Application of ensemble methods to analyse the decline of organochlorine pesticides in relation to the interactions between age, gender and time

Autoři: Aleysha Thomas aff001;  Nicole M. White aff001;  Leisa-Maree Leontjew Toms aff002;  Kerrie Mengersen aff001
Působiště autorů: ARC Centre of Excellence for Mathematical and Statistical Frontiers, Queensland University of Technology, Brisbane, Queensland, Australia aff001;  School of Public Health and Social Work, Queensland University of Technology, Brisbane, Queensland, Australia aff002
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223956


Organochlorine pesticides (OCPs) are toxic chemicals that persist in human tissue. Short and long term exposure to OCPs have been shown to have adverse effects on human health. This motivates studies into the concentrations of pesticides in humans. However these studies typically emphasise the analysis of the main effects of age group, gender and time of sample collection. The interactions between main effects can distinguish variation in OCP concentration such as the difference in concentrations between genders of the same age group as well as age groups over time. These are less studied but may be equally or more important in understanding effects of OCPs in a population. The aim of this study was to identify interactions relevant to understanding OCP concentrations and utilise them appropriately in models. We propose a two stage analysis comprising of boosted regression trees (BRTs) and hierarchical modelling to study OCP concentrations. BRTs are used to discover influential interactions between age group, gender and time of sampling. Hierarchical models are then employed to test and infer the effect of the interactions on OCP concentrations. Results of our analysis show that the best fitting model of an interaction effect varied between OCPs. The interaction between age group and gender was most influential for hexachlorobenzene (HCB) concentrations. There was strong evidence of an interaction effect between age group and time for β-hexachlorocyclohexane (β-HCH) concentrations in >60 year olds as well as an interaction effect between age group and gender for HCB concentrations for adults aged >45 years. This study highlights the need to consider appropriate interaction effects in the analysis of OCP concentrations and provides further insight into the interplay of main effects on OCP concentration trends.

Klíčová slova:

Age groups – Decision trees – Lipids – Normal distribution – Pesticides – Pollutants – Water pollution


1. Laug EP, Kunze FM, Prickett C. Occurrence of DDT in human fat and milk. AMA archives of industrial hygiene and occupational medicine. 1951;3(3):245–246. 14810251

2. Egan H, Goulding R, Roburn J, Tatton J. Organo-chlorine pesticide residues in human fat and human milk. BMJ. 1965;2(5453):66–69. doi: 10.1136/bmj.2.5453.66 14308202

3. Johnson-Restrepo B, Kannan K, Rapaport DP, Rodan BD. Polybrominated Diphenyl Ethers and Polychlorinated Biphenyls in Human Adipose Tissue from New York. Environmental Science & Technology. 2005;39(14):5177–5182. doi: 10.1021/es050399x

4. Kang JH, Son MH, Do Hur S, Hong S, Motoyama H, Fukui K, et al. Deposition of organochlorine pesticides into the surface snow of East Antarctica. Science of the total environment. 2012;433:290–295. doi: 10.1016/j.scitotenv.2012.06.037 22796727

5. Shen L, Wania F, Lei YD, Teixeira C, Muir DC, Bidleman TF. Atmospheric distribution and long-range transport behavior of organochlorine pesticides in North America. Environmental Science & Technology. 2005;39(2):409–420. doi: 10.1021/es049489c

6. Mrema EJ, Rubino FM, Brambilla G, Moretto A, Tsatsakis AM, Colosio C. Persistent organochlorinated pesticides and mechanisms of their toxicity. Toxicology. 2013;307:74–88. doi: 10.1016/j.tox.2012.11.015 23219589

7. Jung D, Becher H, Edler L, Flesch-Janys D, Gurn P, Konietzko J, et al. Elimination of β-hexachlorocyclohexane in occupationally exposed persons. Journal of toxicology and environmental health. 1997;51(1):23–34. doi: 10.1080/00984109708984009 9169059

8. Australian Academy of Science. The use of DDT in Australia. Reports of the Australian Academy of Science. 1972; No. 14. Canberra.

9. Australian Pesticides and Veterinary Medicines Authority. The history of ‘Organochlorine’ pesticides in Australia; 2013. Accessed 29/05/13.

