Abstract  The developmental toxicity of two trimethylbenzene isomers, mesitylene (1,3,5-trimethylbenzene) and pseudocumene (1,2,4-trimethylbenzene) was studied in Sprague-Dawley rats following inhalation exposure. Pregnant rats were exposed whole body to vapours of mesitylene (0, 100, 300, 600, and 1200 ppm) or pseudocumene (0, 100, 300, 600, and 900 ppm), 6h/day, on gestational days (GD) 6 through 20. Significant decrease in maternal body weight gain and food consumption was observed at concentrations of 300 ppm mesitylene, 600 ppm pseudocumene, or greater. Fetal toxicity, expressed as significant reduction in fetal body weight, occurred at 600 and 1200 ppm mesitylene, and at 600 and 900 ppm pseudocumene. There was no evidence of embryolethal or teratogenic effects following inhalation exposure to either of these chemicals. In summary, the no-observed-adverse-effect-level (NOAEL) for maternal toxicity was 100 ppm for mesitylene and 300 ppm for pseudocumene, and the NOAEL for developmental toxicity was 300 ppm for mesitylene and pseudocumene.

Abstract  Groups of CFY rats were exposed to inhalation of ethylbenzene at 600, 1200 or 2400 mg/m3 or xylene at 250, 1900 or 3400 mg/m3 or Aromatol at 500, 1000 or 2000 mg/m3 atmospheric concentration for 24 h/day from day 7 to day 15 of pregnancy, or for 2-4 hours only on the 18th or 20th day of gestation. CFLP mice and NZ rabbits were exposed to inhalation of 500 mg/m3 or 1000 mg/m3 benzene, toluene, ortho-, meta-, para-xylene, ethytbenzene, xylene or Aromatol for 24 h/day from day 6 to day 15 of pregnancy. Untreated animals and groups inhaling pure air served as controls. All components of the xylene and Aromatol crossed the placenta and were present in fetal blood and amniotic fluid, as well. The maternal toxic effects at all solvents were moderate and dose dependent. All solvents (at higher concentrations) brought about skeletal and weight retardation in fetuses of rats and mice. At highest concentration some solvents increased the post-implantation loss in rats and mice. All solvents caused spontaneous abortion in rabbits at 1000 mg/rn3 atmospheric concentration. Only ethylbenzene and Aromatol increased the malformation rate in rats and mice. No other solvent applied proved to be teratogenic either in mice, rats or rabbits.

Abstract  The neurotoxic effects of prenatal organosolvent inhalation were studied in rats, because of the expectation that a developing organism may be more sensitive than the adult to the induction of functional deficits. The aim was to determine whether prenatal exposure to the new organosolvent mixture, Aromatol, and the well known neurotoxic carbon disulphide, would impair reflex ontogeny or produce neurobehavioural dysfunctions in the offspring. Development of gait, motor coordination, and activity, avoidance learning and swimming were tested in the offspring of CFY rat mothers, exposed to CS2 inhalation (0, less than 10, 700 and 2000 mg/m3) and to Aromatol (0, 600, 1000 and 2000 mg/m3) on days 7-15 gestation. Prenatal CS2 inhalation induced dose related perinatal mortality of pups. Eye opening and the auditory startle were retarded. There were immature gait, motor incoordination, diminished open field activity and altered behavioural patterns on day 21 and 36 but they were nearly age-appropriate on day 90. As signs of disturbed learning ability, there were diminished performance and lengthened latency of the conditioned avoidance response, related to the concentrations administered. Contrary to expectations, prenatal Aromatol inhalation had no effect on maturation of gait, behaviour patterns, or learning ability.

Abstract  Catalytic reforming is a refining process that converts naphthenes to aromatics by dehydrogenation to make higher octane gasoline blending components. A portion of this wide boiling range hydrocarbon stream can be separated by distillation and used for other purposes. One such application is a mixture of predominantly 9-carbon aromatic molecules (C9 aromatics, primarily isomers of ethyltoluene and trimethylbenzene), which is removed and used as a solvent--High Flash Aromatic Naphtha. A program was initiated to assess the toxicological properties of High Flash Aromatic Naphtha since there may be human exposure through inhalation or external body contact. The current study was conducted to assess the potential for developmental toxicity in the mouse and for reproductive toxicity in the rat. In the developmental toxicity study in CD-1 mice, exposure of dams by inhalation to near lethal levels (1500 ppm) resulted in fetal mortality, reduced weight, delayed ossification, and an increased incidence of cleft palate. At 500 ppm, a level at which maternal weight gain was slightly reduced, fetal weight gain was also reduced, but there was no other evidence of developmental effects. The lowest exposure level (100 ppm) did not cause any maternal or developmental toxicity. There was no consistent evidence of reproductive toxicity in rats, even at exposure levels which resulted in significantly reduced parental weight gain. In addition, when parental exposure was stopped on GD (gestation day) 20, birth weights as well as postnatal survival were generally similar to control values, even in the 1500 ppm exposure group. Postnatal weight gain was also similar to controls early in weaning, but, if maternal exposure was reinitiated, weight gain was reduced in the high exposure group. However, when exposure was continued until delivery, pups in the high exposure group exhibited reduced litter size, birth weight and poor survival. Thus it was likely that the reduction in fetal weight, seen in the developmental toxicity study in mice, was transient and had no postnatal consequences if maternal exposure was terminated at any time prior to delivery.