Nitrogen pentoxide (PIM 283)

<HTML> <HEAD> <META HTTP-EQUIV="Content-Type" CONTENT="text/html; charset=iso-8859-1"> <TITLE>Nitrogen pentoxide (PIM 283)</TITLE> </HEAD> <BODY BGCOLOR="#FFFFFF"> <A HREF="http://www.inchem.org"><IMG SRC="../../inchemhead.jpg" WIDTH="630" HEIGHT="65" BORDER="0" ALT="IPCS INCHEM Home"></A><CENTER><H1>Nitrogen pentoxide</H1></CENTER> <CENTER><TABLE WIDTH=500> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER><A HREF="#PartTitle:1. NAME">1. NAME</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:1.1 Substance">1.1 Substance</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:1.2 Group">1.2 Group</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:1.3 Synonyms">1.3 Synonyms</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:1.4 Identification numbers">1.4 Identification numbers</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:1.4.1 CAS number">1.4.1 CAS number</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:1.4.2 Other numbers">1.4.2 Other numbers</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:1.5 Brand names, Trade names">1.5 Brand names, Trade names</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:1.6 Manufacturers, Importers">1.6 Manufacturers, Importers</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER><A HREF="#PartTitle:2. SUMMARY">2. SUMMARY</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:2.1 Main risks and target organs">2.1 Main risks and target organs</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:2.2 Summary of clinical effects">2.2 Summary of clinical effects</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:2.3 Diagnosis">2.3 Diagnosis</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:2.4 First-aid measures and management principles">2.4 First-aid measures and management principles</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER><A HREF="#PartTitle:3. PHYSICO-CHEMICAL PROPERTIES">3. PHYSICO-CHEMICAL PROPERTIES</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:3.1 Origin of the substance">3.1 Origin of the substance</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:3.2 Chemical structure">3.2 Chemical structure</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:3.3 Physical properties">3.3 Physical properties</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:3.3.1 Colour">3.3.1 Colour</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:3.3.2 State/form">3.3.2 State/form</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:3.3.3 Description">3.3.3 Description</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:3.4 Hazardous characteristics">3.4 Hazardous characteristics</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER><A HREF="#PartTitle:4. USES/CIRCUMSTANCES OF POISONING">4. USES/CIRCUMSTANCES OF POISONING</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:4.1 Uses">4.1 Uses</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:4.1.1 Uses">4.1.1 Uses</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:4.1.2 Description">4.1.2 Description</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:4.2 High risk circumstance of poisoning">4.2 High risk circumstance of poisoning</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:4.3 Occupationally exposed populations">4.3 Occupationally exposed populations</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER><A HREF="#PartTitle:5. ROUTES OF ENTRY">5. ROUTES OF ENTRY</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:5.1 Oral">5.1 Oral</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:5.2 Inhalation">5.2 Inhalation</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:5.3 Dermal">5.3 Dermal</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:5.4 Eye">5.4 Eye</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:5.5 Parenteral">5.5 Parenteral</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:5.6 Others">5.6 Others</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER><A HREF="#PartTitle:6. KINETICS">6. KINETICS</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:6.1 Absorption by route of exposure">6.1 Absorption by route of exposure</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:6.2 Distribution by route of exposure">6.2 Distribution by route of exposure</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:6.3 Biological half-life by route of exposure">6.3 Biological half-life by route of exposure</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:6.4 Metabolism">6.4 Metabolism</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:6.5 Elimination by route of exposure">6.5 Elimination by route of exposure</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER><A HREF="#PartTitle:7. TOXICOLOGY">7. TOXICOLOGY</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:7.1 Mode of Action">7.1 Mode of Action</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:7.2 Toxicity">7.2 Toxicity</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:7.2.1 Human data">7.2.1 Human data</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:7.2.1.1 Adults">7.2.1.1 Adults</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:7.2.1.2 Children">7.2.1.2 Children</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:7.2.2 Relevant animal data">7.2.2 Relevant animal data</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:7.2.3 Relevant in vitro data">7.2.3 Relevant in vitro data</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:7.2.4 Workplace standards">7.2.4 Workplace standards</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:7.2.5 Acceptable daily intake (ADI) and other guideline levels">7.2.5 Acceptable daily intake (ADI) and other guideline levels</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:7.3 Carcinogenicity">7.3 Carcinogenicity</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:7.4 Teratogenicity">7.4 Teratogenicity</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:7.5 Mutagenicity">7.5 Mutagenicity</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:7.6 Interactions">7.6 Interactions</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER><A HREF="#PartTitle:8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS">8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:8.1 Material sampling plan">8.1 Material sampling plan</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:8.1.1 Sampling and specimen collection">8.1.1 Sampling and specimen collection</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.1.1.1 Toxicological analyses">8.1.1.1 Toxicological analyses</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.1.1.2 Biomedical analyses">8.1.1.2 Biomedical analyses</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.1.1.3 Arterial blood gas analysis">8.1.1.3 Arterial blood gas analysis</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.1.1.4 Haematological analyses">8.1.1.4 Haematological analyses</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.1.1.5 Other (unspecified) analyses">8.1.1.5 Other (unspecified) analyses</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:8.1.2 Storage of laboratory samples and specimens">8.1.2 Storage of laboratory samples and