Frank Bringezu - Academia.edu (original) (raw)
Papers by Frank Bringezu
Langmuir, 2001
... T. Pfohl, JH Kim, M. Yasa, HP Miller, GCL Wong, # F. Bringezu, § Z. Wen, L. Wilson,... more ... T. Pfohl, JH Kim, M. Yasa, HP Miller, GCL Wong, # F. Bringezu, § Z. Wen, L. Wilson, MW Kim, Y. Li, and CR Safinya* . ... A micromanipulation/microinjection system was used to fill and control the composition of a solution in a single lithographic microchannel. ...
Mutagenesis
Genotoxicity testing is an important part of standard safety testing strategies. Animal studies h... more Genotoxicity testing is an important part of standard safety testing strategies. Animal studies have always been a key component, either as a mandatory part of the regulatory test battery, or to follow-up questionable in vitro findings. The strengths and weaknesses of in vivo assays is a continuous matter of debate, including their capacity to predict (human) carcinogenicity. We have therefore analysed the sensitivity of five routinely used in vivo tests to determine, in addition to other aspects, which tests or combination of tests best identify 73 chemicals classified as IARC Group 1 and 2A carcinogens. The in vivo tests included the micronucleus (MN), unscheduled DNA synthesis (UDS), comet, Pig-a and transgenic rodent assays (TGR). The individual assays detect 74.2% (49/66, MN), 64.3% (9/14, UDS), 92.1% (35/38, comet), 82.4% (14/17, Pig-a) and 90.3% (28/31, TGR) of the probable and confirmed human carcinogens that were tested in these assays. Combining assays that cover different genotoxicity endpoints and multiple tissues, e.g. the bone marrow MN and the liver comet assays, increases the sensitivity further (to 94%). Correlations in terms of organ-specificity for these assays with human cancer target organs revealed only a limited correlation for the hematopoietic system but not for other organs. The data supports the use of the comet and TGR assays for detection of 'site-of-first-contact' genotoxicants, but these chemicals were generally also detected in assays that measure genotoxicity in tissues not directly exposed, e.g. liver and the hematopoietic system. In conclusion, our evaluation confirmed a high sensitivity of the five in vivo genotoxicity assays for prediction of human carcinogens, which can be further increased by combining assays. Moreover, the addition of the comet to the in vivo MN test would identify all DNA reactive human carcinogens. Importantly, integration of some of the study readouts into one experiment is an animal-saving alternative to performing separate experiments.
J Phys Chem B, 2001
ABSTRACT Diastereomers of 1-alkyl-2-acylglycerophosphocholines containing 2-methyl-branched fatty... more ABSTRACT Diastereomers of 1-alkyl-2-acylglycerophosphocholines containing 2-methyl-branched fatty acids at the C2 position of the glycerol are synthesized and separated, varying the acyl-chain systematically (m = 13, 15, 17). The physicochemical properties are studied in monolayers at the air−water interface by pressure area isotherms and grazing incidence X-ray diffraction (GIXD) measurements. The phase behavior is examined by a combination of differential scanning calorimetry and time-resolved X-ray diffraction experiments. In monolayers at the air−water interface, the introduction of a methyl-branch disturbs the lateral packing drastically, resulting in phases with strongly tilted chains and an undefined tilt azimuth. The monolayer structures of the diastereomeric fractions cannot be distinguished. The comparison of the lyotropic mesophases of the aqueous dispersions shows comparable structural parameters. The temperature dependency of the d spacings is nonlinear and is discussed in terms of a critical swelling of the bilayer. The present experiments show that the two racemic pairs of the resolved diastereomers (SS + RR/SR + RS) exhibit pronounced differences in the thermodynamic parameters of phase transitions both in two-dimensional (monolayers at the air/water interface) and three-dimensional systems (aqueous dispersions). However, the influence of the chiral carbon atoms is not sufficient to change the structure of the phases despite being able to affect their stability.