10. Longnecker MP, Rogan WJ, Lucier G. The human health effects of DDT (dichlorodiphenyltrichloroethane) and PCBs (polychlorinated biphenyls) and an overview of organochlorines in public health 1. Annual review of public health. 1997;18(1):211–244. doi: 10.1146/annurev.publhealth.18.1.211 9143718

11. Beard J, Australian Rural Health Research Collaboration. DDT and human health. Science of the total environment. 2006;355(1):78–89. doi: 10.1016/j.scitotenv.2005.02.022 15894351

12. Arrebola J, Cuellar M, Claure E, Quevedo M, Antelo S, Mutch E, et al. Concentrations of organochlorine pesticides and polychlorinated biphenyls in human serum and adipose tissue from Bolivia. Environmental Research. 2012;112:40–47. doi: 10.1016/j.envres.2011.10.006 22078547

13. Waliszewski SM, Caba M, Herrero-Mercado M, Saldariaga-Noreña H, Meza E, Zepeda R, et al. Organochlorine pesticide residue levels in blood serum of inhabitants from Veracruz, Mexico. Environmental Monitoring and Assessment. 2012;184(9):5613–5621. doi: 10.1007/s10661-011-2366-2 21922174

14. Jakszyn P, Goñi F, Etxeandia A, Vives A, Millán E, López R, et al. Serum levels of organochlorine pesticides in healthy adults from five regions of Spain. Chemosphere. 2009;76(11):1518–1524. doi: 10.1016/j.chemosphere.2009.05.048 19586652

15. Jensen AA. Polychlorobiphenyls (PCBs), polychlorodibenzo-p-dioxins (PCDDs) and polychlorodibenzofurans (PCDFs) in human milk, blood and adipose tissue. Science of the total environment. 1987;64(3):259–293. doi: 10.1016/0048-9697(87)90250-6 3110947

16. Waliszewski S, Aguirre A, Infanzon R, Silva C, Siliceo J. Organochlorine pesticide levels in maternal adipose tissue, maternal blood serum, umbilical blood serum, and milk from inhabitants of Veracruz, Mexico. Archives of Environmental Contamination and Toxicology. 2001;40(3):432–438. doi: 10.1007/s002440010194 11443377

17. Toms LM, Harden F, Hobson P, Sjödin A, Mueller J. Temporal trend of organochlorine pesticides in Australia. Organohalogen Compounds. 2012;74: 775–778.

18. Mueller JF, Harden F, Toms LM, Symons R, Fürst P. Persistent organochlorine pesticides in human milk samples from Australia. Chemosphere. 2008;70(4):712–720. doi: 10.1016/j.chemosphere.2007.06.037 17675211

19. Solomon GM, Weiss PM. Chemical contaminants in breast milk: time trends and regional variability. Environmental Health Perspectives. 2002;110(6):A339–A347. doi: 10.1289/ehp.021100339 12055065

20. Polder A, Gabrielsen G, Odland J, Savinova T, Tkachev A, Løken K, et al. Spatial and temporal changes of chlorinated pesticides, PCBs, dioxins (PCDDs/PCDFs) and brominated flame retardants in human breast milk from Northern Russia. Science of the total environment. 2008;391(1):41–54. doi: 10.1016/j.scitotenv.2007.10.045 18063018

21. Porta M, Puigdomènech E, Ballester F, Selva J, Ribas-Fitó N, Llop S, et al. Monitoring concentrations of persistent organic pollutants in the general population: the international experience. Environment international. 2008;34(4):546–561. doi: 10.1016/j.envint.2007.10.004 18054079

22. Thomas A, Toms LML, Harden FA, Hobson P, White NM, Mengersen KL, et al. Concentrations of organochlorine pesticides in pooled human serum by age and gender. Environmental Research. 2017;154:10–18. doi: 10.1016/j.envres.2016.12.009 27992738

23. Wolff MS, Anderson HA, Britton JA, Rothman N. Pharmacokinetic variability and modern epidemiology-the example of dichlorodiphenyltrichloroethane, body mass index, and birth cohort. Cancer Epidemiology Biomarkers & Prevention. 2007;16(10):1925–1930. doi: 10.1158/1055-9965.EPI-07-0394

24. Laden F, Neas LM, Spiegelman D, Hankinson SE, Willett WC, Ireland K, et al. Predictors of plasma concentrations of DDE and PCBs in a group of US women. Environmental health perspectives. 1999;107(1):75–81. doi: 10.1289/ehp.9910775 9872720

25. James RA, Hertz-Picciotto I, Willman E, Keller JA, Charles MJ. Determinants of serum polychlorinated biphenyls and organochlorine pesticides measured in women from the child health and development study cohort, 1963-1967. Environmental health perspectives. 2002;110(7):617–624. doi: 10.1289/ehp.02110617 12117636

26. Porta M, López T, Gasull M, Rodríguez-Sanz M, Garí M, Pumarega J, et al. Distribution of blood concentrations of persistent organic pollutants in a representative sample of the population of Barcelona in 2006, and comparison with levels in 2002. Science of the total environment. 2012;423:151–161. doi: 10.1016/j.scitotenv.2012.02.001 22397902