specimens</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.1.2.1 Toxicological analyses">8.1.2.1 Toxicological analyses</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.1.2.2 Biomedical analyses">8.1.2.2 Biomedical analyses</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.1.2.3 Arterial blood gas analysis">8.1.2.3 Arterial blood gas analysis</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.1.2.4 Haematological analyses">8.1.2.4 Haematological analyses</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.1.2.5 Other (unspecified) analyses">8.1.2.5 Other (unspecified) analyses</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:8.1.3 Transport of laboratory samples and specimens">8.1.3 Transport of laboratory samples and specimens</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.1.3.1 Toxicological analyses">8.1.3.1 Toxicological analyses</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.1.3.2 Biomedical analyses">8.1.3.2 Biomedical analyses</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.1.3.3 Arterial blood gas analysis">8.1.3.3 Arterial blood gas analysis</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.1.3.4 Haematological analyses">8.1.3.4 Haematological analyses</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.1.3.5 Other (unspecified) analyses">8.1.3.5 Other (unspecified) analyses</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:8.2 Toxicological Analyses and Their Interpretation">8.2 Toxicological Analyses and Their Interpretation</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:8.2.1 Tests on toxic ingredient(s) of material">8.2.1 Tests on toxic ingredient(s) of material</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.2.1.1 Simple Qualitative Test(s)">8.2.1.1 Simple Qualitative Test(s)</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.2.1.2 Advanced Qualitative Confirmation Test(s)">8.2.1.2 Advanced Qualitative Confirmation Test(s)</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.2.1.3 Simple Quantitative Method(s)">8.2.1.3 Simple Quantitative Method(s)</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.2.1.4 Advanced Quantitative Method(s)">8.2.1.4 Advanced Quantitative Method(s)</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:8.2.2 Tests for biological specimens">8.2.2 Tests for biological specimens</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.2.2.1 Simple Qualitative Test(s)">8.2.2.1 Simple Qualitative Test(s)</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.2.2.2 Advanced Qualitative Confirmation Test(s)">8.2.2.2 Advanced Qualitative Confirmation Test(s)</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.2.2.3 Simple Quantitative Method(s)">8.2.2.3 Simple Quantitative Method(s)</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.2.2.4 Advanced Quantitative Method(s)">8.2.2.4 Advanced Quantitative Method(s)</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.2.2.5 Other Dedicated Method(s)">8.2.2.5 Other Dedicated Method(s)</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:8.2.3 Interpretation of toxicological analyses">8.2.3 Interpretation of toxicological analyses</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:8.3 Biomedical investigations and their interpretation">8.3 Biomedical investigations and their interpretation</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:8.3.1 Biochemical analysis">8.3.1 Biochemical analysis</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.3.1.1 Blood, plasma or serum">8.3.1.1 Blood, plasma or serum</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.3.1.2 Urine">8.3.1.2 Urine</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:8.3.1.3 Other fluids">8.3.1.3 Other fluids</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:8.3.2 Arterial blood gas analyses">8.3.2 Arterial blood gas analyses</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:8.3.3 Haematological analyses">8.3.3 Haematological analyses</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:8.3.4 Interpretation of biomedical investigations">8.3.4 Interpretation of biomedical investigations</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:8.4 Other biomedical (diagnostic) investigations and their interpretation">8.4 Other biomedical (diagnostic) investigations and their interpretation</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:8.5 Overall Interpretation of all toxicological analyses and toxicological investigations">8.5 Overall Interpretation of all toxicological analyses and toxicological investigations</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:8.6 References">8.6 References</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER><A HREF="#PartTitle:9. CLINICAL EFFECTS">9. CLINICAL EFFECTS</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:9.1 Acute poisoning">9.1 Acute poisoning</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.1.1 Ingestion">9.1.1 Ingestion</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.1.2 Inhalation">9.1.2 Inhalation</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.1.3 Skin exposure">9.1.3 Skin exposure</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.1.4 Eye contact">9.1.4 Eye contact</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.1.5 Parenteral exposure">9.1.5 Parenteral exposure</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.1.6 Other">9.1.6 Other</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:9.2 Chronic poisoning">9.2 Chronic poisoning</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.2.1 Ingestion">9.2.1 Ingestion</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.2.2 Inhalation">9.2.2 Inhalation</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.2.3 Skin exposure">9.2.3 Skin exposure</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.2.4 Eye contact">9.2.4 Eye contact</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.2.5 Parenteral exposure">9.2.5 Parenteral exposure</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.2.6 Other">9.2.6 Other</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:9.3 Course, prognosis, cause of death">9.3 Course, prognosis, cause of death</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:9.4 Systematic description of clinical effects">9.4 Systematic description of clinical effects</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.4.1 Cardiovascular">9.4.1 Cardiovascular</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.4.2 Respiratory">9.4.2 Respiratory</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.4.3 Neurological">9.4.3 Neurological</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:9.4.3.1 Central Nervous System (CNS)">9.4.3.1 Central Nervous System (CNS)</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:9.4.3.2 Peripheral nervous system">9.4.3.2 Peripheral nervous system</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:9.4.3.3 Autonomic nervous system">9.4.3.3 Autonomic nervous system</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:9.4.3.4 Skeletal and smooth muscle">9.4.3.4 Skeletal and smooth muscle</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.4.4 Gastrointestinal">9.4.4 