Evaluation of the genotoxicity potential and chronic inhalation toxicity of 1,1-dichloro-1-fluoroethane (HCFC-141 b)
Identifieur interne : 000802 ( Istex/Corpus ); précédent : 000801; suivant : 000803Evaluation of the genotoxicity potential and chronic inhalation toxicity of 1,1-dichloro-1-fluoroethane (HCFC-141 b)
Auteurs : R.-J. Millischer ; C. G. De Rooij ; G. M. Rush ; C. H. Farr ; R. Ben-Dyke ; C. J. Hardy ; D. J. Lewis ; G. Hodson-WalkerSource :
- Food and Chemical Toxicology [ 0278-6915 ] ; 1995.
English descriptors
- Teeft :
- Aberrant cell frequencies, Aberrant cells, Aberration, Alternative fluorocarbon toxicity testing, American college, Ames test, Annual meeting, Assay, Atochem, Autopsy examination, Benign, Benign testicular, Benign tumours, Blood samples, Body weight, Body weight gain, Bone marrow, Cadmium workers, Cell tumours, Chemical safety, Chromosome, Chromosome aberration, Chromosome aberration assay, Chronic toxicity, Clinical signs, Control group, Control groups, Ecetoc, Environmental mutagen society, Epigenetic mechanism, Escherichia coli, Exposure level, Exposure levels, Exposure period, Female rats, Food intake, Full rotation, Genetic toxicity, Genotoxicity, Genotoxicity data, Genotoxicity studies, High exposure group, High exposure level, Human lymphocytes, Hygiene association, Incidence, Industrial medicine, Inhalation, Inhalation study, Intergroup differences, International agency, International programme, Interstitial cell tumours, Intricate parts, Late onset, Leydig, Leydig cell, Leydig cell adenomas, Leydig cell tumors, Leydig cell tumours, Life science research, Macroscopic, Male rats, Metabolic activation, Metabolism, Micronucleus, Micronucleus test, Microscopic pathology examinations, Mouse bone marrow micronucleus assay, Nasal turbinates, Negative control values, Negative results, Normochromatic erythrocytes, Ocular abnormalities, Plasma samples, Polychromatic erythrocytes, Positive control, Positive results, Present study, Rat, Risk factors, Salmonella typhimurium, Sentinel group, Significant increases, Statistical analysis, Statistical significance, Sterile glass bottles, Test concentrations, Test material, Tester strains, Testicular, Testicular masses, Testing program, Testis, Toxicity, Toxicological significance, Toxicology, Toxicology centre, Tumour, Typhimurium, Unpublished report, Vapour, Vapour phase, Weight loss, Wide variety.
Abstract
Abstract: A battery of in vitro and in vivo tests were conducted on HCFC-141b as a vapour. Bacterial gene mutation assays with Escherichia coli and Salmonella typhimurium were negative in all tester strains. In vitro chromosomal aberration assays were positive on CHO cells but negative on human lymphocytes. Moreover, HCFC-141b was negative in vivo in a mouse micronucleus inhalation assay. On the basis of these data and previously reported genotoxicity testing, HCFC-141b is considered non-genotoxic. Groups of 80 male and 80 female Sprague-Dawley rats were exposed, by inhalation (6 hr/day, 5 days/wk) to vapours of HCFC-141b for 104 wk at target concentrations of 0 (control), 1500, 5000 and 20,000 ppm (increased from 15,000 ppm after 17 wk of exposure). No exposure-related effects of toxicological significance were noted with respect to survival, clinical signs, ophthalmoscopy, haematology, clinical chemistry, urinalysis or organ weight analysis. Reduced food intake and body weight gain were noted in both sexes of the 15,000 ppm group during the first 16 wk; thereafter, body weight gains in all groups were similar although the intergroup differences in body weight remained evident. Reduced food intake persisted in both sexes through wk 52 and in females during the second year of exposure. Treatment-related effects on macroscopic pathology were confined to increased incidences of testicular masses and altered appearance. Microscopic pathology examinations confirmed the testes as the target organ with findings of increased incidences of benign interstitial cell tumours and hyperplasia at 5000 and 20,000 ppm. The no-observable-adverse-effect level (NOAEL) was 1500 ppm. The testicular changes at high exposure levels were considered to be due to a change of the senile hormonal imbalance in geriatric rats and of little significance for the assessment of human health effects.
