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

ACIDIFIED SODIUM CHLORITE 19
incidences of bone marrow hyperplasia were significantly increased in all exposed
females. The authors concluded that there was no evidence of carcinogenic activity
of sodium chlorate in male mice at the doses tested and equivocal evidence of
carcinogenic activity in female mice based on marginal increases in incidence of
pancreatic islet neoplasms (National Toxicology Program, 2005).
Rats
Sodium and potassium chlorate were evaluated as promoters of renal
tumours in groups of 15 male F344 rats. The initiation was by administration of N-
ethyl-N-hydroxyethyl-nitrosamine at 500 mg/l in drinking-water 3 times a week for
2 weeks at the start of the study. Sodium chlorate was administered in the drinkingwater
at a concentration of 10 g/l for 25 weeks. Based on drinking-water
consumption, the doses were reported to be 686 mg/kg bw per day in the initiated
mice and 654 mg/kg bw per day in the mice consuming sodium chlorate without
initiator (equivalent to 541 and 516 mg chlorate/kg bw per day). Two further groups
consumed distilled water in place of the sodium chlorate with or without initiation.
Chlorate administration resulted in no significant increases in incidence of dysplastic
foci or renal cell tumours, compared with the relevant initiated or control groups
(Kurokawa et al., 1985).
Groups of 50 male and 50 female F344/N rats were exposed to sodium
chlorate in the drinking-water for 2 years at doses equivalent to approximately 5, 35
and 75 mg/kg bw per day for males and 5, 45 and 95 mg/kg bw per day for females.
Survival rates, mean body weights and water consumption were similar between
test and control groups throughout the study. There were positive trends in the
incidence of thyroid gland follicular cell carcinoma in male rats and thyroid gland
follicular cell adenoma and carcinoma (combined) in males and females. The
incidence of thyroid gland follicular cell hypertrophy was significantly increased in
all exposed male groups and in the two high-dose groups of females. Thyroid gland
focal follicle mineralization occurred in most females in the mid- and high-dose
groups. The incidences of haematopoietic cell proliferation in the spleen of highdose
males and bone marrow hyperplasia in the mid- and high-dose male groups
were significantly greater than controls. The authors concluded that there was
some evidence of carcinogenic activity of sodium chlorate in male and female rats
based on increased incidence of thyroid gland neoplasms (National Toxicology
Program, 2005).
Because a NOAEL was not identified in this study, the Committee decided
to apply a benchmark dose (BMD) approach to derive a point of departure on the
dose–response curve (see Annex 3 of reference 176 in Annex 1). A summary of the
key neoplastic and non-neoplastic findings is shown in Table 4.
The United States Environmental Protection Agency (USEPA) BMD
software version 1.4.1 (United States Environmental Protection Agency, 2007) was
used for modelling the data on rat thyroid gland follicular cell hypertrophy, which
was the effect observed at the lowest dose levels. A range of models were applied
in order to derive the BMD for a 10% increase in follicular cell hypertrophy
(BMD10) and the corresponding 95% lower confidence limit (BMDL10), as shown in