Abuse pattern of gestational toluene exposure and early postnatal development in rats

Bowen, Scott E.; Batis, Jeffery; Mohammadi, Michael H.; Hannigan, John H.

doi:10.1016/j.ntt.2004.09.007

Cited by 61 publications

(73 citation statements)

References 67 publications

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“…These very high maternal solvent exposures typical of abuse can lead to perinatal death [3], morphological teratogenicity (e.g., [7]), prematurity and/or growth restriction, microcephaly, digital and/or facial dysmorphology, and the possibility of long-term detrimental outcomes [3,49,[59][60][61]. Using this same pattern of exposure in our preclinical model, we have shown that prenatal toluene exposure delays postnatal development, restricts growth, and increases likelihood of morphological and neurobehavioral teratogenic outcome [5,8].…”

Section: Discussionmentioning

confidence: 99%

“…Exposures to 8,000 ppm or 12,000 ppm toluene (#T324; Fisher Scientific, Fair Lawn, NJ, USA) were conducted twice a day between 0900 and 1400 hrs with 2 hours between the start of the first and second exposures. These two high toluene concentrations and the binge pattern of exposure were chosen to mimic the range of high-dose "binge" exposures seen in human abusers [9,60], exposures that have developmental/teratogenic effects in rats [5,8,12] and that contrast with occupational exposures that produce limited developmental effects. For example, pregnant rats exposed to 1,500 ppm toluene vapor for even 6 hrs/day from GD6 to GD20 had only a 7% decrease in fetal weight [52].…”

Section: Prenatal Inhalation Exposure Proceduresmentioning

confidence: 99%

“…Vapor exposures were given in sealed 36-liter cylindrical glass jars with acrylic lids described in detail in Bowen et al [5]. Briefly, the lids were equipped with an injection port, a fan, and a stainless steel mesh box holding filter paper.…”

Section: Prenatal Inhalation Exposure Proceduresmentioning

confidence: 99%

“…Some studies in animal models have assessed postnatal outcomes of offspring exposed prenatally to inhalants (e.g., [5,8,12,30,33,34,57]), including studies modeling occupational exposures (e.g., [52]), but little is known about the distribution and accumulation of toluene in blood and body tissues of pregnant organisms, or their fetuses, exposed to abuse patterns of inhaled solvents. It is possible that the brief, repeated, high blood toluene levels (BTLs) associated with toluene abuse, and occurring at certain critical periods of perinatal neural maturation in the rat, may lead to greater teratogenic damage with more severe, life-long biobehavioral consequences than following the relatively constant, lower-concentration exposures that mimic occupational settings [52].…”

Section: Introductionmentioning

confidence: 99%

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Maternal and fetal blood and organ toluene levels in rats following acute and repeated binge inhalation exposure☆

Bowen¹,

Hannigan²,

Irtenkauf³

2007

Reproductive Toxicology

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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 8,000 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.

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Section: Discussionmentioning

confidence: 99%

Section: Prenatal Inhalation Exposure Proceduresmentioning

confidence: 99%

Section: Prenatal Inhalation Exposure Proceduresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Maternal and fetal blood and organ toluene levels in rats following acute and repeated binge inhalation exposure☆

Bowen¹,

Hannigan²,

Irtenkauf³

2007

Reproductive Toxicology

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show abstract

“…Using a preclinical model, we have shown that prenatal exposure to brief, abuse-level concentrations of toluene results in abnormal postnatal development and an increased likelihood of teratogenic outcomes [8]. Specifically, offspring of female rats exposed repeatedly to 15 mins of 8,000 ppm or 12,000 ppm of toluene twice per day during gestation display delayed postnatal development up to postnatal day 16 (PN16), decreased muscle tone to PN12, deficits in motor coordination assessed as negative geotaxis, and increased rates of physical abnormalities and "runting" [8].…”

Section: Introductionmentioning

confidence: 99%

Gestational toluene exposure effects on spontaneous and amphetamine-induced locomotor behavior in rats

Bowen

Mohammadi

Batis

et al. 2007

Neurotoxicology and Teratology

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The abuse of volatile organic solvents (inhalants) continues to be a major health concern throughout the world. Toluene, which is found in many products such as glues and household cleaners, is among the most commonly abused organic solvents. The neurobehavioral teratogenic sequelae of solvent abuse (i.e., repeated, brief inhalation exposures to very high concentrations of solvents) have not been examined thoroughly. In a preclinical model of inhalant abuse, timed-pregnant Sprague-Dawley rats were exposed to 0, 8,000, or 12,000 parts per million (ppm) for 15 min twice daily from gestation day 8 (GD8) through GD20. In the first experiment, separate groups of offspring were observed individually in an open-field on postnatal day 22 (PN22), PN42 or PN63. In the second experiment, other offspring given identical prenatal toluene exposures were observed in an "open-field" following an acute i.p. injection of amphetamine (0, 0.56, 1.78 mg/kg) on PN28. Automated measurements of distance traveled and ambulatory time were recorded. Prenatal toluene exposure resulted in small alterations in spontaneous activity compared to non-exposed rats. Prenatal exposure to 12,000 ppm toluene resulted in significant hyposensitivity to the locomotor stimulatory effects of the amphetamine challenge in male but not female rats on PN28. The results demonstrate that prenatal exposure to abuse patterns of high concentrations of toluene through inhalation can alter spontaneous and amphetamine-induced locomotor behavior in rats. The expression of these effects also appears to depend upon the postnatal age of testing. These results imply that abuse of organic solvents during pregnancy in humans may also produce long-lasting effects on biobehavioral development.

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Teratogenic exposures

Običan

Scialli

2011

American J of Med Genetics Pt C

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A consideration of teratogenic exposures includes not only an agent (chemical, radiation, biologic) but an exposure level and timing of exposure. There are criteria by which exposures are evaluated for a causal connection with an abnormal outcome. We here review some teratogenic exposures and discuss how they were initially described and confirmed. We have limited our discussion to some of the exposures for which a connection to structural malformations has been accepted in some quarters, and we indicate some exposures for which a causal association awaits confirmation. We recommend that counselors find a reliable and updatable source of information on exposures during pregnancy.

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Abuse pattern of gestational toluene exposure and early postnatal development in rats

Cited by 61 publications

References 67 publications

Maternal and fetal blood and organ toluene levels in rats following acute and repeated binge inhalation exposure☆

Maternal and fetal blood and organ toluene levels in rats following acute and repeated binge inhalation exposure☆

Gestational toluene exposure effects on spontaneous and amphetamine-induced locomotor behavior in rats

Teratogenic exposures

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