Inhalent abuse

Date of Search: 03/08/2016

Sources Searched: Medline,  Embase, PsycINFO, CINAHL

 Search History:

1. Medline; “lighter fluid*”.ti,ab; 35 results.

2. Medline; “lighter fuel”.ti,ab; 7 results.

3. Medline; butane.ti,ab; 2220 results.

4. Medline; exp BUTANES/; 900 results.

5. Medline; 1 OR 2 OR 3 OR 4; 2834 results.

6. Medline; pregn*.ti,ab; 406421 results.

7. Medline; exp PREGNANCY/; 790329 results.

8. Medline; 6 OR 7; 873358 results.

9. Medline; 5 AND 8; 32 results.

10. Medline; exp INHALANT ABUSE/; 154 results.

11. Medline; 8 AND 10; 3 results.

12. Medline; (inhal* adj2 abuse*).ti,ab; 439 results.

13. Medline; 8 AND 12; 23 results.

14. EMBASE; “lighter fluid*”.ti,ab; 30 results.

15. EMBASE; “lighter fuel”.ti,ab; 11 results.

16. EMBASE; butane.ti,ab; 2324 results.

17. EMBASE; exp BUTANE/; 2058 results.

18. EMBASE; 14 OR 15 OR 16 OR 17; 3559 results.

19. EMBASE; pregn*.ti,ab; 506321 results.

20. EMBASE; exp PREGNANCY/; 623464 results.

21. EMBASE; 19 OR 20; 799144 results.

22. EMBASE; 18 AND 21; 27 results.

23. EMBASE; exp INHALANT ABUSE/; 439 results.

24. EMBASE; 21 AND 23; 12 results.

25. EMBASE; exp FETUS/; 161192 results.

26. EMBASE; 18 AND 25; 11 results.

27. EMBASE; (fetus OR fetal OR foetal).ti,ab; 292936 results.

28. EMBASE; 18 AND 27; 11 results.

29. EMBASE; 25 OR 27; 351744 results.

30. EMBASE; 23 AND 29; 3 results.


32. EMBASE; 21 AND 31; 0 results.

33. EMBASE; 29 AND 31; 0 results.

34. EMBASE; “Volatile Substance Abuse”.ti,ab; 86 results.

35. EMBASE; 21 AND 34; 0 results.

36. EMBASE; 29 AND 34; 0 results.

37. EMBASE; exp PRENATAL DRUG EXPOSURE/; 8371 results.

38. EMBASE; 18 AND 37; 2 results.

39. Medline; (fetus OR fetal OR foetal).ti,ab; 249411 results.

40. Medline; exp PRENATAL EXPOSURE DELAYED EFFECTS/; 22678 results.

41. Medline; exp MATERNAL-FETAL EXCHANGE/; 28242 results.

42. Medline; 39 OR 40 OR 41; 281962 results.

43. Medline; 5 AND 42; 17 results.

44. CINAHL; “lighter fluid*”.ti,ab; 4 results.

45. CINAHL; “lighter fuel”.ti,ab; 0 results.

46. CINAHL; butane.ti,ab; 28 results.

47. CINAHL; 44 OR 46; 31 results.

48. CINAHL; exp INHALANT ABUSE/; 253 results.

49. CINAHL; exp PREGNANCY/; 106970 results.

50. CINAHL; 48 AND 49; 2 results.

51. CINAHL; (fetus OR fetal OR foetal).ti,ab; 16277 results.

52. CINAHL; exp MATERNAL-FETAL EXCHANGE/; 673 results.


54. CINAHL; 51 OR 52 OR 53; 19341 results.

55. CINAHL; 47 AND 54; 1 results.

56. CINAHL; 48 AND 54; 2 results.

57. EMBASE; “fetal solvent syndrome”.ti,ab; 12 results.

58. PsycInfo; “lighter fluid*”.ti,ab; 6 results.

59. PsycInfo; “lighter fuel”.ti,ab; 1 results.

60. PsycInfo; INHALANT ABUSE/; 535 results.

61. PsycInfo; butane.ti,ab; 35 results.

62. PsycInfo; “Volatile Substance Abuse”.ti,ab; 22 results.

63. PsycInfo; 58 OR 59 OR 60 OR 61 OR 62; 569 results.

64. PsycInfo; pregn*.ti,ab; 37694 results.

65. PsycInfo; exp PREGNANCY/; 20854 results.

66. PsycInfo; exp FETUS/; 1809 results.

67. PsycInfo; (fetus OR fetal OR foetal).ti,ab; 11144 results.

68. PsycInfo; exp PRENATAL EXPOSURE/; 5525 results.

69. PsycInfo; 64 OR 65 OR 66 OR 67 OR 68; 48725 results.

70. PsycInfo; 63 AND 69; 15 results.

71. PsycInfo; “fetal solvent syndrome”.ti,ab; 6 results.

72. Medline; “fetal solvent syndrome”.ti,ab; 11 results.

73. Medline; exp HYDROCARBONS, ALICYCLIC/; 183483 results.

74. Medline; exp SUBSTANCE-RELATED DISORDERS/; 241442 results.

75. Medline; 8 AND 73 AND 74; 72 results.

76. Medline; inhal*.ti,ab; 91531 results.

77. Medline; 8 AND 74 AND 76; 61 results.

78. EMBASE; inhal*.ti,ab; 119300 results.

79. EMBASE; exp SUBSTANCE ABUSE/; 46589 results.

80. EMBASE; 21 AND 78 AND 79; 13 results.

81. EMBASE; 37 AND 78 AND 79; 3 results.

82. CINAHL; “fetal solvent syndrome”.ti,ab; 0 results.

83. CINAHL; exp SUBSTANCE ABUSE/; 37511 results.

84. CINAHL; inhal*.ti,ab; 8866 results.

85. CINAHL; 49 AND 83 AND 84; 0 results.

86. CINAHL; 54 AND 83 AND 84; 1 results.

87. PsycInfo; exp DRUG ABUSE/; 97485 results.

88. PsycInfo; inhal*.ti,ab; 4276 results.

89. PsycInfo; 69 AND 87 AND 88; 20 results.

90. PsycInfo; “fetal solvent syndrome”.ti,ab; 6 results.

91. Medline; INHALATION EXPOSURE/; 7297 results.

92. Medline; 5 AND 8 AND 91; 0 results.