The Journal of Physical Chemistry B, May 1, 2007
This paper reports the first study on the interaction of the antimicrobial peptide dicynthaurin w... more This paper reports the first study on the interaction of the antimicrobial peptide dicynthaurin with 1,2-dipalmitoyl-glycerophosphatidyl-glycerol investigated in monolayers at the air-liquid interface. The influence of the peptide on the two-dimensional phase behavior of the negatively charged lipid was elucidated by means of pressure-area isotherm measurements, fluorescence microscopy, and grazing incidence X-ray diffraction measurements. The pure peptide forms a stable monolayer at the air-liquid interface up to 30 mN/m as shown for both the monomeric and the dimeric cynthaurins. The peptide lipid interaction was monitored in isotherm measurements showing a strong adsorption of the peptide and stabilization at the interface promoted by the lipid monolayer. The X-ray diffraction measurements in agreement with fluorescence microscopy studies showed that the peptide destabilizes the condensed chain lattice, leading to a complete fluidization of the condensed lipid phase on physiological buffer. The adsorption of the peptide to the negatively charged lipid monolayer and the fluidization of the condensed chain lattice suggest a direct link to the peptides' ability to expand the bacterial membrane that would be relevant for the in vivo mode of action.
Monolayers of chemically modified triple-chain phospholipids have been investigated at the air/wa... more Monolayers of chemically modified triple-chain phospholipids have been investigated at the air/water interface using pressure-area isotherms. The condensed phases of the lipids were characterized by grazing incidence X-ray diffraction (GIXD). Increasing chain length corresponds to a temperature effect, which was quantified for different lipids, depending on the head group structure using isotherm (two-dimensional systems) and DSC (three-dimensional systems) measurements. The combination of structure investigations revealed generic phase diagrams, which describe the phase behavior of multiple-chain lipids in two dimensions. For the 1-acyl-2-O-alkyl phospholipids, the generic phase diagram exhibits only L(2d), LS and LE phases while the exchange of the position of the branched acyl and the non-branched alkyl chains at the glycerol backbone leads to a much richer polymorphism (L(2h), L(2d), Ov, LS, S, tau, LE). Here we present the first experimental evidence of the unusual tau phase for multiple-chain lipid monolayers. This phase exhibits an undistorted in-plane lattice despite of tilted chains.
Biophysical Journal, 2003
The Journal of Physical Chemistry B, Jul 1, 2007
The interaction of the antimicrobial peptide dicynthaurin (ala) monomer with model membranes of z... more The interaction of the antimicrobial peptide dicynthaurin (ala) monomer with model membranes of zwitterionic and negatively charged lipids and mixtures thereof was studied by means of isothermal titration calorimetry (ITC), fluorescent leakage, and dynamic light scattering (DLS) measurements. For the ITC analysis, we have applied the surface partitioning equilibrium model which shows that the interaction is predominately driven by hydrophobic effects (Kb between 2 x 10(4) and 1 x 10(5) M(-1)). Under low salt conditions, the enhanced electrostatic interaction leads to larger peptide concentrations immediately above the vesicle surface, which initiates the insertion of the peptide into the bilayer more effectively. Fluorescent leakage measurements have shown a fast leakage of the fluorescent dye within seconds after peptide addition. The analysis of the leakage kinetics was performed in terms of an initial pore formation model (up to t = 1000 s) that takes the reversible surface aggregation of bound peptide monomers into account. From this analysis, a minimum aggregation number of n = 7 +/- 2 per pore is obtained.
Journal of High Resolution Chromatography, 1996
The Journal of Physical Chemistry, 1995
ABSTRACT
Il Nuovo Cimento D, 1994
ABSTRACT We present the results of thermodynamical and X-ray grazing incidence diffraction experi... more ABSTRACT We present the results of thermodynamical and X-ray grazing incidence diffraction experiments performed on Langmuir monolayers of ether lipids with hydrophilic spacers between the glycerol backbone and the phosphatidylcholine head group: DHPC, DH-E01-PC, and DH-E02-PC. As a spacer the oxy-ethylene group is used, which is a typical hydrophilic unit of non-ionic tensides. It turns out that the introduction of the hydrophilic spacers leads to a fluidization of the monolayer and reduces the tilt angle of the chains.
