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

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 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.

Reproductive Toxicology and Teratology of Abused Toluene

“…These findings are consistent with those of a previous study assessing blood and organ toluene levels in a rat model of maternal inhalant abuse [Bowen et al 2007b]. Toluene exposures (8,000 ppm or 12,000 ppm for 15, 30, or 45 min) occurred twice daily from gestational day 8 (GD8) through GD20.…”

“…Maternal blood and tissue, placenta, amniotic fluid, and fetal brain specimens were obtained after dams were sacrificed on GD20. Maternal blood toluene levels increased with inhaled toluene concentration and exposure duration [Bowen et al 2007b] Similarly, toluene levels in placenta and amniotic fluid increased with exposure duration, and higher toluene levels were found in fetal brains as the vapor concentrations increased. While toluene levels in most maternal tissues were reported to be higher than in maternal blood, the levels in amniotic fluid were not.…”

“…This, in addition to the finding that toluene levels in several maternal tissues (e.g., cerebellum, heart, liver) failed to increase beyond the levels observed after 30 min exposures, suggests that toluene becomes concentrated and/or saturated in some maternal organs. Even though toluene levels were lower in amniotic fluid than in maternal blood, these data demonstrate that toluene readily reaches biologically meaningful local concentrations in a variety of tissues and potential sites of action throughout the maternal-placental-fetal unit [Bowen et al 2007b]. …”

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

“…Some of these factors including route of administration, dosage and timing of exposure, influence the toluene developmental toxicity and impact on biobehavioral maturation of offspring. To our knowledge, relatively fewer studies have examined gross dysmorphology after repeated, high-dose binge patterns of prenatal toluene exposure [8,10,11,19,54]. In our previous study, prenatal binge exposure to repeated 15-min bouts of toluene (8,000 or 12,000 ppm) twice a day (30-min total daily exposure) from Gestation Day 8 (GD8) through GD20, resulted in significantly increased numbers of minor malformations, “runting” and fetal or postnatal death [8].…”

Measurement of Toluene Concentrations in the Blood of Fetuses of Pregnant Rats Exposed to Low Concentration Toluene Using Headspace-Solid Phase Micro Extraction-Gas Chromatography-Mass Spectrometry

“…14) The concentration of toluene within organisms starts decreasing rapidly immediately after exposure, but it can accumulate easily in tissues high in lipid content. 14,15) The lipid content of fetuses is generally lower than that of adults, 16) which may be one of the causes of the difference in the blood toluene level between mother rats and fetuses found by this study. Although blood lipid level was not measured in this study, it has been shown that lipid soluble compounds such as polychlorinated biphenyl (PCB) was parallel to the serum lipid level.…”