Title: Prenatal diagnosis of multiple fetal anomalies in naphthalene-addicted pregnant women: a case report. 

Citation: Clinical and experimental obstetrics & gynecology, Jan 2014, vol. 41, no. 2, p. 217-218, 0390-6663 (2014)

 Author(s): Boynukalin, F K, Baykal, C

 Abstract: Naphthalene is one of the abused inhalants. It has been associated with acute and chronic health problems. To the authors’ knowledge, prenatal exposure to naphthalene has never been discussed in humans. The authors discuss a case of naphthalene-addicted pregnant women with multiple fetal anomalies. At 15 weeks gestation, ultrasound screening demostrated multiple fetal anomalies: anencephaly, scoliosis, diffuse subcutaneous edema, flexion contracture of lower extremities, and hypoplastic left ventricle. Four weeks later obstetrical ultrasonography revealed that there was no fetal cardiac activity. The patient had a medical abortion. A stronger knowledge basis regarding naphthalene-related fetal anomaly is required to ensure accurate direct link, however the probability of naphthalene-related fetal anomaly must be considered.

 Source: Medline 

Title: Binge toluene exposure in pregnancy and pre-weaning developmental consequences in rats

 Citation: Neurotoxicology and Teratology, July 2013, vol./is. 38/(29-35), 0892-0362;1872-9738 (July 2013)

 Author(s): Bowen S.E., Hannigan J.H.

 Language: English

 Abstract: Binge Toluene Exposure in Pregnancy and Pre-weaning Developmental Consequences in Rats. Bowen, S.E. and Hannigan, J.H. The persistent rate of abuse of inhaled organic solvents, especially among women of child-bearing age, raises the risk for teratogenic effects of maternal toluene abuse. In this study, timed-pregnant Sprague Dawley rats were exposed from Gestation Day (GD) 8 to GD20 to 12,000 or 8000 parts per million (ppm) toluene, or 0. ppm (controls) for 30. min twice daily, 60. min total daily exposure. Pups were assessed from postnatal day (PN) 4 to PN21 using a developmental battery measuring growth (i.e., body weight), maturational milestones (e.g., eye opening & incisor eruption), and biobehavioral development (e.g., negative geotaxis & surface righting). Pups exposed in utero to 12,000. ppm or 8000. ppm toluene weighed significantly less than the non-exposed control pups beginning at PN4 and PN12 (respectively) until PN21. Toluene resulted in significant increases in an index of poor perinatal outcome, specifically a composite of malformations, defined “runting” and neonatal death. No significant delays were observed in reaching maturational milestones. The results reveal that brief, repeated, prenatal exposure to high concentrations of toluene can cause growth retardation and malformations in rats. A comparison of the present, conservative results with findings in previous studies implies that binge patterns of toluene exposure in pregnant rats modeling human solvent abuse can result in developmental and morphological deficits in offspring. These results do not exclude the possibility that maternal toxicity as well as teratogenic effects of toluene may contribute to outcomes. The results suggest that abuse of inhaled organic solvents like toluene may result in similar early developmental outcomes in humans. © 2013 Elsevier Inc.

 Publication Type: Journal: Article

 Source: EMBASE 

Title: Prenatal exposure to alcohol and illicit substances.

 Citation: Comprehensive addictive behaviors and disorders, Vol. 1: Principles of addiction., Jan 2013, (2013), p. 193-1133 (2013)

 Author(s): Schacht, Rebecca L.

 Abstract: In this chapter, we briefly review research on the effects of in utero exposure to alcohol and illicit substances, including marijuana, cocaine, methamphetamines, opioids, benzodiazepines, and inhalants. We limit our discussion to human findings, as a review of animal research is beyond the scope of this chapter (PsycINFO Database Record (c) 2016 APA, all rights reserved)(create)

 Source: PsycInfo

Title: Two serious and challenging medical complications associated with volatile substance misuse: Sudden sniffing death and fetal solvent syndrome.

 Citation: Substance Use & Misuse, May 2011, vol. 46, no. s1, p. 68-72, 1082-6084 (May 2011)

 Author(s): Bowen, Scott E.

