PMID- 3220203
OWN - NLM
STAT- MEDLINE
DCOM- 19890323
LR  - 20190908
IS  - 0272-0590 (Print)
IS  - 0272-0590 (Linking)
VI  - 11
IP  - 2
DP  - 1988 Aug
TI  - The acute toxicity of 2,3,4,7,8-pentachlorodibenzofuran (4PeCDF) in the male 
      Fischer rat.
PG  - 236-49
AB  - Polychlorinated dibenzofurans are ubiquitous environmental pollutants which have 
      great potential for human exposure. To characterize the toxicity of 
      2,3,4,7,8-pentachlorodibenzofuran (4PeCDF), male F344 rats were administered a 
      single oral dose of 0, 100, 250, 500, 1000, or 2000 micrograms 4PeCDF/kg. A 
      progressive and dose-dependent loss of body weight was evident by 3 days after 
      treatment. Signs of toxicity included piloerection, hair loss, hypoactivity, 
      morbidity, and death. Death occurred as soon as 14 days after treatment and 
      continued throughout the 35-day observation period. The LD50/35 was estimated to 
      be 916 micrograms/kg with a 95% confidence interval of 565-1484 micrograms/kg. 
      Dose-dependent increases were observed in serum cholesterol, triglyceride, and 
      bile acid concentrations and in sorbitol dehydrogenase and aspartate 
      aminotransferase activities. The hematocrit, hemoglobin, mean corpuscular volume, 
      and mean corpuscular hemoglobin concentrations were depressed in a dose-dependent 
      fashion. Hepatic ethoxyresorufin-O-deethylase (EROD) activity was increased in 
      all treatment groups approximately 25 times above that of control animals. 
      Lymphoid depletion in the thymus and spleen was observed in the three highest 
      doses and thymic atrophy was present at all dose levels. Absolute liver weight 
      and the liver:body weight ratio were significantly increased above controls. 
      Hepatotoxicity was dose-dependent and was characterized by lipid accumulation 
      resulting in hepatocytomegaly. Epithelial hyperplasia and focal ulcerations of 
      the forestomach was observed in animals administered 500 micrograms 4PeCDF/kg. 
      Spontaneous cardiomyopathy was exacerbated by treatment with 2000 micrograms/kg. 
      Since 4PeCDF and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produce a similar 
      spectrum of toxic effects, the biochemical mechanism(s) of toxicity for these 
      chemicals may be similar.
FAU - Brewster, D W
AU  - Brewster DW
AD  - Systemic Toxicology Branch, National Institute of Environmental Health Sciences, 
      Research Triangle Park, North Carolina 27709.
FAU - Uraih, L C
AU  - Uraih LC
FAU - Birnbaum, L S
AU  - Birnbaum LS
LA  - eng
GR  - 5T32ES0712/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Fundam Appl Toxicol
JT  - Fundamental and applied toxicology : official journal of the Society of 
      Toxicology
JID - 8200838
RN  - 0 (Benzofurans)
RN  - 0 (Bile Acids and Salts)
RN  - 0 (Triglycerides)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - U4C2RV3124 (2,3,4,7,8-pentachlorodibenzofuran)
SB  - IM
MH  - Animals
MH  - Benzofurans/blood/*toxicity
MH  - Bile Acids and Salts/metabolism
MH  - Body Weight/drug effects
MH  - Cholesterol/blood
MH  - Cytochrome P-450 CYP1A1
MH  - Cytochrome P-450 Enzyme System/metabolism
MH  - Lethal Dose 50
MH  - Liver/enzymology/pathology
MH  - Macaca mulatta
MH  - Male
MH  - Organ Size/drug effects
MH  - Oxidoreductases/metabolism
MH  - Rats
MH  - Rats, Inbred F344
MH  - Triglycerides/blood
EDAT- 1988/08/01 00:00
MHDA- 1988/08/01 00:01
CRDT- 1988/08/01 00:00
PHST- 1988/08/01 00:00 [pubmed]
PHST- 1988/08/01 00:01 [medline]
PHST- 1988/08/01 00:00 [entrez]
AID - 10.1016/0272-0590(88)90148-0 [doi]
PST - ppublish
SO  - Fundam Appl Toxicol. 1988 Aug;11(2):236-49. doi: 10.1016/0272-0590(88)90148-0.