinated biphenyls and dioxins and its effect on neonatal neurological development, Early Human Development, Volume 41, Issue 2, 1995, at http://www.sciencedirect.com/science/article/pii/037837829401611R)

-- A 2010 study (Verner et al.) assessed infant blood PCB-153 levels at delivery and on a month-by-month basis during the first year of life in a longitudinal birth cohort.  “Whereas inattention was related to prenatal exposure, activity level (non-elicited activity -- considered to be impairment) was best predicted by postnatal exposure….. These findings are consistent with previous reports indicating PCB-induced behavioural alteration in attention and activity level.” (italics and parenthetical expression added)   (Verner et al., Alteration of infant attention and activity by polychlorinated biphenyls:  unravelling critical windows of susceptibility using physiologically based pharmacokinetic modeling, Neurtoxicology, 2010;31(5):424-31)

 

 

-- A research group (Schantz et al.) found an association between the amount of PCBs in breast milk and developmental scores:  as PCB concentrations in the mother’s milk increased from the 5th percentile to the 95th percentile, scores on the Bayley MDI decreased by 9.9 points. (Schantz et al., Effects of PCB Exposure on Neuropsychological Function in Children   Environmental Health Perspectives, Vol. 111, p. 367, at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241394/pdf/ehp0111-000357.pdf   p. 363) These tests are scored on a scale like that used for IQ tests, such that a 9.9-point decrease would be the distance between the center of the range in the population and the upper end of the bottom quarter, a very substantial decline.  And that major decline apparently resulted merely from higher concentrations of PCBs, at background levels such as are found in breast milk ingested by many thousands of infants, even without taking into account effects of different durations of breastfeeding.

 

-- A study of children of 8000 mothers who ate Lake Michigan fish (Jacobson et al.) found that “Higher PCB concentrations in breast milk were … associated with poorer performance” on tests measuring both verbal and numerical memory. (Jacobson JL, Jacobson SW, Humphrey HEB. 1990a. Effects of in utero exposure to polychlorinated biphenyls and related contaminants on cognitive functioning in young children. J Pediatr 116:38–45. As reported in Schantz et al., Effects of PCB Exposure on Neuropsychological Function in Children, Environmental Health Perspectives • Volume 111 | Number 3 | March 2003, p.371 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241394/pdf/ehp0111-000357.pdf)  Again, this found effects of merely higher concentrations of the toxins in breast milk, without taking into consideration effects of longer durations of breastfeeding.

-- According to a 2011 study by a German scientist (Winneke, with the Division of Neurobehavioral Toxicology, Medical Institute of Environmental Hygiene, Heinrich-Heine-Universität), “Several prospective cohort studies…have demonstrated that pre- and early postnatal exposure to PCBs is associated with deficit or retardation of mental and/or motor development….” (Winneke G. et al., Developmental aspects of environmental neurotoxicology: lessons from lead and polychlorinated biphenyls.  J Neurol Sci. 2011 Sep 15;308(1-2):9-15. doi: 10.1016/j.jns.2011.05.020. Epub 2011 Jun 15.  at www.ncbi.nlm.nih.gov/pubmed/21679971)

-- A 2010 review article (Eubig et al.) generalized that “children and laboratory animals exposed to lead or PCBs show deficits in many aspects of attention and executive function that have been shown to be impaired in children diagnosed with ADHD, including tests of working memory, response inhibition, vigilance, and alertness.”  (Eubig et al., Lead and PCBs as risk factors for attention deficit/hyperactivity disorder, Environ Health Perspect. 2010 Dec;118(12):1654-67. doi: 10.1289/ehp.0901852. Epub 2010 Sep 9)  This should be considered together with knowledge of the tremendous increase in PCB concentrations in children due to breastfeeding (see Section 3.a of www.pollution-effects.info/).