Gastrointestinal</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.4.5 Hepatic">9.4.5 Hepatic</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.4.6 Urinary">9.4.6 Urinary</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:9.4.6.1 Renal">9.4.6.1 Renal</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:9.4.6.2 Others">9.4.6.2 Others</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.4.7 Endocrine and reproductive systems">9.4.7 Endocrine and reproductive systems</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.4.8 Dermatological">9.4.8 Dermatological</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.4.9 Eye, ears, nose, throat: local effects">9.4.9 Eye, ears, nose, throat: local effects</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.4.10 Haematological">9.4.10 Haematological</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.4.11 Immunological">9.4.11 Immunological</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.4.12 Metabolic">9.4.12 Metabolic</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:9.4.12.1 Acid-base disturbances">9.4.12.1 Acid-base disturbances</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:9.4.12.2 Fluid and electrolyte disturbances">9.4.12.2 Fluid and electrolyte disturbances</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>         <A HREF="#DivisionTitle:9.4.12.3 Others">9.4.12.3 Others</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.4.13 Allergic reactions">9.4.13 Allergic reactions</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.4.14 Other clinical effects">9.4.14 Other clinical effects</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:9.4.15 Special risks">9.4.15 Special risks</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:9.5 Others">9.5 Others</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:9.6 Summary">9.6 Summary</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER><A HREF="#PartTitle:10. MANAGEMENT">10. MANAGEMENT</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:10.1 General principles">10.1 General principles</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:10.2 Life supportive procedures and symptomatic treatment">10.2 Life supportive procedures and symptomatic treatment</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:10.3 Decontamination">10.3 Decontamination</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:10.4 Enhanced elimination">10.4 Enhanced elimination</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:10.5 Antidote treatment">10.5 Antidote treatment</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:10.5.1 Adults">10.5.1 Adults</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>      <A HREF="#SubSectionTitle:10.5.2 Children">10.5.2 Children</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:10.6 Management discussion">10.6 Management discussion</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER><A HREF="#PartTitle:11. ILLUSTRATIVE CASES">11. ILLUSTRATIVE CASES</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:11.1 Case reports from literature">11.1 Case reports from literature</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER><A HREF="#PartTitle:12. ADDITIONAL INFORMATION">12. ADDITIONAL INFORMATION</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:12.1 Specific preventive measures">12.1 Specific preventive measures</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER>   <A HREF="#SectionTitle:12.2 Other">12.2 Other</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER><A HREF="#PartTitle:13. REFERENCES">13. REFERENCES</A></TD></TR> <TR HEIGHT=30><TD ALIGN=LEFT VALIGN=CENTER><A HREF="#PartTitle:14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESSES">14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESSES</A></TD></TR> </TABLE></CENTER> <PRE> NITROGEN OXIDES International Programme on Chemical Safety Poisons Information Monograph (Group Monograph) G017 Chemical <A NAME = "PartTitle:1. NAME"></A>1. NAME <A NAME = "SectionTitle:1.1 Substance"></A>1.1 Substance <PIM1.1>Nitrogen oxides</PIM1.1> <A NAME = "EndSectionTitle:1.1 Substance"></A><A NAME = "SectionTitle:1.2 Group"></A>1.2 Group <PIM1.2>Nitric oxide</PIM1.2> <PIM1.2>Nitrous oxide</PIM1.2> <PIM1.2>Nitrogen dioxide</PIM1.2> <PIM1.2>Nitrogen pentoxide</PIM1.2> <A NAME = "EndSectionTitle:1.2 Group"></A><A NAME = "SectionTitle:1.3 Synonyms"></A>1.3 Synonyms Nitiric oxide: <PIM1.3>mononitrogen monoxide</PIM1.3>; <PIM1.3>nitrogen monoxide</PIM1.3> Nitrous oxide: <PIM1.3>dinitrogen monoxide</PIM1.3>: <PIM1.3>laughing gas</PIM1.3>; <PIM1.3>factitious air</PIM1.3>; <PIM1.3>hyponitrous acid anhydride</PIM1.3>; <PIM1.3>mononitrogen monoxide</PIM1.3>; <PIM1.3>nitric oxide</PIM1.3>; <PIM1.3>nitrogen oxide</PIM1.3>; Nitrogen pentoxide: <PIM1.3>dinitrogen pentoxide</PIM1.3>; <PIM1.3>nitric anhydride</PIM1.3>; Nitrogen dioxide: <PIM1.3>nitrogen tetroxide</PIM1.3> <A NAME = "EndSectionTitle:1.3 Synonyms"></A><A NAME = "SectionTitle:1.4 Identification numbers"></A>1.4 Identification numbers <A NAME = "SubSectionTitle:1.4.1 CAS number"></A>1.4.1 CAS number <PIM1.4.1>Nitric oxide <PrimaryCasNo>10102-43-9</PrimaryCasNo></PIM1.4.1> <PIM1.4.1>Nitrous oxide <SecondaryCasNo>10024-97-2</SecondaryCasNo></PIM1.4.1> <PIM1.4.1>Nitrogen dioxide <SecondaryCasNo>10102-44-0</SecondaryCasNo></PIM1.4.1> <A NAME = ":1.4.1 CAS number"></A><A NAME = "SubSectionTitle:1.4.2 Other numbers"></A>1.4.2 Other numbers <A NAME = ":1.4.2 Other numbers"></A><A NAME = "EndSectionTitle:1.4 Identification numbers"></A><A NAME = "SectionTitle:1.5 Brand names, Trade names"></A>1.5 Brand names, Trade names <A NAME = "EndSectionTitle:1.5 Brand names, Trade names"></A><A NAME = "SectionTitle:1.6 Manufacturers, Importers"></A>1.6 Manufacturers, Importers <A NAME = "EndSectionTitle:1.6 Manufacturers, Importers"></A><A NAME = "EndPartTitle:1. NAME"></A><A NAME = "PartTitle:2. SUMMARY"></A>2. SUMMARY <A NAME = "SectionTitle:2.1 Main risks and target organs"></A>2.1 Main risks and target organs <PIM2.1>Inhalation of any oxides of nitrogen causes toxic effects. The main target organ is the lung.</PIM2.1> <A NAME = "EndSectionTitle:2.1 Main risks and target organs"></A><A NAME = "SectionTitle:2.2 Summary of clinical effects"></A>2.2 Summary of clinical effects <PIM2.2>There may be three stages of toxicity. Initially there may be mild irritation of the upper respiratory tract, cough, sore throat, conjunctivitis, dyspnoea, headache, vertigo, and tightness of the chest.<NL> <NL> After a latent period of 3 to 30 hours, inflammation of the lungs, pulmonary oedema, dyspnoea, wheezing and cyanosis resulting in severe respiratory failure.<NL> <NL> Approximately half the patients who survive pulmonary oedema develop bronchiolitis obliterans within a few weeks.</PIM2.2> <A NAME = "EndSectionTitle:2.2 Summary of clinical effects"></A><A NAME = "SectionTitle:2.3 Diagnosis"></A>2.3 Diagnosis <PIM2.3>Diagnosis depends on a history of exposure and the presence of symptoms and signs related to the respiratory system.<NL> <NL> Arterial blood gas studies may show hypoxia, hypercapnia and acidosis.<NL> <NL> Pulmonary function tests may show obstructive, restrictive and diffusion defects.