The Journal of Physical Chemistry B, 2007
This paper reports the first study on the interaction of the antimicrobial peptide dicynthaurin w... more This paper reports the first study on the interaction of the antimicrobial peptide dicynthaurin with 1,2-dipalmitoyl-glycerophosphatidyl-glycerol investigated in monolayers at the air-liquid interface. The influence of the peptide on the two-dimensional phase behavior of the negatively charged lipid was elucidated by means of pressure-area isotherm measurements, fluorescence microscopy, and grazing incidence X-ray diffraction measurements. The pure peptide forms a stable monolayer at the air-liquid interface up to 30 mN/m as shown for both the monomeric and the dimeric cynthaurins. The peptide lipid interaction was monitored in isotherm measurements showing a strong adsorption of the peptide and stabilization at the interface promoted by the lipid monolayer. The X-ray diffraction measurements in agreement with fluorescence microscopy studies showed that the peptide destabilizes the condensed chain lattice, leading to a complete fluidization of the condensed lipid phase on physiological buffer. The adsorption of the peptide to the negatively charged lipid monolayer and the fluidization of the condensed chain lattice suggest a direct link to the peptides' ability to expand the bacterial membrane that would be relevant for the in vivo mode of action.
The Journal of Physical Chemistry B, 1998
ABSTRACT Langmuir monolayers of fatty acids and their methyl and ethyl esters show different text... more ABSTRACT Langmuir monolayers of fatty acids and their methyl and ethyl esters show different textures. Stripe textures are observed in myristic acid monolayers. Continuous changes of molecular orientation occur in palmitic acid layers as well, although there are no stripe textures. In monolayers of fatty acid methyl and ethyl esters such continuous changes of orientation are not observed. The domains of methyl palmitate and ethyl palmitate are subdivided into segments of equal brightness. Grazing incidence synchrotron X-ray diffraction (GID) studies were performed to analyze the reason for this deviating behavior at the molecular level. The diffraction patterns of myristic acid suggest that the tilt azimuth is dispersed by about 5° around a nearest-neighbor direction. Such dispersions of the tilt azimuth occur in palmitic acid and methyl palmitate layers as well. The monolayers of these substances differ from those of myristic acid only in the degree of the dispersion.
Physical Chemistry Chemical Physics, 2000
ABSTRACT Glycerophosphoethanolamines with α-branched fatty acids were synthesized, varying the si... more ABSTRACT Glycerophosphoethanolamines with α-branched fatty acids were synthesized, varying the side-chain length. Differential scanning calorimetry and X-ray diffraction were applied to investigate the influence of the chemical alteration on the physico-chemical parameters and the structures formed in lipid–water dispersions. The results show that the introduction and stepwise elongation of side-chains decrease the transition temperature from gel to liquid-crystalline phases. The Tm values pass through a minimum and increase slightly on going to the triple-chain lipid. The change in the transition parameters is connected with a modified polymorphism. Short side-chains induce a tilt in the gel state and the elongation of the branch leads to interdigitated gel phases. With increasing side-chain length, non-lamellar liquid-crystalline phases are stabilized. For the long-branched derivative, an interdigitation of head-groups from adjacent bilayers is proposed.
Physica B: Condensed Matter, 1998
Physica B: Condensed Matter, 1998
Materials Science and Engineering: C, 1999
Langmuir, 2005
Monolayer properties such as phase behavior, collapse pressure, and surface viscosity are determi... more Monolayer properties such as phase behavior, collapse pressure, and surface viscosity are determined by monolayer composition. Learning how to control these properties through simple additives is important to understanding lung surfactant monolayers and to designing optimal replacement surfactants for treatment of disease. The properties of Infasurf, a replacement lung surfactant derived from calf lung lavage organic extract, can be modified in a controlled fashion by adding hexadecanol (HD). Grazing incidence X-ray diffraction shows that the HD preferentially interacts with dipalmitoylphosphatidylcholine (DPPC), the main phospholipid component of Infasurf, in the same way as in binary mixtures of DPPC and HD. HD intercalates between the DPPC chains, which leads to a tighter packing of the two-dimensional lattice and greater stability of the solid phase. This molecular reorganization triggers changes at the macroscopic scale, leading to a greatly increased solid-phase fraction at a given surface pressure and order of magnitude increases in the surface shear viscosity. However, the collapse pressure decreases, and, hence, the minimum surface tension of the film increases.
Langmuir, 2003
... KEP acknowledges University of California TRDRP Grant 7RT-0118. This article references 54 ot... more ... KEP acknowledges University of California TRDRP Grant 7RT-0118. This article references 54 other publications. (1) Teague, SV; Pinkerton, KE; Goldsmith, M.; Gebremichael, A.; Chang, S.; Jenkins, RA; Moneyhun, JH J. Inhalation Toxicol.1994, 6, 79−93. ...