27. Wang HS, Chen ZJ, Wei W, Man YB, Giesy JP, Du J, et al. Concentrations of organochlorine pesticides (OCPs) in human blood plasma from Hong Kong: Markers of exposure and sources from fish. Environment international. 2013;54:18–25. doi: 10.1016/j.envint.2013.01.003 23376599

28. Woodruff TJ, Zota AR, Schwartz JM. Environmental chemicals in pregnant women in the United States: NHANES 2003-2004. Environmental Health Perspectives. 2011;119(6):878–885. doi: 10.1289/ehp.1002727 21233055

29. Toms LM, Thompson J, Rotander A, Hobson P, Calafat AM, Kato K, et al. Decline in perfluorooctane sulfonate and perfluorooctanoate serum concentrations in an Australian population from 2002 to 2011. Environment international. 2014;71:74–80. doi: 10.1016/j.envint.2014.05.019 24980755

30. Frugé AD, Cases MG, Schildkraut JM, Demark-Wahnefried W. Associations between obesity, body fat distribution, weight loss and weight cycling on serum pesticide concentrations. Journal of food & nutritional disorders. 2016;5(3).

31. Breiman L, Friedman J, Stone CJ, Olshen RA. Classification and regression trees. Boca Raton, Florida: Chapman & Hall/CRC; 1984.

32. Schapire RE. In: Denison DD, Hansen MH, Holmes CC, Mallick B, Yu B, editors. The Boosting Approach to Machine Learning: An Overview. New York, NY: Springer; 2003. p. 149–171.

33. Zhang H, Singer BH. Recursive partitioning and applications. 2nd ed. New York, NY: Springer; 2010.

34. Friedman J, Hastie T, Tibshirani R. Additive logistic regression: a statistical view of boosting. The annals of statistics. 2000;28(2):337–407. doi: 10.1214/aos/1016218222

35. Greenwell B, Boehmke B, Cunningham J, GBM Developers. gbm: Generalized Boosted Regression Models; 2019. R package version 2.1.5. Available from:

36. Elith J, Leathwick JR, Hastie T. A working guide to boosted regression trees. Journal of Animal Ecology. 2008;77(4):802–813. doi: 10.1111/j.1365-2656.2008.01390.x 18397250

37. Friedman JH. Greedy function approximation: a gradient boosting machine. Annals of statistics. 2001;29(5):1189–1232. doi: 10.1214/aos/1013203450

38. Walsh CD, Mengersen KL. Ordering of hierarchies in hierarchical models: Bone mineral density estimation. In: Alston C, Mengersen K, Pettitt A, editors. Case Studies in Bayesian Statistical Modelling and Analysis. Chichester, West Sussex: John Wiley & Sons, Ltd; 2012. p. 159–170.

39. R Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria; 2016. Available from:

40. Plummer M, Best N, Cowles K, Vines K. CODA: Convergence Diagnosis and Output Analysis for MCMC. R News. 2006;6(1):7–11. Available from:

41. Plummer M. rjags: Bayesian Graphical Models using MCMC; 2019. R package version 4-9. Available from:

42. Gelman A, Meng XL, Stern H. Posterior predictive assessment of model fitness via realized discrepancies. Statistica sinica. 1996;6:733–807.

43. Spiegelhalter DJ, Best NG, Carlin BP, Van Der Linde A. Bayesian measures of model complexity and fit. Journal of the Royal Statistical Society: Series B (Statistical Methodology). 2002;64(4):583–639. doi: 10.1111/1467-9868.00353

44. Wolff MS, Deych E, Ojo F, Berkowitz GS. Predictors of organochlorines in New York City pregnant women, 1998-2001. Environmental Research. 2005;97(2):170–177. doi: 10.1016/j.envres.2004.07.014 15533333

45. Leathwick J, Elith J, Francis M, Hastie T, Taylor P. Variation in demersal fish species richness in the oceans surrounding New Zealand: an analysis using boosted regression trees. Marine Ecology Progress Series. 2006;321:267–281. doi: 10.3354/meps321267

46. Gelman A, Hill J, Yajima M. Why we (usually) don’t have to worry about multiple comparisons. Journal of Research on Educational Effectiveness. 2012;5(2):189–211. doi: 10.1080/19345747.2011.618213

47. Norén K, Meironyté D. Certain organochlorine and organobromine contaminants in Swedish human milk in perspective of past 20–30 years. Chemosphere. 2000;40(9):1111–1123. doi: 10.1016/s0045-6535(99)00360-4 10739053

