Organ-specific DNA damage of tris(2,3-dibromopropyl)-phosphate and its diester metabolite in the rat

Søderlund, Erik J.; Brunborg, Gunnar; Dybing, Erik; Trygg, Bente; Nelson, Sidney D.; Holme, Jørn A.

doi:10.1016/0009-2797(92)90110-7

Cited by 6 publications

(4 citation statements)

References 27 publications

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“…TDBPP induced a significant increase in sister chromatid exchanges (SCE) in Chinese hamster V79 cells in the presence and absence of metabolic activation (Furukawa et al, 1978;Sala et al, 1982, as cited by NICNAS, 2005, in mouse lymphoma L5178Y cells (Brusick et al, 1979), and in the human fibroblastic cell line HE 2144 at 0.070 mg TDBPP/mL in the absence of metabolic activation (Sasaki et al, 1980, as cited in NICNAS, 2005. In isolated rat hepatocytes TDBPP induced unscheduled DNA synthesis (Holme et al, 1983;Soderlund et al, 1992Soderlund et al, , 1985 and DNA damage (Soderlund et al, 1992).…”

Section: Hazard Identificationmentioning

confidence: 98%

“…In isolated rat hepatocytes TDBPP induced unscheduled DNA synthesis (Holme et al, 1983;Soderlund et al, 1992Soderlund et al, , 1985 and DNA damage (Soderlund et al, 1992).…”

Section: Hazard Identificationmentioning

confidence: 99%

“…injection of 350 μmol TDBPP/kg b.w. (Holme et al, 1983;Soderlund et al, 1992, as cited by NICNAS, 2005). …”

Section: Hazard Identificationmentioning

confidence: 99%

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Scientific Opinion on Emerging and Novel Brominated Flame Retardants (BFRs) in Food

2012

EFS2

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EFSA was asked to deliver a scientific opinion on brominated flame retardants (BFRs) other than PBDEs, PBBs, HBCDDs, TBBPA and brominated phenols and their derivatives. The BFRs that are the subject of the current opinion, were classified in groups termed "emerging" and "novel" BFRs. Information on 17 emerging and 10 novel BFRs was collected. The information varied widely for these BFRs. There is a lack of experimental data on physico-chemical characteristics, stability/reactivity and current use and production volume of all the emerging and novel BFRs. Due to the very limited information on occurrence, exposure and toxicity, the CONTAM Panel could not perform a risk characterisation for any of the BFRs considered. Instead, an attempt was made to identify those BFRs that could be a potential health concern and should be considered first for future investigations. For this purpose the Panel first evaluated the available experimental data on occurrence in food, behaviour in the environment and toxicity. Secondly, a modelling exercise was performed focussing on the potential of the emerging and novel BFRs for persistence in the environment and for their possible bioaccumulation potential. There is convincing evidence that tris(2,3-dibromopropyl) phosphate (TDBPP) and dibromoneopentyl glycol (DBNPG) are genotoxic and carcinogenic, warranting further surveillance of their occurrence in the environment and in food. Based on the limited experimental data on environmental behaviour, 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) and hexabromobenzene (HBB) were identified as compounds that could raise a concern for bioaccumulation. For the modelling exercise, the CONTAM Panel selected two environmental characteristics, overall persistence and potential for bioaccumulation, as being most relevant to provide insight into the possibility that emerging or novel BFRs The less well known and less studied BFRs, subject of the current opinion, were grouped into two classes, referred to herein as "emerging" and "novel" BFRs. Emerging BFRs are defined as chemicals which are applied as flame retardants and that have been identified in any environmental compartment, in wildlife, in food or in humans. It should be noted that the definition for the emerging BFRs, used in this opinion, does not imply that there is evidence for an increasing trend in the concentration of these BFRs in the environment, in food or in human samples. Novel BFRs are defined as chemicals applied as flame retardants, with confirmed presence in materials and/or goods in concentrations above 0.1 %, but not identified in environmental samples, wildlife, food or humans. In total, information on 27 BFRs, of which 17 were identified as "emerging" and 10 as "novel", was collected by the CONTAM Panel, and it was noted that the available information varied widely for the various individual BFRs.In general, there is a lack of experimental data on physico-chemical characteristics and stability/reactivity for all the emerging and novel BFRs. This sometimes hampered ...