 Abstract: Volatile substance misuse is a prevalent and often overlooked behavior among adolescents, including reported use among young pregnant women. Several medical repercussions can arise from the improper use of volatile substances, yet they are often underappreciated among scientists and health professionals. This brief review reports on the recent advances made in the preclinical and clinical data about two serious medical complications surrounding volatile substance misuse: sudden sniffing death and fetal solvent syndrome. Suggestions for treatment interventions are discussed. The paper’s limitations are noted. (PsycINFO Database Record (c) 2015 APA, all rights reserved)(journal abstract)

 Source: PsycInfo 

Title: Substance use in pregnancy: No. 256, April 2011

 Citation: International Journal of Gynecology and Obstetrics, August 2011, vol./is. 114/2(190-202), 0020-7292;1879-3479 (August 2011)

Author(s): anonymous

 Language: English

 Abstract: Objective: To improve awareness and knowledge of problematic substance use in pregnancy and to provide evidence-based recommendations for the management of this challenging clinical issue for all health care providers. Options: This guideline reviews the use of screening tools, general approach to care, and recommendations for clinical management of problematic substance use in pregnancy. Outcomes: Evidence-based recommendations for screening and management of problematic substance use during pregnancy and lactation. Evidence: Medline, PubMed, CINAHL, and The Cochrane Library were searched for articles published from 1950 using the following key words: substance-related disorders, mass screening, pregnancy complications, pregnancy, prenatal care, cocaine, cannabis, methadone, opioid, tobacco, nicotine, solvents, hallucinogens, and amphetamines. Results were initially restricted to systematic reviews and randomized control trials/controlled clinical trials. A subsequent search for observational studies was also conducted because there are few RCTs in this field of study. Articles were restricted to human studies published in English. Additional articles were located by hand searching through article reference lists. Searches were updated on a regular basis and incorporated in the guideline up to December 2009. Grey (unpublished) literature was also identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Values: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on the Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table 1). Benefits, harms, and costs: This guideline is intended to increase the knowledge and comfort level of health care providers caring for pregnant women who have substance use disorders. Improved access to health care and assistance with appropriate addiction care leads to reduced health care costs and decreased maternal and neonatal morbidity and mortality.

 Publication Type: Journal: Article

 Source: EMBASE 

Title: Perinatal toluene use: Associated risks and considerations

 Citation: Addictive Disorders and their Treatment, March 2011, vol./is. 10/1(1-5), 1531-5754 (March 2011)

 Author(s): Clark C.T., Richards E.M., Antoine D.G., Chisolm M.S.

 Language: English

 Abstract: The prevalence of toluene abuse in women of reproductive age is growing and little is known about toluenes effects on neonatal outcomes. The authors report the case of a 28-year-old woman with major depression, panic disorder, and multi-drug dependence (nicotine, cocaine, opiates, and toluene) and discuss approaches to the evaluation and treatment of these clinically complex patients. The authors also suggest preventive measures as well as areas for future research. Copyright © 2011 by Lippincott Williams & Wilkins.

 Publication Type: Journal: Article

 Source: EMBASE

 Full Text:

Available from Ovid in Addictive Disorders and Their Treatment

Title: Two serious and challenging medical complications associated with volatile substance misuse: sudden sniffing death and fetal solvent syndrome

 Citation: Substance use & misuse, 2011, vol./is. 46 Suppl 1/(68-72), 1532-2491 (2011)

 Author(s): Bowen S.E.

 Language: English

Abstract: Volatile substance misuse is a prevalent and often overlooked behavior among adolescents, including reported use among young pregnant women. Several medical repercussions can arise from the improper use of volatile substances, yet they are often underappreciated among scientists and health professionals. This brief review reports on the recent advances made in the preclinical and clinical data about two serious medical complications surrounding volatile substance misuse: sudden sniffing death and fetal solvent syndrome. Suggestions for treatment interventions are discussed. The paper’s limitations are noted.

 Publication Type: Journal: Review

 Source: EMBASE 

Title: Brain damage in a large cohort of solvent abusers.

 Citation: Acta neuropathologica, Apr 2010, vol. 119, no. 4, p. 435-445, 1432-0533 (April 2010)

Author(s): Al-Hajri, Zahra, Del Bigio, Marc R

Abstract: The neuropathology of solvent inhalation consists of patchy myelin loss with white matter macrophages that contain granular inclusions. It has been described only in a small number of cases. We sought to characterize the abnormalities in greater detail. In a retrospective study from 1995 to 2009, we encountered 88 autopsy cases with documented history of solvent abuse by inhalation and 1 with industrial exposure. Among these are 6 fetuses and infants with maternal exposure, 23 children (12-17 years), and 60 adults (18-66 years). Available brain samples from 75 cases were stained with solochrome cyanein (to demonstrate myelin) and periodic acid-Schiff (PAS) (to highlight the inclusions). Forty brains of ethanol and/or illicit drug exposed individuals and ten cases of multiple sclerosis were examined as controls. We found that 16 cases (age 23-49, median 37 years) had well-established leukoencephalopathy with multifocal myelin loss and abundant macrophages that stain with PAS and which contain birefringent inclusions. Six cases (age 15-55, median 27 years) had early leukoencephalopathy with scattered macrophages but no obvious myelin changes. Clusters of PAS-staining but non-birefringent macrophages were seen in 2/10 cases of (active) multiple sclerosis and in none of the ethanol/drug exposed brains. Ultrastructurally, inclusions from solvent cases differed from multiple sclerosis cases. Although exposure to solvents is impossible to quantify, there appears to be a duration-dependent effect. Brain damage related to solvent abuse can begin within only a few years of the onset. In the context of substance abuse, the changes are relatively specific for solvent inhalation and do not appear to result from demyelination alone. Interaction with ethanol cannot be excluded as a compounding risk factor.

