Cobalt - Toxicology of Metals - page 513

7.6 Reprotoxicity
7.6.1 Effects on Reproductive Organs and Fertility

to 200 mg/kg/day. Postnatal developmental param-
eters were also transiently altered in the pups of rats
treated daily with 50 mg/kg cobalt sulfate.
In vitro incubation of postblastocyst mouse embryos
with cobalt(II) ions (100

Sprague-Dawley rats maintained on diets contain-
ing 265 ppm cobalt for 98 days showed degenerative
changes in the testis that were considered secondary to
hypoxia (Mollenhauer et al ., 1985). Decreases in sperm
motility and/or increased abnormal sperm were
noted in mice, but not in rats, exposed to 3 mg/m 3 or
more in 13-week inhalation studies with cobalt sulfate
(National Toxicology Program, 1991). After 13 weeks
of chronic exposure to 100-400 ppm cobalt chloride
in drinking water, male CD-1 mice showed marked
dose-related decreases in fertility, testicular weight,
and sperm concentration and motility, and increases in
circulating levels of testosterone (Pedigo et al ., 1988).
Pedigo and Vernon (1993) also reported that treatment
of male mice with cobalt chloride (400 ppm in the diet
during 10 weeks) increased preimplantation losses in
the dominant lethal assay.

mol/L) adversely affected
the development stages and decreased the trophoblast
area (10

µ

µ mol/L) (Paksy et al ., 1999).

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7.6.2 Developmental Effects

Only a few studies have been conducted with solu-
ble cobalt compounds to explore their potential effects
on development, and the results are mostly inconclu-
sive because of the high doses used and the frequent
presence of maternal toxicity.
Wide (1984) reported that a single intravenous injec-
tion of cobalt chloride in pregnant NMRI mice (approxi-
mately 1.2 mg/kg bw) on day 8 of gestation signifi cantly
affected fetal development; in animals injected at day
3 of gestation, no interference with implantation was
noted. Oral administration of cobalt(II) chloride to
pregnant Wistar rats (12, 24, or 48 mg/kg per day from
day 14 of gestation through day 21 of lactation) signifi -
cantly affected the late period of gestation, as well as
postnatal survival and development of the pups (from
12 mg/kg per day). Signs of maternal toxicity were
apparently also noted (Domingo et al ., 1985). A study
conducted in pregnant Sprague-Dawley rats (Pater-
nain et al ., 1988) concluded that the administration of
cobalt chloride (up to a dose of 100 mg/kg by gavage,
from day 6-15 of gestation) was not embryotoxic or
teratogenic, despite signs of maternal toxicity. The fetal
and postnatal developmental effects of cobalt(II) sulfate
have been investigated in C57BL mice, Sprague-Daw-
ley rats and/or New Zealand rabbits (Szakmary et al .,
2001). Several developmental alterations (elevated fre-
quency of fetuses with body weight or skeletal retar-
dation, embryolethality, increased anomalies in several
organs) were observed in mice and rats treated with
cobalt (0-50 and 0-100 mg/kg/day, respectively). No
teratogenic effect was noted in rabbits treated with up