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Section: Hazard Identificationmentioning

confidence: 98%

“…In isolated rat hepatocytes TDBPP induced unscheduled DNA synthesis (Holme et al, 1983;Soderlund et al, 1992Soderlund et al, , 1985 and DNA damage (Soderlund et al, 1992).…”

Section: Hazard Identificationmentioning

confidence: 99%

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Scientific Opinion on Emerging and Novel Brominated Flame Retardants (BFRs) in Food

2012

EFS2

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“…TRIS has been shown to be a potent multiorgan genotoxic chemical that causes extensive DNA damage in various organs (Soderlund et al 1992). Its mutagenic mechanism is via a reactive metabolite, 2-bromoacrolein, which is genotoxic and forms DNA adducts (Van Beerendonk et al 1994).…”

Section: Discussionmentioning

confidence: 99%

Chronic Toxicity and Carcinogenic Potential of Tris-(1,3-Dichloro-2-propyl) Phosphate in Sprague-Dawley Rat

Freudenthal¹,

Henrich

2000

Int J Toxicol

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The Flammable Fabrics Act of 1953 and its amendments established a need for flame-resistant fabrics. Tris-(1,3-dichloro-2-propyl) phosphate (TDCPP) was briefly used in apparel fabrics to assist in the compliance with federal flammability standards, and continues to be used as a flame retardant in flexible polyurethane foams. A chronic toxicity and carcinogenicity bioassay was conducted in Sprague-Dawley rats to determine the toxicologic and carcinogenic potential of TDCPP after repeated exposure. Four groups of animals, each consisting of 60 male and 60 female rats, received via their diet a daily dose of either 0, 5, 20, or 80 mg TDCPP per kg body weight for up to 24 months. Diets were adjusted after each weekly (first 13 weeks) or biweekly (weeks 14 through 104) body weight and food consumption measurement to achieve and maintain the indicated doses. Ten animals per sex were taken from each group for interim sacrifice at the end of the 12th month. Body weights, food consumption, clinical signs, and hematological and clinical chemistry parameters were measured periodically, and ophthalmoscopic examinations were conducted on all animals. After complete postmortem examination of all animals, microscopic examination of all tissues was conducted for the control and high-dose animals. Liver, kidneys, testes, and adrenal glands were examined from all animals. Mortality was significantly higher and body weights were significantly lower in the high-dose group when compared to control animals. Certain hematology parameters, such as hemoglobin, hematocrit, and total erythrocyte values, were decreased in the high-dose animals. Ophthalmoscope examination revealed no treatment-related changes. Microscopic examination revealed a higher incidence of benign neoplasms and non-neoplastic alterations in several organs of the mid and high dose animals. The no-observed-adverse-effect level (NOAEL) for chronic toxicity and neoplastic activity was the dietary dose of 5 mg/kg/day.

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Mutational specificity: Spectrum of mutations in kidney, stomach, and liver fromlacl transgenic mice recovered after treatment with tris(2,3-dibromopropyl)phosphate

Boer

Mirsalis

Provost³

et al. 1996

Environ. Mol. Mutagen.

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Organ-specific DNA damage of tris(2,3-dibromopropyl)-phosphate and its diester metabolite in the rat

Cited by 6 publications

References 27 publications

Scientific Opinion on Emerging and Novel Brominated Flame Retardants (BFRs) in Food

Scientific Opinion on Emerging and Novel Brominated Flame Retardants (BFRs) in Food

Chronic Toxicity and Carcinogenic Potential of Tris-(1,3-Dichloro-2-propyl) Phosphate in Sprague-Dawley Rat

Mutational specificity: Spectrum of mutations in kidney, stomach, and liver fromlacl transgenic mice recovered after treatment with tris(2,3-dibromopropyl)phosphate

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