Skip to main content

Advertisement

SpringerLink
Log in

Gestational di-n-butyl phthalate exposure induced developmental and teratogenic anomalies in rats: a multigenerational assessment

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

With the limited but ongoing usage of di-n-butyl phthalate (DBP) as plasticizer, the health effects of both phthalate and its alternatives are far from being understood. Multigenerational effects of phthalates were evaluated in rats upon exposure to DBP, aiming to provide some evidences about its potential in causing developmental teratogenicity. Gestational rats were exposed to DBP (500 mg/kg bw/day) and control groups with olive oil. On the 18th day of gestation, fetuses (F1) isolated from a few dams were subjected to prenatal screening, and the other rats were allowed to litter, and later postnatal screening was made. DBP-toxicated (F1) rats were crossed and reared up to three generations (F2 and F3) by adopting the same experimental design. A considerable decrease in the weight of placenta, low number of corpora lutea and increased resorptions, and pre- and postimplantation loss were observed in F1, F2, and F3 generations. Further, there was a decrease in the number of live births and fetal body weight with high mortality, the developmental indices showed reduction in litter size and sex ratio, and a considerable incidence of skeletal and malformation complex involving face and eye was observed in later generations compared to the first. The pre-weaning indices in neonates showed a considerable delay in physical growth milestones and poor scores in sensory motor development. Alterations noticed in the levels of thyroid profile and testosterone found to have a role in sensory motor, craniofacial development, and eye formation. In brief, results confirm multigenerational and fetotoxic effects of DBP; thereby, findings imply that developing tissues are the targets and endocrine disruption appears to be the underlying mechanism of phthalate action.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Altman J, Sudarshan K (1975) Postnatal development of locomotion in the laboratory rat. Anim Behav 23(4):896–920

    Article  CAS  Google Scholar 

  • Bae J, Kim S, Kannan K, Louis GMB (2015) Couples’ urinary bisphenol A and phthalate metabolite concentrations and the secondary sex ratio. Environ Res 137:450–457

    Article  CAS  Google Scholar 

  • Bailey J, Knight A, Balcombe J (2005) The future of teratology research is in vitro. Biog Amines 19(2):97–145

    Article  CAS  Google Scholar 

  • Ema M, Amano H, Itami T, Kawasaki H (1993) Teratogenic evaluation of di-n-butyl phthalate in rats. Toxicol Lett 69(2):197–203

    Article  CAS  Google Scholar 

  • Ema M, Amano H, Ogawa Y (1994) Characterization of the developmental toxicity of di-n-butyl phthalate in rats. Toxicol 86(3):163–174

    Article  CAS  Google Scholar 

  • Ema M, Miyawaki E, Kawashima K (2000) Effects of dibutyl phthalate on reproductive function in pregnant and pseudopregnant rats. Reprod Toxicol 14(1):13–19

    Article  CAS  Google Scholar 

  • Gilbert-Barness E (2010) Teratogenic causes of malformations. Ann of Clin lab Sci 40(2):99–114

    CAS  Google Scholar 

  • Foster PMD (2006) Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters. Int J Androl 29:140–147

    Article  CAS  Google Scholar 

  • Franciszek B, Szumiło J, Dudka J et al (2005) Morphological studies in modern teratological investigations. Folia Morphol (Warsz) 64(1):1–8

    Google Scholar 

  • Gray LE Jr, Laskey J, Ostby J (2006) Chronic di-n-butyl phthalate exposure in rats reduces fertility and alters ovarian function during pregnancy in female Long Evans hooded rats. Toxicol Sci 93(1):189–195

    Article  CAS  Google Scholar 

  • James WH (2008) Evidence that mammalian sex ratios at birth are partially controlled by parental hormone levels around the time of conception. J Endocrinol 198:3–15

    Article  CAS  Google Scholar 

  • Jobling MS, Hutchison GR, van den Driesche S, Sharpe RM (2011) Effects of di(n-butyl) phthalate exposure on fetal rat germ cell number and differentiation: identification of age-specific windows of vulnerability. Int J Androl 34:e386–e396

    Article  CAS  Google Scholar 

  • Koch HM, Calafat AM (2009) Human body burdens of chemicals used in plastic manufacture. Phil Trans R Soc B 364(1526):2063–2078

    Article  CAS  Google Scholar 

  • Latini G, De Felice C, Presta G et al (2003) In utero exposure to di-(2-ethylhexyl)phthalate and duration of human pregnancy. Environ Health Perspect 111(14):1783–1785

    Article  CAS  Google Scholar 

  • Liu C, Zhao L, Wei L, Li L (2015) DEHP reduces thyroid hormones via interacting with hormone synthesis-related proteins, deiodinases, transthyretin, receptors, and hepatic enzymes in rats. Environ Sci Pollut Res 22:12711–12719

    Article  CAS  Google Scholar 

  • Li Y, Zhuang M, Li T, Nian S (2009) Neurobehavioral toxicity study of dibutyl phthalate on rats following in utero and lactational exposure. J App Toxicol 29:603–611

    Article  CAS  Google Scholar 

  • Meikle AW (2004) The interrelationships between thyroid dysfunction and hypogonadism in men and boys. Thyroid 14(Supplement 1):S17–S25