Url:
DOI: 10.1016/0278-6915(95)00015-T
Links to Exploration step
ISTEX:E495573A51B2328B54686FE79353A55F7A036D27Le document en format XML
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Hodson-Walker</name><affiliation><mods:affiliation>Pharmaco:LSR, Eye, Suffolk, UK</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Food and Chemical Toxicology</title><title level="j" type="abbrev">FCT</title><idno type="ISSN">0278-6915</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1995">1995</date><biblScope unit="volume">33</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="491">491</biblScope><biblScope unit="page" to="500">500</biblScope></imprint><idno type="ISSN">0278-6915</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0278-6915</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Aberrant cell frequencies</term><term>Aberrant cells</term><term>Aberration</term><term>Alternative fluorocarbon toxicity testing</term><term>American college</term><term>Ames test</term><term>Annual meeting</term><term>Assay</term><term>Atochem</term><term>Autopsy examination</term><term>Benign</term><term>Benign testicular</term><term>Benign tumours</term><term>Blood samples</term><term>Body weight</term><term>Body weight gain</term><term>Bone marrow</term><term>Cadmium workers</term><term>Cell tumours</term><term>Chemical safety</term><term>Chromosome</term><term>Chromosome aberration</term><term>Chromosome aberration assay</term><term>Chronic toxicity</term><term>Clinical signs</term><term>Control group</term><term>Control groups</term><term>Ecetoc</term><term>Environmental mutagen society</term><term>Epigenetic mechanism</term><term>Escherichia coli</term><term>Exposure level</term><term>Exposure levels</term><term>Exposure period</term><term>Female rats</term><term>Food intake</term><term>Full rotation</term><term>Genetic toxicity</term><term>Genotoxicity</term><term>Genotoxicity data</term><term>Genotoxicity studies</term><term>High exposure group</term><term>High exposure level</term><term>Human lymphocytes</term><term>Hygiene association</term><term>Incidence</term><term>Industrial medicine</term><term>Inhalation</term><term>Inhalation study</term><term>Intergroup differences</term><term>International agency</term><term>International programme</term><term>Interstitial cell tumours</term><term>Intricate parts</term><term>Late onset</term><term>Leydig</term><term>Leydig cell</term><term>Leydig cell adenomas</term><term>Leydig cell tumors</term><term>Leydig cell tumours</term><term>Life science research</term><term>Macroscopic</term><term>Male rats</term><term>Metabolic activation</term><term>Metabolism</term><term>Micronucleus</term><term>Micronucleus test</term><term>Microscopic pathology examinations</term><term>Mouse bone marrow micronucleus assay</term><term>Nasal turbinates</term><term>Negative control values</term><term>Negative results</term><term>Normochromatic erythrocytes</term><term>Ocular abnormalities</term><term>Plasma samples</term><term>Polychromatic erythrocytes</term><term>Positive control</term><term>Positive results</term><term>Present study</term><term>Rat</term><term>Risk factors</term><term>Salmonella typhimurium</term><term>Sentinel group</term><term>Significant increases</term><term>Statistical analysis</term><term>Statistical significance</term><term>Sterile glass bottles</term><term>Test concentrations</term><term>Test material</term><term>Tester strains</term><term>Testicular</term><term>Testicular masses</term><term>Testing program</term><term>Testis</term><term>Toxicity</term><term>Toxicological significance</term><term>Toxicology</term><term>Toxicology centre</term><term>Tumour</term><term>Typhimurium</term><term>Unpublished report</term><term>Vapour</term><term>Vapour phase</term><term>Weight loss</term><term>Wide variety</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: A battery of in vitro and in vivo tests were conducted on HCFC-141b as a vapour. Bacterial gene mutation assays with Escherichia coli and Salmonella typhimurium were negative in all tester strains. In vitro chromosomal aberration assays were positive on CHO cells but negative on human lymphocytes. Moreover, HCFC-141b was negative in vivo in a mouse micronucleus inhalation assay. On the basis of these data and previously reported genotoxicity testing, HCFC-141b is considered non-genotoxic. Groups of 80 male and 80 female Sprague-Dawley rats were exposed, by inhalation (6 hr/day, 5 days/wk) to vapours of HCFC-141b for 104 wk at target concentrations of 0 (control), 1500, 5000 and 20,000 ppm (increased from 15,000 ppm after 17 wk of exposure). No exposure-related effects of toxicological significance were noted with respect to survival, clinical signs, ophthalmoscopy, haematology, clinical chemistry, urinalysis or organ weight analysis. Reduced food intake and body weight gain were noted in both sexes of the 15,000 ppm group during the first 16 wk; thereafter, body weight gains in all groups were similar although the intergroup differences in body weight remained evident. Reduced food intake persisted in both sexes through wk 52 and in females during the second year of exposure. Treatment-related effects on macroscopic pathology were confined to increased incidences of testicular masses and altered appearance. Microscopic pathology examinations confirmed the testes as the target organ with findings of increased incidences of benign interstitial cell tumours and hyperplasia at 5000 and 20,000 ppm. The no-observable-adverse-effect level (NOAEL) was 1500 ppm. The testicular changes at high exposure levels were considered to be due to a change of the senile hormonal imbalance in geriatric rats and of little significance for the assessment of human health effects.