Upper respiratory tract uptake of naphthalene

John B. Morris, Alan R Buckpitt

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Naphthalene is a nasal toxicant and carcinogen in the rat. Upper respiratory tract (URT) uptake of naphthalene was measured in the male and female F344 rat at exposure concentrations of 1, 4, 10, or 30 ppm at inspiratory flow rates of 150 or 300 ml/min. To assess the potential importance of nasal cytochrome P450 (CYP) metabolism, groups of rats were pretreated with the CYP inhibitor 5-phenyl-1-pentyne (PP) (100 mg/ kg, ip). In vitro metabolism of naphthalene was similar in nasal tissues from both genders and was reduced by 80% by the inhibitor. URT uptake in female rats was concentration dependent with uptake efficiencies (flow 150 ml/min) of 56, 40, 34, and 28% being observed at inspired concentrations of 1, 4, 10, and 30 ppm, respectively. A similar effect was observed in male rats (flow 150 ml/min) with uptake efficiencies of 57, 49, 37, and 36% being observed. Uptake was more efficient in the male than female rat, likely due to their larger size (226 vs. 144 g). Uptake of naphthalene was significantly reduced by inhibitor pretreatment with the effect being greater at the lower inspired concentrations. Specifically, in pretreated female rats (150 ml/min), URT uptake averaged 25, 29, and 26% at inspired concentrations of 4, 10, and 30 ppm, respectively. Thus, the concentration dependence of uptake was virtually abolished by PP pretreatment. These results provide evidence that nasal CYP metabolism of naphthalene contributes to URT scrubbing of this vapor and is also involved in the concentration dependence of uptake that is observed.

Original languageEnglish (US)
Pages (from-to)383-391
Number of pages9
JournalToxicological Sciences
Volume111
Issue number2
DOIs
StatePublished - 2009

Fingerprint

Respiratory System
Rats
Nose
Cytochrome P-450 Enzyme System
Metabolism
Inbred F344 Rats
Carcinogens
naphthalene
Vapors
Flow rate
Tissue

Keywords

  • Inhalation dosimetry
  • Naphthalene
  • Nose
  • Upper respiratory tract

ASJC Scopus subject areas

  • Toxicology

Cite this

Upper respiratory tract uptake of naphthalene. / Morris, John B.; Buckpitt, Alan R.

In: Toxicological Sciences, Vol. 111, No. 2, 2009, p. 383-391.

Research output: Contribution to journalArticle

Morris, John B. ; Buckpitt, Alan R. / Upper respiratory tract uptake of naphthalene. In: Toxicological Sciences. 2009 ; Vol. 111, No. 2. pp. 383-391.
@article{8bf9404ddae041c688dc43ec1e83cbc1,
title = "Upper respiratory tract uptake of naphthalene",
abstract = "Naphthalene is a nasal toxicant and carcinogen in the rat. Upper respiratory tract (URT) uptake of naphthalene was measured in the male and female F344 rat at exposure concentrations of 1, 4, 10, or 30 ppm at inspiratory flow rates of 150 or 300 ml/min. To assess the potential importance of nasal cytochrome P450 (CYP) metabolism, groups of rats were pretreated with the CYP inhibitor 5-phenyl-1-pentyne (PP) (100 mg/ kg, ip). In vitro metabolism of naphthalene was similar in nasal tissues from both genders and was reduced by 80{\%} by the inhibitor. URT uptake in female rats was concentration dependent with uptake efficiencies (flow 150 ml/min) of 56, 40, 34, and 28{\%} being observed at inspired concentrations of 1, 4, 10, and 30 ppm, respectively. A similar effect was observed in male rats (flow 150 ml/min) with uptake efficiencies of 57, 49, 37, and 36{\%} being observed. Uptake was more efficient in the male than female rat, likely due to their larger size (226 vs. 144 g). Uptake of naphthalene was significantly reduced by inhibitor pretreatment with the effect being greater at the lower inspired concentrations. Specifically, in pretreated female rats (150 ml/min), URT uptake averaged 25, 29, and 26{\%} at inspired concentrations of 4, 10, and 30 ppm, respectively. Thus, the concentration dependence of uptake was virtually abolished by PP pretreatment. These results provide evidence that nasal CYP metabolism of naphthalene contributes to URT scrubbing of this vapor and is also involved in the concentration dependence of uptake that is observed.",
keywords = "Inhalation dosimetry, Naphthalene, Nose, Upper respiratory tract",
author = "Morris, {John B.} and Buckpitt, {Alan R}",
year = "2009",
doi = "10.1093/toxsci/kfp138",
language = "English (US)",
volume = "111",
pages = "383--391",
journal = "Toxicological Sciences",
issn = "1096-6080",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Upper respiratory tract uptake of naphthalene

AU - Morris, John B.

