Handbook of Solvents - George Wypych - ChemTech - Ventech!

20.3 Pregnancy outcome following solvent exposure 1335
working of the data shows p values of >0.4 in all cases. 9 Sporadic malformations (cleft palate
and open eye) did not differ significantly between treated and control groups, neither did
the incidence of dead or resorbed embryos and fetuses. A small degree of retarded ossification
was seen in fetuses from dams given 4 ml/kg.
Nawrot and Staples 4 investigated the effects of oral administration by gavage of 0.3,
0.5 or 1.0 ml/kg on days 6-15 of pregnancy or 1.0 ml/kg on days 12-15 of pregnancy in the
mouse. After dosing on days 6-15, 0.5 and 1.0 ml/kg caused some maternal mortality and
embryolethality. Fetal weight was significantly reduced at all 3 dose levels but no increase
in malformations was seen. There were similar findings after dosing on days 12-15 except
that resorptions occurred later in gestation. The study is reported in abstract only and no further
details are given.
Murray et al. 5 exposed groups of 35-37 mice to 0 or 500 ppm benzene for 7 hr/day on
days 6-15 of pregnancy. Acceptable teratological methods were used. 9 There was no evidence
of maternal toxicity. There were no effects on implants/dam, live fetuses/dam,
resorptions/dam or malformation rates. Fetal body weight was significantly reduced and delayed
ossification significantly increased in fetuses from the benzene group.
Iwanaga et al. 6 demonstrated an increased postnatal susceptibility to benzene toxicity
in mice exposed prenatally to benzene by injection of the dams with 4 ml benzene/kg on day
9 or 12 of gestation. At 10 weeks of age the offspring were injected with 5 daily doses of 0.1
ml benzene/kg and the effects on erythrocytes, leukocytes, body weight, thymus and spleen
were more marked than in non-prenatally exposed controls.
There have been several inhalational studies on benzene in the rat. In an unpublished
study summarized by Murray et al., 5 teratogenic effects were observed at 500 ppm when
rats were exposed to 0, 10, 50 or 500 ppm benzene for 7 hr/day on days 6-15 of pregnancy
and a low incidence of exencephaly, kinked ribs and abnormal ossification of the forepaws
was noted at 500 ppm. In another unpublished study quoted by Murray et al. 5 no teratogenicity
but increased embryoloethality was seen after exposure to 10 or 40 ppm for 6
hours/day on days 6-15 of pregnancy in the rat.
Hudak and Ungvary 7 exposed groups of 19-26 rats to 0 or 313 ppm benzene for 24
hours/day on days 9-14 of pregnancy. Acceptable teratological methods were used. 9 There
was no maternal mortality but maternal weight gain was significantly reduced. There were
no significant effects on live fetuses/dam, resorbed or dead fetuses/dam or malformation
rate. Mean fetal weight was significantly reduced and retarded ossification, abnormal fusion
of sternebrae and extra ribs were all significantly increased in the benzene-exposed
group.
Green et al. 8 exposed groups of 14-18 rats to 100, 300 or 2200 ppm benzene for 6
hours/day on days 6-15 of pregnancy, each benzene-exposed group having a concurrent 0
ppm control group. Maternal weight gain was significantly reduced in the 2200 ppm group,
but not at lower exposure levels. There were no significant effects on implants/dam, live fetuses/dam,
resorptions/dam or malformation rates. There was a significant 10% reduction in
fetal weight in the 2200 ppm benzene group and skeletal anomalies were sporadically increased
in benzene-exposed groups (missing sternebrae at 100 ppm, delayed ossification of
sternebrae in female offspring only at 300 ppm and 2200 ppm and missing sternebrae at
2200 ppm). The authors suggest the higher number of affected female fetuses is in accordance
with other observations on the increased susceptibility of females to benzene toxic-