</div></front></TEI><istex><corpusName>elsevier</corpusName><keywords><teeft><json:string>tumour</json:string><json:string>toxicity</json:string><json:string>leydig</json:string><json:string>ecetoc</json:string><json:string>testis</json:string><json:string>leydig cell tumours</json:string><json:string>genotoxicity</json:string><json:string>assay</json:string><json:string>micronucleus</json:string><json:string>vapour</json:string><json:string>toxicology</json:string><json:string>testicular</json:string><json:string>atochem</json:string><json:string>chromosome</json:string><json:string>macroscopic</json:string><json:string>typhimurium</json:string><json:string>unpublished report</json:string><json:string>food intake</json:string><json:string>significant increases</json:string><json:string>inhalation</json:string><json:string>body weight gain</json:string><json:string>test material</json:string><json:string>benign</json:string><json:string>salmonella typhimurium</json:string><json:string>intergroup differences</json:string><json:string>body weight</json:string><json:string>chronic toxicity</json:string><json:string>life science research</json:string><json:string>test concentrations</json:string><json:string>microscopic pathology examinations</json:string><json:string>genotoxicity data</json:string><json:string>escherichia coli</json:string><json:string>leydig cell tumors</json:string><json:string>tester strains</json:string><json:string>alternative fluorocarbon toxicity testing</json:string><json:string>positive results</json:string><json:string>exposure level</json:string><json:string>toxicology centre</json:string><json:string>chemical safety</json:string><json:string>benign testicular</json:string><json:string>aberrant cell frequencies</json:string><json:string>negative results</json:string><json:string>testing program</json:string><json:string>high exposure level</json:string><json:string>ames test</json:string><json:string>rat</json:string><json:string>negative control values</json:string><json:string>clinical signs</json:string><json:string>inhalation study</json:string><json:string>vapour phase</json:string><json:string>metabolic activation</json:string><json:string>genetic toxicity</json:string><json:string>toxicological significance</json:string><json:string>exposure levels</json:string><json:string>female rats</json:string><json:string>sterile glass bottles</json:string><json:string>full rotation</json:string><json:string>chromosome aberration assay</json:string><json:string>international programme</json:string><json:string>positive control</json:string><json:string>chromosome aberration</json:string><json:string>mouse bone marrow micronucleus assay</json:string><json:string>blood samples</json:string><json:string>sentinel group</json:string><json:string>autopsy examination</json:string><json:string>risk factors</json:string><json:string>cell tumours</json:string><json:string>exposure period</json:string><json:string>ocular abnormalities</json:string><json:string>plasma samples</json:string><json:string>nasal turbinates</json:string><json:string>human lymphocytes</json:string><json:string>statistical analysis</json:string><json:string>intricate parts</json:string><json:string>normochromatic erythrocytes</json:string><json:string>genotoxicity studies</json:string><json:string>annual meeting</json:string><json:string>aberrant cells</json:string><json:string>male rats</json:string><json:string>control groups</json:string><json:string>control group</json:string><json:string>high exposure group</json:string><json:string>polychromatic erythrocytes</json:string><json:string>leydig cell</json:string><json:string>international agency</json:string><json:string>industrial medicine</json:string><json:string>benign tumours</json:string><json:string>statistical significance</json:string><json:string>hygiene association</json:string><json:string>micronucleus test</json:string><json:string>bone marrow</json:string><json:string>testicular masses</json:string><json:string>leydig cell adenomas</json:string><json:string>epigenetic mechanism</json:string><json:string>wide variety</json:string><json:string>interstitial cell tumours</json:string><json:string>late onset</json:string><json:string>present study</json:string><json:string>cadmium workers</json:string><json:string>american college</json:string><json:string>environmental mutagen society</json:string><json:string>weight loss</json:string><json:string>aberration</json:string><json:string>metabolism</json:string><json:string>incidence</json:string></teeft></keywords><author><json:item><name>R.