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

ACIDIFIED SODIUM CHLORITE 29
Groups of 16 pregnant New Zealand White rabbits received 0, 200, 600 or
1200 mg sodium chlorite/l (corrected for the purity of 80.6%) in their drinking-water
from GD 7 to GD 19. Based on water consumption, which decreased with increasing
sodium chlorite concentration, the calculated average intakes were reported to be
equal to 0, 13, 35.5 and 53.1 mg sodium chlorite/kg bw per day, or 0, 9.8, 26.6 and
39.8 mg chlorite/kg bw per day, respectively. Clinical condition, body weight and
food and water consumption were recorded until necropsy on GD 28. Live fetuses
were weighed and examined for abnormalities. During GD 7–11, there was a
significant dose-related decrease in food consumption in the 600 mg/l and 1200 mg/
l groups and an associated decrease in body weight in the 1200 mg/l group, but no
statistically significant changes in absolute body weights throughout the study. No
treatment-related abnormalities were observed at maternal necropsy, and the mean
number of corpora lutea, implantations, preimplantation losses and live fetuses and
sex distribution were similar in all groups. The 600 and 1200 mg/l groups showed
an increase in minor skeletal abnormalities and skeletal variants related to
incomplete ossification of the pubis and sternebrae. No other treatment-related
abnormalities were observed. The authors concluded that there was evidence of a
slight effect of sodium chlorite on embryonic growth retardation and development,
which was considered to be due to the maternal effects of sodium chlorite rather
than direct action on the fetus (Harrington et al., 1995b). This study indicates a
NOEL of 13 mg sodium chlorite/kg bw per day, or 9.8 mg chlorite/kg bw per day.
(c)
Sodium chlorate: developmental toxicity
Sodium chlorate was administered to pregnant CD rats by gavage at
doses of 0, 10, 100 or 1000 mg/kg bw per day on days 6–15 of gestation. No
treatment-related effects were observed in maternal body weight gain, food
consumption, clinical observation, number of implantations or gross necropsy.
Examinations of fetuses on day 20 showed no effects on fetal weight or sex ratio,
and no external, visceral or skeletal abnormalities were detected. A NOAEL of
1000 mg/kg bw per day was identified from this study (Bio/dynamics Inc., 1987b).
2.2.6 Special studies
(a)
Blood
Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency
have been identified as being especially sensitive to the effects of oxidant stress
such as that caused by chlorine dioxide and chlorite, because they have a reduced
ability to form GSH. Two strains of mice, C57L/J (low G6PD activity) and A/J (high
G6PD activity), have been used to study the effects of chlorite. Sodium chlorite was
administered orally by gavage to groups of at least 22 mice (sex not specified) at 0
or 200 mg/kg bw at 12-h intervals. Animals were killed after the third dose, and the
blood was analysed for haematological parameters, osmotic fragility and G6PD in
the erythrocytes. Some groups of animals had 2 cm of tail severed after the second
dose, in order to examine clot formation. Significant differences were seen between
the two strains of mice receiving no treatment, with red blood cells, haematocrit and
reticulocyte count being significantly higher in the C57L/J strain than in the A/J