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

ACIDIFIED SODIUM CHLORITE 7
(b)
Sodium chlorite and chlorate
36
Cl compounds were administered by gavage to groups of four male
Sprague-Dawley rats at the following doses: 0.15 mg chlorite/kg bw, 3.26 mg
hypochlorous acid/kg bw, 1.5 mg chlorine dioxide/kg bw and 0.065 mg chlorate/kg
bw. Separate groups were used for determination of the 36 Cl content of blood and
tissue samples, protein binding and excretion over 72 h. The time taken to absorb
50% of the dose for each chlorine species was found to be longest for hypochlorous
acid (4.42 ± 1.31 h), followed by chlorite (3.5 ± 1.06 h), chlorate (1.74 ± 0.66 h) and
chlorine dioxide (0.18 ± 0.01 h). The time taken to eliminate 50% of the dose from
the plasma when detected as 36 Cl was longest for hypochlorous acid (77.0 ± 8.8 h),
followed by chlorine dioxide (43.9 ± 2.3 h), chlorate (36.7 ± 5.8 h) and chlorite (35.2
± 3.0 h). After 72 h, radioactivity from chlorite was found at the highest level in
the plasma, followed by stomach, testes, skin, lung, duodenum, kidney, carcass,
spleen, ileum, bone marrow and liver. Radioactivity from hypochlorous acid was
highest in plasma, followed by bone marrow, kidney, testes, lung, skin, duodenum,
spleen, stomach, liver, carcass and ileum. Radioactivity from chlorine dioxide
was highest in the kidney, followed by lung, plasma, stomach, ileum, liver,
duodenum, spleen and bone marrow. Radioactivity from chlorate was highest in
plasma, followed by stomach, lung, testes, kidney, skin, duodenum, spleen, ileum,
carcass, liver and bone marrow. In blood, chlorite levels were distributed evenly
between plasma and packed cells, whereas chlorate preferentially accumulated in
the plasma.
The percentage of the initial dose excreted within 72 h ranged from 28%
for hypochlorous acid to 43% for chlorate, with 75–87% present in the urine and the
remainder in the faeces. No 36 Cl was detected in expired air (Abdel-Rahman et al.,
1982a).
2.1.2 Biotransformation
In the studies of the germicidal ASC product described in section 1.2 above,
chloride and chlorite, but not chlorate, were detected in rat urine. Between 8 and
72 h following oral administration, the chloride and chlorite were present at equal
concentrations; however, during the first 8 h and between 120 and 144 h, chloride
was excreted to a greater extent than chlorite. Following dermal administration, the
total excretion of chloride and chlorite was approximately the same. The authors
reported these as metabolites of chlorine dioxide (Scatina et al., 1983).
In the studies of Abdel-Rahman et al. (1982a), described in section 2.1.1,
chloride, chlorite and chlorate were found in rat urine after administration of chlorine
dioxide, chlorite and chlorate. The major metabolite in all cases was chloride,
representing 26.9% of the initial dose of chlorine dioxide, 31.6% of the initial dose
of chlorite and 20.5% of the initial dose of chlorate (Abdel-Rahman et al., 1982a).
In the above studies, it is unclear if the substances described as
“metabolites” resulted from degradation of the administered substances prior to
absorption or are biotransformation products within the body.