</PIM2.3> <A NAME = "EndSectionTitle:2.3 Diagnosis"></A><A NAME = "SectionTitle:2.4 First-aid measures and management principles"></A>2.4 First-aid measures and management principles <PIM2.4>First-aid measures:<NL> <NL> Remove the patient to from the source of exposure and admit to hospital as soon as possible.<NL> <NL> Management principles:<NL> <NL> Establish an adequate airway and maintain respiration.<NL> Give oxygen and assisted ventilation if necessary. Treat bronchospasm with bronchodilators.<NL> Remove secretions.<NL> Give corticosteroids if moderate respiratory symptoms or pulmonary oedema are present.<NL> Keep under observation.</PIM2.4> <A NAME = "EndSectionTitle:2.4 First-aid measures and management principles"></A><A NAME = "EndPartTitle:2. SUMMARY"></A><A NAME = "PartTitle:3. PHYSICO-CHEMICAL PROPERTIES"></A>3. PHYSICO-CHEMICAL PROPERTIES <A NAME = "SectionTitle:3.1 Origin of the substance"></A>3.1 Origin of the substance <PIM3.1>Oxides of nitrogen are synthesized or occur as by-products of chemical processes or fires.<NL> <NL> On a global scale, quantities of nitric oxide and nitrogen dioxide produced naturally by bacterial and volcanic action and by lightning by far outweigh those generated by man's activities (WHO, 1977).The major source of man-made emission of oxides of nitrogen is the combustion of fossil fuels in stationary sources (heating, power generation) and in motor vehicles (internal combustion engines).Other sources are industrial processes such as manufacture of nitric acid and explosives, smoking, gas-fired appliances and oil stoves.<NL> <NL> Burning plastics, shoe polish, nitrocellulose, and welding operations produce oxides of nitrogen (Horvath, 1980).<NL> <NL> Nitric oxide is prepared industrially by passing air through an electric arc or by oxidation of ammonia over platinum gauze.<NL> <NL> Laboratory preparation is by reacting sodium nitrite with ferrous sulphate.<NL> <NL> Nitrous oxide is prepared by thermal decomposition of ammonium nitrate.<NL> <NL> Nitrogen dioxide is prepared industrially from nitric oxide and in the laboratory from lead nitrate.<NL> <NL> Nitrogen pentoxide is produced by dehydration of nitric acid by phosphorus pentoxide (Budavari, 1996).</PIM3.1> <A NAME = "EndSectionTitle:3.1 Origin of the substance"></A><A NAME = "SectionTitle:3.2 Chemical structure"></A>3.2 Chemical structure <PIM3.2>Nitric oxide<NL> Molecular weight 30.01<NL> <NL> Nitrogen dioxide <NL> Molecular weight 44.02<NL> <NL> Nitrogen pentoxide <NL> Molecular weight 108.02</PIM3.2> <A NAME = "EndSectionTitle:3.2 Chemical structure"></A><A NAME = "SectionTitle:3.3 Physical properties"></A>3.3 Physical properties <A NAME = "SubSectionTitle:3.3.1 Colour"></A>3.3.1 Colour <PIM3.3.1>See section 3.3.3</PIM3.3.1> <A NAME = ":3.3.1 Colour"></A><A NAME = "SubSectionTitle:3.3.2 State/form"></A>3.3.2 State/form <PIM3.3.2>See section 3.3.2</PIM3.3.2> <A NAME = ":3.3.2 State/form"></A><A NAME = "SubSectionTitle:3.3.3 Description"></A>3.3.3 Description <PIM3.3.3>Nitrogen dioxide<NL> Molecular formula: NO2<NL> Boiling point 21.15癈<NL> Melting point -9.3癈 <NL> Molecular mass 44.02<NL> Condensation point 21癈<NL> Specific gravity at 20癈 1.448 (liquid)<NL> <NL> A reddish brown gas. Liquid below 21.15癈. <NL> <NL> Nitrogen pentoxide<NL> Molecular formula: N2O5<NL> Boiling point 47.0癈<NL> Melting point 30癈<NL> Molecular mass 108.02<NL> <NL> Colourless hexagonal crystals.<NL> <NL> Nitrous oxide<NL> Molecular formula: N2O<NL> Boiling point 88.46癈 <NL> Melting point -90.81癈<NL> Vapour pressure (Pascals at 20癈) 4.93 (Mellor, 1967)<NL> Solubility: Soluble in alcohol and ether. <NL> <NL> A colourless gas with slightly sweetish odour and taste. <NL> <NL> Nitric oxide<NL> Molecular formula NO<NL> Boiling point: -151.8 癈<NL> Molecular mass: 30.01<NL> <NL> A colourless gas.<NL> <NL> (Budavari, 1996)</PIM3.3.3> <A NAME = ":3.3.3 Description"></A><A NAME = "EndSectionTitle:3.3 Physical properties"></A><A NAME = "SectionTitle:3.4 Hazardous characteristics"></A>3.4 Hazardous characteristics <PIM3.4>Nitrogen dioxide<NL> It has an irritating odour and is highly poisonous.Under normal atmospheric conditions it exists in equilibrium with nitrogen tetroxide (N204). Heavier than air. Nitrogen dioxide produces nitrous acid (HN02) and nitric acid (HN03) on contact with water.<NL> <NL> Nitrogen pentoxide<NL> Sublimes at -32.4癈 but undergoes moderately rapid decomposition into 02 and the NO2/N204 equilibrium mixture at temperatures above -10癈. Freely soluble in chloroform without appreciable decomposition.<NL> <NL> Nitrous oxide<NL> Supports combustion.Very stable and rather inert chemically at room temperatures.Dissociation begins above 300癈 when the gas becomes a strong oxidizing agent.<NL> <NL> Nitric oxide<NL> Burns when heated with hydrogen. It combines with oxygen to form nitrogen dioxide and with halogens to form nitrosyl halides, e.g. NOCl.<NL> <NL> (Budavari, 1996)</PIM3.4> <A NAME = "EndSectionTitle:3.4 Hazardous characteristics"></A><A NAME = "EndPartTitle:3. PHYSICO-CHEMICAL PROPERTIES"></A><A NAME = "PartTitle:4. USES/CIRCUMSTANCES OF POISONING"></A>4. USES/CIRCUMSTANCES OF POISONING <A NAME = "SectionTitle:4.1 Uses"></A>4.1 Uses <A NAME = "SubSectionTitle:4.1.1 Uses"></A>4.1.1 Uses <A NAME = ":4.1.1 Uses"></A><A NAME = "SubSectionTitle:4.1.2 Description"></A>4.1.2 Description <PIM4.1.2>Nitric oxide<NL> In the manufacture of nitric acid, bleaching of rayon; as a stabilizer (to prevent free radical decomposition) for propylene, methyl ether etc.<NL> <NL> Nitrogen dioxide <NL> Intermediate in nitric and sulphuric acid production. It is also used in nitration of organic compounds and explosives in the manufacturing of oxidized cellulose compounds. Has been used to bleach flour. Proposed as oxidizing agent in rocket propulsion.<NL> <NL> Nitrogen pentoxide <NL> Used in chloroform solution as a nitrating agent.<NL> <NL> Nitrous oxide<NL> To oxidize organic compounds at temperatures above 300癈 to make nitrites from alkali metals at their boiling points, in rocket fuel formulations (with carbon disulphide) and in the preparation of whipped cream. Also used as an anaesthetic gas (Budavari, 1996).</PIM4.1.2> <A NAME = ":4.1.2 Description"></A><A NAME = "EndSectionTitle:4.1 Uses"></A><A NAME = "SectionTitle:4.2 High risk circumstance of poisoning"></A>4.2 High risk circumstance of poisoning <PIM4.2>Poisoning occurs following exposure to industrial, manufacturing or agricultural sources which evolve nitrous fumes (oxides of nitrogen). <NL> <NL> Nitrogen dioxide and nitric oxide are the principal hazards. Nitrous oxide is narcotic in high concentrations but it is less irritant than other oxides of nitrogen.</PIM4.2> <A NAME = "EndSectionTitle:4.2 High risk circumstance of poisoning"></A><A NAME = "SectionTitle:4.3 Occupationally exposed populations"></A>4.3 Occupationally exposed populations <PIM4.3>Occupational exposure usually occurs from manufacture of dyes, fertilizers, celluloid and lacquers; and from welding glass blowing and food bleaching.<NL> <NL> Firemen may be exposed to nitrogen oxide during chemical plant fires or from burning mattresses (Ellenhorn & Barceloux, 1988).