Developmental Immunotoxicity in SD Rat Pups Exposed by Di(n-butyl) Phthalate through Pre and Postnatal

SD Rat에 있어서 출생 전.후에 걸친 Di(n-butyl) Phthalate 노출에 의한 발생면역독성

  • 엄준호 (식품의약품안전청, 국립독성연구소 독성부) ;
  • 정승태 (식품의약품안전청, 국립독성연구소 독성부) ;
  • 이종권 (식품의약품안전청, 국립독성연구소 독성부) ;
  • 박재현 (식품의약품안전청, 국립독성연구소 독성부) ;
  • 권태우 (식품의약품안전청, 국립독성연구소 독성부) ;
  • 김지영 (식품의약품안전청, 국립독성연구소 독성부) ;
  • 오혜영 (식품의약품안전청, 국립독성연구소 독성부) ;
  • 김형수 (식품의약품안전청, 국립독성연구소 독성부)
  • Published : 2002.12.01

Abstract

Phthalate esters have possible effects on the endocrine system. Di-n-butyl phthalate (DBP) is one of the most commonly wed phthalic acid esters (PAEs). It is extensively wed as a plasticizer in elastomers, as a solvent for printing inks and resins, and as a textile lubricating agent. It is also present in the formulations of various cosmetic products. DBP has been identified as a reproductive toxicant in several animal species and also know as a endocrine disruptor. The objective of this study was to investigate the effect of DBP on developmental immune Junction wing rat pups as experimental animals. Timed-bred pregnant SD rats were orally dosed with 0, 250, 500, or 750 mg DBP/kg body weight once a day from gestational day (GD) 5 to 18 and postpartum day (PD) 3 to 18. On PD22, the dams and their pups were euthanized and examined for alteration in parameters associated to immune function. The results showed no significant changes in body weight, thymus weight, thymus and spleen cellularities, the polyclonal activation respones of splenocyte with ConA and LPS, and also the distribution of arterial blood cells and thymocyto subsets in both rat dam and pups. However DBP exposure on rat dam resulted in increases of liver weights of dam and their pups except 750 mg DBP/kg, and body and spleen weights in pups except 750 mg DBP/kg. On the other hands, distribution rates of CD8+ T cells at 500 mg DBP/kg and B cells at 750 mg DBP/kg among splenocyte subsets were significantly increased in rat pups, unlike dams. Reasons of these distribution alterations of CD8+ T cells and B cells in rat pups are under study.

