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Developmental toxicity of prenatal exposure to toluene

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Abstract

Organic solvents have become ubiquitous in our environment and are essential for industry. Many women of reproductive age are incresingly exposed to solvents such as toluene in occupational settings (ie, long-term, lowconcentration exposures) or through inhalant abuse (eg, episodic, binge exposures to high concentrations). The risk for teratogenic outcome is much less with low to moderate occupational solvent exposure compared with the greater potential for adverse pregnancy outcomes, developmental delays, and neurobehavioral problems in children born to women exposed to high concentrations of abused organic solvents such as toluene, 1,1,1-trichloroethane, xylenes, and nitrous oxide. Yet the teratogenic effects of abuse patterns of exposure to toluene and other inhalants remain understudied. We briefly review how animal models can aid, substantially in clarifying the developmental risk of exposure to solvents for adverse biobehavioral outcomes following abuse patterns of use and in the absence of associated health problems and co-drug abuse (eg, alcohol). Our studies also begin to establish the importance of dose (concentration) and critical perinatal periods of exposure to specific outcomes. The present results with our clinically relevant animal model of repeated, brief, high-concentration binge prenatal toluene exposure demonstrate the dose-dependent effect of toluene on prenatal development, early postnatal maturation, spontaneous exploration, and amphetamine-induced locomotor activity. The results imply that abuse patterns of toluene exposure may be more deleterious than typical occupational exposure on fetal development and suggest that animal models are effective in studying the mechanisms and risk factors of organic solvent teratogenicity.

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References

  1. Agency for Toxic Substances and Disease Registry (ATSDR).Toxicological profile for toluene. In:US Public Health Service. Atlanta, GA: US Department of Health and Human Services; 2000.

    Google Scholar 

  2. Hobara T, Okuda M, Gotoh M, Oki K, Segawa H, Kunitsugu I. Estimation of the lethal toluene concentration from the accidental death of painting workers.Ind Health. 2000;38:228–231

    Article  PubMed  CAS  Google Scholar 

  3. Jones RD, Winter DP. Two case reports of deaths on industrial premises attributed to 1,1,1-trichloroethane.Arch Environ Health. 1983;38:59–61.

    PubMed  CAS  Google Scholar 

  4. McCarthy TB, Jones RD. Industrial gassing poisonings due to trichlorethylene, perchlorethylene, and 1-1-1 trichloroethane, 1961–80.Br J Ind Med. 1983;40:450–455.

    PubMed  CAS  Google Scholar 

  5. Cavender F. Aromatic hydrocarbons. In: Clayton G, Clayton F, eds.Patty's Industrial Hygiene and Toxicology. vol. 2, part B. New York, NY: Wiley; 1994:1301–1326.

    Google Scholar 

  6. Kurtzman TL, Otsuka KN, Wahl RA. Inhalant abuse by adolescents.J Adolesc Health. 2001;28:170–180.

    Article  PubMed  CAS  Google Scholar 

  7. Wu LT, Pilowsky DJ, Schlenger WE. Inhalant abuse and dependence among adolescents in the United States.J Am Acad Child Adolesc Psychiatry. 2004;43:1206–1214.

    Article  PubMed  Google Scholar 

  8. SAMHSA. Technical appendices and selected data tables. In:Summary of Findings From the 2004 National Survey on Drug Use and Health. Rockville, MD: US Department of Health and Human Services; 2002.

    Google Scholar 

  9. SAMHSA. Technical appendices and selected data tables. In:Summary of Findings From the 2000 National Household Survey on Drug Abuse. Rockville, MD: US Department of Health and Human Services; 2001.

    Google Scholar 

  10. Weir E. Inhalant use and addiction in Canada.CMAJ. 2001;164:397.

    PubMed  CAS  Google Scholar 

  11. Pearson MA, Hoyme HE, Seaver LH, Rimsza ME. Toluene embryopathy: delineation of the phenotype and comparison with fetal alcohol syndrome.Pediatrics. 1994;93:211–215.

    PubMed  CAS  Google Scholar 

  12. Beauvais F, Wayman JC, Jumper-Thurman P, Plested B, Helm H. Inhalant abuse among American Indian, Mexican American, and non-Latino white adolescents.Am J Drug Alcohol Abuse. 2002;28:171–187.

    Article  PubMed  Google Scholar 

  13. Maxwell JC. Deaths related to the inhalation of volatile substances in Texas: 1988–1998.Am J Drug Alcohol Abuse. 2001;27:689–697.

    Article  PubMed  CAS  Google Scholar 

  14. McGarvey EL, Clavet GJ, Mason W, Waite D. Adolescent inhalant abuse: environments of use.Am J Drug Alcohol Abuse. 1999;25:731–741.

    Article  PubMed  CAS  Google Scholar 

  15. Bukowski JA. Review of the epidemiological evidence relating toluene to reproductive outcomes.Regul Toxicol Pharmacol. 2001;33:147–156.

