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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1973-1975
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Studies are published in the literature, performed by the original manufacturers of the registered substance in an experienced toxicology laboratory.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Toxicological and environmental factors involved in the selection of decabromodiphenyl oxide as a fire retardant chemical.
Author:
Norris et al.
Year:
1973
Bibliographic source:
Appl Pol Symp 22:195–219.
Reference Type:
publication
Title:
Toxicological and environmental factors involved in the selection of decabromodiphenyl oxide as a fire retardant chemical.
Author:
Norris et al.
Year:
1974
Bibliographic source:
JFF/Combust Toxicol 1:52–77.
Reference Type:
publication
Title:
Toxicology of octabromobiphenyl and decabromodiphenyl oxide.
Author:
Norris et al.
Year:
1975
Bibliographic source:
Environ Health Perspect 11:153–161.
Reference Type:
publication
Title:
Toxicology and human health assessment of decabromodiphenyl ether.
Author:
Hardy et al.
Year:
2009
Bibliographic source:
Critical Reviews in Toxicology 39(S3):1-44.

Materials and methods

Test guideline
Qualifier:
no guideline followed
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The former low purity commercial product (77.4% BDE-209, 21.8% nonabromodiphenyl ether (nonaBDE), and 0.8% octabromodiphenyl ether (octaBDE))was used to study tissue levels after repeated doses. 14C-DecaBDE was used in a single dose study.
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
other: gavage or diet
Duration and frequency of treatment / exposure:
single dose or up to 180 d in diet
Doses / concentrations
Remarks:
Doses / Concentrations:
14C-DecaBDE, single dose = 1 mg/kg, gavage.
Low purity DecaBDE product (77.4% BDE-209, 21.8% nonabromodiphenyl ether (nonaBDE), and 0.8% octabromodiphenyl ether (octaBDE)) = 0, 0.01, 0.1, and 1.0 mg/kg bw in diet
No. of animals per sex per dose:
varied
Control animals:
yes, concurrent no treatment

Results and discussion

Main ADME resultsopen allclose all
Type:
excretion
Results:
<1% of 14C-activity recovered in expired air, urine after a single oral dose
Type:
excretion
Results:
>99% 14-C activity recovered in feces 48 hr after a single oral dose.
Type:
other:
Results:
half-life of 14C-activity in the body < 24 hr after a single oral dose
Type:
distribution
Results:
After 180 days, diet exposure to the low purity product, [Br-] liver, kidney, skeletal muscle, serum, testes comparable to controls. [Br-] adipose increased; at 12 months [Br-] all tissues comarable to controls.

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:
The first work on BDE-209’s ADME properties was reported in the early 1970s (Norris et al. 1974, 1973, 1975). Norris et al. (1975) administered a single dose of 1.0 mg/kg 14CBDE- 209 (specific activity: 1.1 μCi/mg; purity not specified) by gavage in corn oil to 3 male and 3 female Sprague-Dawley rats. Tissues (adipose, heart, liver, pancreas, skin) on day 16 post-dosing showed no 14C-label with the exception of the adrenal (0.01% of the dose/g of tissue) and spleen (0.06%). The 14C-activity in these 2 tissues was at the limit of detection. The half-life of the disappearance of 14C-activity from the body of treated rats was <24 h.

Norris et al. (1974, 1975) also reported total bromine concentrations, using neutron activation analysis, in the adipose tissue, kidney, liver, serum, skeletal muscle, and testes in male and female Sprague-Dawley rats maintained on diets providing 0, 0.01, 0.1, and 1.0 mg of a former commercial product, i.e., FR-300-BA (The Dow Chemical Company, Midland, MI, USA)/kg-day for 3, 6, or 12 months. FR-300-BA was composed of 77.4% BDE-209, 21.8% nonabromodiphenyl ether (nonaBDE), and 0.8% octabromodiphenyl ether (octaBDE). After 180 days of treatment, bromine concentrations in liver, kidney, skeletal muscle, serum, and testes of treated rats were comparable to that of controls. Bromine concentrations in adipose tissue from treated rats (~3 μg bromine/g) were increased, compared to controls (~1 μg bromine/g). However, after 12 months of treatment, liver and adipose tissue bromine concentrations were comparable to controls. In addition, elimination of bromine from liver and adipose tissue was followed in male Sprague-Dawley rats maintained for 90 days on diets providing 1.0 mg FR-300-BA/kg-day and afterward fed control diet. Adipose tissue, kidney, liver, and serum were analyzed for bromine by neutron activation analysis. On recovery day 0, measurable levels of bromine were reported in the liver (~5 μg bromine/g) compared to controls (>~2 but <4 μg bromine/g); no difference in bromine content in kidney or serum was reported between the controls and treated rats. After 10 days on the control diet, bromine concentrations in the liver of treated rats were comparable to controls. Adipose bromine levels in the treated group (~2.5–4 µg bromine/g) were higher than the controls (~0–2 µg bromine/g) during the recovery period.
Details on excretion:
The first work on BDE-209’s ADME properties was reported in the early 1970s (Norris et al. 1974, 1973, 1975). Norris et al. (1975) administered a single dose of 1.0 mg/kg 14CBDE- 209 (specific activity: 1.1 μCi/mg; purity not specified) by gavage in corn oil to 3 male and 3 female Sprague-Dawley rats. 14C-activity in expired air and urine, measured at 24-h intervals over a 16-day period, was <1%. The principal route of excretion was the feces, and both genders eliminated the 14C-activity at similar rates. Within the first 24 h postdosing, 90.6% of the administered dose was detected in the feces, and >99% of the 14C-activity was accounted for by day 2.