<NL> <NL> Nitrogen oxides are also released from processes such as electroplating, engraving, photogravure operations etc. (Gosselin et al., 1984).<NL> <NL> Severe symptoms and death has been reported in farmers working in or near silos. This syndrome, known as silo filler's disease, is due to acute exposure to oxides of nitrogen produced by silage (Ellenhorn & Barceloux 1988).<NL> <NL> Occupational exposure occurs in anaesthesia. </PIM4.3> <A NAME = "EndSectionTitle:4.3 Occupationally exposed populations"></A><A NAME = "EndPartTitle:4. USES/CIRCUMSTANCES OF POISONING"></A><A NAME = "PartTitle:5. ROUTES OF ENTRY"></A>5. ROUTES OF ENTRY <A NAME = "SectionTitle:5.1 Oral"></A>5.1 Oral <PIM5.1>Not known.</PIM5.1> <A NAME = "EndSectionTitle:5.1 Oral"></A><A NAME = "SectionTitle:5.2 Inhalation"></A>5.2 Inhalation <PIM5.2>Inhalation of some oxides of nitrogen such as nitric oxide and nitrogen dioxide causes poisoning. On contact with air, nitric oxide is converted to highly poisonous nitrogen dioxide. <NL> <NL> The effects of nitrogen dioxide are insidious: inhalation may cause only slight pain or go unnoticed, but may cause death later.</PIM5.2> <A NAME = "EndSectionTitle:5.2 Inhalation"></A><A NAME = "SectionTitle:5.3 Dermal"></A>5.3 Dermal <PIM5.3>Nitric acid , formed when fumes of nitrogen oxides mix with sweat, has caused skin burns (Haddad and Winchester, 1990).</PIM5.3> <A NAME = "EndSectionTitle:5.3 Dermal"></A><A NAME = "SectionTitle:5.4 Eye"></A>5.4 Eye <PIM5.4>Fumes of nitrogen oxides can cause eye irritation (Haddad and Winchester, 1990).</PIM5.4> <A NAME = "EndSectionTitle:5.4 Eye"></A><A NAME = "SectionTitle:5.5 Parenteral"></A>5.5 Parenteral <PIM5.5>Not known.</PIM5.5> <A NAME = "EndSectionTitle:5.5 Parenteral"></A><A NAME = "SectionTitle:5.6 Others"></A>5.6 Others <PIM5.6>Not known.</PIM5.6> <A NAME = "EndSectionTitle:5.6 Others"></A><A NAME = "EndPartTitle:5. ROUTES OF ENTRY"></A><A NAME = "PartTitle:6. KINETICS"></A>6. KINETICS <A NAME = "SectionTitle:6.1 Absorption by route of exposure"></A>6.1 Absorption by route of exposure <PIM6.1>Nitrogen oxides are largely absorbed by and react with pulmonary alveolar structures and terminal respiratory bronchioles.<NL> <NL> They are less soluble than most irritant gases and have a greater tendency to reach the bronchioles and alveoli (Haddad and Winchester, 1990).</PIM6.1> <A NAME = "EndSectionTitle:6.1 Absorption by route of exposure"></A><A NAME = "SectionTitle:6.2 Distribution by route of exposure"></A>6.2 Distribution by route of exposure <PIM6.2>Within the lungs, nitrogen oxides react with water to form nitrous and nitric acids causing extensive local damage.</PIM6.2> <A NAME = "EndSectionTitle:6.2 Distribution by route of exposure"></A><A NAME = "SectionTitle:6.3 Biological half-life by route of exposure"></A>6.3 Biological half-life by route of exposure <PIM6.3>The biological half-life of endogenous nitrogen oxides in vascular endothelium is very short.</PIM6.3> <A NAME = "EndSectionTitle:6.3 Biological half-life by route of exposure"></A><A NAME = "SectionTitle:6.4 Metabolism"></A>6.4 Metabolism <PIM6.4>No data available.</PIM6.4> <A NAME = "EndSectionTitle:6.4 Metabolism"></A><A NAME = "SectionTitle:6.5 Elimination by route of exposure"></A>6.5 Elimination by route of exposure <PIM6.5>No data available.</PIM6.5> <A NAME = "EndSectionTitle:6.5 Elimination by route of exposure"></A><A NAME = "EndPartTitle:6. KINETICS"></A><A NAME = "PartTitle:7. TOXICOLOGY"></A>7. TOXICOLOGY <A NAME = "SectionTitle:7.1 Mode of Action"></A>7.1 Mode of Action <PIM7.1>Of the five principal oxides of nitrogen, nitrous oxide is comparatively harmless. The principal target organ for other oxides is the lung. Nitric oxide is less toxic tot he lung than nitrogen dioxide. Little is known about toxicology of nitrogen trioxide (N2O3) and nitrogen pentoxide (N2O5) (Gosselin et al., 1984).<NL> <NL> It is now generally accepted that nitrogen dioxide is the principal causative factor of the pulmonary changes following the inhalation of oxides of nitrogen ("nitrous fumes") (Milne, 1969).<NL> <NL> Nitrogen oxides are irritant and destructive to lung tissues because they are slowly hydrolysed to acids. The upper respiratory tract is largely spared perhaps because these gases have a low solubility in aqueous media and because they are only slowly hydrolysed.<NL> <NL> The mild upper respiratory irritant effect is a result of nitrogen dioxide being converted to nitric acid in the presence of water.<NL> <NL> Nitric acid destroys respiratory epithelium and alveolar membranes and may produce metabolic acidosis. The mild initial irritant effects allow widespread dissemination of nitrogen oxides throughout the lungs and result in diffuse delayed inflammation.<NL> <NL> Fibrotic destruction of terminal bronchioles (bronchiolitis obliterans) occurs as a late complication (Ellenhorn & Barceloux, 1988).<NL> <NL> Nitrogen dioxide decomposition may also produce nitrates which are capable of causing vasodilatation and mild methaemoglobinaemia.</PIM7.1> <A NAME = "EndSectionTitle:7.1 Mode of Action"></A><A NAME = "SectionTitle:7.2 Toxicity"></A>7.2 Toxicity <A NAME = "SubSectionTitle:7.2.1 Human data"></A>7.2.1 Human data <A NAME = "DivisionTitle:7.2.1.1 Adults"></A>7.2.1.1 Adults <PIM7.2.1.1>The presence of nitrogen dioxide may be difficult to perceive and it is frequently undetectable at concentrations causing mucosal irritation. Early symptoms are often mild, even in cases where there is serious late toxicity. At levels of 100 to 150 ppm toxicity occurs within 30 to 60 minutes and at levels of 200 to 700 ppm fatalities result after short exposure (Ellenhorn & Barceloux, 1988). <NL> <NL> Chest discomfort occurs after exposure to 15 ppm for 1 hour and the sensation becomes unpleasant at 25 ppm. After 1 minute at 50 ppm subjects feel substernal pain. Longer exposure at this concentration causes reversible inflammatory changes in the lungs. Higher concentrations may be fatal (Dreisbach, 1987).</PIM7.2.1.1> <A NAME = "EndDivisionTitle:7.2.1.1 Adults"></A><A NAME = "DivisionTitle:7.2.1.2 Children"></A>7.2.1.2 Children <PIM7.2.1.2>No data available.</PIM7.2.1.2> <A NAME = "EndDivisionTitle:7.2.1.2 Children"></A><A NAME = ":7.2.1 Human data"></A><A NAME = "SubSectionTitle:7.2.2 Relevant animal data"></A>7.2.2 Relevant animal data <PIM7.2.2>In the rat, exposure to 0.5 ppm for 4 hours causes reversible degranulation of lung cells. Mice exposed continuously for 3 months to 0.5 ppm become more susceptible to infection when challenged with pneumococci. Weight loss occurs in monkeys exposed to this concentration but other animals are not affected.<NL> <NL> In the rat, continuous exposure to 2 ppm of NO2 for 3 days caused epithelial hyperplasia in the terminal bronchioles. Exposure for more than one year caused thinning of the membrane lining the lungs.<NL> <NL> Intermittent exposure of rats to 4 ppm for a year caused no discernible permanent damage to the lungs (Dreisbach, 1987).<NL> <NL> Animals exposed to 70 ppm for 8 hours developed periorbital oedema and corneal opacities (Ellenhorn and Barceloux, 1988).</PIM7.2.2> <A NAME = ":7.2.2 Relevant animal data"></A><A NAME = "SubSectionTitle:7.2.3 Relevant in vitro data"></A>7.2.3 Relevant in vitro data <PIM7.2.3>No data available.