    Article  CAS  Google Scholar 

  • Mylchreest E, Cattley RC, Foster PM (1998) Male reproductive tract malformations in rats following gestational and lactational exposure to di(nbutyl) phthalate: an antiandrogenic mechanism? Toxicol Sci 43:47–60

    Article  CAS  Google Scholar 

  • O’Connor JC, Frame SR, Ladics GS (2002) Evaluation of a 15-day screening assay using intact male rats for identifying antiandrogens. Toxicol Sci 69(1):92–108

    Article  Google Scholar 

  • Pantaleoni G, Fanini D, Mariasponta A et al (1988) Effects of maternal exposure to polychlorobiphenyls (PCBs) on Fl generation behavior in the rat. Fundam Appl Toxicol 11:440–449

    Article  CAS  Google Scholar 

  • Parks LG, Ostby JS, Lambright CR et al (2000) The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicol Sci 58:339–349

    Article  CAS  Google Scholar 

  • Ragge NK, Subak-Sharpe ID, Collin JRO (2007) A practical guide to the management of anophthalmia and microphthalmia. Eye 21:1290–1300

    Article  CAS  Google Scholar 

  • Richardson SJ, Wijayagunaratne RC, D’Souza DG et al (2015) Transport of thyroid hormones via the choroid plexus into the brain: the roles of transthyretin and thyroid hormone transmembrane. Front Neurosci 9:1–8

    Article  Google Scholar 

  • Saillenfait AM, Langonne I, Leheup B (2001) Effects of mono-n-butyl phthalate on the development of rat embryos: in vivo and in vitro observations. Pharmacol Toxicol 89:104–112

    Article  CAS  Google Scholar 

  • Saillenfait AM, Gallissot F, Sabaté J-P (2009) Differential developmental toxicities of di-n-hexyl phthalate and dicyclohexyl phthalate administered orally to rats. J Appl Toxicol 29:510–521

    Article  CAS  Google Scholar 

  • Salazar V, Castillo C, Ariznavarreta C et al (2004) Effect of oral intake of dibutyl phthalate on reproductive parameters of Long Evans rats and pre-pubertal development of their offspring. Toxicology 205(1–2):131–137

    Article  CAS  Google Scholar 

  • Masaru S, Wakui S, Wempe MF et al (2013) Male Sprague-Dawley rats exposed to in utero di(n-butyl) phthalate: dose dependent and age-related morphological changes in leydig cell smooth endoplasmic reticulum. Toxicol Pathol 41:984–991

    Article  Google Scholar 

  • Singh AR, Lawrence WH, Autian J (1972) Teratogenicity of phthalate esters in rats. J Pharm Sci 61(1):51–55

    Article  CAS  Google Scholar 

  • Tanaka T (2002) Reproductive and neurobehavioural toxicity study of bis(2-ethylhexyl) phthalate (DEHP) administered to mice in the diet. Food Chem Toxicol 40:1499–1506

    Article  CAS  Google Scholar 

  • Tanimura T, Ema M, Kihara T (1980) Effects of combined treatment with methylmercury and polychlorinated biphenyls (PCBs) on the development of mouse offspring. In: Persaud TVN (ed) Advances in the study of birth defects: neural and behavioral teratology, vol 4. University Park Press, Baltimore, pp. 163–198

    Google Scholar 

  • Wo’jtowicz Anna K, Konrad AS, Agnieszka WnukMałgorzata Kajta (2016) Dibutyl phthalate (DBP)-induced apoptosis and neurotoxicity are mediated via the aryl hydrocarbon receptor (AhR) but not by estrogen receptor alpha (ERa), estrogen receptor beta (ERb), or peroxisome proliferator-activated receptor gamma (PPARc) in mouse cortical neurons. Neurotox Res 1–13 doi:10.1007/s12640-016-9665-x

  • Harold ZI (2013) Exposure to lipophilic chemicals as a cause of neurological impairments, neurodevelopmental disorders and neurodegenerative diseases. Interdiscip Toxicol 6(3):103–110

    Google Scholar 

  • Zhang Y, Jiang X, Chen B (2004) Reproductive and developmental toxicity in F1 Sprague-Dawley male rats exposed to di-n-butyl phthalate in utero and during lactation and determination of its NOAEL. Reprod Toxicol 18(5):669–676

    Article  CAS  Google Scholar 

  • Ziejewski MK, Solomon HM, Rendemonti J, Stanislaus D (2015) Comparison of a modified mid-coronal sectioning technique and Wilson’s technique when conducting eye and brain examinations in rabbit teratology studies. Birth Defects Res B 104:23–34

    Article  CAS  Google Scholar 

  • Zoeller RT, Rovet J (2004) Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings. J Neuroendocrinol 16:809–818

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Zoology, Bangalore University, Bangalore, 560 056, India

    P. Mahaboob Basha & M. J. Radha

Authors
  1. P. Mahaboob Basha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. J. Radha
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. Mahaboob Basha.

Additional information

Responsible editor: Philippe Garrigues

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mahaboob Basha, P., Radha, M.J. Gestational di-n-butyl phthalate exposure induced developmental and teratogenic anomalies in rats: a multigenerational assessment. Environ Sci Pollut Res 24, 4537–4551 (2017). https://doi.org/10.1007/s11356-016-8196-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-016-8196-6

Keywords

Search

Navigation