Environmental Science and Pollution Research

, Volume 21, Issue 18, pp 11066–11074 | Cite as

Reproductive toxicity of lead, cadmium, and phthalate exposure in men

  • Niraj PantEmail author
  • G. Kumar
  • A. D. Upadhyay
  • D. K. Patel
  • Y. K. Gupta
  • P. K. Chaturvedi
Research Article


Environmental toxicants viz lead or cadmium and phthalate esters (di(2-ethylhexyl) phthalate [DEHP], dibutyl phthalate [DBP], and diethyl phthalate [DEP]) widely found in different environmental strata are linked to deteriorating male reproductive health. The objective was to assess the relationships between the seminal lead, cadmium, and phthalate (DEHP, DBP, DEP) concentrations at environmental level and serum hormone levels and semen quality in non-occupationally exposed men and specify the effect of individual and combined exposure of toxicants on semen quality. A study of 60 male partners of couples attending the Andrology Laboratory of the Reproductive Biology Department, All India Institute of Medical Sciences (AIIMS), New Delhi, India for semen analysis to assess their inability to achieve a pregnancy was selected for the study. The results of univariate and stepwise multiple regression analysis in the unadjusted model showed a significant correlation between lead or cadmium and phthalates DEHP/DBP/DEP and sperm motility, sperm concentration, and DNA damage. After adjusting for potential confounders, an association with lead or DEHP was only observed. The present data shows that lead (Pb) or cadmium (Cd) or phthalates might independently contribute to decline in semen quality and induce DNA damage. Phthalates might influence reproductive hormone testosterone. These findings are significant in light of the fact that men are exposed to a volley of chemicals; however, due to the small sample size, our finding needs to be confirmed in a larger population.


Lead Cadmium Phthalate esters Semen quality Testosterone DNA damage 



This work was supported by the grant from the Government of India Ministry of Science and Technology, Department of Science and Technology (DST), Technology Bhavan, New Delhi (grant no. SR/WOS-A/LS-283/2009). The authors are thankful to Dr. HB Singh (DST) for support and guidance. Mr. Akshay Lal Mahto is gratefully acknowledged for technical assistance.