-J. Millischer</name><affiliations><json:string>Elf Atochem S.A., 4 cours Michelet, Cedex 42, 92091 Paris La Défense, France</json:string></affiliations></json:item><json:item><name>C.G. de Rooij</name><affiliations><json:string>Solvay S.A., Brussels, Belgium</json:string></affiliations></json:item><json:item><name>G.M. Rush</name><affiliations><json:string>AlliedSignal Inc., Morristown, NJ 07962, USA</json:string></affiliations></json:item><json:item><name>C.H. Farr</name><affiliations><json:string>Elf Atochem N.A., King of Prussia, PA 19406, USA</json:string></affiliations></json:item><json:item><name>R. Ben-Dyke</name><affiliations><json:string>Ben-Dyke Associates Inc., Whitehouse Station, NJ 08889, USA</json:string></affiliations></json:item><json:item><name>C.J. Hardy</name><affiliations><json:string>Huntingdon Research Centre Ltd, Huntingdon, Cambridgeshire, UK</json:string></affiliations></json:item><json:item><name>D.J. Lewis</name><affiliations><json:string>Huntingdon Research Centre Ltd, Huntingdon, Cambridgeshire, UK</json:string></affiliations></json:item><json:item><name>G. Hodson-Walker</name><affiliations><json:string>Pharmaco:LSR, Eye, Suffolk, UK</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>AIHA : American Industrial Hygiene Association</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>CHO : Chinese hamster ovary</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>ECETOC : European Chemical Industry Ecology and Toxicology Centre</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>HPRT : hypoxanthine phosphoribosyltrans-ferase</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>IPCS : International Programme on Chemical Safety</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>LH : luteinizing hormone</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>NOAEL : noobservable-adverse-effect level</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PAFT : Program for Alternative Fluorocarbon Toxicity Testing</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PCE : polychromatic erythrocytes</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PNE : normochromatic erythrocytes</value></json:item></subject><arkIstex>ark:/67375/6H6-3MVWKGJS-9</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>Full-length article</json:string></originalGenre><abstract>Abstract: A battery of in vitro and in vivo tests were conducted on HCFC-141b as a vapour. Bacterial gene mutation assays with Escherichia coli and Salmonella typhimurium were negative in all tester strains. In vitro chromosomal aberration assays were positive on CHO cells but negative on human lymphocytes. Moreover, HCFC-141b was negative in vivo in a mouse micronucleus inhalation assay. On the basis of these data and previously reported genotoxicity testing, HCFC-141b is considered non-genotoxic. Groups of 80 male and 80 female Sprague-Dawley rats were exposed, by inhalation (6 hr/day, 5 days/wk) to vapours of HCFC-141b for 104 wk at target concentrations of 0 (control), 1500, 5000 and 20,000 ppm (increased from 15,000 ppm after 17 wk of exposure). No exposure-related effects of toxicological significance were noted with respect to survival, clinical signs, ophthalmoscopy, haematology, clinical chemistry, urinalysis or organ weight analysis. Reduced food intake and body weight gain were noted in both sexes of the 15,000 ppm group during the first 16 wk; thereafter, body weight gains in all groups were similar although the intergroup differences in body weight remained evident. Reduced food intake persisted in both sexes through wk 52 and in females during the second year of exposure. Treatment-related effects on macroscopic pathology were confined to increased incidences of testicular masses and altered appearance. Microscopic pathology examinations confirmed the testes as the target organ with findings of increased incidences of benign interstitial cell tumours and hyperplasia at 5000 and 20,000 ppm. The no-observable-adverse-effect level (NOAEL) was 1500 ppm. The testicular changes at high exposure levels were considered to be due to a change of the senile hormonal imbalance in geriatric rats and of little significance for the assessment of human health effects.</abstract><qualityIndicators><score>10</score><pdfWordCount>6698</pdfWordCount><pdfCharCount>41848</pdfCharCount><pdfVersion>1.2</pdfVersion><pdfPageCount>10</pdfPageCount><pdfPageSize>540 x 792 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>285</abstractWordCount><abstractCharCount>1898</abstractCharCount><keywordCount>10</keywordCount></qualityIndicators><title>Evaluation of the genotoxicity potential and chronic inhalation toxicity of 1,1-dichloro-1-fluoroethane (HCFC-141 b)</title><pmid><json:string>7797176</json:string></pmid><pii><json:string>0278-6915(95)00015-T</json:string></pii><genre><json:string>research-article</json:string></genre><serie><title>Testicular Cancer</title><language><json:string>unknown</json:string></language><pages><first>643</first><last>655</last></pages></serie><host><title>Food and Chemical Toxicology</title><language><json:string>unknown</json:string></language><publicationDate>1995</publicationDate><issn><json:string>0278-6915</json:string></issn><pii><json:string>S0278-6915(00)X0012-9</json:string></pii><volume>33</volume><issue>6</issue><pages><first>491</first><last>500</last></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>1992</json:string><json:string>5000</json:string><json:string>1500, 5000</json:string><json:string>1993</json:string><json:string>1995</json:string><json:string>1500</json:string></date><geogName></geogName><orgName><json:string>Good Laboratory Practice</json:string><json:string>Research on Cancer</json:string><json:string>Charles River Breeding Laboratories</json:string><json:string>Organisation for Economic Cooperation and Development</json:string><json:string>American Industrial Hygiene Association</json:string><json:string>Rhone Poulenc Chemicals Ltd</json:string><json:string>LaRoche Chemicals Inc.