</PIM7.2.3> <A NAME = ":7.2.3 Relevant in vitro data"></A><A NAME = "SubSectionTitle:7.2.4 Workplace standards"></A>7.2.4 Workplace standards <PIM7.2.4>Nitrogen dioxide:<NL> Threshold limit value (time weighted average):<NL> 3 ppm (6 mg/m3)<NL> <NL> Threshold limit value - STEL: 5 ppm (10 mg/m3)<NL> <NL> NIOSH recommends 1 ppm of nitrogen dioxide as a workplace environmental standard (NIOSH, 1976).<NL> <NL> Nitric oxide:<NL> Threshold limit value: 25 ppm</PIM7.2.4> <A NAME = ":7.2.4 Workplace standards"></A><A NAME = "SubSectionTitle:7.2.5 Acceptable daily intake (ADI) and other guideline levels"></A>7.2.5 Acceptable daily intake (ADI) and other guideline levels <PIM7.2.5>Not relevant.</PIM7.2.5> <A NAME = ":7.2.5 Acceptable daily intake (ADI) and other guideline levels"></A><A NAME = "EndSectionTitle:7.2 Toxicity"></A><A NAME = "SectionTitle:7.3 Carcinogenicity"></A>7.3 Carcinogenicity <PIM7.3>Unknown</PIM7.3> <A NAME = "EndSectionTitle:7.3 Carcinogenicity"></A><A NAME = "SectionTitle:7.4 Teratogenicity"></A>7.4 Teratogenicity <PIM7.4>Unknown</PIM7.4> <A NAME = "EndSectionTitle:7.4 Teratogenicity"></A><A NAME = "SectionTitle:7.5 Mutagenicity"></A>7.5 Mutagenicity <PIM7.5>Unknown</PIM7.5> <A NAME = "EndSectionTitle:7.5 Mutagenicity"></A><A NAME = "SectionTitle:7.6 Interactions"></A>7.6 Interactions <PIM7.6>Unknown</PIM7.6> <A NAME = "EndSectionTitle:7.6 Interactions"></A><A NAME = "EndPartTitle:7. TOXICOLOGY"></A><A NAME = "PartTitle:8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS"></A>8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS <A NAME = "SectionTitle:8.1 Material sampling plan"></A>8.1 Material sampling plan <A NAME = "SubSectionTitle:8.1.1 Sampling and specimen collection"></A>8.1.1 Sampling and specimen collection <A NAME = "DivisionTitle:8.1.1.1 Toxicological analyses"></A>8.1.1.1 Toxicological analyses <A NAME = "EndDivisionTitle:8.1.1.1 Toxicological analyses"></A><A NAME = "DivisionTitle:8.1.1.2 Biomedical analyses"></A>8.1.1.2 Biomedical analyses <A NAME = "EndDivisionTitle:8.1.1.2 Biomedical analyses"></A><A NAME = "DivisionTitle:8.1.1.3 Arterial blood gas analysis"></A>8.1.1.3 Arterial blood gas analysis <A NAME = "EndDivisionTitle:8.1.1.3 Arterial blood gas analysis"></A><A NAME = "DivisionTitle:8.1.1.4 Haematological analyses"></A>8.1.1.4 Haematological analyses <A NAME = "EndDivisionTitle:8.1.1.4 Haematological analyses"></A><A NAME = "DivisionTitle:8.1.1.5 Other (unspecified) analyses"></A>8.1.1.5 Other (unspecified) analyses <A NAME = "EndDivisionTitle:8.1.1.5 Other (unspecified) analyses"></A><A NAME = ":8.1.1 Sampling and specimen collection"></A><A NAME = "SubSectionTitle:8.1.2 Storage of laboratory samples and specimens"></A>8.1.2 Storage of laboratory samples and specimens <A NAME = "DivisionTitle:8.1.2.1 Toxicological analyses"></A>8.1.2.1 Toxicological analyses <A NAME = "EndDivisionTitle:8.1.2.1 Toxicological analyses"></A><A NAME = "DivisionTitle:8.1.2.2 Biomedical analyses"></A>8.1.2.2 Biomedical analyses <A NAME = "EndDivisionTitle:8.1.2.2 Biomedical analyses"></A><A NAME = "DivisionTitle:8.1.2.3 Arterial blood gas analysis"></A>8.1.2.3 Arterial blood gas analysis <A NAME = "EndDivisionTitle:8.1.2.3 Arterial blood gas analysis"></A><A NAME = "DivisionTitle:8.1.2.4 Haematological analyses"></A>8.1.2.4 Haematological analyses <A NAME = "EndDivisionTitle:8.1.2.4 Haematological analyses"></A><A NAME = "DivisionTitle:8.1.2.5 Other (unspecified) analyses"></A>8.1.2.5 Other (unspecified) analyses <A NAME = "EndDivisionTitle:8.1.2.5 Other (unspecified) analyses"></A><A NAME = ":8.1.2 Storage of laboratory samples and specimens"></A><A NAME = "SubSectionTitle:8.1.3 Transport of laboratory samples and specimens"></A>8.1.3 Transport of laboratory samples and specimens <A NAME = "DivisionTitle:8.1.3.1 Toxicological analyses"></A>8.1.3.1 Toxicological analyses <A NAME = "EndDivisionTitle:8.1.3.1 Toxicological analyses"></A><A NAME = "DivisionTitle:8.1.3.2 Biomedical analyses"></A>8.1.3.2 Biomedical analyses <A NAME = "EndDivisionTitle:8.1.3.2 Biomedical analyses"></A><A NAME = "DivisionTitle:8.1.3.3 Arterial blood gas analysis"></A>8.1.3.3 Arterial blood gas analysis <A NAME = "EndDivisionTitle:8.1.3.3 Arterial blood gas analysis"></A><A NAME = "DivisionTitle:8.1.3.4 Haematological analyses"></A>8.1.3.4 Haematological analyses <A NAME = "EndDivisionTitle:8.1.3.4 Haematological analyses"></A><A NAME = "DivisionTitle:8.1.3.5 Other (unspecified) analyses"></A>8.1.3.5 Other (unspecified) analyses <A NAME = "EndDivisionTitle:8.1.3.5 Other (unspecified) analyses"></A><A NAME = ":8.1.3 Transport of laboratory samples and specimens"></A><A NAME = "EndSectionTitle:8.1 Material sampling plan"></A><A NAME = "SectionTitle:8.2 Toxicological Analyses and Their Interpretation"></A>8.2 Toxicological Analyses and Their Interpretation <A NAME = "SubSectionTitle:8.2.1 Tests on toxic ingredient(s) of material"></A>8.2.1 Tests on toxic ingredient(s) of material <A NAME = "DivisionTitle:8.2.1.1 Simple Qualitative Test(s)"></A>8.2.1.1 Simple Qualitative Test(s) <A NAME = "EndDivisionTitle:8.2.1.1 Simple Qualitative Test(s)"></A><A NAME = "DivisionTitle:8.2.1.2 Advanced Qualitative Confirmation Test(s)"></A>8.2.1.2 Advanced Qualitative Confirmation Test(s) <A NAME = "EndDivisionTitle:8.2.1.2 Advanced Qualitative Confirmation Test(s)"></A><A NAME = "DivisionTitle:8.2.1.3 Simple Quantitative Method(s)"></A>8.2.1.3 Simple Quantitative Method(s) <A NAME = "EndDivisionTitle:8.2.1.3 Simple Quantitative Method(s)"></A><A NAME = "DivisionTitle:8.2.1.4 Advanced Quantitative Method(s)"></A>8.2.1.4 Advanced Quantitative Method(s) <A NAME = "EndDivisionTitle:8.2.1.4 Advanced Quantitative Method(s)"></A><A NAME = ":8.2.1 Tests on toxic ingredient(s) of material"></A><A NAME = "SubSectionTitle:8.2.2 Tests for biological specimens"></A>8.2.2 Tests for biological specimens <A NAME = "DivisionTitle:8.2.2.1 Simple Qualitative Test(s)"></A>8.2.2.1 Simple Qualitative Test(s) <A NAME = "EndDivisionTitle:8.2.2.1 Simple Qualitative Test(s)"></A><A NAME = "DivisionTitle:8.2.2.2 Advanced Qualitative Confirmation Test(s)"></A>8.2.2.2 Advanced Qualitative Confirmation Test(s) <A NAME = "EndDivisionTitle:8.2.2.2 Advanced Qualitative Confirmation Test(s)"></A><A NAME = "DivisionTitle:8.2.2.3 Simple Quantitative Method(s)"></A>8.2.2.3 Simple Quantitative Method(s) <A NAME = "EndDivisionTitle:8.2.2.3 Simple Quantitative Method(s)"></A><A NAME = "DivisionTitle:8.2.2.4 Advanced Quantitative Method(s)"></A>8.2.2.4 Advanced Quantitative Method(s) <A NAME = "EndDivisionTitle:8.2.2.4 Advanced Quantitative Method(s)"></A><A NAME = "DivisionTitle:8.2.2.5 Other Dedicated Method(s)"></A>8.2.2.5 Other Dedicated Method(s) <A NAME = "EndDivisionTitle:8.2.2.5 Other Dedicated Method(s)"></A><A NAME = ":8.2.2 Tests for biological specimens"></A><A NAME = "SubSectionTitle:8.2.3 Interpretation of toxicological analyses"></A>8.2.3 Interpretation of toxicological analyses <A NAME = ":8.2.3 Interpretation of toxicological analyses"></A><A NAME = "EndSectionTitle:8.2 Toxicological Analyses and Their Interpretation"></A><A NAME = "SectionTitle:8.3 