  1. Akinloye O, Arowojolu AO, Shittu OB, Anetor JI (2006) Cadmium toxicity: a possible cause of male infertility in Nigeria. Reprod Biol 6:17–30Google Scholar
  2. Anderson D, Dobrzyńska MM, Basaran N (1997) Effect of various genotoxins and reproductive toxins in human lymphocytes and sperm in the Comet assay. Teratogen Carcinogen Mutagen 17:29–43CrossRefGoogle Scholar
  3. Anderson D, Yu TW, Hinçcal F (1999) Effect of some phthalate esters in human cells in the comet assay. Teratog Carcinog Mutagen 19:275–280CrossRefGoogle Scholar
  4. Benoff S, Hauser R, Marmar JL, Hurley IR, Napolitano B, Centola GM (2009) Cadmium concentrations in blood and seminal plasma: correlations with sperm number and motility in three male populations (Infertility Patients, Artificial Insemination Donors, and Unselected Volunteers). Mol Med 15:248–262Google Scholar
  5. Bernard A (2008) Cadmium and its adverse effects on human health. Indian J Med Res 128:557–564Google Scholar
  6. Biasiak J (2001) DNA-damaging effect of cadmium and protective action of quercetin. Pol J Environ Stud 10:437–442Google Scholar
  7. Bonde JP, Joffe M, Apostoli P, Dale A, Kiss P, Spano M (2002) Sperm count and chromatin structure in men exposed to inorganic lead: lowest adverse effect levels. Occup Environ Med 59:234–242CrossRefGoogle Scholar
  8. Ciarrocca M, Capozzella A, Tomei F, Tiziana G, Caciari T (2013) Exposure to cadmium in male urban and rural workers and effects on FSH, LH and testosterone. Chemosphere 90:2077–2084CrossRefGoogle Scholar
  9. Danadevi K, Rozati R, Banu BS, Rao PH, Grover P (2003) DNA damage in workers exposed to lead using comet assay. Toxicology 187:183–193CrossRefGoogle Scholar
  10. Duty SM, Singh NP, Silva MJ, Barr DB, Brock JW, Ryan L (2003) The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay. Environ Health Perspect 111:1164–1169CrossRefGoogle Scholar
  11. Duty SM, Calafat AM, Silva MJ, Ryan L, Hauser R (2005) Phthalate exposure and reproductive hormones in adult men. Hum Reprod 20:604–610CrossRefGoogle Scholar
  12. Fabjan E, Hulzebos E, Mennes W, Piersm AH (2006) A category approach for reproductive effects of phthalates. Crit Rev Toxicol 36:695–726CrossRefGoogle Scholar
  13. Fotakis G, Cemeli E, Anderson D, Timbrell JA (2005) Cadmium chloride-induced DNA and lysosomal damage in a hepatoma cell line. Toxicol in Vitro 19:481–489CrossRefGoogle Scholar
  14. Grover P, Rekhadevi PV, Danadevi K, Vuyyuri SB, Mahboob M, Rahman MF (2010) Genotoxicity evaluation in workers occupationally exposed to lead. Int J Hyg Environ Health 213:99–106CrossRefGoogle Scholar
  15. Hauser R, Meeker JD, Singh NP, Silva MJ, Ryan L, Duty S (2007) DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites. Hum Reprod 22:688–695CrossRefGoogle Scholar
  16. Hernandez-Ochoa I, Garcıa-Vargas G, Lopez-Carrillo L, Rubio-Andrade M, Moran-Martınez J, Cebrian ME, Quintanilla-Vega B (2005) Low lead environmental exposure alters semen quality and sperm chromatin condensation in northern Mexico. ReprodToxicol 20:221–228Google Scholar
  17. Hovatta O, Venalainen ER, Kuusimaki L, Heikkila J, Hirvi T, Reima I (1998) Aluminium, lead and cadmium concentrations in seminal plasma and spermatozoa, and semen quality in Finnish men. Human Reprod 13:115–119CrossRefGoogle Scholar
  18. Huang LP, Lee CC, Hsu PC, Shih TS (2011) The association between semen quality in workers and the concentration of di(2-ethylhexyl) phthalate in polyvinyl chloride pellet plant air. Fertil Steril 96:90–94Google Scholar
  19. Iavicoli I, Fontana L, Bergamaschi A (2009) The effects of metals as endocrine disruptors. J Toxicol Environ Health Part B 12:206–223CrossRefGoogle Scholar
  20. Jönsson BA, Richthoff J, Rylander L, Giwercman A, Hagmar L (2005) Urinary phthalate metabolites and biomarkers of reproductive function in young men. Epidemiology 16:487–493CrossRefGoogle Scholar