</json:string><json:string>United States Environmental Protection Agency</json:string><json:string>Ministry of International</json:string><json:string>International Agency</json:string><json:string>Daikin Industries Ltd</json:string><json:string>Environmental Mutagen Society, Norfolk, Virginia, USA</json:string><json:string>OECD</json:string><json:string>Huntingdon Research Centre Ltd, Huntingdon, Cambridgeshire, UK</json:string><json:string>AlliedSignal Inc.</json:string><json:string>Asahi Glass Co.</json:string><json:string>Ben-Dyke Associates Inc.</json:string><json:string>US EPA</json:string><json:string>International Congress</json:string></orgName><orgName_funder></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Brian Joyner</json:string><json:string>M. H. Debets</json:string><json:string>Stephen Magda</json:string><json:string>Toshihiko Kawano</json:string><json:string>Henry Trochimowicz</json:string><json:string>Derek Coombs</json:string><json:string>Joel Seckar</json:string><json:string>Gary Roy</json:string><json:string>Fumiaki Sato</json:string><json:string>Felix</json:string><json:string>J. F. Hardisty</json:string></persName><placeName><json:string>UK</json:string><json:string>US</json:string><json:string>Toxicity</json:string><json:string>Mutagenicity</json:string><json:string>Whitehouse Station</json:string><json:string>Brussels</json:string><json:string>Rome</json:string><json:string>Genotoxicity</json:string><json:string>Ireland</json:string><json:string>France</json:string><json:string>NJ</json:string><json:string>Morristown</json:string><json:string>Italy</json:string><json:string>Belgium</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>Henderson et al., 1970</json:string><json:string>Roberts et al., 1989</json:string><json:string>Harris and Anders (1991)</json:string><json:string>Armstrong and Kazantzis, 1983</json:string><json:string>J. Millischer et al.</json:string><json:string>Damjanov et al., 1979</json:string><json:string>Loughlin et al., 1980</json:string><json:string>B/ir, 1992</json:string><json:string>Roberts et al. 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Contributing companies include: Akzo Chemicals International B.V., AlliedSignal Inc., Asahi Glass Co. Ltd, Daikin Industries Ltd, E.I. DuPont de Nemours and Co. Inc., Elf Atochem N.A., Elf Atochem S.A., LaRoche Chemicals Inc., Rhone Poulenc Chemicals Ltd, Showa Denko K.K., and Solvay S.A.</note><note type="content">Section title: Research section</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Evaluation of the genotoxicity potential and chronic inhalation toxicity of 1,1-dichloro-1-fluoroethane (HCFC-141 b)</title><author xml:id="author-0000"><persName><forename type="first">R.-J.</forename><surname>Millischer</surname></persName><affiliation>Author for correspondence.</affiliation><affiliation>Elf Atochem S.A., 4 cours Michelet, Cedex 42, 92091 Paris La Défense, France</affiliation></author><author xml:id="author-0001"><persName><forename type="first">C.G.</forename><surname>de Rooij</surname></persName><affiliation>Solvay S.A., Brussels, Belgium</affiliation></author><author xml:id="author-0002"><persName><forename type="first">G.M.</forename><surname>Rush</surname></persName><affiliation>AlliedSignal Inc., Morristown, NJ 07962, USA</affiliation></author><author xml:id="author-0003"><persName><forename type="first">C.H.</forename><surname>Farr</surname></persName><affiliation>Elf Atochem N.A., King of Prussia, PA 19406, USA</affiliation></author><author xml:id="author-0004"><persName><forename type="first">R.</forename><surname>Ben-Dyke</surname></persName><affiliation>Ben-Dyke Associates Inc., Whitehouse Station, NJ 08889, USA</affiliation></author><author xml:id="author-0005"><persName><forename type="first">C.J.</forename><surname>Hardy</surname></persName><affiliation>Huntingdon Research Centre Ltd, Huntingdon, Cambridgeshire, UK</affiliation></author><author xml:id="author-0006"><persName><forename type="first">D.J.</forename><surname>Lewis</surname></persName><affiliation>Huntingdon Research Centre Ltd, Huntingdon, Cambridgeshire, UK</affiliation></author><author xml:id="author-0007"><persName><forename type="first">G.</forename><surname>Hodson-Walker</surname></persName><affiliation>Pharmaco:LSR, Eye, Suffolk, UK</affiliation></author><idno type="istex">E495573A51B2328B54686FE79353A55F7A036D27</idno><idno type="ark">ark:/67375/6H6-3MVWKGJS-9</idno><idno type="DOI">10.1016/0278-6915(95)00015-T</idno><idno type="PII">0278-6915(95)00015-T</idno></analytic><monogr><title level="j">Food and Chemical Toxicology</title><title level="j" type="abbrev">FCT</title><idno type="pISSN">0278-6915</idno><idno type="PII">S0278-6915(00)X0012-9</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1995"></date><biblScope unit="volume">33</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="491">491</biblScope><biblScope unit="page" to="500">500</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1995</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: A battery of in vitro and in vivo tests were conducted on HCFC-141b as a vapour. Bacterial gene mutation assays with Escherichia