Source: Medline

Full Text:

Available from ProQuest in Acta Neuropathologica

Available from Springer Link Journals in Acta Neuropathologica

Title: Reproductive toxicology and teratology of abused toluene.

 Citation: Systems biology in reproductive medicine, Apr 2010, vol. 56, no. 2, p. 184-200, 1939-6376 (April 2010)

 Author(s): Hannigan, John H, Bowen, Scott E

 Abstract: Toluene is an organic solvent that is widely used by industry and is ubiquitous in our environment. As a result, exposure to solvents like toluene in work-related settings (i.e., relatively constant, low-level exposures) or through inhalant abuse (i.e., relatively intermittent, high-level exposures) is increasing for many women of reproductive age. Evidence suggests that the risk for pregnancy problems, as well as developmental delays and neurobehavioral difficulties, is higher for the children of women who have been exposed to high concentrations of organic solvents during pregnancy than for those who have not. These risks appear to be higher in cases of abuse exposure to solvents such as toluene, particularly in comparison to the risk for teratogenic outcomes with occupational solvent exposure. Despite this, the reproductive toxicology and teratology following abuse of toluene and other inhalants remains under-investigated. This brief review describes the current state of our understanding of the reproductive and teratogenic risk of gestational toluene abuse. The data to date suggest that the high levels of toluene exposure typical with inhalant abuse are more detrimental to fetal development than typical occupational exposure, and preclinical paradigms can be beneficial for investigating the processes and risks of prenatal solvent exposure. While substantial research has been done on the reproductive effects of occupational exposures to organic solvents, more research is needed on the outcomes and mechanisms of exposures typical of inhalant abuse.

 Source: Medline 

Title: Alterations in rat fetal morphology following abuse patterns of toluene exposure

 Citation: Reproductive Toxicology, April 2009, vol./is. 27/2(161-169), 0890-6238 (April 2009)

 Author(s): Bowen S.E., Irtenkauf S., Hannigan J.H., Stefanski A.L.

 Language: English

 Abstract: Toluene is a commonly abused organic solvent. Inhalant abusers are increasingly women in their prime childbearing years. Children born to mothers who abused solvents during pregnancy may exhibit characteristics of a “fetal solvent syndrome” which may include dysmorphic features. This study examined the teratological effects of an abuse pattern of binge toluene exposure during gestation on skeletal and soft tissue abnormalities, body weight, and body size in fetal rats. Pregnant Sprague-Dawley rats were exposed for 30 min, twice daily, from gestational day (GD) 8 through GD20 to either air (0 ppm), 8000 ppm, 12,000 ppm, or 16,000 ppm toluene. Two-thirds of each litter was prepared for skeletal examination using Alizarin Red S staining while the remaining third of each litter was fixed in Bouin’s solution for Wilson’s soft tissue evaluation. Exposure to toluene at all levels significantly reduced growth, including decreases in placental weight, fetal weight, and crown-rump length. In addition, numerous gross morphological anomalies were observed such as short or missing digits and missing limbs. Skeletal examination revealed that ossification of the extremities was significantly reduced as a result of toluene exposure at all levels. Specific skeletal defects included misshapen scapula, missing and supernumerary vertebrae and ribs, and fused digits. Soft tissue anomalies were also observed at all toluene levels and there was a dose-dependent increase in the number of anomalies which included cryptorchidism, displaced abdominal organs, gastromegaly, distended/hypoplastic bladder, and delayed cardiac development, among others. These results indicate that animals exposed prenatally to levels and patterns of toluene typical of inhalant abuse are at increased risk for skeletal and soft tissue abnormalities. © 2009 Elsevier Inc. All rights reserved.

 Publication Type: Journal: Article

 Source: EMBASE 

Title: Effects of abuse pattern of gestational toluene exposure on metabolism, feeding and body composition 

Citation: Physiology and Behavior, March 2008, vol./is. 93/4-5(984-993), 0031-9384 (18 Mar 2008)

 Author(s): Jarosz P.A., Fata E., Bowen S.E., Jen K.-L.C., Coscina D.V.

 Language: English

 Abstract: Aims: Inhalant abuse during pregnancy lowers birth weight and impedes early development. These studies explored the effects of brief, repeated, prenatal toluene exposures in pregnant female rats on body weight, metabolic rate, body composition, and food intake in their offspring. Method: Rats were exposed to 0, 8000, 12,000, or 16,000 ppm of toluene twice daily for 15 min from gestational days 8 to 20. The effects of such exposures on post-weaning litter weights, oxygen consumption, carbon dioxide output, and body fat content were determined in 2 cohorts (n = 23, n = 24) of offspring. Food intakes and weight changes in response to 3 different diets (regular chow, purified diet, purified high fat diet) were examined in another cohort (n = 24) from postnatal days 72 to116. Results: Litter weights showed a significant linear decrease as a function of toluene dose. Offspring exposed to the 16,000 ppm toluene dose displayed statistically lower energy expenditures than control rats. Male rats exposed to 8000 or 16,000 ppm toluene had significantly greater percentage of body fat as well as total body fat than the other groups. Toluene also significantly suppressed weight gain over the time chow was consumed compared to the 0 ppm control group. Finally there were trends for a main effect of toluene dose on food intake during chow and during high fat diet consumption, with rats in the 12,000 ppm group consuming more than the 0 ppm group on both diets. Discussion: These data suggest that, in addition to other previously documented abnormalities in neurological development and behavior, the physiological regulation of metabolism and body composition in males as well as food intake and weight gain in both sexes may be altered by prenatal exposure to toluene. © 2008 Elsevier Inc. All rights reserved.