  21. Jurasović J, Cvitković P, Pizent A, Colak B, Telisman S (2004) Semen quality and reproductive endocrine function with regard to blood cadmium in Croatian male. Biometals 17(6):735–743CrossRefGoogle Scholar
  22. Jurewicz J, Hanke W (2011) Exposure to phthalates: reproductive outcome and children health. A review of epidemiological studies. Int J Occup Med Environ Health 24:115–141CrossRefGoogle Scholar
  23. Jurewicz J, Radwan M, Sobala W, Ligocka D, Radwan P, Bochenek M, Hawuła W, Jakubowski L, Hanke W (2013) Human urinary phthalate metabolites level and main semen parameters, sperm chromatin structure, sperm aneuploidy and reproductive hormones. Reprod Toxicol 42:232–241CrossRefGoogle Scholar
  24. Kašuba V, Rozgaj R, Milić M, Zelježić D, Kopjar N, Pizent A, Kljaković-Gašpić Z, Jazbec A (2012) Evaluation of genotoxic effects of lead in pottery-glaze workers using micronucleus assay, alkaline comet assay and DNA diffusion assay. Int Arch Occup Environ Health 85:807–818CrossRefGoogle Scholar
  25. Keck C, Bramkamp G, Behre HM, Muller C, Jockenhovel F, Nieschlag E (1995) Lack of correlation between cadmium in seminal plasma and fertility status of nonexposed individuals and two cadmium-exposed patients. Reprod Toxicol 9:35–40CrossRefGoogle Scholar
  26. Kleinsasser NH, Kastenbauer ER, Weissacher H, Muenzenrieder RK, Harréus UA (2000a) Phthalates demonstrate genotoxicity on human mucosa of the upper aerodigestive tract. Environ Mol Mutagen 35:9–12CrossRefGoogle Scholar
  27. Kleinsasser NH, Weissacher H, Kastenbauer ER, Dirschedl P, Wallner BC, Harréus UA (2000b) Altered genotoxicity in mucosal cells of head and neck cancer patients due to environmental pollutants. Eur Arch Otorhinolaryngol 257:337–342CrossRefGoogle Scholar
  28. Kleinsasser NH, Wallner BC, Kastenbauer ER, Weissacher H, Harréus UA (2001) Genotoxicity of di-butyl-phthalate and di-iso-butyl-phthalate in human lymphocytes and mucosal cells. Teratog Carcinog Mutagen 21:189–196CrossRefGoogle Scholar
  29. Kwack SJ, Kim KB, Kim HS, Lee BM (2009) Comparative toxicological evaluation of phthalate diesters and metabolites in Sprague-Dawley male rats for risk assessment. J Toxicol Environ Health A 72:1446–1454CrossRefGoogle Scholar
  30. Meeker JD, Rossano Mary G, Protas B, Padmanabhan V, Diamond MP, Puscheck E, Daly D, Paneth N, Wirth JJ (2010) Environmental exposure to metals and male reproductive hormones: circulating testosterone is inversely associated with blood molybdenum. Fertil Steril 93:130–135CrossRefGoogle Scholar
  31. Mei TX, Ling L, Song QR (2009) Combined toxic effects of DBP and DEHP on spermatogenesis in male rats. J Environ Health 26:853–856Google Scholar
  32. Mendiola J, Moreno JM, Roca M, Vergara-Juárez N, Martínez-García MJ, García-Sánchez A, Elvira-Rendueles B, Moreno-Grau S, López-Espín JJ, Ten J (2011) Relationships between heavy metal concentrations in three different body fluids and male reproductive parameters: a pilot study. Environ Hlth 10:6–11Google Scholar
  33. Menke A, Guallar E, Meredith SS, Rohrmann S, Basaria S, Rifai N, William G, NelsonElizabeth Platz A (2008) The association of urinary cadmium with sex steroid hormone concentrations in a general population sample of US adult men. BMC Public Health 8:72–78CrossRefGoogle Scholar
  34. Mouron SA, Golijow CD, Dulout FN (2001) DNA damage by cadmium and arsenic salts assessed by the single cell gel electrophoresis assay. Mutat Res/Genetic Toxicol Environ Mutag 498:47–55CrossRefGoogle Scholar
  35. Palus J, Rudzynski K, Dziubaltowska E, Wyszynska K, Natarajan AT, Nilsson R (2003) Genotoxic effects of occupational exposure to lead and cadmium. Mutat Res 540:19–28CrossRefGoogle Scholar
