PMID- 18080900
OWN - NLM
STAT- MEDLINE
DCOM- 20080103
LR  - 20131121
IS  - 1528-7394 (Print)
IS  - 0098-4108 (Linking)
VI  - 71
IP  - 2
DP  - 2008
TI  - Toxicological effects of in utero and lactational exposure of rats to a mixture 
      of environmental contaminants detected in Canadian Arctic human populations.
PG  - 93-108
AB  - As part of the program to investigate mixture effects of environmental 
      pollutants, this study describes clinical, biochemical, and histopathological 
      effects in rats perinatally exposed to a mixture of persistent organochlorine 
      pollutants and methylmercury that simulates the blood contaminant profile of 
      humans residing in the Canadian Arctic. Groups of pregnant rats were administered 
      orally 0, 0.05, 0.5, or 5 mg/kg body weight (bw)/d of a reconstituted mixture of 
      organochlorine pollutants (referred to as mixture hereafter) from gestational day 
      (GD) 1 to postnatal day (PND) 23. Positive and vehicle controls were given 
      Aroclor 1254 (Aroclor hereafter, 15 mg/kg bw) and corn oil (vehicle), 
      respectively. After parturition, the pups were colled to 8 per litter on PND 4, 
      and killed on PND 35, 77, or 350, when tissues were collected for analysis. 
      Gestational and lactational exposure of rats to mixture up to 5 mg/kg bw produced 
      adverse effects in the offspring, including growth suppression, decreased spleen 
      and thymic weights, increased serum cholesterol and liver microsomal enzyme 
      activities, lower liver retinoid levels, and histological changes in the liver, 
      thyroid, and spleen. Histological changes in the liver consisted of hepatic 
      inflammation, vacuolation, and hypertrophy, while alterations in the thyroid were 
      characterized by hypertrophy and hyperplasia of follicles. The hepatic and 
      thyroidal effects were mild even at the highest dose. The spleen showed a 
      dose-dependent atrophy in the lymphoid nodules and periarteriolar lymphatic 
      sheath regions. Aroclor produced effects similar to those seen in the highest 
      mixture group. In summary, this study demonstrates that exposure to the 
      reconstituted mixture at 5 mg/kg bw produced growth suppression, changes in organ 
      weights, and biochemical and histopathological changes in liver, thyroid, and 
      spleen. This study also demonstrated that the blood level in rats given the 
      5-mg/kg dose, where most of the effects were observed, is 100-fold higher than 
      the blood level in the 0.05-mg/kg group, which is comparable to that found in 
      humans living in the Canadian Arctic region.
FAU - Chu, Ih
AU  - Chu I
AD  - Environmental and Occupational Toxicology Division, Healthy Environments and 
      Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada. 
      Ih_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 - Wade, Mike G
AU  - Wade MG
FAU - Yagminas, Al
AU  - Yagminas A
FAU - Li, Nanqin
AU  - Li N
FAU - Moir, David
AU  - Moir D
FAU - El Abbas, Lubna
AU  - El Abbas L
FAU - Hakansson, Helen
AU  - Hakansson H
FAU - Gill, Santokh
AU  - Gill S
FAU - Mueller, Rudi
AU  - Mueller R
FAU - Pulido, Olga
AU  - Pulido O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Toxicol Environ Health A
JT  - Journal of toxicology and environmental health. Part A
JID - 100960995
RN  - 0 (Environmental Pollutants)
RN  - 0 (Hydrocarbons, Chlorinated)
RN  - 0 (Methylmercury Compounds)
RN  - 0 (Retinoids)
RN  - 0 (Thyroid Hormones)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
SB  - IM
MH  - Animals
MH  - Arctic Regions
MH  - Aryl Hydrocarbon Hydroxylases/metabolism
MH  - Canada
MH  - Cholesterol/blood
MH  - Environmental Pollutants/blood/pharmacokinetics/*toxicity
MH  - Female
MH  - Humans
MH  - Hydrocarbons, Chlorinated/blood/pharmacokinetics/*toxicity
MH  - Kidney/drug effects/growth & development
MH  - Lactation
MH  - Liver/drug effects/growth & development/metabolism/pathology
MH  - Male
MH  - *Maternal-Fetal Exchange
MH  - Methylmercury Compounds/blood/pharmacokinetics/*toxicity
MH  - Organ Size/drug effects
MH  - Ovary/drug effects/growth & development
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Retinoids/metabolism
MH  - Spleen/drug effects/growth & development/pathology
MH  - Thymus Gland/drug effects/growth & development
MH  - Thyroid Gland/drug effects/pathology
MH  - Thyroid Hormones/blood
EDAT- 2007/12/18 09:00
MHDA- 2008/01/04 09:00
CRDT- 2007/12/18 09:00
PHST- 2007/12/18 09:00 [pubmed]
PHST- 2008/01/04 09:00 [medline]
PHST- 2007/12/18 09:00 [entrez]
AID - 788580549 [pii]
AID - 10.1080/15287390701612811 [doi]
PST - ppublish
SO  - J Toxicol Environ Health A. 2008;71(2):93-108. doi: 10.1080/15287390701612811.