AU - Buckpitt, Alan R

PY - 2009

Y1 - 2009

N2 - Naphthalene is a nasal toxicant and carcinogen in the rat. Upper respiratory tract (URT) uptake of naphthalene was measured in the male and female F344 rat at exposure concentrations of 1, 4, 10, or 30 ppm at inspiratory flow rates of 150 or 300 ml/min. To assess the potential importance of nasal cytochrome P450 (CYP) metabolism, groups of rats were pretreated with the CYP inhibitor 5-phenyl-1-pentyne (PP) (100 mg/ kg, ip). In vitro metabolism of naphthalene was similar in nasal tissues from both genders and was reduced by 80% by the inhibitor. URT uptake in female rats was concentration dependent with uptake efficiencies (flow 150 ml/min) of 56, 40, 34, and 28% being observed at inspired concentrations of 1, 4, 10, and 30 ppm, respectively. A similar effect was observed in male rats (flow 150 ml/min) with uptake efficiencies of 57, 49, 37, and 36% being observed. Uptake was more efficient in the male than female rat, likely due to their larger size (226 vs. 144 g). Uptake of naphthalene was significantly reduced by inhibitor pretreatment with the effect being greater at the lower inspired concentrations. Specifically, in pretreated female rats (150 ml/min), URT uptake averaged 25, 29, and 26% at inspired concentrations of 4, 10, and 30 ppm, respectively. Thus, the concentration dependence of uptake was virtually abolished by PP pretreatment. These results provide evidence that nasal CYP metabolism of naphthalene contributes to URT scrubbing of this vapor and is also involved in the concentration dependence of uptake that is observed.

AB - Naphthalene is a nasal toxicant and carcinogen in the rat. Upper respiratory tract (URT) uptake of naphthalene was measured in the male and female F344 rat at exposure concentrations of 1, 4, 10, or 30 ppm at inspiratory flow rates of 150 or 300 ml/min. To assess the potential importance of nasal cytochrome P450 (CYP) metabolism, groups of rats were pretreated with the CYP inhibitor 5-phenyl-1-pentyne (PP) (100 mg/ kg, ip). In vitro metabolism of naphthalene was similar in nasal tissues from both genders and was reduced by 80% by the inhibitor. URT uptake in female rats was concentration dependent with uptake efficiencies (flow 150 ml/min) of 56, 40, 34, and 28% being observed at inspired concentrations of 1, 4, 10, and 30 ppm, respectively. A similar effect was observed in male rats (flow 150 ml/min) with uptake efficiencies of 57, 49, 37, and 36% being observed. Uptake was more efficient in the male than female rat, likely due to their larger size (226 vs. 144 g). Uptake of naphthalene was significantly reduced by inhibitor pretreatment with the effect being greater at the lower inspired concentrations. Specifically, in pretreated female rats (150 ml/min), URT uptake averaged 25, 29, and 26% at inspired concentrations of 4, 10, and 30 ppm, respectively. Thus, the concentration dependence of uptake was virtually abolished by PP pretreatment. These results provide evidence that nasal CYP metabolism of naphthalene contributes to URT scrubbing of this vapor and is also involved in the concentration dependence of uptake that is observed.

KW - Inhalation dosimetry

KW - Naphthalene

KW - Nose

KW - Upper respiratory tract

UR - http://www.scopus.com/inward/record.url?scp=70349297243&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349297243&partnerID=8YFLogxK

U2 - 10.1093/toxsci/kfp138

DO - 10.1093/toxsci/kfp138

M3 - Article

C2 - 19648534

AN - SCOPUS:70349297243

VL - 111

SP - 383

EP - 391

JO - Toxicological Sciences

JF - Toxicological Sciences

SN - 1096-6080

IS - 2

ER -