Biomedical investigations and their interpretation"></A>8.3 Biomedical investigations and their interpretation <A NAME = "SubSectionTitle:8.3.1 Biochemical analysis"></A>8.3.1 Biochemical analysis <A NAME = "DivisionTitle:8.3.1.1 Blood, plasma or serum"></A>8.3.1.1 Blood, plasma or serum <A NAME = "EndDivisionTitle:8.3.1.1 Blood, plasma or serum"></A><A NAME = "DivisionTitle:8.3.1.2 Urine"></A>8.3.1.2 Urine <A NAME = "EndDivisionTitle:8.3.1.2 Urine"></A><A NAME = "DivisionTitle:8.3.1.3 Other fluids"></A>8.3.1.3 Other fluids <A NAME = "EndDivisionTitle:8.3.1.3 Other fluids"></A><A NAME = ":8.3.1 Biochemical analysis"></A><A NAME = "SubSectionTitle:8.3.2 Arterial blood gas analyses"></A>8.3.2 Arterial blood gas analyses <A NAME = ":8.3.2 Arterial blood gas analyses"></A><A NAME = "SubSectionTitle:8.3.3 Haematological analyses"></A>8.3.3 Haematological analyses <A NAME = ":8.3.3 Haematological analyses"></A><A NAME = "SubSectionTitle:8.3.4 Interpretation of biomedical investigations"></A>8.3.4 Interpretation of biomedical investigations <A NAME = ":8.3.4 Interpretation of biomedical investigations"></A><A NAME = "EndSectionTitle:8.3 Biomedical investigations and their interpretation"></A><A NAME = "SectionTitle:8.4 Other biomedical (diagnostic) investigations and their interpretation"></A>8.4 Other biomedical (diagnostic) investigations and their interpretation <A NAME = "EndSectionTitle:8.4 Other biomedical (diagnostic) investigations and their interpretation"></A><A NAME = "SectionTitle:8.5 Overall Interpretation of all toxicological analyses and toxicological investigations"></A>8.5 Overall Interpretation of all toxicological analyses and toxicological investigations <PIM8.5>Sample collection<NL> Collect blood samples to assess arterial blood gases and methaemoglobin levels.<NL> <NL> Biomedical analysis<NL> Arterial blood gas studies show hypoxia, hypercapnia and acidosis with early changes in the alveolar - arterial oxygen gradient.<NL> <NL> Pulmonary function tests show obstructive, restrictive and diffusion defects as a result of destruction of alveoli, interstitium and bronchioles (Ellenhorn & Barceloux, 1988).</PIM8.5> <A NAME = "EndSectionTitle:8.5 Overall Interpretation of all toxicological analyses and toxicological investigations"></A><A NAME = "SectionTitle:8.6 References"></A>8.6 References <A NAME = "EndSectionTitle:8.6 References"></A><A NAME = "EndPartTitle:8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS"></A><A NAME = "PartTitle:9. CLINICAL EFFECTS"></A>9. CLINICAL EFFECTS <A NAME = "SectionTitle:9.1 Acute poisoning"></A>9.1 Acute poisoning <A NAME = "SubSectionTitle:9.1.1 Ingestion"></A>9.1.1 Ingestion <PIM9.1.1>Unknown</PIM9.1.1> <A NAME = ":9.1.1 Ingestion"></A><A NAME = "SubSectionTitle:9.1.2 Inhalation"></A>9.1.2 Inhalation <PIM9.1.2>The irritant effects of oxides of nitrogen cause inflammation of the lungs, leading to profuse exudation into the alveolar spaces. Pulmonary oedema, rapid breathing and cyanosis are early features.<NL> <NL> Relapse may occur after 2 to 3 weeks with the onset of bronchiolitis obliterans.<NL> <NL> Chest X-ray shows fluffy confluent bilateral infiltrates in patients with pulmonary oedema, and a nodular pattern in cases of bronchiolitis obliterans.</PIM9.1.2> <A NAME = ":9.1.2 Inhalation"></A><A NAME = "SubSectionTitle:9.1.3 Skin exposure"></A>9.1.3 Skin exposure <PIM9.1.3>Skin burns can occur when nitrous fumes mix with sweat to form nitric acid. </PIM9.1.3> <A NAME = ":9.1.3 Skin exposure"></A><A NAME = "SubSectionTitle:9.1.4 Eye contact"></A>9.1.4 Eye contact <PIM9.1.4>Exposure to nitrogen oxides can cause conjunctivitis. </PIM9.1.4> <A NAME = ":9.1.4 Eye contact"></A><A NAME = "SubSectionTitle:9.1.5 Parenteral exposure"></A>9.1.5 Parenteral exposure <PIM9.1.5>Not relevant.</PIM9.1.5> <A NAME = ":9.1.5 Parenteral exposure"></A><A NAME = "SubSectionTitle:9.1.6 Other"></A>9.1.6 Other <PIM9.1.6>Not relevant.</PIM9.1.6> <A NAME = ":9.1.6 Other"></A><A NAME = "EndSectionTitle:9.1 Acute poisoning"></A><A NAME = "SectionTitle:9.2 Chronic poisoning"></A>9.2 Chronic poisoning <A NAME = "SubSectionTitle:9.2.1 Ingestion"></A>9.2.1 Ingestion <PIM9.2.1>Unknown.</PIM9.2.1> <A NAME = ":9.2.1 Ingestion"></A><A NAME = "SubSectionTitle:9.2.2 Inhalation"></A>9.2.2 Inhalation <PIM9.2.2>No adverse effects were found in workers exposed for several years at 30 to 35 ppm oxides of nitrogen (ACGIH, 1986).</PIM9.2.2> <A NAME = ":9.2.2 Inhalation"></A><A NAME = "SubSectionTitle:9.2.3 Skin exposure"></A>9.2.3 Skin exposure <PIM9.2.3>No data available.</PIM9.2.3> <A NAME = ":9.2.3 Skin exposure"></A><A NAME = "SubSectionTitle:9.2.4 Eye contact"></A>9.2.4 Eye contact <PIM9.2.4>No data available.</PIM9.2.4> <A NAME = ":9.2.4 Eye contact"></A><A NAME = "SubSectionTitle:9.2.5 Parenteral exposure"></A>9.2.5 Parenteral exposure <PIM9.2.5>Unknown.</PIM9.2.5> <A NAME = ":9.2.5 Parenteral exposure"></A><A NAME = "SubSectionTitle:9.2.6 Other"></A>9.2.6 Other <PIM9.2.6>Unknown.</PIM9.2.6> <A NAME = ":9.2.6 Other"></A><A NAME = "EndSectionTitle:9.2 Chronic poisoning"></A><A NAME = "SectionTitle:9.3 Course, prognosis, cause of death"></A>9.3 Course, prognosis, cause of death <PIM9.3>Clinical features depend on the duration and intensity of exposure and follow a triphasic pattern. <NL> <NL> Initially, there is mild irritation of the upper respiratory tract. <NL> <NL> Mild cases become asymptomatic within several hours. The severity of initial symptoms does not correlate well with subsequent pulmonary pathology, although patients with mild nitrogen dioxide exposure often recover without any late complications.<NL> <NL> After a latent period of 32 hours (in some instances lasting up to 72 hours) patients may develop inflammation of the lungs and pulmonary oedema.<NL> <NL> About 50% patients surviving pulmonary oedema develop bronchiolitis obliterans in 2 to 6 weeks.<NL> <NL> In a few instances, bronchiolitis obliterans may be the initial presentation with symptoms including progressive dyspnoea, cyanosis, cough and wheezing.<NL> <NL> The patient may be even more intensely ill during this relapse than during the initial reaction.<NL> <NL> Recovery can take up to 6 months. Emphysematous change persists, depending on the severity of the original damage.<NL> <NL> Death can occur due to asphyxia within a few hours of the onset of pulmonary oedema.<NL> <NL> Exposure to high concentrations in the region of 100 to 500 ppm may leads to sudden death from bronchospasm and respiratory failure. Delayed pulmonary oedema can cause death. Several weeks after exposure, bronchiolitis obliterans can cause death.</PIM9.3> <A NAME = "EndSectionTitle:9.3 Course, prognosis, cause of death"></A><A NAME = "SectionTitle:9.4 Systematic description of clinical effects"></A>9.4 Systematic description of clinical effects <A NAME = "SubSectionTitle:9.4.1 Cardiovascular"></A>9.4.1 Cardiovascular <PIM9.4.1>Rapid and weak pulse, cyanosis, venous congestion and hypotension occur secondary to anoxia and haemoconcentration (Gosselin et al. 1984). Hypotension may occur due to a direct effect of nitrates on blood vessels (Haddad and Winchester, 1990).