PMID- 17123804
OWN - NLM
STAT- MEDLINE
DCOM- 20070222
LR  - 20191210
IS  - 0940-2993 (Print)
IS  - 0940-2993 (Linking)
VI  - 58
IP  - 4
DP  - 2007 Jan
TI  - Bioassay by intratracheal instillation for detection of lung toxicity due to fine 
      particles in F344 male rats.
PG  - 211-21
AB  - We have established and documented an in vivo bioassay for detection of hazards 
      with intratracheally instilled fine particles, which can be used for risk 
      assessment of toxicity of materials inhaled into deep lung tissue of humans 
      (Yokohira et al. Establishment of a bioassay system for detection of lung 
      toxicity due to fine particle instillation: sequential histopathological changes 
      with acute and subacute lung damage due to intratracheal instillation of quartz 
      in F344 male rats. J Toxicol Pathol 2005;18:13-8). For validation we here 
      examined toxicity of fine particles from quartz, hydrotalcite, potassium 
      octatitanate, palladium oxide and carbon black with this bioassay. A total of 
      108, 10-week-old F344/DuCrj male rats were randomly divided into 8 groups. Groups 
      1 to 5 underwent intratracheal instillation of the 5 test particles (4 mg/rat) 
      suspended in 0.2 ml vehicle (saline or 10% propylene glycol and 1% sodium 
      carboxymethyl cellulose in saline: PG-CMC) with a specially designed aerolizer, 
      and subgroups of 7 rats were killed on Days 1 and 28 thereafter. Groups 6 and 7 
      similarly were exposed to saline and PG-CMC, respectively, as vehicle controls, 
      while group 8 was maintained untreated. Using histopathological changes and 
      immunohistochemically assessed bromodeoxyuridine (BrdU) labeling indices, 
      inducible nitric oxide synthase (iNOS) and matrix metalloproteinase-3 (MMP-3) 
      levels as end points, the quartz treated group exhibited high toxicity, while the 
      values for the other particle-treated groups pointed to only slight effects. 
      Although additional efforts are needed to establish advantages and disadvantages 
      with our bioassay, models featuring intratracheal instillation clearly can be 
      useful for detection of acute or subacute lung toxicity due to inhaled fine 
      particles by using histopathological scoring and markers like BrdU and iNOS for 
      screening purposes in short-term studies.
FAU - Yokohira, Masanao
AU  - Yokohira M
AD  - Onco-Pathology, Department of Pathology and Host-Defense, Faculty of Medicine, 
      Kagawa University, Kita-gun, Kagawa 761-0793, Japan.
FAU - Takeuchi, Hijiri
AU  - Takeuchi H
FAU - Yamakawa, Keiko
AU  - Yamakawa K
FAU - Saoo, Kousuke
AU  - Saoo K
FAU - Matsuda, Yoko
AU  - Matsuda Y
FAU - Zeng, Yu
AU  - Zeng Y
FAU - Hosokawa, Kyoko
AU  - Hosokawa K
FAU - Imaida, Katsumi
AU  - Imaida K
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Validation Study
DEP - 20061122
PL  - Germany
TA  - Exp Toxicol Pathol
JT  - Experimental and toxicologic pathology : official journal of the Gesellschaft fur 
      Toxikologische Pathologie
JID - 9208920
RN  - 0 (Biomarkers)
RN  - 0 (Particulate Matter)
RN  - 0 (Soot)
RN  - 14808-60-7 (Quartz)
RN  - 17432CG1KU (hydrotalcite)
RN  - 59766-31-3 (potassium octatitanate)
RN  - 5QB0T2IUN0 (Aluminum Hydroxide)
RN  - 5TWQ1V240M (Palladium)
RN  - B30901Q32J (palladium oxide)
RN  - D1JT611TNE (Titanium)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - G34N38R2N1 (Bromodeoxyuridine)
RN  - NBZ3QY004S (Magnesium Hydroxide)
SB  - IM
MH  - Aluminum Hydroxide/administration & dosage/toxicity
MH  - Animals
MH  - Biological Assay/*methods
MH  - Biomarkers/analysis
MH  - Bromodeoxyuridine/metabolism
MH  - Immunohistochemistry
MH  - Lung Diseases/chemically induced/*diagnosis/pathology
MH  - Magnesium Hydroxide/administration & dosage/toxicity
MH  - Male
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Palladium/administration & dosage/toxicity
MH  - Particulate Matter/*administration & dosage/*adverse effects
MH  - Quartz/administration & dosage/toxicity
MH  - Rats
MH  - Rats, Inbred F344
MH  - Soot/administration & dosage/toxicity
MH  - Titanium/administration & dosage/toxicity
EDAT- 2006/11/25 09:00
MHDA- 2007/02/23 09:00
CRDT- 2006/11/25 09:00
PHST- 2006/06/08 00:00 [received]
PHST- 2006/10/05 00:00 [accepted]
PHST- 2006/11/25 09:00 [pubmed]
PHST- 2007/02/23 09:00 [medline]
PHST- 2006/11/25 09:00 [entrez]
AID - S0940-2993(06)00106-0 [pii]
AID - 10.1016/j.etp.2006.10.001 [doi]
PST - ppublish
SO  - Exp Toxicol Pathol. 2007 Jan;58(4):211-21. doi: 10.1016/j.etp.2006.10.001. Epub 
      2006 Nov 22.