    Article  PubMed  CAS  Google Scholar 

  16. Jones HE, Balster RL. Inhalant abuse in pregnancy.Obstet Gynecol Clin North Am. 1998;25:153–167.

    Article  PubMed  CAS  Google Scholar 

  17. Flanagan RJ, Ives RJ. Volatile substance abuse.Bull Narc. 1994;46:49–78.

    PubMed  CAS  Google Scholar 

  18. Till C, Koren G, Rovet JF. Prental exposure to organic solvents and child neurobehavioral performance.Neurotoxicol Teratol. 2001;23:235–245.

    Article  PubMed  CAS  Google Scholar 

  19. Arnold GL, Kirby RS, Langendoerfer S, Wilkins-Haug L. Toluene embryopathy: clinical delineation and developmental follow-up.Pediatrics. 1994;93:216–220.

    PubMed  CAS  Google Scholar 

  20. Goodwin TM. Toluene abuse and renal tubular acidosis in pregnancy.Obstet Gynecol. 1988;71:715–718.

    PubMed  CAS  Google Scholar 

  21. Hersh JH. Toluene embryopathy: two new cases.J Med Genet. 1989;26:333–337.

    Article  PubMed  CAS  Google Scholar 

  22. Hersh JH, Podruch PE, Rogers, G, Weisskopf B. Toluene embryopathy.J Pediatr. 1985;106:922–927.

    Article  PubMed  CAS  Google Scholar 

  23. Toutant C, Lippmann S. Fetal solvents syndrome.Lancet. 1979;313:1356.

    Article  Google Scholar 

  24. Wilkins-Haug L, Gabow PA. Toluene abuse during pregnancy: obstetric complications and perinatal outcomes.Obstet Gynecol. 1991;77:504–509.

    PubMed  CAS  Google Scholar 

  25. Hunter AG, Thompson D, Evans JA. Is there a fetal gasoline syndrome?.Teratology. 1979;20:75–79.

    Article  PubMed  CAS  Google Scholar 

  26. Stoler JM. Reassessment of patients with the diagnosis of fetal alcohol syndrome.Pediatrics. 1999;103:1313–1315.

    Article  PubMed  CAS  Google Scholar 

  27. Stratton K, Howe C, Battaglia FE.Fetal Alcohol Syndrome: Diagnosis, Epidemiology, Prevention, and Treatment. Washington, DC: National Academy Press; 1996.

    Google Scholar 

  28. Hannigan JH, Armant DR. Alcohol in pregnancy and neonatal outcome.Semin Neonatol. 2000;5:243–254.

    Article  PubMed  CAS  Google Scholar 

  29. Riley EP, McGee CL. Fetal alcohol spectrum disorders an overview with emphasis on changes in brain and behavior.Exp Biol Med. 2005;230:357–365.

    CAS  Google Scholar 

  30. Mattson SN, Riley EP. A review of the neurobehavioral deficits in children with fetal alcohol syndrome or prenatal exposure to alcohol.Alcohol Clin Exp Res. 1998;22:279–294.

    Article  PubMed  CAS  Google Scholar 

  31. Roebuck TM, Mattson SN, Riley EP. Prenatal exposure to alcohol: effects on brain structure and neuropyschological functioning. In: Hannigan JH, Spear NE, Spear LP, eds.Alcohol and Alcoholism: Effects on Brain and Development. Mahwah, NJ: LA Erlbaum, 1999:1–16.

    Google Scholar 

  32. Wilkins-Haug L. Teratogen update: toluene.Teratology. 1997;55:145–151.

    Article  PubMed  CAS  Google Scholar 

  33. Abel EL, Riley EP. Studies of prenatal alcohol exposure: methodological considerations. In: West, JR, ed.Alcohol and Brain Development. New York, NY: Oxford Press, 1986:105–119.

    Google Scholar 

  34. Hannigan JH. What research with animals is telling us about alcohol-related neurodevelopmental disorder.Pharmacol Biochem Behav. 1996;55:489–499.

    Article  PubMed  CAS  Google Scholar 

  35. Hannigan JH, Abel EL.Animal Models of Fetal Alcohol Syndrome. Cambridge, UK: Cambridge University Press, 1996:77–102.

    Google Scholar 

  36. Courtney KD, Andrews JE, Springer J, et al. A perinatal study of toluene in CD-1 mice.Fundam, Appl Toxicol. 1986;6:145–154.

    Article  CAS  Google Scholar 

  37. Hudák A, Rodics K, Stuber I, Ungvary GY. The effects of toluence inhalation on pregnant CFY rats and their offspring.Munkavedelem. 1977;23:25–30.

    Google Scholar 

  38. Hudák A, Ungváry G. Embryotoxic effects of benzene and its methyl derivatives; toluene, xylene.Toxicology. 1978;11:55–63.

    Article  PubMed  Google Scholar 

  39. Nawrot PS, Staples RE. Embryofetal toxicity and teratogenicity of benzene and toluene in the mouse [abstract].Teratology. 1979;19:41A.

    Google Scholar 

  40. Shigeta S, Aikawa H, Misawa T, Yokoyama M. Effects of learning schedules on operant behavior in toluene inhaled rats.Nippon Eiseigaku Zasshi. 1981;36:541–549. Japanese.

