Abstract
A rat model was developed to study toluene-abuse embryopathy, a clinical syndrome which occurs in offspring of women who abuse toluene during pregnancy. On d 6-19 of gestation, eight dams received a daily gavage dose of toluene, 650 mg/kg body weight, diluted in corn oil, whereas eight control dams and eight pair-fed dams received corn oil. The fetuses were delivered on d 19 of gestation. In the toluene-exposed group, the weights of the fetuses were reduced by 21.6% (p < 0.001), and a delay in skeletal ossification was demonstrated. Toluene exposure significantly reduced the weight of the fetal brain by 11.9% (p < 0.001), as well as the weights of the heart, liver, and kidney. Organ weight/body weight ratios did not differ significantly. Morphometric analysis of brain sections demonstrated that toluene exposure resulted in smaller brains together with an increase in the size of the ventricular system and a reduction in the size of the caudate nucleus. Although toluene exposure resulted in a 13.7% reduction in maternal food consumption, the observations made in the pair-fed group did not differ from those made in the control group. These findings suggest that prenatal exposure to toluene results in generalized fetal growth retardation, and that these effects are not due to the reduction in maternal food consumption.
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Abbreviations
- ANOVA:
-
analysis of variance
References
Benignus VA 1981 Health effects of toluene: a review. Neurotoxicology 2: 567–588
Rosenberg NL, Kleinschmidt-DeMasters BK, Davis KA, Dreisbach JN, Hormes JT, Filley CM 1988 Toluene abuse causes diffuse central nervous system white matter changes. Ann Neurol 23: 611–614
Streicher HZ, Gabow PA, Moss AH, Kono D, Kaehny WD 1981 Syndromes of toluene sniffing in adults. Ann Intern Med 94: 758–762
Carroll E 1977 Notes on the epidemiology of inhalants. NIDA Res Monogr 15: 14–27
Padilla E, Padilla A, Morales A 1979 Inhalant, marihuana, and alcohol abuse among barrio children and adolescents. Int J Addict 14: 945–964
Comstock EG, Comstock BS 1977 Medical evaluation of inhalant abusers. NIDA Res Mongr 15: 54–80
Goodwin TM 1988 Toluene abuse and renal tubular acidosis in pregnancy. Obstet Gynecol 71: 715–718
Toutant C, Lippmann S 1979 Fetal solvents syndrome. Lancet 1: 1356
Hersh JH, Podruch PE, Rogers G, Weisskopf B 1985 Toluene embryopathy. J Pediatr 106: 922–927
Hersh JH 1989 Toluene embryopathy: Two new cases. J Med Genet 26: 333–337
Arnold GL, Kirby RS, Langendoerfer S, Wilkins-Haug L 1994 Toluene embryopathy: Clinical delineation and developmental follow-up. Pediatrics 93: 216–220
Pearson MA, Hoyme HE, Seaver LH, Rimsza ME 1994 Toluene embryopathy: Delineation of the phenotype and comparison with fetal alcohol syndrome. Pediatrics 93: 211–215
Ng TP, Foo SC, Yoong T 1992 Risk of spontaneous abortion in workers exposed to toluene. Br J Ind Med 49: 804–808
Syrovadko ON 1977 Working conditions and health status of women handling organo-siliceous varnishes containing toluene. Gig Tr Prof Zabol 4: 15–19
McDonald JC, Lavoie J, Cote R, McDonald AD 1987 Chemical exposures at work in early pregnancy and congenital defect: a case referent study. Br J Ind Med 44: 527–533
Bruckner JV, Peterson RG 1981 Evaluation of toluene and acetone inhalant abuse. I. Pharmacology and pharmacodynamics. Toxicol Appl Pharmacol 61: 27–38
Bruckner JV, Peterson RG 1981 Evaluation of toluene and acetone inhalant abuse. II. Model development and toxicology. Toxicol Appl Pharmacol 61: 302–312
Konietzko H, Keilbach J, Drysch K 1980 Cumulative effects of daily toluene exposure. Int Arch Occup Environ Health 46: 53–58
Documentation of the Threshold Limit Values and Biological Exposure Indices, 5th Ed. 1986 American Conference of Governmental Industrial Hygienists Inc., Cincinnati, pp 578–579
Longley E, Jones A, Welch R, Lomaev O 1967 Two acute toluene episodes in merchant ships. Arch Environ Health 14: 481–487
Hudak A, Ungvary G 1978 Embryotoxic effects of benzene and its methyl derivatives: toluene, xylene. Toxicology 11: 55–63