 

Postnatal exposure to PCBs also had apparent effects of slowing the responses of the tested children in the Boucher et al. study, effects that the authors of the above study said “seem linear.” (Boucher et al., Response Inhibition and Error Monitoring during a Visual Go/No-Go Task in Inuit Children Exposed to Lead, Polychlorinated Biphenyls, and Methylmercury,   Environ Health Perspect. Apr 2012; 120(4): 608–615 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339450 In other words, the greater the postnatal exposure, the greater the apparent effect of slowing the responses, another dose-response relationship found in a postnatal toxic exposure.  (See Figure 1 in that study.)  The effect was not large among the children tested, but bear in mind that the severity of the effect could increase with age, as has been found to be the case with effects of PCBs on IQ, in several studies. (Boucher at al., Prenatal Exposure to Polychlorinated Biphenyls: A Neuropsychologic Analysis, Environ Health Perspect. Jan 2009; 117(1): 7–16. PMCID: PMC2627868 at www.ncbi.nlm.nih.gov/pmc/articles/PMC2627868)

-- A 2015 study by a team of six scientists refers to “the extensive brain development that occurs postnatally, including cell differentiation that has been shown to be altered by PCBs ….” (Verner et al., Measured Prenatal and Estimated Postnatal Levels of Polychlorinated Biphenyls (PCBs) and ADHD-Related Behaviors in 8-Year-Old Children, Environmental Health Perspectives, 2015, http://dx.doi.org/10.1289/ehp.1408084, at  http://ehp.niehs.nih.gov/wp-content/uploads/advpub/2015/3/ehp.1408084.acco.pdf)

*-- Another 2015 study found no effects of prenatal exposures to PCBs but did find higher PCB levels at 2 months of age to be associated with increased duration of inattention. (Verner et al. Prenatal and early-life polychlorinated biphenyl (PCB) levels and behavior in Inuit preschoolers, Environment International, Vol. 78, May, 2015, at http://www.sciencedirect.com/science/article/pii/S0160412015000318)

-- A 2004 Dutch prospective study (therefore allowing accurate measures of exposures, compared with retrospective studies) investigated mental abilities of nine-year-old children in relation to their histories of breastfeeding versus formula feeding; the authors grouped the children into six different categories, according to shorter or longer durations of breastfeeding, formula feeding, and higher or lower exposures of each of those groups to prenatal toxins.  The formula-fed children performed better than their breastfed counterparts, and the children who were breastfed for longer periods performed worse than those breastfed for shorter periods, in scores on a test of executive function.  Those relationships held consistently, when the subjects were grouped according to both higher prenatal exposures to toxins and lower prenatal exposures to toxins.  Scores of formula-fed children were only insignificantly higher than those of children breastfed for shorter durations (6 to 16 weeks). (Vreugdenhil et al., Effects of Perinatal Exposure to PCBs on Neuropsychological Functions in the Rotterdam Cohort at 9 Years of Age, Neuropsychology, 2004, Vol. 18, No. 1, 185–193  at http://psycnet.apa.org/journals/neu/18/1/185.pdf)

 

According to an article in an industrial health journal, "Even low levels of dioxin or PCB exposure during the perinatal period can greatly influence neurological development" in this way and "can cause irreversible neurological damage." (Industrial Health 2000, 38, 259–268 Review Article:  The Effects of Dioxin on Reproduction and Development  Junzo YONEMOTO  National Institute for Environmental Studies, Japan  p. 262; at http://www.jicosh.gr.jp/en/indu_hel/pdf/IH38_33.pdf 

Also Glorieux et al., 1988; Rovet et al., 1987; Haddow et al., 1999)." (Prioritization of Toxic Air Contaminants  -- Children's Environmental Health Protection Act (State of California), October, 2001

 

To illustrate the potency of some of these developmental toxins, it is worth considering a test performed on rhesus monkeys with Aroclor 1248, a commonly-used commercial product that contained PCBs. 