    PubMed  CAS  Google Scholar 

  41. Gospe SM, Jr, Zhou SS. Toluene abuse embryopathy: longitudinal neurodevelopmental effects of prenatal exposure to toluene in rats.Reprod Toxicol. 1998;12:119–126.

    Article  PubMed  CAS  Google Scholar 

  42. York RG, Sowry BM, Hastings L, Manson JM. Evaluation of teratogenicity and neurotoxicity with maternal inhalation exposure to methyl chloroform.J Toxicol Environ Health. 1982;9:251–266.

    Article  PubMed  CAS  Google Scholar 

  43. Thiel R, Chahoud I. Postnatal development and behaviour of Wistar rats after prenatal toluene exposure.Arch Toxicol. 1997;71:258–265.

    Article  PubMed  CAS  Google Scholar 

  44. Hass U, Lund SP, Hougaard KS, Simonsen L. Developmental neurotoxicity after toluene inhalation exposure in rats.Neurotoxicol Teratol. 1999;21:349–357.

    Article  PubMed  CAS  Google Scholar 

  45. Hougaard KS, Hass U, Lund SP, Simonsen L. Effects of prenatal exposure to toluene on postnatal development and behavior in rats.Neurotoxicol Teratol. 1999;21:241–250.

    Article  PubMed  CAS  Google Scholar 

  46. Blanchard BA, Riley EP, Hannigan JH. Deficits on a spatial navigation task following prenatal exposure to ethanol.Neurotoxicol Teratol. 1987;9:253–258.

    Article  PubMed  CAS  Google Scholar 

  47. Hannigan JH, Cortese BM, DiCerbo JA, Radford LD. Scopolamine does not differentially affect Morris maze performance in adult rats exposed prenatally to alcohol.Alcohol. 1993;10:529–535.

    Article  PubMed  CAS  Google Scholar 

  48. Vorhees CV, Rauch S, Hitzemann R. Effects of short-term prenatal alcohol exposure on neuronal membrane order in rats.Brain Res. 1988;466:161–166.

    PubMed  CAS  Google Scholar 

  49. Sharp CW, Rosenberg NL. Inhalants. In: Lowinson JH, Ruiz P, Millman RB, Langrod JG, eds.Substance Abuse: A Comprehensive Textbook. 3rd ed. Baltimore, MD: Williams and Wilkins, 1996:246–264.

    Google Scholar 

  50. McGarvey EL, Clavet GJ, Mason W, Waite D. Adolescent inhalant abuse: environments of use.Am J Drug Alcohol Abuse. 1999;25:731–741.

    Article  PubMed  CAS  Google Scholar 

  51. Jones HE, Kunko PM, Robinson SE, Balster RL. Developmental consequences of intermittent and continuous prenatal exposure to 1,1,1-trichloroethane in mice.Pharmacol Biochem Behav. 1996;55:635–646.

    Article  PubMed  CAS  Google Scholar 

  52. Coleman CN, Mason T, Hooker EP, Robinson SE. Developmental effects of intermittent prenatal exposure to 1,1,1-trichloroethane in the rat.Neurotoxicol Teratol. 1999;21:699–708.

    Article  PubMed  CAS  Google Scholar 

  53. Jones HE, Balster RL. Neurobehavioral consequences of intermittent prenatal exposure to high concentrations of toluene.Neurotoxicol Teratol. 1997;19:305–313.

    Article  PubMed  CAS  Google Scholar 

  54. Bowen SE, Batis JC, Mohammadi MH, Hannigan JH. Abuse pattern of gestational toluene exposure and early postnatal development in rats.Neurotoxicol Teratol. 2005;27:105–116.

    Article  PubMed  CAS  Google Scholar 

  55. Gospe SM, Zhou SS, Saeed DB, Zeman FJ. Development of a rat model of toluene-abuse embryopathy.Pediatr Res. 1996;40:82–87.

    Article  PubMed  Google Scholar 

  56. Klaassen CD, Rozman K. Absorption, distribution, and excretion of toxicants. In: Amdur MO, Doull J, Klaassen CD, eds.Casarett and Doull's Toxicology: The Basic Science of Poisons. 4th ed. New York, NY: McGraw-Hill; 1993;33–63.

    Google Scholar 

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Authors and Affiliations

  1. Department of Psychology, Wayne State University, Detroit, MI

    Scott E. Bowen & John H. Hannigan

  2. Behavioral Pharmacology and Toxicology Laboratory, Wayne State University, Detroit, MI

    Scott E. Bowen

  3. Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI

    Scott E. Bowen & John H. Hannigan

  4. C. S. Mott Center for Human Growth and Development, Neurobehavioral Teratology Laboratory, Wayne State University, Detroit, MI

    John H. Hannigan

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  1. Scott E. Bowen
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  2. John H. Hannigan
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Correspondence to Scott E. Bowen.

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Published: June 16, 2006

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Bowen, S.E., Hannigan, J.H. Developmental toxicity of prenatal exposure to toluene. AAPS J 8, 49 (2006). https://doi.org/10.1007/BF02854915

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