  36. Pan G, Hanaoka T, Yoshimura M, Zhang S, Wang P, Tsukino H, Inoue K, Nakazawa H, Tsugane S, Takahashi K (2006) Decreased serum free testosterone in workers exposed to high levels of di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP): a cross-sectional study in China. Environ Health Perspect 114:1643–1649Google Scholar
  37. Pant N, Upadhyay G, Pandey S, Mathur N, Saxena DK, Srivastava SP (2003) Lead and cadmium concentration in the seminal plasma of men in the general population: correlation with sperm quality. Reprod Toxicol 17:447–450Google Scholar
  38. Pant N, Shukla M, Patel KD, Shukla Y, Mathur N, Gupta YK, Saxena DK (2008) Correlation of phthalate exposures with semen quality. Toxicol App Pharmacol 231:112–116CrossRefGoogle Scholar
  39. Pizent A, Tariba B, Živkovic T (2012) Reproductive toxicity of metals in men. Arh Hig Rada Toksikol 1:35–46Google Scholar
  40. Sengupta P (2013) Environmental and occupational exposure of metals and their role in male reproductive functions. Drug Chem Toxicol 36:353–368CrossRefGoogle Scholar
  41. ShuGuang LI, JiCan D, LiQian Z, Jing Z, ZiQiang Z, Bo C (2011) An association of elevated serum prolactin with phthalate exposure in adult men. Biomed Environ Sci 24:31–39Google Scholar
  42. Siu ER, Mruk DD, Porto CS, Cheng CY (2009) Cadmium-induced testicular injury. Toxicol Appl Pharmacol 238:240–249CrossRefGoogle Scholar
  43. Telisman S, Cvitkovic P, Jurasovic J, Pizent A, Gavella M, Rocic B (2000) Semen quality and reproductive endocrine function in relation to biomarkers of lead, cadmium, zinc, and copper in men. Environ Health Perspect 108:45–53CrossRefGoogle Scholar
  44. Telisman S, Colak B, Pizent A, Jurasović J, Cvitković P (2007) Reproductive toxicity of low-level lead exposure in men. Environ Res 105:256–266CrossRefGoogle Scholar
  45. Tong S, von Schirnding YE, Prapamontol T (2000) Environmental lead exposure: a public health problem of global dimensions. Bull WHO 78:1068–1077Google Scholar
  46. Vigeh M, Smith DR, Hsu PC (2011) How does lead induce male infertility? Iran J Reprod Med 9:1–8Google Scholar
  47. World Health Organization (2010) WHO laboratory manual for the examination of human semen and semen-cervical mucus interaction, 5th edn. Cambridge University Press, CambridgeGoogle Scholar
  48. Xu B, Chia SE, Tsakok M, Ong CN (1993) Trace elements in blood and seminal plasma and their relationship to sperm quality. Reprod Toxicol 7:613–618Google Scholar
  49. Zeng X, Lin T, Zhou Y, Kong Q (2002) Alterations of serum hormone levels in male workers occupationally exposed to cadmium. J Toxicol Environ Health A 65:513–521CrossRefGoogle Scholar
  50. Zeng X, Jin T, Buchet JP, Jiang X, Kong Q, Ye T, Bernard A, Nordberg GF (2004) Impact of cadmium exposure on male sex hormones: a population-based study in China. Environ Res 96:338–344CrossRefGoogle Scholar
  51. Zhang Y, Zheng L, Chen B (2006) Phthalate exposure and human semen quality in Shanghai: a cross-sectional study. Biomed Environ Sci 19:205–209Google Scholar
  52. Zhijian C, Jialin L, Shijie C, Wei Z, Wei W, Lifen J, Hongping D, Jiliang H (2006) Evaluating the genotoxic effects of workers exposed to lead using micronucleus assay, comet assay and TCR gene mutation test. Toxicology 223:219–226CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Niraj Pant
    • 1
    Email author
  • G. Kumar
    • 2
  • A. D. Upadhyay
    • 3
  • D. K. Patel
    • 4
  • Y. K. Gupta
    • 2
  • P. K. Chaturvedi
    • 1
  1. 1.Department of Reproductive BiologyAll India Institute of Medical Sciences (AIIMS)Ansari NagarIndia
  2. 2.Department of PharmacologyAIIMSNew DelhiIndia
  3. 3.Department of BiostatisticsAIIMSNew DelhiIndia
  4. 4.Analytical Chemistry Section, Indian Institute of Toxicology Research, Lucknow, IndiaCouncil of Scientific and Industrial ResearchNew DelhiIndia

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