Langmuir, 2001
... T. Pfohl, JH Kim, M. Yasa, HP Miller, GCL Wong, # F. Bringezu, § Z. Wen, L. Wilson,... more ... T. Pfohl, JH Kim, M. Yasa, HP Miller, GCL Wong, # F. Bringezu, § Z. Wen, L. Wilson, MW Kim, Y. Li, and CR Safinya* . ... A micromanipulation/microinjection system was used to fill and control the composition of a solution in a single lithographic microchannel. ...
Mutagenesis
Genotoxicity testing is an important part of standard safety testing strategies. Animal studies h... more Genotoxicity testing is an important part of standard safety testing strategies. Animal studies have always been a key component, either as a mandatory part of the regulatory test battery, or to follow-up questionable in vitro findings. The strengths and weaknesses of in vivo assays is a continuous matter of debate, including their capacity to predict (human) carcinogenicity. We have therefore analysed the sensitivity of five routinely used in vivo tests to determine, in addition to other aspects, which tests or combination of tests best identify 73 chemicals classified as IARC Group 1 and 2A carcinogens. The in vivo tests included the micronucleus (MN), unscheduled DNA synthesis (UDS), comet, Pig-a and transgenic rodent assays (TGR). The individual assays detect 74.2% (49/66, MN), 64.3% (9/14, UDS), 92.1% (35/38, comet), 82.4% (14/17, Pig-a) and 90.3% (28/31, TGR) of the probable and confirmed human carcinogens that were tested in these assays. Combining assays that cover different genotoxicity endpoints and multiple tissues, e.g. the bone marrow MN and the liver comet assays, increases the sensitivity further (to 94%). Correlations in terms of organ-specificity for these assays with human cancer target organs revealed only a limited correlation for the hematopoietic system but not for other organs. The data supports the use of the comet and TGR assays for detection of 'site-of-first-contact' genotoxicants, but these chemicals were generally also detected in assays that measure genotoxicity in tissues not directly exposed, e.g. liver and the hematopoietic system. In conclusion, our evaluation confirmed a high sensitivity of the five in vivo genotoxicity assays for prediction of human carcinogens, which can be further increased by combining assays. Moreover, the addition of the comet to the in vivo MN test would identify all DNA reactive human carcinogens. Importantly, integration of some of the study readouts into one experiment is an animal-saving alternative to performing separate experiments.
J Phys Chem B, 2001
ABSTRACT Diastereomers of 1-alkyl-2-acylglycerophosphocholines containing 2-methyl-branched fatty... more ABSTRACT Diastereomers of 1-alkyl-2-acylglycerophosphocholines containing 2-methyl-branched fatty acids at the C2 position of the glycerol are synthesized and separated, varying the acyl-chain systematically (m = 13, 15, 17). The physicochemical properties are studied in monolayers at the air−water interface by pressure area isotherms and grazing incidence X-ray diffraction (GIXD) measurements. The phase behavior is examined by a combination of differential scanning calorimetry and time-resolved X-ray diffraction experiments. In monolayers at the air−water interface, the introduction of a methyl-branch disturbs the lateral packing drastically, resulting in phases with strongly tilted chains and an undefined tilt azimuth. The monolayer structures of the diastereomeric fractions cannot be distinguished. The comparison of the lyotropic mesophases of the aqueous dispersions shows comparable structural parameters. The temperature dependency of the d spacings is nonlinear and is discussed in terms of a critical swelling of the bilayer. The present experiments show that the two racemic pairs of the resolved diastereomers (SS + RR/SR + RS) exhibit pronounced differences in the thermodynamic parameters of phase transitions both in two-dimensional (monolayers at the air/water interface) and three-dimensional systems (aqueous dispersions). However, the influence of the chiral carbon atoms is not sufficient to change the structure of the phases despite being able to affect their stability.