 Publication Type: Journal: Article

 Source: EMBASE 

Title: Maternal and fetal blood and organ toluene levels in rats following acute and repeated binge inhalation exposure.

 Citation: Reproductive toxicology (Elmsford, N.Y.), Nov 2007, vol. 24, no. 3-4, p. 343-352, 0890-6238 (2007 Nov-Dec)

 Author(s): Bowen, Scott E, Hannigan, John H, Irtenkauf, Susan

 Abstract: Inhalation of organic solvents is a persistent form of drug abuse with particular concern being the abuse of inhalants by women of child-bearing age. While studies have begun assessing postnatal outcomes of offspring exposed prenatally to inhalants, relatively little is known about the distribution of toluene in blood and body tissues of pregnant, inhalant-abusing women, or in the fetuses. The present study assessed the tissue toluene levels attained following brief toluene exposures using a pre-clinical rat model of maternal inhalant abuse. Timed-pregnant Sprague-Dawley rats were exposed to toluene at 8000 or 12,000 parts per million (ppm) for 15, 30 or 45 min/exposure. Exposures occurred twice each day from gestational day 8 (GD8) through GD20. Immediately following the second exposure on GD8, GD14 and GD20 blood was taken from the saphenous vein of the dams. Following saphenous vein blood collection on GD20, dams were sacrificed and trunk blood was collected along with maternal tissue specimens from cerebellum, heart, lung, kidney and liver. The placenta, amniotic fluid and fetal brain were also collected. Results demonstrated that maternal saphenous blood toluene levels increased as the inhaled concentration of toluene and duration of exposure increased. The maternal cerebellum, heart, kidney and liver appeared to be saturated after 30 min on GD20 such that toluene levels in those organs were equivalent across all ambient concentrations of inhaled toluene. Toluene levels also increased in fetal brain as the inhaled concentration of toluene increased and in placenta and amniotic fluid as the duration of exposure increased. Toluene levels in all tissues at GD20, except maternal lung and amniotic fluid, were higher than in maternal saphenous blood suggesting that toluene concentrated in those organs. Measurement of toluene levels in blood and other tissues following repeated toluene exposure demonstrated that toluene readily reaches a variety of potential sites of action throughout the maternal-placental-fetal unit.

 Source: Medline 

Title: Developmental toxicity of prenatal exposure to toluene.

 Citation: The AAPS journal, Jan 2006, vol. 8, no. 2, p. E419., 1550-7416 (2006)

 Author(s): Bowen, Scott E, Hannigan, John H

 Abstract: Organic solvents have become ubiquitous in our environment and are essential for industry. Many women of reproductive age are increasingly exposed to solvents such as toluene in occupational settings (ie, long-term, low-concentration 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.

 Source: Medline

 Full Text:

Available from Springer Link Journals in AAPS Journal, The

Available from National Library of Medicine in AAPS Journal, The

Available from National Library of Medicine in AAPS Journal, The

Title: Developmental neurotoxicity of toluene: In vivo and in vitro effects on astroglial cells

 Citation: Developmental Neuroscience, 2003, vol./is. 25/1(14-19), 0378-5866 (2003)

 Author(s): Burry M., Guizzetti M., Oberdoerster J., Costa L.G.

Language: English

 Abstract: Toluene, an inexpensive and available industrial solvent, has become increasingly popular as a drug of abuse. Inhaling toluene leads to a feeling of euphoria and several reports have shown that children born to women who had abused toluene during pregnancy present a syndrome (toluene embryopathy or fetal solvent syndrome) that is characterized by CNS effects (e.g. microencephaly), growth retardation and facial dysmorphologies. The characteristics of the fetal solvent syndrome are very similar to those observed in the fetal alcohol syndrome. As exposure of rats to ethanol during the brain growth spurt has been shown to cause microencephaly and to affect glial cell proliferation and maturation, the present study examines the effects of toluene administration (250, 500 and 750 mg/kg) in neonatal rats from postnatal day 4 to 10. This treatment resulted in a significant decrease in both brain and body weights, and in a significant reduction of levels of glial fibrillary acidic protein, but not of neuron-specific enolase in rat brain. In vitro experiments demonstrate that pharmacologically relevant concentrations of toluene (250-1,000 muM) significantly inhibit proliferation of rat cortical astrocytes without causing overt cytotoxicity. These results indicate that toluene does not cause selective microencephaly; however, it affects brain weight, and appears to target developing astrocytes, possibly by inhibiting their proliferation. Copyright © 2003 S. Karger AG, Basel.

 Publication Type: Journal: Article

 Source: EMBASE

 Full Text:

Available from ProQuest in Developmental Neuroscience

Title: Intrauterine cerebral infarcts and bilateral frontal cortical leukomalacia following chronic maternal inhalation of carburetor cleaning fluid during pregnancy.