coli and Salmonella typhimurium were negative in all tester strains. In vitro chromosomal aberration assays were positive on CHO cells but negative on human lymphocytes. Moreover, HCFC-141b was negative in vivo in a mouse micronucleus inhalation assay. On the basis of these data and previously reported genotoxicity testing, HCFC-141b is considered non-genotoxic. Groups of 80 male and 80 female Sprague-Dawley rats were exposed, by inhalation (6 hr/day, 5 days/wk) to vapours of HCFC-141b for 104 wk at target concentrations of 0 (control), 1500, 5000 and 20,000 ppm (increased from 15,000 ppm after 17 wk of exposure). No exposure-related effects of toxicological significance were noted with respect to survival, clinical signs, ophthalmoscopy, haematology, clinical chemistry, urinalysis or organ weight analysis. Reduced food intake and body weight gain were noted in both sexes of the 15,000 ppm group during the first 16 wk; thereafter, body weight gains in all groups were similar although the intergroup differences in body weight remained evident. Reduced food intake persisted in both sexes through wk 52 and in females during the second year of exposure. Treatment-related effects on macroscopic pathology were confined to increased incidences of testicular masses and altered appearance. Microscopic pathology examinations confirmed the testes as the target organ with findings of increased incidences of benign interstitial cell tumours and hyperplasia at 5000 and 20,000 ppm. The no-observable-adverse-effect level (NOAEL) was 1500 ppm. The testicular changes at high exposure levels were considered to be due to a change of the senile hormonal imbalance in geriatric rats and of little significance for the assessment of human health effects.</p></abstract><textClass><keywords scheme="keyword"><list><head>Abbreviations</head><item><term>AIHA</term><term>American Industrial Hygiene Association</term></item><item><term>CHO</term><term>Chinese hamster ovary</term></item><item><term>ECETOC</term><term>European Chemical Industry Ecology and Toxicology Centre</term></item><item><term>HPRT</term><term>hypoxanthine phosphoribosyltrans-ferase</term></item><item><term>IPCS</term><term>International Programme on Chemical Safety</term></item><item><term>LH</term><term>luteinizing hormone</term></item><item><term>NOAEL</term><term>noobservable-adverse-effect level</term></item><item><term>PAFT</term><term>Program for Alternative Fluorocarbon Toxicity Testing</term></item><item><term>PCE</term><term>polychromatic erythrocytes</term></item><item><term>PNE</term><term>normochromatic erythrocytes</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1995">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-3MVWKGJS-9/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla"><item-info><jid>FCT</jid><aid>9500015T</aid><ce:pii>0278-6915(95)00015-T</ce:pii><ce:doi>10.1016/0278-6915(95)00015-T</ce:doi><ce:copyright type="unknown" year="1995"></ce:copyright></item-info><head><ce:article-footnote><ce:label>☆</ce:label><ce:note-para>The genotoxicity data have been presented in part at the 24th Annual Meeting of The Environmental Mutagen Society, Norfolk, Virginia, USA, April 1993 and The 6th International Congress of Toxicology, Rome, Italy, June 1992.</ce:note-para></ce:article-footnote><ce:article-footnote><ce:label>☆☆</ce:label><ce:note-para>These studies were sponsored by The Program For Alternative Fluorocarbon Toxicity Testing (PAFT). Contributing companies include: Akzo Chemicals International B.V., AlliedSignal Inc., Asahi Glass Co. Ltd, Daikin Industries Ltd, E.I. DuPont de Nemours and Co. Inc., Elf Atochem N.A., Elf Atochem S.A., LaRoche Chemicals Inc., Rhone Poulenc Chemicals Ltd, Showa Denko K.K., and Solvay S.A.</ce:note-para></ce:article-footnote><ce:dochead><ce:textfn>Research section</ce:textfn></ce:dochead><ce:title>Evaluation of the genotoxicity potential and chronic inhalation toxicity of 1,1-dichloro-1-fluoroethane (HCFC-141 b)</ce:title><ce:author-group><ce:author><ce:given-name>R.-J.</ce:given-name><ce:surname>Millischer</ce:surname><ce:cross-ref refid="COR1"><ce:sup>‡</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF1"><ce:sup>1</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>C.G.</ce:given-name><ce:surname>de Rooij</ce:surname><ce:cross-ref refid="AFF2"><ce:sup>2</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>G.M.</ce:given-name><ce:surname>Rush</ce:surname><ce:cross-ref refid="AFF3"><ce:sup>3</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>C.H.</ce:given-name><ce:surname>Farr</ce:surname><ce:cross-ref refid="AFF4"><ce:sup>4a</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>R.</ce:given-name><ce:surname>Ben-Dyke</ce:surname><ce:cross-ref refid="AFF5"><ce:sup>4b</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>C.J.</ce:given-name><ce:surname>Hardy</ce:surname><ce:cross-ref refid="AFF6"><ce:sup>5</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>D.J.</ce:given-name><ce:surname>Lewis</ce:surname><ce:cross-ref refid="AFF6"><ce:sup>5</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>G.