Who Food Additives Series 59 Safety Evaluation Of ... - ipcs inchem

ACIDIFIED SODIUM CHLORITE 27
Sodium chlorite was administered to pregnant female Sprague-Dawley rats
via intraperitoneal injection, gavage or drinking-water. The intraperitoneal injection
group of animals received 10 mg/kg bw per day on GD 8–15 (13 rats), 20 mg/kg bw
per day on GD 8–15 (10 rats) or 50 mg/kg bw per day on GD 8–10 or 16–17 (7 rats).
The animals dosed by gavage received 200 mg/kg bw per day on GD 8–10.
Concentrations in drinking-water were 0.1%, 0.5% or 2% (equal to sodium chlorite
doses of 106, 500 and 564 mg/kg bw per day, respectively, or 79, 372 and 420 mg/
kg bw per day expressed as chlorite) on GD 8–15 (10 animals per group). Some
rats underwent caesarean section on day 22, and others were allowed to deliver at
term. Litter size, number of living and dead pups, weights of pups and crown–rump
measurements were recorded. Offspring were examined for gross malformations
and then sacrificed. Half underwent examination of soft tissues, and the remainder
underwent examination for skeletal malformations. Six pups from each litter were
selected at random, and their postnatal growth was recorded at days 1, 8, 15, 22
and 29.
Intraperitoneal injection of sodium chlorite resulted in deaths, vaginal and
urethral bleeding and weight loss at 20 and 50 mg/kg bw per day. At 10 mg/kg bw
per day intraperitoneal injection, there were no deaths or bleeding, but weight loss
was still observed. Effects of gavage at 200 mg/kg bw per day were similar to those
seen at 50 mg/kg bw per day intraperitoneal injection. Following administration in
drinking-water, body weight gain of the dams was decreased at 0.5% and 2%
sodium chlorite, but increased at 0.1%, compared with controls. Water consumption
was significantly reduced during the treatment period in all groups compared with
controls, and food consumption was reduced in all except the 0.1% sodium chlorite
group. Irregular blood cells, ruptured cells and haemolysis were observed in the
dams receiving 2% sodium chlorite. In the offspring, the crown–rump distance was
significantly decreased in all treatment groups. Increased numbers of dead and
resorbed fetuses were reported, particularly at the higher doses, but there were no
differences in postnatal growth of pups or the numbers of skeletal or soft tissue
malformations (Couri et al., 1982).
Groups of 12 male Long-Evans rats were administered sodium chlorite at 0,
1, 10 or 100 mg/l in their drinking-water for 56 days prior to breeding and during the
10-day breeding period. Female rats (24 per dose group) were given the same
concentrations for 14 days prior to breeding and throughout breeding, gestation and
lactation until the pups were weaned on day 21. Water consumption was recorded
but not reported. Following the breeding period, blood samples were taken and a
gross necropsy was carried out on the male rats (organs not specified). The testis,
epididymis, prostate and seminal vesicles were removed, weighed and examined
histopathologically, except for the right cauda epididymis, which was minced,
following which the sperm cells were examined for motility and abnormalities and
counted. Dams were observed for fertility, length of gestation, body weight gain and
maternal behaviour. At sacrifice, 21 days after birth, blood samples were taken from
the dams, and a gross necropsy was carried out (organs not specified). The
reproductive tract was removed for histopathological examination. Litters were
evaluated for viability, litter size (~13 per dam), day of eye opening, body weight
gain and gross external abnormalities. At necropsy, 10 pups per sex per dose were