Citation: Journal of perinatology : official journal of the California Perinatal Association, Dec 2003, vol. 23, no. 8, p. 693-696, 0743-8346 (December 2003)

 Author(s): Bharti, Des

 Abstract: Little is known about the effect of inhalation of methanol and other solvents on the pregnancy and the growth of the fetus. We report a preterm male infant who developed cerebral infarcts in utero, leading to large areas of bilateral frontal cortical leukomalacia following chronic maternal inhalation of carburetor-cleaning fluid during pregnancy. The infant presented with acute fetal distress with significant metabolic acidosis at birth. Initial hypotonia was followed by generalized hypertonicity. This infant did not exhibit typical facial features of fetal alcohol syndrome.

 Source: Medline

 Full Text:

Available from Nature Publishing Group in Journal of Perinatology

Available from ProQuest in Journal of Perinatology 

Title: Developmental neurotoxicity: Do similar phenotypes indicate a common mode of action? A comparison of fetal alcohol syndrome, toluene embryopathy and maternal phenylketonuria

 Citation: Toxicology Letters, February 2002, vol./is. 127/1-3(197-205), 0378-4274 (28 Feb 2002)

 Author(s): Costa L.G., Guizzetti M., Burry M., Oberdoerster J.

Language: English

 Abstract: Developmental neurotoxicity can be ascribed to in utero exposure to exogenous substances or to exposure of the fetus to endogenous compounds that accumulate because of genetic mutations. One of the best recognized human neuroteratogens is ethanol. The Fetal Alcohol Syndrome (FAS) is characterized by growth deficiency, particular facial features, and central nervous system (CNS) dysfunctions (mental retardation, microencephaly and brain malformations). Abuse of toluene by pregnant women can lead to an embryopathy (fetal solvent syndrome, (FSS)) whose characteristics are similar to FAS. Phenylketonuria (PKU) is a genetic defect in phenylalanine (Phe) metabolism. Offspring of phenylketonuric mothers not under strict dietary control are born with maternal PKU (mPKU), a syndrome with similar characteristics as FAS and FSS. While ethanol has been shown to cause neuronal death, no such evidence is available for toluene or Phe and/or its metabolites. On the other hand, alterations in astrocyte proliferation and maturation have been found, mostly in in vitro studies, which may represent a potential common mode of action for at least some of the CNS effects found in FAS, mPKU, and FSS. Further in vivo and in vitro studies should validate this hypothesis and elucidate possible molecular targets. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

 Publication Type: Journal: Conference Paper

 Source: EMBASE

Title: Prenatal exposure to toluene results in abnormal neurogenesis and migration in rat somatosensory cortex 

Citation: Pediatric Research, March 2000, vol./is. 47/3(362-368), 0031-3998 (March 2000)

 Author(s): Gospe Jr. S.M., Zhou S.S.

 Language: English

 Abstract: Toluene inhalant abuse during pregnancy may result in growth-retarded microcephalic newborns who subsequently demonstrate developmental impairment. By using a rat model of toluene-abuse embryopathy, we studied the effects of prenatal toluene exposure on the generation and migration of cortical neurons. Dams were exposed by gavage to either corn oil or toluene diluted in corn oil on d 6-21 of gestation. The time of origin of cortical neurons was determined in the mature pups of dams injected with the thymidine analogue 5′-bromodeoxyuridine on 1 d during the period from d 13-21 of gestation, 5′- Bromodeoxyuridine-labeled neurons were identified by immunohistochemistry in a 400-mum-wide column of somatosensory cortex. The brains of the toluene- exposed pups had a significant reduction in the number of neurons within each cortical layer (p < 0.001). Depending on the cortical layer, the generation of neurons in the toluene-exposed pups was delayed by 1 or 2 d. In addition, the brains of the toluene-exposed pups also showed evidence of abnormal neuronal migration. However, there were no differences in either brain weight or body weight between the control and toluene-exposed pups. These observations suggest that although prenatal toluene exposure results in abnormal neuronal proliferation and migration, brain weight in the toluene- exposed pups may be preserved by enhanced development of glia or the neuropil.

 Publication Type: Journal: Article 

Source: EMBASE 

Full Text:

Available from Nature Publishing Group in Pediatric Research

Available from Free Access Content in Pediatric Research 

Title: Inhalant abuse in pregnancy.

 Citation: Obstetrics and gynecology clinics of North America, Mar 1998, vol. 25, no. 1, p. 153-167, 0889-8545 (March 1998)

 Author(s): Jones, H E, Balster, R L

 Abstract: Information from a variety of sources suggests the possibility of adverse effects of maternal inhalant abuse, although a well-controlled, prospective study in this area has not been conducted. One source of this concern is the data from occupational exposure to some of the abused solvents, specifically toluene and TCE, with numerous reports suggesting increased spontaneous abortion and fetal malformations. There are also data suggesting decreased fertility and an increased risk for spontaneous abortion in health care workers exposed to nitrous oxide. The relevance of these studies to problems of inhalant abuse is not clear. Although the chemicals involved are the same, there are many differences in the exposure parameters, the populations exposed, and the types of associated risk factors. Nonetheless, there are more than 100 cases reported in the literature of children born to solvent-abusing mothers. Many of these children were small at birth, and some have craniofacial abnormalities not unlike that seen in children with FAS. In the few studies reporting the findings of follow-up in these children, some evidence has been obtained for retardation in growth and development and for residual deficits in cognitive, speech, and motor skills. Clearly, more research is needed to rule out the concomitant risk factors and to identify specific chemicals and patterns of use associated with adverse effects. Animal studies provide more direct evidence that prenatal exposure to toluene or TCE can produce reduced birth weights, occasional skeletal abnormalities, and delayed neurobehavioral development, even under conditions designed to mimic inhalant abuse patterns. Additional research is needed to identify other chemicals with adverse effects, critical periods of exposure, effects of combinations of inhalants, or interactions with drugs of abuse. The research literature seems sufficient to alert clinicians to possible problems in patients who abuse inhalants while pregnant. Diagnosis and good prenatal care for these women are important. The evidence for neonatal withdrawal is limited at this time; however, infants born to women who have recently used inhalants should be observed carefully for an alcohol-like withdrawal syndrome. Although it is not possible to link a specific birth defect or developmental problem in the child of an inhalant abuser to prenatal exposure to a specific chemical, it is clear that inhalant abuse and its associated lifestyle place children at increased risk. A wider appreciation of this is needed among health care professionals and the general public.