</ce:given-name><ce:surname>Hodson-Walker</ce:surname><ce:cross-ref refid="AFF7"><ce:sup>6</ce:sup></ce:cross-ref></ce:author><ce:affiliation id="AFF1"><ce:label>a</ce:label><ce:textfn>Elf Atochem S.A., 4 cours Michelet, Cedex 42, 92091 Paris La Défense, France</ce:textfn></ce:affiliation><ce:affiliation id="AFF2"><ce:label>b</ce:label><ce:textfn>Solvay S.A., Brussels, Belgium</ce:textfn></ce:affiliation><ce:affiliation id="AFF3"><ce:label>c</ce:label><ce:textfn>AlliedSignal Inc., Morristown, NJ 07962, USA</ce:textfn></ce:affiliation><ce:affiliation id="AFF4"><ce:label>d</ce:label><ce:textfn>Elf Atochem N.A., King of Prussia, PA 19406, USA</ce:textfn></ce:affiliation><ce:affiliation id="AFF5"><ce:label>e</ce:label><ce:textfn>Ben-Dyke Associates Inc., Whitehouse Station, NJ 08889, USA</ce:textfn></ce:affiliation><ce:affiliation id="AFF6"><ce:label>f</ce:label><ce:textfn>Huntingdon Research Centre Ltd, Huntingdon, Cambridgeshire, UK</ce:textfn></ce:affiliation><ce:affiliation id="AFF7"><ce:label>g</ce:label><ce:textfn>Pharmaco:LSR, Eye, Suffolk, UK</ce:textfn></ce:affiliation><ce:correspondence id="COR1"><ce:label>‡</ce:label><ce:text>Author for correspondence.</ce:text></ce:correspondence></ce:author-group><ce:date-accepted day="20" month="12" year="1994"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>A battery of <ce:italic>in vitro</ce:italic> and <ce:italic>in vivo</ce:italic> tests were conducted on HCFC-141b as a vapour. Bacterial gene mutation assays with <ce:italic>Escherichia coli</ce:italic> and <ce:italic>Salmonella typhimurium</ce:italic> were negative in all tester strains. <ce:italic>In vitro</ce:italic> chromosomal aberration assays were positive on CHO cells but negative on human lymphocytes. Moreover, HCFC-141b was negative <ce:italic>in vivo</ce:italic> in a mouse micronucleus inhalation assay. On the basis of these data and previously reported genotoxicity testing, HCFC-141b is considered non-genotoxic. Groups of 80 male and 80 female Sprague-Dawley rats were exposed, by inhalation (6 hr/day, 5 days/wk) to vapours of HCFC-141b for 104 wk at target concentrations of 0 (control), 1500, 5000 and 20,000 ppm (increased from 15,000 ppm after 17 wk of exposure). No exposure-related effects of toxicological significance were noted with respect to survival, clinical signs, ophthalmoscopy, haematology, clinical chemistry, urinalysis or organ weight analysis. Reduced food intake and body weight gain were noted in both sexes of the 15,000 ppm group during the first 16 wk; thereafter, body weight gains in all groups were similar although the intergroup differences in body weight remained evident. Reduced food intake persisted in both sexes through wk 52 and in females during the second year of exposure. Treatment-related effects on macroscopic pathology were confined to increased incidences of testicular masses and altered appearance. Microscopic pathology examinations confirmed the testes as the target organ with findings of increased incidences of benign interstitial cell tumours and hyperplasia at 5000 and 20,000 ppm. The no-observable-adverse-effect level (NOAEL) was 1500 ppm. The testicular changes at high exposure levels were considered to be due to a change of the senile hormonal imbalance in geriatric rats and of little significance for the assessment of human health effects.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords class="abr"><ce:section-title>Abbreviations</ce:section-title><ce:keyword><ce:text>AIHA</ce:text><ce:keyword><ce:text>American Industrial Hygiene Association</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>CHO</ce:text><ce:keyword><ce:text>Chinese hamster ovary</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>ECETOC</ce:text><ce:keyword><ce:text>European Chemical Industry Ecology and Toxicology Centre</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>HPRT</ce:text><ce:keyword><ce:text>hypoxanthine phosphoribosyltrans-ferase</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>IPCS</ce:text><ce:keyword><ce:text>International Programme on Chemical Safety</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>LH</ce:text><ce:keyword><ce:text>luteinizing hormone</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>NOAEL</ce:text><ce:keyword><ce:text>noobservable-adverse-effect level</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>PAFT</ce:text><ce:keyword><ce:text>Program for Alternative Fluorocarbon Toxicity Testing</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>PCE</ce:text><ce:keyword><ce:text>polychromatic erythrocytes</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>PNE</ce:text><ce:keyword><ce:text>normochromatic erythrocytes</ce:text></ce:keyword></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Evaluation of the genotoxicity potential and chronic inhalation toxicity of 1,1-dichloro-1-fluoroethane (HCFC-141 b)</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Evaluation of the genotoxicity potential and chronic inhalation toxicity of 1,1-dichloro-1-fluoroethane (HCFC-141 b)</title></titleInfo><name type="personal"><namePart type="given">R.-J.</namePart><namePart type="family">Millischer</namePart><affiliation>Elf Atochem S.A., 4 cours Michelet, Cedex 42, 92091 Paris La Défense, France</affiliation><description>Author for correspondence.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C.G.</namePart><namePart type="family">de Rooij</namePart><affiliation>Solvay S.A., Brussels, Belgium</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">G.M.</namePart><namePart type="family">Rush</namePart><affiliation>AlliedSignal Inc., Morristown, NJ 07962, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C.H.