“In rhesus monkey infants whose mothers were or had been exposed to Aroclor 1248 during gestation and lactation, behavioral testing showed hyperactivity and retarded learning ability….  These effects were reported at doses of about 0.006 mg Aroclor 1248/kg bw/day to the mothers.” (Ahlborg et al., Risk Assessment of Polychlorinated Biphenyls (PCBs). Environmental Report in the Nord Series. Nord 26. Copenhagen: Nordic Council of Ministers, 1992.  Assuming a recognized average weight of 5.3 kg (12 pounds) per female monkey, this works out to 0.032 mg per monkey per day, or a dose of less than one 800,000th of one ounce of Aroclor per day per gestating/lactating female monkey.)  Remember that, according to an expert study, “There is excellent correspondence between the effects of developmental PCB exposure in the monkey and that observed in humans, including learning deficits and changes in activity.” (Rice et al., Lessons for Neurotoxicology from Selected Model Compounds:  SGOMSEC Joint Report, Environ Health Perspect 1 04(Suppl 2):205-215 (1996), at

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1469598/pdf/envhper00345-0042.pdfR)

 

When considering the effects of 1/800,000th of an ounce of a PCB-containing product (see above), also bear in mind that 600,000 tons of PCBs were produced in the U.S. between 1930 and 1977, that they are very stable and are contained in considerable equipment that is still in use (and sometimes leaking); they are also heavily present in landfills, which are a major source of emissions of toxins to the atmosphere (especially during fires), not to mention the landfills’ drainage to water supplies.  Also bear in mind their persistence in the environment and their presence in diesel emissions (C.A. Laroo et al., Emissions of PCDD/Fs, PCBs and PAHs from a Modern Diesel Engine Equipped with Catalyzed Emission Control Systerms, Environmental Science and technology, ACS Publications, June 30, 2011), which have been increasing rapidly in the U.S., according to the EPA's latest data.  In addition, indoor air in houses with floors finished with PCB-containing wood finish have been found to contain high levels of PCB. (Environ Health. 2008; 7: 2. Published online 2008 January 17. doi: 10.1186/1476-069X-7-2  Rudel et al; licensee BioMed Central Ltd.  PCB-containing wood floor finish is a likely source of elevated PCBs in residents' blood, household air and dust: a case study of exposure).

 

For additional relevant studies, see www.breastfeeding-studies.info.

 

 

Appendix C:  Additional evidence of highly concentrated exposures of breastfed infants to PBDEs, and that toxin’s effect of reducing testosterone levels:

C.1:  Extremes of exposure of breastfed infants:

A study by a team of seven scientists estimated PBDE intake from food to be 307 ng/kg/day for nursing infants compared with 0.9 ng/kg/day in adult females. (Schecter et al., Polybrominated Diphenyl Ether (PBDE) Levels in an Expanded Market Basket Survey of U.S. Food and Estimated PBDE Dietary Intake by Age and Sex   Environ Health Perspect. 2006 October; 114(10): 1515–1520. Published online 2006 July 13. doi: 10.1289/ehp.9121, PMCID: PMC1626425) 

The EPA quotes estimates from two other studies that were almost that extreme. (p. 5-55 of EPA:  An exposure assessment of polybrominated diphenyl ethers. National Center for Environmental Assessment, Washington, DC; EPA/600/R-08/086F. online at http://www.epa.gov/ncea  or directly at  http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=210404 )  

 

In the only study quoted by the EPA making such a comparison, based on measurements of 244 children, the average total concentration of PBDEs in breastfed children at age four was still nearly three times as high as in formula-fed children. (Near end of Section 5.6.2 ("Impacts to Infants from Consumption of Breast Milk"), p. 5-79, of An exposure assessment of polybrominated diphenyl ethers. National Center for Environmental Assessment, Washington, DC; EPA/600/R-08/086F. online at http://www.epa.gov/ncea  or directly at  http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=210404

 