Hudak A, Rodics K, Stuber I, Ungvary G 1977 The effects of toluene inhalation on pregnant CFY rats and their offspring. Munkavedelem 23( suppl 1-3): 25–30
Ungvary G, Tatrai E 1985 On the embryotoxic effects of benzene and its alkyl derivatives in mice, rats and rabbits. Arch Toxicol Suppl 8: 425–430
Courtney KD, Andrews JE, Springer J, Menache M, Williams T, Dalley L, Graham JA 1986 A perinatal study of toluene in CD-1 mice. Fundam Appl Toxicol 6: 145–154
Nawrot PS, Staples RE 1979 Embryo-fetal toxicity and teratogenicity of benzene and toluene in the mouse. Teratology 19: 41A
Donald JM, Hooper K, Hopenhayn-Rich C 1991 Reproductive and developmental toxicity of toluene: a review. Environ Health Perspect 94: 237–244
Gospe SM, Saeed DB, Zhou SS, Zeman FJ 1994 The effects of high-dose toluene on embryonic development in the rat. Pediatr Res 36: 811–815
Zeman FJ 1968 Effects of maternal protein restriction on the kidney of the newborn young of rats. J Nutr 94: 111–116
Taubeneck MW, Daston GP, Rogers JM, Gershwin ME, Ansari A, Keen CL 1995 Tumor necrosis factor-α alters maternal and embryonic zinc metabolism and is developmentally toxic in mice. J Nutr 125: 908–919
Gospe SM, Al-Bayati MAS 1994 Comparison of oral and inhalation exposures to toluene. J Am Coll Toxicol 13: 21–32
Jones AD, Dunlap MR, Gospe SM 1994 Stable isotope dilution GC/MS for determination of toluene in submilliliter volumes of whole blood. J Anal Toxicol 18: 251–254
McLeod MJ 1980 Differential staining of cartilage and bone in whole mouse fetuses by Alcian blue and Alizarin red S. Teratology 22: 299–301
Aliverti V, Ronanomi L, Giavini E, Leone VG, and Mariani L 1979 The extent of fetal ossification as an index of delayed development in teratogenic studies on the rat. Teratology 20: 237–242
Barrow MV, Taylor WJ 1969 A rapid method for detecting malformations in rat fetuses. J Morphol 127: 291–306
Paxinos G, Tork I, Tecott L, Valentino KL 1991 Atlas of the Developing Rat Brain. Academic Press, San Diego, CA
da Silva VA, Malheiros LR, Paumgartten FJR, de Matos Sa-Rego M, Riul TR, Golovatte MAR 1990 Developmental toxicity of in utero exposure to toluene on malnourished and well nourished rats. Toxicology 64: 155–168
Dobbing J 1981 The later development of the brain and its vulnerability. In: Davis JA, Dobbing J (eds) Scientific Foundations of Paediatrics, 2nd Ed. William Heinemann Medical Books, London, pp 744–759
Brown RM, Fishman RHB 1984 An overview and summary of the behavioral and neural consequences of perinatal exposure to psychotropic drugs. In: Yanai J (ed) Neurobehavioral Teratology. Elsevier, Amsterdam, pp 3–54
Bayer SA, Altman HJ 1995 Neurogenesis and neuronal migration. In: Paxinos G (ed) The Rat Nervous System, 2nd Ed. Academic Press, San Diego, CA, pp 1041–1078
Ghantous H, Danielsson BRG 1986 Placental transfer and distribution of toluene, xylene and benzene, and their metabolites during gestation in mice. Biol Res Pregnancy Perinatol 7: 98–105
Brown-Woodman PD, Webster WS, Picker K, Huq F 1994 In vitro assessment of individual and interactive effects of aromatic hydrocarbons on embryonic development of the rat. Reprod Toxicol 8: 121–135
Fish I, Winick M 1969 Cellular growth in various regions of the developing rat brain. Pediatr Res 3: 407–412
Acknowledgements
The authors thank R. Munn, L. Hoang, and J. Nguyen for technical assistance, and Drs. C. Keen and W. Ellis for assistance with various aspects of this study.
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Supported in part by Grant RO3-DA06665 from the National Institute on Drug Abuse.
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Gospe, S., Zhou, S., Saeed, D. et al. Development of a Rat Model of Toluene-Abuse Embryopathy. Pediatr Res 40, 82–87 (1996). https://doi.org/10.1203/00006450-199607000-00015
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DOI: https://doi.org/10.1203/00006450-199607000-00015
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