Teratogen update: Toluene

Wilkins‐Haug, Louise

doi:10.1002/(sici)1096-9926(199702)55:2<145::aid-tera5>3.0.co;2-2

Cited by 69 publications

(32 citation statements)

References 26 publications

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“…The results also indicate that toluene concentrates in certain compartments, including maternal liver and brain, placenta, and fetal brain, at levels substantially higher than the apparent asymptotic level in maternal blood. 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%

“…Children who have been exposed to toluene in utero may also suffer from deficits in later development [7,32]. Toluene is lipid soluble, freely crosses the placenta [20,60], and clinical cases of toluene-related embryopathy and malformations are evident in women who have abused toluene during their pregnancies [3,21,27,28,49,59,60]. Very high concentrations of inhaled maternal solvent exposure typical of abuse can lead to perinatal death [3,61].…”

Section: Introductionmentioning

confidence: 99%

“…The term fetal solvent syndrome has been proposed to describe this constellation of morphological and behavioral effects, following the model of fetal alcohol spectrum disorders (FASDs) [3,11,49,59], which may be considered special cases of a fetal solvent syndrome, given the comparable phenotypes in toluene embryopathy and FASDs [32]. Up to 3 years of age, children exposed prenatally to toluene resulting from maternal inhalant abuse showed pronounced developmental delays, language impairment, hyperactivity, cerebellar dysfunction, and postnatal growth retardation [3,27,28,49], a pattern of teratogenicity common to all human studies of excessive in utero exposure to toluene [60]. The popularity of these organic solvents, combined with what little is known about their prenatal effects, means that greater and more focused attention should be placed on studying the effects of abused inhaled solvents and pregnancy outcome.…”

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: Introductionmentioning

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

View full text Add to dashboard Cite

show abstract

“…The risk of major malformations after exposure to organic solvents was higher in women who reported symptoms related to the exposure (such as eye/respiratory irritation and headache) 10 . Organic solvents such as toluene are also considered neurotoxins, possibly increasing the risk for developmental delay 11 . Toluene is an industrial chemical, used widely as a solvent in paints and glues, that crosses the placenta readily.…”

mentioning

confidence: 99%

Prenatal diagnosis of schizencephaly after inhalation of organic solvents

Witters

Cannie

Casaer

et al. 2007

Ultrasound in Obstet & Gyne

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Proactive approach for the evaluation of fetal safety in chemical industries

McMartin¹,

Koren²

1999

Teratology

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Women, their families, and employers are concerned about potential fetal risks that may be associated with occupational exposure to chemicals. In an attempt to quantify potential fetal risks in the petroleum industry, we conducted a literature review of selected chemical compounds to which Imperial Oil Limited (IOL) female personnel may be exposed. Medline, Toxline, and Dissertation Abstracts databases were utilized to search for all research papers published in any language from 1966–1996. Chemical exposures in these papers were compared to IOL chemical exposure indices from a specific refinery and chemical plant. In total, 559 studies obtained from the literature search related to the chemicals used in a specific refinery and chemical plant. Of these, only 21 studies explicitly stated some sort of exposure level for the various chemicals. Most of the selected female reproductive toxicology studies summarized explicitly stated chemical exposure levels: either as parts per million, stratifying as to number of days of exposure, or as estimates of the percentage of the threshold limit value. On comparing the occupational literature that presented either actual or estimated values of chemical exposure dose with the IOL routine rating factors in IOL's Products and Chemicals Divisions, we found that IOL chemical exposure levels overall were lower than those reported in the literature to be associated with fetal risks. A new proactive approach is presented to inform female workers and their families of the relative safety/risk of routine occupational exposures. This approach allows for the mitigation of the misperception of teratogenic risk and unjustified fears associated with it. Teratology 60:130–136, 1999. © 1999 Wiley‐Liss, Inc.

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Teratogen update: Toluene

Cited by 69 publications

References 26 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☆

Prenatal diagnosis of schizencephaly after inhalation of organic solvents

Proactive approach for the evaluation of fetal safety in chemical industries

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