Changes in developmental body weight as a function of toluene exposure

Abstract

<jats:p> Inhalant abuse is a globally prevalent health issue with particular concerns about substance-abusing pregnant women. In both animal models and clinical case reports of toluene exposure, the primary physiological outcome measure of prenatal inhalant exposure is low birth weight (BW). However, the effect of prenatal toluene exposure on animal BW varies widely in the literature. To clarify this effect and investigate possible design moderators of pup BW, a systematic review and meta-analytic techniques were applied to the existing peer-reviewed animal literature of prenatal and postnatal exposure models to the inhaled solvent toluene. Of 288 studies screened, 24 studies satisfied the inclusion criteria. Evaluation of these studies indicated that toluene exposure was negatively associated with pup BW ( d = −0.39), with external inhaled concentration, route of administration, day of weighing, and toluene exposure magnitude moderating this association. Investigators doing animal studies should be cognizant of these factors before investigating the reproductive and developmental outcomes associated with prenatal and postnatal toluene exposure. </jats:p>

Growth changes after inhalant abuse and toluene exposure: A systematic review and meta-analysis of human and animal studies

“…47 The lack of studies using females is particularly concerning because a weight impairment and any associated loss of adiposity 11 during adolescence can cause disruptions to pubertal and metabolic processes due to the endocrinological activity of adipose tissue. 57 Furthermore, as shown by Callan et al, exposure to toluene during pregnancy can impair developmental body weight, 52 and inhalant abuse is most prevalent in females during childbearing years. 2,3 Thus, inhalant abuse in females has the potential to affect not only the individual but also her offspring.…”

“…Some findings are consistent with the literature; for example, toluene exposure has been previously associated with weight gain in mice. 52 It would also be expected that toluene would have a larger effect during adolescence, when growth is accelerating, as opposed to adulthood when growth (particularly height) is more stable. However, data are not consistently available across all subgroups.…”

“…The effects of inhalant abuse in females have been explored before in a meta-analysis that considered whether toluene exposure during the prenatal period affected birth weight of the offspring. 52 This meta-analysis only included animal studies, and the only growth outcome was birth weight; however, many of the study characteristics explored were the same. The average effect size for weight in the individual from this meta-analysis was −0.73, compared to −0.39 for the effect on birth weight following prenatal exposure.…”

“…To analyse concentration effectively, these were collapsed into the following groups: 0–500 ppm, 501–2000 ppm, 2001–5000 ppm and >5000 ppm. These groupings were chosen for consistency with previous meta-analysis on toluene exposure 52 and provided an approximately even pool of comparisons across the subgroups. Additional analysis was performed post hoc comparing occupational exposure concentrations (≤1000 ppm) with inhalant abuse concentrations (>1000 ppm).…”

Prenatal toluene exposure impairs performance in the Morris Water Maze in adolescent rats

“…It is worth noting that the authors of the prior study used an industrial exposure paradigm (persistent low concentrations of toluene), which may require third trimester exposure to impair memory function. Indeed, prior work has demonstrated that the deleterious effects of toluene exposure are dependent on “dose”, which in inhalation models is a function of concentration and frequency and duration of exposure, with shorter, higher-concentration exposures producing the most profound effects (Jarosz et al, 2008, Callan et al, 2015). …”