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Administrative data

Description of key information

14 d, 13 wk, 2 year studies in rats and mice.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

The results of Norris et al. (1973, 1974, 1975) demonstrate that the former lower purity form of DecaBDE is capable of causing changes in liver weight and hepatocytomegaly, probably due to enzyme induction, as supported by the subtle changes in CYP documented by Van der Ven et al. (2008). Though Van der Ven et al. (2008) concluded that the commercial form of BDE-209 caused an effect on the weights of the epididymis and seminal vesicle, Hardy et al. (2008) showed that there were no statistically significant differences for these endpoints, nor was there a visible dose response from these data (Hardy et al., 2008). When considered in toto with the absence of any histopathological changes in these tissues or with sperm parameters, Van der Ven et al.’s (2008) conclusions are not supported by their data. Finally, the NTP (1986) study demonstrated that dietary exposures did not cause any gross or microscopic pathological effects in rats or mice at doses up to 5% in the diet for 90 d. In their 2 year study at doses up to 5% of the diet, nonneoplastic effects reported in male rats were confined to the liver, spleen, and mandibular lymph nodes (NTP 1986). In female rats, the only nonneoplastic effect to increase with dose was an increase in nephropathy; however, this lesion was present in 84% of control animals and is a common age-related lesion occurring in this strain of rat. Degeneration of the eye was observed in low-dose female rats (30%; cf. controls and high-dose groups = 10%). The NTP (1986) did not consider this effect to be treatment related, because this effect has been correlated with exposure to artificial light due to cage placement, and as a result, US NTP’s long-term studies presently incorporate cage rotation into the study design. This 2-year study was conducted prior to US NTP instituting cage rotation as a part of their experimental protocols. In male mice, nonneoplastic lesions were observed in the liver, mandibular lymph node, and thyroid. Non-neoplastic lesions in female mice were limited to the mandibular lymph node. Notably, no test-article-related effect on mortality or body weight was detected in the NTP 2 year studies in both species. NTP estimated the doses in the 2 year study were: 1120 or 2240 mg/kg bw/d (male rats), 1200 or 2550 mg/kg bw/d (female rats), 3200 or 6650 mg/kg bw/d (male mice), and 3760 or 7780 mg/kg bw/d (female mice) at the low and high doses, respectively. These results indicate a NOAEL in repeated dose stuides of at least 1000 mg/kg bw/d for the commercial DecaBDE product.

Justification for classification or non-classification

DecaBDE has a NOAEL of at least 1000 mg/kg bw/d in repeatd doses studies. Classification is not required.