48. Mannetje A, Coakley J, Bridgen P, Brooks C, Harrad S, Smith AH, et al. Current concentrations, temporal trends and determinants of persistent organic pollutants in breast milk of New Zealand women. Science of the Total Environment. 2013;458:399–407. doi: 10.1016/j.scitotenv.2013.04.055 23685364

49. Dewan P, Jain V, Gupta P, Banerjee BD. Organochlorine Pesticide Residues In Maternal Blood, Cord Blood, Placenta, And Breastmilk And Their Relation To Birth Size. Chemosphere. 2013;90(5):1704–1710. doi: 10.1016/j.chemosphere.2012.09.083 23141556

50. Siddiqui M, Saxena M, Bhargava A, Seth T, Murti CK, Kutty D. Agrochemicals In The Maternal Blood, Milk, And Cord Blood: A Source Of Toxicants For Prenates And Neonates. Environmental Research. 1981;24(1):24–32. doi: 10.1016/0013-9351(81)90128-6 6163625

51. Meng G, Feng Y, Nie Z, Wu X, Wei H, Wu S, et al. Internal exposure levels of typical POPs and their associations with childhood asthma in Shanghai, China. Environmental research. 2016;146:125–135. doi: 10.1016/j.envres.2015.12.026 26748225

52. Schade G, Heinzow B. Organochlorine pesticides and polychlorinated biphenyls in human milk of mothers living in northern Germany: current extent of contamination, time trend from 1986 to 1997 and factors that influence the levels of contamination. Science of the total environment. 1998;215(1):31–39. doi: 10.1016/s0048-9697(98)00008-4 9599454

53. Bjermo H, Darnerud PO, Lignell S, Pearson M, Rantakokko P, Nälsén C, et al. Fish intake and breastfeeding time are associated with serum concentrations of organochlorines in a Swedish population. Environment International. 2013;51:88–96. doi: 10.1016/j.envint.2012.10.010 23201820

54. Saoudi A, Fréry N, Zeghnoun A, Bidondo ML, Deschamps V, Göen T, et al. Serum levels of organochlorine pesticides in the French adult population: the French National Nutrition and Health Study (ENNS), 2006–2007. Science of the Total Environment. 2014;472:1089–1099. doi: 10.1016/j.scitotenv.2013.11.044 24361744

55. Luo D, Zhou T, Tao Y, Feng Y, Shen X, Mei S. Exposure to organochlorine pesticides and non-Hodgkin lymphoma: a meta-analysis of observational studies. Scientific reports. 2016;6:25768. doi: 10.1038/srep25768 27185567

56. Malarvannan G, Kunisue T, Isobe T, Sudaryanto A, Takahashi S, Prudente M, et al. Organohalogen compounds in human breast milk from mothers living in Payatas and Malate, the Philippines: levels, accumulation kinetics and infant health risk. Environmental Pollution. 2009;157(6):1924–1932. doi: 10.1016/j.envpol.2009.01.010 19232797

57. Tue NM, Sudaryanto A, Minh TB, Nhat BH, Isobe T, Takahashi S, et al. Kinetic differences of legacy organochlorine pesticides and polychlorinated biphenyls in Vietnamese human breast milk. Chemosphere. 2010;81(8):1006–1011. doi: 10.1016/j.chemosphere.2010.09.013 20870263

58. Hardell E, Carlberg M, Nordström M, van Bavel B. Time trends of persistent organic pollutants in Sweden during 1993–2007 and relation to age, gender, body mass index, breast-feeding and parity. Science of the total environment. 2010;408(20):4412–4419. doi: 10.1016/j.scitotenv.2010.06.029 20643475

59. Salihovic S, Lampa E, Lindström G, Lind L, Lind PM, van Bavel B. Circulating levels of persistent organic pollutants (POPs) among elderly men and women from Sweden: results from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). Environment International. 2012;44:59–67. doi: 10.1016/j.envint.2012.01.011 22361238

60. LaKind JS, Berlin CM Jr, Sjödin A, Turner W, Wang RY, Needham LL, et al. Do Human Milk Concentrations Of Persistent Organic Chemicals Really Decline During Lactation? Chemical Concentrations During Lactation And Milk/serum Partitioning. Environmental Health Perspectives. 2009;117(10):1625–1631. doi: 10.1289/ehp.0900876 20019916

61. Kang JH, Park H, Chang YS, Choi JW. Distribution of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in human serum from urban areas in Korea. Chemosphere. 2008;73(10):1625–1631. doi: 10.1016/j.chemosphere.2008.07.087 18829066

Článek vyšel v časopise


2019 Číslo 11