A 28-day oral dose toxicity study in Wistar rats enhanced to detect endocrine effects of decabromodiphenyl ether (decaBDE).
Decabromodiphenyl ether (decaBDE) is a widely used brominated flame retardant, considered to be of low toxicity. However, previous toxicity studies applied exposure methods with low bioavailability of this compound, and the actual hazard of decaBDE for humans, which are environmentally exposed to decaBDE, may thus be underestimated in current risk assessments. The present 28 days oral toxicity study in Wistar rats was designed to facilitate detection of endocrine and immune modulating effects of decaBDE using an exposure protocol with improved bioavailability. A technical preparation of high purity decaBDE was thus tested by daily exposure through gavage with an emulsion of soy phospholipon/lutrol as a carrier. Most sensitive effect in males were increased weight of seminal vesicle/coagulation gland with BMDL of 0.2mg/kg bw/day and increased expression of hepatic CYP1A and CYP2B (BMDLs 0.5-0.7 mg/kg bw/day). In females the most sensitive effect was decreased activity of P450c17 (CYP17), which is a key enzyme in the androgen synthesis pathway, in adrenals (BMDL 0.18 mg/kg bw/day). These results suggest that decaBDE may represent an as yet unreported hazard for reproductive health.
Van der Ven
Leo T M
LT
Laboratory for Health Protection Research, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Leo.van.der.ven@rivm.nl
van de Kuil
Ton
T
Leonards
Pim E G
PE
Slob
Wout
W
Cantón
Rocío F
RF
Germer
Silke
S
Visser
Theo J
TJ
Litens
Sabina
S
Håkansson
Helen
H
Schrenk
Dieter
D
van den Berg
Martin
M
Piersma
Aldert H
AH
Vos
Josephus G
JG
Opperhuizen
Antoon
A
D000284:Administration, Oral; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004702:Endocrine Glands / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005411:Flame Retardants / Q000493:pharmacokinetics / Q000633:toxicity*; D055768:Halogenated Diphenyl Ethers; D007107:Immune System / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010647:Phenyl Ethers / Q000493:pharmacokinetics / Q000633:toxicity*; D011075:Polybrominated Biphenyls / Q000493:pharmacokinetics / Q000633:toxicity*; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000187:drug effects; D018570:Risk Assessment; D012669:Seminal Vesicles / Q000187:drug effects / Q000473:pathology; D018675:Toxicity Tests
D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D010647:Phenyl Ethers; D011075:Polybrominated Biphenyls; D003577:Cytochrome P-450 Enzyme System; C010902:decabromobiphenyl ether