The Journal of Physical Chemistry B, May 1, 2007
This paper reports the first study on the interaction of the antimicrobial peptide dicynthaurin w... more This paper reports the first study on the interaction of the antimicrobial peptide dicynthaurin with 1,2-dipalmitoyl-glycerophosphatidyl-glycerol investigated in monolayers at the air-liquid interface. The influence of the peptide on the two-dimensional phase behavior of the negatively charged lipid was elucidated by means of pressure-area isotherm measurements, fluorescence microscopy, and grazing incidence X-ray diffraction measurements. The pure peptide forms a stable monolayer at the air-liquid interface up to 30 mN/m as shown for both the monomeric and the dimeric cynthaurins. The peptide lipid interaction was monitored in isotherm measurements showing a strong adsorption of the peptide and stabilization at the interface promoted by the lipid monolayer. The X-ray diffraction measurements in agreement with fluorescence microscopy studies showed that the peptide destabilizes the condensed chain lattice, leading to a complete fluidization of the condensed lipid phase on physiological buffer. The adsorption of the peptide to the negatively charged lipid monolayer and the fluidization of the condensed chain lattice suggest a direct link to the peptides' ability to expand the bacterial membrane that would be relevant for the in vivo mode of action.
Monolayers of chemically modified triple-chain phospholipids have been investigated at the air/wa... more Monolayers of chemically modified triple-chain phospholipids have been investigated at the air/water interface using pressure-area isotherms. The condensed phases of the lipids were characterized by grazing incidence X-ray diffraction (GIXD). Increasing chain length corresponds to a temperature effect, which was quantified for different lipids, depending on the head group structure using isotherm (two-dimensional systems) and DSC (three-dimensional systems) measurements. The combination of structure investigations revealed generic phase diagrams, which describe the phase behavior of multiple-chain lipids in two dimensions. For the 1-acyl-2-O-alkyl phospholipids, the generic phase diagram exhibits only L(2d), LS and LE phases while the exchange of the position of the branched acyl and the non-branched alkyl chains at the glycerol backbone leads to a much richer polymorphism (L(2h), L(2d), Ov, LS, S, tau, LE). Here we present the first experimental evidence of the unusual tau phase for multiple-chain lipid monolayers. This phase exhibits an undistorted in-plane lattice despite of tilted chains.
Biophysical Journal, 2003
The Journal of Physical Chemistry B, Jul 1, 2007
The interaction of the antimicrobial peptide dicynthaurin (ala) monomer with model membranes of z... more The interaction of the antimicrobial peptide dicynthaurin (ala) monomer with model membranes of zwitterionic and negatively charged lipids and mixtures thereof was studied by means of isothermal titration calorimetry (ITC), fluorescent leakage, and dynamic light scattering (DLS) measurements. For the ITC analysis, we have applied the surface partitioning equilibrium model which shows that the interaction is predominately driven by hydrophobic effects (Kb between 2 x 10(4) and 1 x 10(5) M(-1)). Under low salt conditions, the enhanced electrostatic interaction leads to larger peptide concentrations immediately above the vesicle surface, which initiates the insertion of the peptide into the bilayer more effectively. Fluorescent leakage measurements have shown a fast leakage of the fluorescent dye within seconds after peptide addition. The analysis of the leakage kinetics was performed in terms of an initial pore formation model (up to t = 1000 s) that takes the reversible surface aggregation of bound peptide monomers into account. From this analysis, a minimum aggregation number of n = 7 +/- 2 per pore is obtained.
Journal of High Resolution Chromatography, 1996
The Journal of Physical Chemistry, 1995
ABSTRACT
Il Nuovo Cimento D, 1994
ABSTRACT We present the results of thermodynamical and X-ray grazing incidence diffraction experi... more ABSTRACT We present the results of thermodynamical and X-ray grazing incidence diffraction experiments performed on Langmuir monolayers of ether lipids with hydrophilic spacers between the glycerol backbone and the phosphatidylcholine head group: DHPC, DH-E01-PC, and DH-E02-PC. As a spacer the oxy-ethylene group is used, which is a typical hydrophilic unit of non-ionic tensides. It turns out that the introduction of the hydrophilic spacers leads to a fluidization of the monolayer and reduces the tilt angle of the chains.
