Handbook of Solvents - George Wypych - ChemTech - Ventech!

1336 Kristen I. McMartin, Gideon Koren
ity. 9 In addition, they observed a non-significant low incidence of hemorrhages in all 3
benzene-exposed groups which were not seen in control fetuses.
In conclusion, embryolethal and teratogenic effects are not seen even at maternally
toxic doses but significant fetotoxicity in terms of reduced body weight sometimes accompanied
by increases in skeletal variants and delayed ossification is seen at doses which are
not necessarily toxic to the dam. The absence of any such effects in a large number of adequately
conducted studies reported in full suggests these observations may be of no biological
significance. The role that benzene-induced maternal anemia may play in any adverse
effects on the offspring is not known. 9
Toluene
Euler 10 exposed mice to a mixture of toluene and trichloroethylene similar to that
which has been used in the soling of shoes. The mixture was composed of 32 ppm (120
mg/m 3 ) toluene and 64 ppm (340 mg/m 3 ) trichloroethylene, equivalent to inhaling 157
mg/kg toluene and 406 mg/kg trichloroethylene in the mice. They inhaled the mixture for 10
days before mating or during part or the whole of pregnancy. Differences were noted between
treated and control groups in pregnancy rates, length of pregnancy, damaged embryos,
birth weights and neonatal mortality but the direction and magnitude of these
differences is not stated. No groups were exposed to toluene alone.
Nawrot and Staples 4 gave mice 0.3, 0.5, or 1.0 ml toluene/kg orally by gavage on days
6-15 of pregnancy or 1.0 ml/kg on days 12-15 of pregnancy. There was no maternal toxicity
except a decrease in maternal weight gain in those dosed on days 12-15. There was a significant
increase in embrylolethality at all 3 dose levels and a significant reduction in fetal
weight in the 0.5 and 1.0 ml/kg groups after dosing on days 6-15. Those dosed with 1.0
ml/kg on days 6-15 had a significant increase in numbers of fetuses with cleft palate which
was not simply due to general growth retardation. Treatment on days 12-15 only had no adverse
effects on the offspring. The study is reported in abstract only and no further details
are given.
Teratological investigations on inhaled toluene in mice and rats have been carried out
by Hudak et al. 7 Mice were exposed to 0, 133 or 399 ppm (500 or 1500 mg/m 3 ) toluene for
24 hr/day on days 6-13 of pregnancy. In the high dose group all 15 exposed dams died
within the first 24 hr of exposure. No maternal deaths occurred in the 11 mice exposed to
133 ppm and there were no effects on implants/dam, live fetuses/dam, dead and resorbed fetuses/dam,
malformations or anomaly rates, but fetal weight was significantly reduced by
10% in comparison with controls. It is not stated whether 133 ppm had any effect on maternal
weight gain. 7
In conclusion, similar to benzene, toluene does not appear to be teratogenic. It is
fetotoxic, causing a reduction in fetal weight in mice and rats and retarded ossification and
some increase in skeletal anomalies in rats at doses that are below those toxic to the dam as
well as at toxic doses. 9 Embryolethality has also been seen with inhalation of very high concentrations
lethal to some of the dams or following oral administration of non-toxic doses. 9
Tetrachloroethylene
Schwetz et al. 11 exposed rats and mice to 300 ppm tetrachloroethylene for 7 h/day on
days 6-15 of pregnancy. The dams were killed just before term and the fetuses examined by
acceptable teratological methods but results are given on a per litter basis only. The number
of treated animals in each case was 17 and the number of controls (air exposed) 30 for both
rat and mouse studies.