According to a study(1), “combustion sources are probably more important PBDE contributors to outdoor air levels and have more influence on the food chain, which is one of the major routes for human and wildlife PBDE exposure.”   The dominant effect of combustion sources of PBDEs in outdoor air is probably the main reason why urban air has been found to have almost ten times the concentration of PBDEs as rural air, as reported by the U.S. Agency for Toxic Substances and Disease Registry. (Section 4.1 of ATDSR document on PBDEs at http://www.atsdr.cdc.gov/toxprofiles/tp68-c4.pdf)

   

 

A 2015 Australian study stated that, despite declines of emissions of PBDEs (mainly resulting from major reductions in use that had become effective in 2004), “the PBDE exposure of fetuses and breast-fed infants (the most sensitive groups) has remained rather constant. Gyalpo et al., Insights into PBDE Uptake, Body Burden, and Elimination Gained from Australian Age-Concentration Trends Observed Shortly after Peak Exposure, Environ Health Perspect, 2015 Oct;123(10):978-84. doi: 10.1289/ehp.1408960. Epub 2015 Mar 13, http://www.ncbi.nlm.nih.gov/pubmed/25768049   Another EPA report states that research found that “Infant exposures (to PBDEs) were dominated by breast milk ingestion.”National Center for Environmental Assessment, Office of Research and Development, U.S. EPA,  An Exposure Assessment of Polybrominated Diphenyl Ethers,  EPA/600/R-08/086F May 2010, p. 5-56  One study team calculated that 91% of a typical U.S. breastfed infant’s total exposure to PBDEs was from breast milk. Johnson-Restrepo, An assessment of sources and pathways of human exposure to polybrominated diphenyl ethers in the United States, Chemosphere, 2009 Jul;76(4):542-8. doi: 10.1016/j.chemosphere.2009.02.068. Epub 2009 Apr 5.  at http://www.ncbi.nlm.nih.gov/pubmed/19349061

 

C.2:  Testosterone-reducing effects of PBDEs:

A 2013 study (Johnson et al.) found a 9.4% decrease in testosterone levels with each interquartile increase in deca-BDE concentration in house dust, with a fairly high level of statistical significance (p-value - .02).Johnson et al., Associations between brominated flame retardants in house dust and hormone levels in men, Sci Total Environ. 2013 Feb 15; Table 3, PMCID: PMC3572297, 445-446: 177–184.at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572297/    This has special importance in that deca-BDEs were still in wide use in consumer electronic products and home furnishings until 2015, and will long be part of human environments and exposures. Putting the interquartile differences into other words, the above means that the rather common difference in household PBDE dust levels between the bottom quarter and the top quarter of this kind of population would be associated with a 28% (3 times 9.4%) reduction in testosterone levels. Remember that testosterone is important to development of the brain (see Section 4.a)

 

Although effects related to differences between quartiles of PBDE exposure are significant, effects that could result from the more extreme exposures of those in the top few percent should be of far greater concern. In the above study of 38 households, one of those households (constituting over 2% of the population studied) had decaBDE exposure that was 27 times the exposure at the 25th percentile. (see Table 1 in that study)  That extreme exposure in the top 2% of this study group was completely in line with other studies -- see the Schecter et al. and Chinese studies above. It is entirely likely that a significant percentage of exposed children in the Johnson et al. study would have had far greater reductions of the neurodevelopmentally-important testosterone than the 28% reduction associated with top-quartile-versus-bottom-quartile levels of PBDEs.

 

Notes:_________________

1)  Wang et al., Emission estimation and congener-specific characterization of polybrominated diphenyl ethers from various stationary and mobile sources, Environmental Pollution, Vol. 158, issue 10, Oct. 2010, pp. 3108-3115 at http://www.sciencedirect.com/science/article/pii/S0269749110002769 ; also  Wang et al., Polybrominated diphenyl ethers in various atmospheric environments of Taiwan: Their levels, source identification and influence of combustion sources, Chemosphere, Volume 84, Issue 7, Aug. 2011  at http://www.sciencedirect.com/science/article/pii/S0045653511006515