PMID- 16177236
OWN - NLM
STAT- MEDLINE
DCOM- 20060110
LR  - 20131121
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 88
IP  - 2
DP  - 2005 Dec
TI  - Toxicological effects of gestational and lactational exposure to a mixture of 
      persistent organochlorines in rats: systemic effects.
PG  - 645-55
AB  - A large multi-disciplinary study was conducted to investigate the systemic, 
      neurodevelopmental, neurochemical, endocrine, and molecular pathological effects 
      of a mixture of reconstituted persistent organochlorine pollutants (POP) based on 
      the blood profiles of Canadians residing in the Great Lakes/St. Lawrence region. 
      This report outlines the overall study design and describes the systemic effects 
      in rat offspring perinatally exposed to the POP mixture. Maternal rats were 
      administered orally 0, 0.013, 0.13, 1.3, or 13 mg/kg bw/day of the mixture from 
      gestational day (GD) 1 to postnatal day (PND) 23. Positive and negative controls 
      were given Aroclor 1254 (15 mg/kg bw/day) and corn oil (vehicle), respectively. 
      The rat pups were reared, culled to 8 per litter, and killed on postnatal days 
      35, 70, and 350, at which time tissues were collected for analysis. Exposure to 
      high doses of the mixture elicited clinical, biochemical, and pathological 
      changes and high mortality rates in rat offspring. Aroclor 1254 produced similar 
      effects but a lower mortality than was seen in POP mixture groups. Biochemical 
      changes consisted of increased liver microsomal activities and elevated serum 
      cholesterol. Hepatomegaly was observed in the highest dose group of the mixture 
      and in the positive control. Liver, thymus, and spleen were the target organs of 
      action. Microscopic changes in the liver consisted of vacuolation and 
      hypertrophy, and those in the thymus were characterized by reduced cortical and 
      medullary volume. The spleen showed a treatment-related reduction in lymphocyte 
      density and lymphoid areas. This study demonstrates that exposure to the POP 
      mixture up to 13 mg/kg/day perinatally produced growth suppression, elevated 
      serum cholesterol, increased liver microsomal enzyme activities, and 
      immunopathological changes in the thymus and spleen, and lethality. Most of the 
      effects were seen at dose levels much higher than expected human exposure.
FAU - Chu, Ih
AU  - Chu I
AD  - Environmental and Occupational Toxicology Division, Healthy Environments and 
      Consumer Safety Branch, Health Canada, Ottawa, Ontario. lh_chu@hc.sc.gc.ca
FAU - Bowers, Wayne J
AU  - Bowers WJ
FAU - Caldwell, Don
AU  - Caldwell D
FAU - Nakai, Jamie
AU  - Nakai J
FAU - Pulido, Olga
AU  - Pulido O
FAU - Yagminas, Al
AU  - Yagminas A
FAU - Wade, Michael G
AU  - Wade MG
FAU - Moir, David
AU  - Moir D
FAU - Gill, Santokh
AU  - Gill S
FAU - Mueller, Rudi
AU  - Mueller R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050921
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Hydrocarbons, Chlorinated)
RN  - 0 (Water Pollutants, Chemical)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Canada
MH  - Cholesterol/blood
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Food Contamination/analysis
MH  - Hepatomegaly/chemically induced/pathology
MH  - Hydrocarbons, Chlorinated/*toxicity
MH  - Lactation/*drug effects
MH  - Longevity/drug effects
MH  - Male
MH  - *Maternal Exposure
MH  - Microsomes, Liver/drug effects/enzymology
MH  - Organ Size/drug effects
MH  - Organogenesis/*drug effects
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Spleen/drug effects/pathology
MH  - Thymus Gland/drug effects/pathology
MH  - Water Pollutants, Chemical/*toxicity
EDAT- 2005/09/24 09:00
MHDA- 2006/01/13 09:00
CRDT- 2005/09/24 09:00
PHST- 2005/09/24 09:00 [pubmed]
PHST- 2006/01/13 09:00 [medline]
PHST- 2005/09/24 09:00 [entrez]
AID - kfi335 [pii]
AID - 10.1093/toxsci/kfi335 [doi]
PST - ppublish
SO  - Toxicol Sci. 2005 Dec;88(2):645-55. doi: 10.1093/toxsci/kfi335. Epub 2005 Sep 21.