 Source: Medline 

Title: Neurobehavioral consequences of intermittent prenatal exposure to high concentrations of toluene.

 Citation: Neurotoxicology and Teratology, Jul 1997, vol. 19, no. 4, p. 305-313, 0892-0362 (Jul-Aug 1997)

 Author(s): Jones, Hendrée E., Balster, Robert L.

 Abstract: The effects of several concentrations of toluene on physical and behavioral development were examined in CD-1 mice prenatally exposed during the last week of gestation. Pregnant mice were exposed to either 200, 400, or 2000 ppm toluene (TOL) for 60 min three times a day during gestational days 12–17. A sham group was exposed concurrently to filtered air. No group differences were observed in maternal weight gain or food consumption or common measures of maternal toxicity. Initial litter characteristics including gestation length, number of litters delivered, and litter size were also similar. At birth, mean initial individual pup weight from representative male and female 2000 TOL-exposed pups was less than sham-exposed pups; however, entire litter weight did not differ. Pups were evaluated on postnatal days 1–20. Pups exposed to 2000 TOL gained less weight and performed more poorly on the behavioral tests of the righting reflex, grip strength, and inverted screen. In contrast, pups exposed to either 200 or 400 TOL did not differ from sham-exposed pups on any of the measures of development or behavior. Implications for inhalant abuse by pregnant women are discussed. (PsycINFO Database Record (c) 2015 APA, all rights reserved)

 Source: PsycInfo 

Title: Does a discrete fetal solvent syndrome exist?

 Citation: Alcoholism Treatment Quarterly, 1996, vol./is. 14/3(59-76), 0734-7324 (1996)

 Author(s): Medrano M.A.

 Language: English

 Abstract: Publications relating to pregnancy outcome of voluntary volatile solvent abuse were obtained from a computerized literature search and a review of Cumulated Index Medicus for the years 1976 to 1993. A brief preliminary review of reports on involuntary exposure was also done. The studies were reviewed regarding such factors as congenital defects and spontaneous abortions. Shortcomings in the methods of determining a causal association between maternal voluntary solvent exposure and the fetal solvent syndrome (Toluene Embryopathy) raise questions concerning the existence of a discrete syndrome. Suggestions are made for further epidemiologic research to demonstrate a causal association.

 Publication Type: Journal: Article 

Source: EMBASE

Title: Newborn renal tubular acidosis associated with prenatal maternal toluene sniffing.

 Citation: Journal of psychoactive drugs, Apr 1996, vol. 28, no. 2, p. 201-204, 0279-1072 (1996 Apr-Jun)

 Author(s): Erramouspe, J, Galvez, R, Fischel, D R

 Abstract: Sniffing of volatile organic solvents containing toluene, such as acrylic paints, glues, adhesives, paint thinners, varnishes and shoe polishes, has become increasingly frequent in recent years. Renal tubular acidosis is one of a number of human complications reported in the offspring of mothers inhaling toluene during pregnancy. This article reports a case of a premature newborn with renal tubular acidosis probably due to maternal sniffing of paint containing toluene. Characteristics of this condition are described as well as its medical management. With increasing frequency of maternal glue and paint sniffing, more cases of newborn renal tubular acidosis will likely appear. Physicians should be prepared to manage neonatal tubular acidosis that may accompany maternal toluene sniffing in order to lessen newborn morbidity and/or mortality. 

Source: Medline  

Title: Fetal methemoglobinemia: a cause of nonimmune hydrops fetalis.

 Citation: American journal of obstetrics and gynecology, Jul 1995, vol. 173, no. 1, p. 232-233, 0002-9378 (July 1995)

 Author(s): Ozmen, S, Seçkin, N, Turhan, N O, Dilmen, G, Dilmen, U

 Abstract: A case of nonimmune hydrops fetalis resulting from fetal methemoglobinemia is presented. A woman with a pregnancy at 17 weeks’ gestation was admitted after combustion gas intoxication. Although the mother totally recovered, the fetus showed signs of nonimmune hydrops fetalis at follow-up. Fetal methemoglobin levels were very high.

 Source: Medline

Title: The effects of high-dose toluene on embryonic development in the rat

 Citation: Pediatric Research, 1994, vol./is. 36/6(811-815), 0031-3998 (1994)

 Author(s): Gospe Jr. S.M., Saeed D.B., Zhou S.S., Zeman F.J.