</namePart><namePart type="family">Farr</namePart><affiliation>Elf Atochem N.A., King of Prussia, PA 19406, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R.</namePart><namePart type="family">Ben-Dyke</namePart><affiliation>Ben-Dyke Associates Inc., Whitehouse Station, NJ 08889, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C.J.</namePart><namePart type="family">Hardy</namePart><affiliation>Huntingdon Research Centre Ltd, Huntingdon, Cambridgeshire, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">D.J.</namePart><namePart type="family">Lewis</namePart><affiliation>Huntingdon Research Centre Ltd, Huntingdon, Cambridgeshire, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">G.</namePart><namePart type="family">Hodson-Walker</namePart><affiliation>Pharmaco:LSR, Eye, Suffolk, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1995</dateIssued><copyrightDate encoding="w3cdtf">1995</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">Abstract: A battery of in vitro and in vivo tests were conducted on HCFC-141b as a vapour. Bacterial gene mutation assays with Escherichia coli and Salmonella typhimurium were negative in all tester strains. In vitro chromosomal aberration assays were positive on CHO cells but negative on human lymphocytes. Moreover, HCFC-141b was negative in vivo in a mouse micronucleus inhalation assay. On the basis of these data and previously reported genotoxicity testing, HCFC-141b is considered non-genotoxic. Groups of 80 male and 80 female Sprague-Dawley rats were exposed, by inhalation (6 hr/day, 5 days/wk) to vapours of HCFC-141b for 104 wk at target concentrations of 0 (control), 1500, 5000 and 20,000 ppm (increased from 15,000 ppm after 17 wk of exposure). No exposure-related effects of toxicological significance were noted with respect to survival, clinical signs, ophthalmoscopy, haematology, clinical chemistry, urinalysis or organ weight analysis. Reduced food intake and body weight gain were noted in both sexes of the 15,000 ppm group during the first 16 wk; thereafter, body weight gains in all groups were similar although the intergroup differences in body weight remained evident. Reduced food intake persisted in both sexes through wk 52 and in females during the second year of exposure. Treatment-related effects on macroscopic pathology were confined to increased incidences of testicular masses and altered appearance. Microscopic pathology examinations confirmed the testes as the target organ with findings of increased incidences of benign interstitial cell tumours and hyperplasia at 5000 and 20,000 ppm. The no-observable-adverse-effect level (NOAEL) was 1500 ppm. The testicular changes at high exposure levels were considered to be due to a change of the senile hormonal imbalance in geriatric rats and of little significance for the assessment of human health effects.</abstract><note>The genotoxicity data have been presented in part at the 24th Annual Meeting of The Environmental Mutagen Society, Norfolk, Virginia, USA, April 1993 and The 6th International Congress of Toxicology, Rome, Italy, June 1992.</note><note>These studies were sponsored by The Program For Alternative Fluorocarbon Toxicity Testing (PAFT). Contributing companies include: Akzo Chemicals International B.V., AlliedSignal Inc., Asahi Glass Co. Ltd, Daikin Industries Ltd, E.I. DuPont de Nemours and Co. Inc., Elf Atochem N.A., Elf Atochem S.A., LaRoche Chemicals Inc., Rhone Poulenc Chemicals Ltd, Showa Denko K.K., and Solvay S.A.</note><note type="content">Section title: Research section</note><subject><genre>Abbreviations</genre><topic>AIHA : American Industrial Hygiene Association</topic><topic>CHO : Chinese hamster ovary</topic><topic>ECETOC : European Chemical Industry Ecology and Toxicology Centre</topic><topic>HPRT : hypoxanthine phosphoribosyltrans-ferase</topic><topic>IPCS : International Programme on Chemical Safety</topic><topic>LH : luteinizing hormone</topic><topic>NOAEL : noobservable-adverse-effect level</topic><topic>PAFT : Program for Alternative Fluorocarbon Toxicity Testing</topic><topic>PCE : polychromatic erythrocytes</topic><topic>PNE : normochromatic erythrocytes</topic></subject><relatedItem type="host"><titleInfo><title>Food and Chemical Toxicology</title></titleInfo><titleInfo type="abbreviated"><title>FCT</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1995</dateIssued></originInfo><identifier type="ISSN">0278-6915</identifier><identifier type="PII">S0278-6915(00)X0012-9</identifier><part><date>1995</date><detail type="volume"><number>33</number><caption>vol.</caption></detail><detail type="issue"><number>6</number><caption>no.</caption></detail><extent unit="issue-pages"><start>433</start><end>543</end></extent><extent unit="pages"><start>491</start><end>500</end></extent></part></relatedItem><identifier type="istex">E495573A51B2328B54686FE79353A55F7A036D27</identifier><identifier type="ark">ark:/67375/6H6-3MVWKGJS-9</identifier><identifier type="DOI">10.1016/0278-6915(95)00015-T</identifier><identifier type="PII">0278-6915(95)00015-T</identifier><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</recordContentSource></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-3MVWKGJS-9/record.json</uri></json:item></metadata></istex></record>Pour manipuler ce document sous Unix (Dilib)
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