The Journal of Physical Chemistry B, 2007
This paper reports the first study on the interaction of the antimicrobial peptide dicynthaurin w... more This paper reports the first study on the interaction of the antimicrobial peptide dicynthaurin with 1,2-dipalmitoyl-glycerophosphatidyl-glycerol investigated in monolayers at the air-liquid interface. The influence of the peptide on the two-dimensional phase behavior of the negatively charged lipid was elucidated by means of pressure-area isotherm measurements, fluorescence microscopy, and grazing incidence X-ray diffraction measurements. The pure peptide forms a stable monolayer at the air-liquid interface up to 30 mN/m as shown for both the monomeric and the dimeric cynthaurins. The peptide lipid interaction was monitored in isotherm measurements showing a strong adsorption of the peptide and stabilization at the interface promoted by the lipid monolayer. The X-ray diffraction measurements in agreement with fluorescence microscopy studies showed that the peptide destabilizes the condensed chain lattice, leading to a complete fluidization of the condensed lipid phase on physiological buffer. The adsorption of the peptide to the negatively charged lipid monolayer and the fluidization of the condensed chain lattice suggest a direct link to the peptides' ability to expand the bacterial membrane that would be relevant for the in vivo mode of action.
The Journal of Physical Chemistry B, 1998
ABSTRACT Langmuir monolayers of fatty acids and their methyl and ethyl esters show different text... more ABSTRACT Langmuir monolayers of fatty acids and their methyl and ethyl esters show different textures. Stripe textures are observed in myristic acid monolayers. Continuous changes of molecular orientation occur in palmitic acid layers as well, although there are no stripe textures. In monolayers of fatty acid methyl and ethyl esters such continuous changes of orientation are not observed. The domains of methyl palmitate and ethyl palmitate are subdivided into segments of equal brightness. Grazing incidence synchrotron X-ray diffraction (GID) studies were performed to analyze the reason for this deviating behavior at the molecular level. The diffraction patterns of myristic acid suggest that the tilt azimuth is dispersed by about 5° around a nearest-neighbor direction. Such dispersions of the tilt azimuth occur in palmitic acid and methyl palmitate layers as well. The monolayers of these substances differ from those of myristic acid only in the degree of the dispersion.
Physical Chemistry Chemical Physics, 2000
ABSTRACT Glycerophosphoethanolamines with α-branched fatty acids were synthesized, varying the si... more ABSTRACT Glycerophosphoethanolamines with α-branched fatty acids were synthesized, varying the side-chain length. Differential scanning calorimetry and X-ray diffraction were applied to investigate the influence of the chemical alteration on the physico-chemical parameters and the structures formed in lipid–water dispersions. The results show that the introduction and stepwise elongation of side-chains decrease the transition temperature from gel to liquid-crystalline phases. The Tm values pass through a minimum and increase slightly on going to the triple-chain lipid. The change in the transition parameters is connected with a modified polymorphism. Short side-chains induce a tilt in the gel state and the elongation of the branch leads to interdigitated gel phases. With increasing side-chain length, non-lamellar liquid-crystalline phases are stabilized. For the long-branched derivative, an interdigitation of head-groups from adjacent bilayers is proposed.
Physica B: Condensed Matter, 1998
Physica B: Condensed Matter, 1998
Materials Science and Engineering: C, 1999
Langmuir, 2005
Monolayer properties such as phase behavior, collapse pressure, and surface viscosity are determi... more Monolayer properties such as phase behavior, collapse pressure, and surface viscosity are determined by monolayer composition. Learning how to control these properties through simple additives is important to understanding lung surfactant monolayers and to designing optimal replacement surfactants for treatment of disease. The properties of Infasurf, a replacement lung surfactant derived from calf lung lavage organic extract, can be modified in a controlled fashion by adding hexadecanol (HD). Grazing incidence X-ray diffraction shows that the HD preferentially interacts with dipalmitoylphosphatidylcholine (DPPC), the main phospholipid component of Infasurf, in the same way as in binary mixtures of DPPC and HD. HD intercalates between the DPPC chains, which leads to a tighter packing of the two-dimensional lattice and greater stability of the solid phase. This molecular reorganization triggers changes at the macroscopic scale, leading to a greatly increased solid-phase fraction at a given surface pressure and order of magnitude increases in the surface shear viscosity. However, the collapse pressure decreases, and, hence, the minimum surface tension of the film increases.
Langmuir, 2003
... KEP acknowledges University of California TRDRP Grant 7RT-0118. This article references 54 ot... more ... KEP acknowledges University of California TRDRP Grant 7RT-0118. This article references 54 other publications. (1) Teague, SV; Pinkerton, KE; Goldsmith, M.; Gebremichael, A.; Chang, S.; Jenkins, RA; Moneyhun, JH J. Inhalation Toxicol.1994, 6, 79−93. ...