 Language: English

 Abstract: Developmental disability, intrauterine growth retardation, renal anomalies, and dysmorphic features have been described in offspring of women who abuse toluene during pregnancy. A Sprague-Dawley rat model was developed to study this clinical syndrome. During d 6-19 of gestation, 11 treated dams received daily gavage doses of toluene, 520 mg/kg body weight, diluted in corn oil, and 11 control dams received corn oil. This dose of toluene simulates the blood toluene levels obtained after an inhalation exposure to 3290 ppm toluene, an inhalation level in the lower end of the range experienced by toluene abusers. Maternal weight gain was 24% less in the toluene-exposed group (p < 0.002); however, there were no maternal deaths. The fetuses were delivered on d 19 of gestation, and 287 fetuses (148 toluene exposed, 139 control) were examined. Toluene treatment did not affect the number of implantations or stillbirths. There were no toluene-induced major congenital malformations or neuropathologic changes noted. In the toluene- treated group, the weights of the fetuses were reduced by 9.4% (p < 0.004) and placental weights were reduced by 10.3% (p < 0.01). Toluene exposure also reduced fetal organ weights as follows: brain 4.6%, heart 5.9%, liver 13.2% (p < 0.02), and kidney 13% (p < 0.05). Organ weight/body weight ratios did not differ significantly, suggesting that prenatal toluene exposure produced a generalized growth retardation.

 Publication Type: Journal: Article

 Source: EMBASE

 Full Text:

Available from Nature Publishing Group in Pediatric Research

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Title: Toluene embryopathy: two new cases.

 Citation: Journal of medical genetics, May 1989, vol. 26, no. 5, p. 333-337, 0022-2593 (May 1989)

 Author(s): Hersh, J H

 Abstract: Toluene embryopathy is characterised by microcephaly, central nervous system dysfunction, attentional deficits and hyperactivity, developmental delay with greater language deficits, minor craniofacial and limb anomalies, and variable growth deficiency. Previously, three affected children, born to women who inhaled toluene regularly throughout pregnancy, have been reported. Two more cases are described emphasising the importance of toluene as a potential human teratogen.

 Source: Medline

 Full Text:

Available from Free Access Content in Journal of Medical Genetics

Available from Highwire Press in Journal of medical genetics

Available from National Library of Medicine in Journal of Medical Genetics

Available from National Library of Medicine in Journal of Medical Genetics

Available from Highwire Press in Journal of Medical Genetics 

Title: Hydranencephaly after maternal butane-gas intoxication during pregnancy.

 Citation: Developmental medicine and child neurology, Jun 1986, vol. 28, no. 3, p. 361-363, 0012-1622 (June 1986)

 Author(s): Fernàndez, F, Pèrez-Higueras, A, Hernàndez, R, Verdú, A, Sánchez, C, González, A, Quero, J

 Abstract: A newborn infant who suffered intra-uterine anoxia is described, whose mother inhaled butane gas accidentally during the sixth month of pregnancy. The infant was born at 39 weeks. Ultrasonography and neuroradiological studies (CT scan and angiography) showed an almost complete absence of both cerebral hemispheres. The thalamus, brainstem and cerebellum were preserved. These findings were compatible with hydranencephaly. The authors believe that the malformation was due to intra-uterine anoxia occurring during fetal brain-development. 

Source: Medline 

Title: Cerebral, renal and splenic lesions due to fetal anoxia and their relationship to malformations.

 Citation: Developmental medicine and child neurology, Aug 1982, vol. 24, no. 4, p. 510-518, 0012-1622 (August 1982)

 Author(s): Gosseye, S, Golaire, M C, Larroche, J C

 Abstract: Two newborn infants who suffered severe intra-uterine anoxia a few weeks before birth are described. Both died shortly after being born spontaneously and slightly prematurely. In one case the mother had attempted suicide by inhaling butane. The infant’s kidneys were hypoplastic and resembled those seen in renal dysplasia, and the brain showed a severe encephalomalacia which would probably have developed into hydranencephaly. The other case was a twin who survived the intra-uterine death of her co-twin: she had hypoplastic kidneys similar to those in the first case, and a hypoplastic spleen. (The brain was not examined.) It is thought that intra-uterine anoxia may produce lesions in fetal organs which appear at birth as congenital developmental malformations. This mechanism is thought to account in particular for some cases of renal dysplasia and for hydranencephaly.

 Source: Medline 

Title: Carbon monoxide (CO) and saturated hydrocarbon gases poisoning during pregnancy. Maternal and fetal prognosis

 Citation: Intensive Care Medicine, 1980, vol./is. 6/1(128), 0342-4642 (1980)

 Author(s): Barois A., Simon N., Goulon M.

 Language: English

 Publication Type: Journal

 Source: EMBASE

 Full Text:

Available from Springer Link Journals in Intensive Care Medicine

Title: Is there a fetal gasoline syndrome?

 Citation: Teratology, Aug 1979, vol. 20, no. 1, p. 75-79, 0040-3709 (August 1979)

 Author(s): Hunter, A G, Thompson, D, Evans, J A

 Abstract: Two children from a small Amerindian community presented with profound retardation, initial hypotonia progressing to hypertonia, scaphocephaly, a prominent occiput, poor postnatal head growth, and additional minor anomalies. Abuse of gasoline by inhalation was a widespread problem in the community, and gasoline inhalation during the pregnancy could be documented in both of the pregnancies. We are raising the question as to whether inhalation of gasoline during pregnancy may be teratogenic in humans.

 Source: Medline

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