Developmental toxicity of in utero exposure to toluene on malnourished and well nourished rats

Silva, V.A. da; Malheiros, Luciana Reis; Paumgartten, Francisco José Roma; Sa-Rego, M. de Matos; Riul, Tania Regina; Golovattei, M. A. R.

doi:10.1016/0300-483x(90)90132-z

Cited by 19 publications

(3 citation statements)

References 25 publications

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“…Repeated 30-and 45-min exposures to 8,000 ppm or 12,000 ppm resulted in ∼35% and ∼70% decreases in BTLs, respectively, by GD20 compared to initial levels on GD8. Some other studies have exposed pregnant animals to toluene on a single day during gestation via intragastric intubation [24][25][26], systemic injection [13,14,38], or in drinking water [38], none of which produce pharmacokinetic functions that faithfully represent those following the inhalation route of administration that defines solvent abuse. Several studies have demonstrated that repeated toluene inhalations yield progressively lower blood and brain toluene levels consistent with tolerance due to up-regulation of hepatic catabolism by cytochrome P450 [37,44,58].…”

Section: Discussionmentioning

confidence: 99%

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%

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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“…In a study by da Silva et al (33), daily s.c. administration of toluene to pregnant rats during the third week of gestation produced growth retardation similar to that seen in our animals. These dams had a 4% decrease (statistically insignificant) in food consumption.…”

mentioning

confidence: 96%

The Effects of High-Dose Toluene on Embryonic Development in the Rat

et al. 1994

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“…A number of experimental studies investigating the reproductive and developmental toxicity of organic solvents including toluene have been conducted in rats, mice and rabbits. These studies provide convincing evidence that exposure of dams to organic solvents during gestation cause long‐term developmental (Hudák & Ungváry 1978; Ungváry & Tátrai 1985; da Silva et al 1990; Brown‐Woodman et al 1991; Hass & Jacobsen 1993; Hass et al 1995 & 1997; Jones & Balster 1997; Hass et al 1999; Hougaard et al 1999), morphological (Klimisch et al 1992; Gospe et al 1996; Gospe & Zhou 1998) and biochemical (Edelfors et al 1996 & 1999) changes in the offspring. The neurotoxic mechanism of organic solvents are unknown, but in vitro experiments show that exposure to organic solvents affects membrane fluidity, ATPase activity and the level of intracellular Ca 2+ (Korpela 1988; Benaim & de Meis 1989; Tähti & Valaja 1991; Edelfors & Ravn‐Jonsen 1992; Edelfors et al 1999).…”

mentioning

confidence: 69%

Changes in Markers of Oxidative Stress and Membrane Properties in Synaptosomes from Rats Exposed Prenatally to Toluene

Edelfors¹,

Hass²,

Hougaard³

2002

Pharmacology & Toxicology

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The present study was undertaken in order to investigate if toluene induced oxidative stress in brains from rats exposed prenatally to 1800 ppm toluene 6 hr/day at days 7-20 during the pregnancy. 35-42 days after birth the rats were killed and synaptosomal fractions were prepared for the experiments. Synaptosomes from rats exposed prenatally to toluene exhibited an increased level of oxidative stress when incubated with toluene in vitro compared to synaptosomes from unexposed offspring. Also the cell membrane was affected, as the calcium leakage was more increased from exposed synaptosomes than from unexposed. The membrane fluidity increased significantly when synaptosomes were incubated with toluene for 10 min. in vitro but the change in fluidity was identical in both groups of offspring. The results indicate that prenatal exposure to toluene induces long-lasting changes in oxidative status and membrane function.Toluene, an aromatic hydrocarbon solvent, is widely used in paints, rubber, in the graphical industry and as a component of gasoline. Toluene is also found in household products including adhesives, paint thinner, and various cleaning fluids. Inhalation of toluene vapours is the main source of human exposure. In the work place, in everyday use of toluene-containing products and in abuse. Abuse by inhalation is an increasing problem and toluene is claimed to be one of the most used substances of abuse (McHugh 1987;Gjerde et al. 1990). Toluene acts directly on the central nervous system and occupational long-term exposure to toluene may result in permanent neurotoxic damage (Triebig 1989;Arlien-Søborg et al. 1992;Hooisma et al. 1994). Although toluene crosses the placental barrier readily, relatively few reports on the effects of in utero exposure to toluene have been published (Ghantous & Danielsson 1986). Data suggest that occupational exposure to high concentrations of solvents increases the risk for miscarriage (Taskinen et al. 1994;Lindbohm 1995). A direct comparison of infants exposed in utero to toluene with infants diagnosed with foetal alcohol syndrome has been conducted (Hersh 1989;Pearson et al. 1994;Jones & Balster 1998). The clinical features of toluene embryopathy are identical to those of the foetal alcohol syndrome; delayed growth and development, and craniofacial anomalies. A number of experimental studies investigating the reproductive and developmental toxicity of organic solvents including toluene have been conducted in rats, mice and rabbits. These studies provide convincing evidence that exposure of dams to organic solvents during gestation cause long-term developmental

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Developmental toxicity of in utero exposure to toluene on malnourished and well nourished rats

Cited by 19 publications

References 25 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☆

The Effects of High-Dose Toluene on Embryonic Development in the Rat

Changes in Markers of Oxidative Stress and Membrane Properties in Synaptosomes from Rats Exposed Prenatally to Toluene

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