Developmental toxic effects of ethylbenzene or toluene alone and in combination with butyl acetate in rats after inhalation exposure

First, the developmental toxic potential of n-butyl acetate (BA) was examined in Sprague-Dawley rats following whole body inhalation exposure, 6 h day-1, from day 6 to 20 of gestation, at concentrations of 0, 500, 1000, 2000 and 3000 ppm. Maternal toxicity was evidenced by significant decreases in body weight gain at 2000 and 3000 ppm, and by reduced food consumption at 1000 ppm and higher concentrations. The effects on prenatal development were limited to a significant decrease in fetal weight at 3000 ppm. Thus, inhaled BA was not a selective developmental toxicant. In the second part of this study, the developmental toxic effects of simultaneous exposures to ethylbenzene (EB) and BA, or to toluene (TOL) and BA were evaluated. Pregnant rats were administered EB (0, 250 or 1000 ppm) and BA (0, 500 or 1500 ppm), or TOL (0, 500 or 1500 ppm) and BA (0, 500, 1500 ppm), separately and in combinations, using a 2 × 2 factorial design. The maternal weight gain was reduced after exposure to 1000 ppm EB, to 1500 ppm BA, or to 1500 ppm TOL, either alone or in binary combinations. A significant reduction of fetal weight was associated with exposure to 1000 ppm EB alone, to either mixtures of EB with BA, or to 1500 ppm TOL alone or combined with BA at either concentration. No embryolethal or teratogenic effects were observed whatever the exposure. There was no evidence of interaction between EB and BA or between TOL and BA in causing maternal or developmental effects. Copyright © 2006 John Wiley & Sons, Ltd

Developmental toxicity of combined ethylbenzene and methylethylketone administered by inhalation to rats

Pregnant Sprague–Dawley rats were exposed to ethylbenzene (EB; 0, 250, or 1000 ppm) and methylethylketone (MEK; 0, 1000, or 3000 ppm), alone and in combination, by inhalation, for 6 h/day, during days 6–20 of gestation. Maternal toxicity, evidenced by decreased in body weight gain and food consumption, tended to be greater after simultaneous exposures to the high concentrations of 1000 ppm EB and 3000 ppm MEK, when compared to the treatments with individual compounds. No significant increase in embryo/fetal lethality or incidence of malformations and variations was observed in any of the treatment groups. Fetal body weight was significantly reduced after individual treatment with 1000 ppm EB or 3000 ppm MEK, and in the combined groups. There was no evidence of interaction between EB and MEK in causing developmental toxicity

Prenatal developmental toxicity studies on di-n-heptyl and di-n-octyl phthalates in Sprague-Dawley rats.

International audienceThis study evaluates the developmental toxicity of two dialkyl phthalate esters, di-n-heptyl phthalate (DHPP) and di-n-octyl (DnOP) phthalate, which have straight-alkyl side chains of seven and eight carbons, respectively. Sprague-Dawley rats were administered 0, 0.25, 0.50, or 1g/kg/day of DHPP or DnOP, by gavage, on gestation days 6-20. DHPP and DnOP had no adverse effect on maternal feed consumption and body weight gain, or on the incidence of post-implantation loss and fetal body weight. There was no increase in the incidence of fetal malformations or external and visceral variations, whatever treatment. A significant increase in rudimentary lumbar ribs was observed at all doses of DHPP and DnOP. The anogenital distance of the male fetuses was significantly decreased at the highest dose of DHPP. This parameter was not affected by DnOP. Thus, the lowest-observed-adverse-effect level (LOAEL) for developmental toxicity was 0.25 g/kg/day for DHPP and DnOP

Developmental toxic potential of di-n-propyl phthalate administered orally to rats.

International audienceThe objective of this study was to evaluate the developmental toxic potential of di-n-propyl phthalate (DnPP) in rats. Pregnant Sprague-Dawley rats were given DnPP at doses of 0 (olive oil), 0.5, 1 and 1.5 g kg⁻¹ per day, by gavage, on gestation days 6-20. Benchmark doses were calculated for the effects of DnPP on fetal weight and anogenital distance of the male fetuses. Maternal body weight gain was significantly reduced at 1.5 g kg⁻¹ per day, over gestation days 6-9. DnPP-treated dams also showed a statistically significant increase in liver weight and a mild but statistically significant peroxisomal enzyme induction at 1 or 1.5 g kg⁻¹ per day. Male and female fetal body weights were significantly reduced at 1.5 g kg⁻¹ per day. There was a statistically significant decrease in the anogenital distance of the male fetuses at 1 and 1.5 g kg⁻¹ per day, and three males (of 75) showed malpositioned testis at the high dose. The mean percentage of fetuses per litter with cervical and thoracic rudimentary ribs was significantly increased at 1 and 1.5 g kg⁻¹ per day. Delayed ossification was seen at 1 g kg⁻¹ per day (phalanges) and 1.5 g kg⁻¹ per day (hyoid, sternebrae, and phalanges). No treatment-related effects on prenatal viability or on fetal external or visceral malformations or variations were observed at any dose. Thus, there was no evidence of teratogenicity up to the high dose of 1.5 g kg⁻¹ per day. The no-observed-adverse-effect level (NOAEL) for developmental toxicity was 0.5 g kg⁻¹ per day