Metabolite characterisation studies

Metabolites identified:
no

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
Based on 14C-aitivity, DecaBDE is rapidly eliminated in the feces. Urine and expired air are not routes of elimination. Accumulation of the former lower purity commercial product, 77.4% BDE-209, 21.8% nonabromodiphenyl ether (nonaBDE), and 0.8% octabromodiphenyl ether (octaBDE), was not observed in repeated dose studies. The method of analysis in the later study was neutron activation, which is specific for detection of bromide ion. Thus, all components of the test substance including metabolites, if any, would be detected.
Executive summary:

The first work on BDE-209’s ADME properties was reported in the early 1970s (Norris et al. 1974, 1973, 1975). Norris et al. (1975) administered a single dose of 1.0 mg/kg 14CBDE- 209 (specific activity: 1.1 μCi/mg; purity not specified) by gavage in corn oil to 3 male and 3 female Sprague-Dawley rats. 14C-activity in expired air and urine, measured at 24-h intervals over a 16-day period, was <1%. The principal route of excretion was the feces, and both genders eliminated the 14C-activity at similar rates. Within the first 24 h postdosing, 90.6% of the administered dose was detected in the feces, and >99% of the 14C-activity was accounted for by day 2. Tissues (adipose, heart, liver, pancreas, skin) on day 16 post-dosing showed no 14C-label with the exception of the adrenal (0.01% of the dose/g of tissue) and spleen (0.06%). The 14C-activity in these 2 tissues was at the limit of detection. The half-life of the disappearance of 14C-activity from the body of treated rats was <24 h.

Norris et al. (1974, 1975) also reported total bromine concentrations, using neutron activation analysis, in the adipose tissue, kidney, liver, serum, skeletal muscle, and testes in male and female Sprague-Dawley rats maintained on diets providing 0, 0.01, 0.1, and 1.0 mg of a former commercial product, i.e., FR-300-BA (The Dow Chemical Company, Midland, MI, USA)/kg-day for 3, 6, or 12 months. FR-300-BA was composed of 77.4% BDE-209, 21.8% nonabromodiphenyl ether (nonaBDE), and 0.8% octabromodiphenyl ether (octaBDE). After 180 days of treatment, bromine concentrations in liver, kidney, skeletal muscle, serum, and testes of treated rats were comparable to that of controls. Bromine concentrations in adipose tissue from treated rats (~3 μg bromine/g) were increased, compared to controls (~1 μg bromine/g). However, after 12 months of treatment, liver and adipose tissue bromine concentrations were comparable to controls. In addition, elimination of bromine from liver and adipose tissue was followed in male Sprague-Dawley rats maintained for 90 days on diets providing 1.0 mg FR-300-BA/kg-day and afterward fed control diet. Adipose tissue, kidney, liver, and serum were analyzed for bromine by neutron activation analysis. On recovery day 0, measurable levels of bromine were reported in the liver (~5 μg bromine/g) compared to controls (>~2 but <4 μg bromine/g); no difference in bromine content in kidney or serum was reported between the controls and treated rats. After 10 days on the control diet, bromine concentrations in the liver of treated rats were comparable to controls. Adipose bromine levels in the treated group (~2.5–4 µg bromine/g) were higher than the controls (~0–2 µg bromine/g) during the recovery period.