Keywords

References

  1. Toxicological Profile for Di-n-butylphthalate, TP-90-10 Agency for Toxic Substances and Disease Registry(ATSDR)
  2. Immunol. Today v.12 Toward an integrated view of thymopoiesis Boyd,R.L.;Hugo,P. https://doi.org/10.1016/0167-5699(91)90161-L
  3. Science v.265 no.5172 Neutrophil and B cell expansion in mice that lack the murine IL-8 receptor homolog Cacalano,G.;Lee,J.;Kikly,K.;Ryan,A.M.;Pitts-Meek,S.;Hultgren,B.;Wood,W.I.;Moore,M.W. https://doi.org/10.1126/science.8036519
  4. Toxicology v.165 no.1 Nagarkatti PS. Enhanced activation-induced cell death as a mechanism of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced immunotoxicity in peripheral T cells Camacho,I.A.;Hassuneh,M.R.;Nagarkatti,M. https://doi.org/10.1016/S0300-483X(01)00391-2
  5. J. Toxicol. Pub. Health v.17 Effect of Di(n-butyl) phthalate on the developing immune system of fetal and neonatal SD rats Chung,S.T.(et al.)
  6. Environ. Health Perspect v.101 Developmental effects of endocrine-disrupting chemicals in wildlife and human Colborn,T.;vom Saal,F.;Soto,A.
  7. J. Exp. Med. v.1 Neutrophil-activating protein 1/interleukin 8 stimulates the binding activity of the leukocyte adhesion receptor CD 11b/CD 18 on humaan neutrophils Detmers,P.A.;Lo,S.K.;Olsen Egbert,E.;Walz,A.;Baggiolini,M.;Cohn,Z.A.
  8. Toxicol. Appl. Pharmacol. v.95 Testicular toxicity and reduced Sertoli cell numbers in neonatal rats by di(2-ethylhexyl) phthalate and the recovery of fertility as adults Dostal,L.A.;Chapin,R.E.;Stefanski,S.A.;Harris,M.W.;Schwetz,B.A. https://doi.org/10.1016/S0041-008X(88)80012-7
  9. Toxicol. Lett. v.98 Further evaluation of developmental toxicity of di-n-butyl phthalate following administration during late pregnancy in rats Ema,M.;Miyawaki,E.;Kawashima,K. https://doi.org/10.1016/S0378-4274(98)00107-6
  10. Eur. J. Haematol. v.47 Human neutrophil migraton into skin chambers is associated with production of NAP-1/IL8 and C5a Follin,P.;Wymann,M.P.;Dewald,B.;Ceska,M.;Dahlgren,C. https://doi.org/10.1111/j.1600-0609.1991.tb00564.x
  11. Toxicology v.122 no.3 Alterations in the developing immune system of the F344 rat after perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin:Ⅱ.Effects on the pup and the adult Gehrs.B.C.;Riddle,M.M.;Williams,W.C.;Smialowicz,R.J. https://doi.org/10.1016/S0300-483X(97)00099-1
  12. J. Immunol. v.163 no.9 An essential role for antibody in neutrophil and eoxinophil recruitment to the cornea:B cell-deficient(microMT) mice fail to develop Th2-dependent, helminth-mediated keratitis Hall,L.R.;Lass,J.H.;Diaconu.E.;Strine,E.R.;Pearlman,E.
  13. Environ. Health Perspect v.105 The estrogenic activity of phthalate esters in vitro Harris,C.A.;Henttu,P.;Parker,M.G.;Sumpter,J.P. https://doi.org/10.2307/3433697
  14. Eur. J. Immunol. v.25 no.10 CD40 ligand-positive CD$8^ +$ T cell clones allow B cell growth and differentiation Hermann,P.;Van Kooten,C.;Gaillard,C.;Banchereau,J.;Blanchard.D. https://doi.org/10.1002/eji.1830251039
  15. Environ. Health Perspect v.107 Prenatal immunotoxicant exposure and postnatal autoinnume disease Holladay,S.D. https://doi.org/10.1289/ehp.99107s5687
  16. Developmental Toxicology(2d ed) Developmental immnotoxicology Holladay,S.D.;Luster,M.I.;Kimmel,C.A.(ed.);Buelke Sam,J.(ed.)
  17. J. Virol. v.72 Evidence for an underlying CD4 helper and CD8 T-cell defect in B-cell-deficient mice:failure to clear persistent virus infection after adoptive immunotherapy with virus-specific memory cells from muMT/muMT mice Homann,D.;Tishon,A.;Berger,D.P,;Weigle,W.O.;von Herrath,M.G.;Oldstone,M.B.
  18. Environ. Health Perspect v.103 A variety of environmentally persistent chemicals, including some phthalate plasicizers, are weakly estrogenic Jobling,S.;Reynolds,T.;White,R.;Parker,M.G.;Sumpter,J.P. https://doi.org/10.2307/3432434
  19. J. Exp. Med. v.176 Interleukin 8(IL-8) selectively inhibits immunoglobulin E production induced by IL-4 in human B cells Kimata,H.;Yoshida,A.;Ishioka,C.;Lindley,I.;Mikawa,H. https://doi.org/10.1084/jem.176.4.1227
  20. Environmental Health Criteria 189:Di-n-Butyl phthalate Long,G.;Meek,E.
  21. Toxicol. Appl. Pharmacol. v.156 Disruption of androgen-regulated male reproductive development by Di(n-butyl) phthalate during late gestation in rats is different from flutamide Mychreest,E.;Sar,M.;Cattley,R.C.;Foster,P.M. https://doi.org/10.1006/taap.1999.8643
  22. Toxicol Sci. v.55 Dose-dependent alterations in androgen-regulated male reproductive development in rats exposed to Di(n-butyl) phthalate during late gestation Mychreest,E.;Wallace,D.G.;Fostre,P.M. https://doi.org/10.1093/toxsci/55.1.143
  23. Final report on the reproductive toxicity of Di(n-buthyl) (CAS No. 84-74-2) In Sprague-Dawley Rats. NYIS Publication No. PB92111996 National Toxicology Program(NTP)
  24. Int J. Clin. Lab. Res. v.22 no.1 Both CD$8^ +$ and CD$16^ +$ human T cell clones can provide B cell help for immunoglobulin production Simonelli,C.;Rugiu,F.S.;Manetti,R.;Parronchi,P.;Piccinni,M.P.;Almerigogna,F.;Romagnani,S.;Maggi,E. https://doi.org/10.1007/BF02591391