</PIM9.4.1> <A NAME = ":9.4.1 Cardiovascular"></A><A NAME = "SubSectionTitle:9.4.2 Respiratory"></A>9.4.2 Respiratory <PIM9.4.2>Usually no symptoms occur at the time of exposure with the exception of a slight cough and perhaps fatigue and nausea. Exposure to low concentrations may result in impaired pulmonary defence mechanisms (macrophages, cilia) with complications.<NL> <NL> Only relatively high concentrations of nitrogen oxides produce prompt coughing, choking, production of mucoid and frothy sputum, headache, nausea, abdominal pain and dyspnoea and tightness and burning pain in the chest. There may be haemoptysis.<NL> <NL> Inhalation of nitrogen dioxide for a short period causes increased airways resistance (Horvath, 1980). This seems to be due to histamine release (Guidotti, 1978).<NL> <NL> A symptom-free period may follow exposure and lasts for 5 to 72 hours. Fatigue, uneasiness, restlessness, cough, tachypnoea and dyspnoea, appear insidiously as adult respiratory distress syndrome gradually develops.<NL> <NL> Increasingly rapid and shallow respiration, cyanosis, coughing with frothy expectoration, and physical signs of bronchospasm and pulmonary oedema such as crackles and wheezes can be observed. Vital capacity is rapidly reduced. A serous exudate may develop in the pleural cavity, but its volume is usually small. Anxiety, mental confusion, lethargy, and finally loss of consciousness occur as a result of hypoxia.<NL> <NL> Chest X-ray may show widespread, coarse mottling throughout the lung fields. Lungs may be radiologically clear within a few days, in parallel with clinical improvement (Milne, 1969). Circulatory collapse is secondary to anoxia and haemoconcentration.<NL> <NL> Death may occur within a few hours of the first evidence of pulmonary oedema.<NL> <NL> Sometimes a second acute phase follows the initial pulmonary reaction after a quiescent period of 2 to 6 weeks. Cough, tachypnoea, dyspnoea, fever, tachycardia and cyanosis at this stage are usually due to bronchiolar inflammation which may lead to bronchiolitis obliterans (Milne, 1969).The relapse may be abrupt and fulminating, leading either to death or a slow convalescence.<NL> <NL> Chest X-ray reveals widespread bilateral mottling.<NL> <NL> Blood gas analysis indicates hypoxia.<NL> <NL> In non-fatal cases, convalescence may be complicated by infection, bronchitis, bronchiolitis obliterans, pneumonia and general weakness. Rarely, diffuse pulmonary fibrosis may develop. </PIM9.4.2> <A NAME = ":9.4.2 Respiratory"></A><A NAME = "SubSectionTitle:9.4.3 Neurological"></A>9.4.3 Neurological <A NAME = "DivisionTitle:9.4.3.1 Central Nervous System (CNS)"></A>9.4.3.1 Central Nervous System (CNS) <PIM9.4.3.1>The effects are secondary to hypoxia. There may be confusion.</PIM9.4.3.1> <A NAME = "EndDivisionTitle:9.4.3.1 Central Nervous System (CNS)"></A><A NAME = "DivisionTitle:9.4.3.2 Peripheral nervous system"></A>9.4.3.2 Peripheral nervous system <PIM9.4.3.2>Not known</PIM9.4.3.2> <A NAME = "EndDivisionTitle:9.4.3.2 Peripheral nervous system"></A><A NAME = "DivisionTitle:9.4.3.3 Autonomic nervous system"></A>9.4.3.3 Autonomic nervous system <PIM9.4.3.3>Not known</PIM9.4.3.3> <A NAME = "EndDivisionTitle:9.4.3.3 Autonomic nervous system"></A><A NAME = "DivisionTitle:9.4.3.4 Skeletal and smooth muscle"></A>9.4.3.4 Skeletal and smooth muscle <PIM9.4.3.4>Not known</PIM9.4.3.4> <A NAME = "EndDivisionTitle:9.4.3.4 Skeletal and smooth muscle"></A><A NAME = ":9.4.3 Neurological"></A><A NAME = "SubSectionTitle:9.4.4 Gastrointestinal"></A>9.4.4 Gastrointestinal <PIM9.4.4>There may be nausea.</PIM9.4.4> <A NAME = ":9.4.4 Gastrointestinal"></A><A NAME = "SubSectionTitle:9.4.5 Hepatic"></A>9.4.5 Hepatic <PIM9.4.5>Not known</PIM9.4.5> <A NAME = ":9.4.5 Hepatic"></A><A NAME = "SubSectionTitle:9.4.6 Urinary"></A>9.4.6 Urinary <A NAME = "DivisionTitle:9.4.6.1 Renal"></A>9.4.6.1 Renal <PIM9.4.6.1>Unknown</PIM9.4.6.1> <A NAME = "EndDivisionTitle:9.4.6.1 Renal"></A><A NAME = "DivisionTitle:9.4.6.2 Others"></A>9.4.6.2 Others <PIM9.4.6.2>Unknown</PIM9.4.6.2> <A NAME = "EndDivisionTitle:9.4.6.2 Others"></A><A NAME = ":9.4.6 Urinary"></A><A NAME = "SubSectionTitle:9.4.7 Endocrine and reproductive systems"></A>9.4.7 Endocrine and reproductive systems <PIM9.4.7>Unknown</PIM9.4.7> <A NAME = ":9.4.7 Endocrine and reproductive systems"></A><A NAME = "SubSectionTitle:9.4.8 Dermatological"></A>9.4.8 Dermatological <PIM9.4.8>Skin burns from nitric acid may occur due to the mixture of fumes with sweat (Haddad and Winchester, 1990).</PIM9.4.8> <A NAME = ":9.4.8 Dermatological"></A><A NAME = "SubSectionTitle:9.4.9 Eye, ears, nose, throat: local effects"></A>9.4.9 Eye, ears, nose, throat: local effects <PIM9.4.9>There may be conjunctivitis and sore throat.</PIM9.4.9> <A NAME = ":9.4.9 Eye, ears, nose, throat: local effects"></A><A NAME = "SubSectionTitle:9.4.10 Haematological"></A>9.4.10 Haematological <PIM9.4.10>Severe haemoconcentration occurs due to the fluid loss in pulmonary oedema. Leucocytosis can occur even in the acute initial phase (Haddad and Winchester, 1990).<NL> <NL> Changes in blood chemistry (such as decreased red cell membrane acetylcholinesterase activity, red cell glucose-6-phosphate dehydrogenase, total haemoglobin and haematocrit and an increase in red cell peroxidized lipids) have been seen in young adults exposed to nitrogen dioxide 1 or 2 ppm for 3 hours daily for 3 days (Gosselin et al., 1984).<NL> <NL> Methaemoglobinaemia has been reported (Haddad and Winchester, 1990).</PIM9.4.10> <A NAME = ":9.4.10 Haematological"></A><A NAME = "SubSectionTitle:9.4.11 Immunological"></A>9.4.11 Immunological <PIM9.4.11>Unknown.</PIM9.4.11> <A NAME = ":9.4.11 Immunological"></A><A NAME = "SubSectionTitle:9.4.12 Metabolic"></A>9.4.12 Metabolic <A NAME = "DivisionTitle:9.4.12.1 Acid-base disturbances"></A>9.4.12.1 Acid-base disturbances <PIM9.4.12.1>Metabolic acidosis can occur due to the formation of nitrous acid and the development of lactic acidosis (Haddad and Winchester, 1990).</PIM9.4.12.1> <A NAME = "EndDivisionTitle:9.4.12.1 Acid-base disturbances"></A><A NAME = "DivisionTitle:9.4.12.2 Fluid and electrolyte disturbances"></A>9.4.12.2 Fluid and electrolyte disturbances <PIM9.4.12.2>Pulmonary inflammation and oedema result in fluid loss from blood.</PIM9.4.12.2> <A NAME = "EndDivisionTitle:9.4.12.2 Fluid and electrolyte disturbances"></A><A NAME = "DivisionTitle:9.4.12.3 Others"></A>9.4.12.3 Others <PIM9.4.12.3>Unknown</PIM9.4.12.3> <A NAME = "EndDivisionTitle:9.4.12.3 Others"></A><A NAME = ":9.4.12 Metabolic"></A><A NAME = "SubSectionTitle:9.4.13 Allergic reactions"></A>9.4.13 Allergic reactions <PIM9.4.13>Unknown</PIM9.4.13> <A NAME = ":9.4.13 Allergic reactions"></A><A NAME = "SubSectionTitle:9.4.14 Other clinical effects"></A>9.4.14 Other clinical effects <PIM9.4.14>Unknown</PIM9.4.14> <A NAME = ":9.4.14 Other clinical effects"></A><A NAME = "SubSectionTitle:9.4.15 Special risks"></A>9.4.15 Special risks <PIM9.4.15>Pregnancy: Unknown.<NL> <NL> Breast feeding: Unknown.<NL> <NL> Enzyme deficiencies: Unknown.</PIM9.4.15> <A NAME = ":9.4.15 Special risks"></A><A NAME = "EndSectionTitle:9.4 Systematic description of clinical effects"></A><A NAME = "SectionTitle:9.5 Others"></A>9.5 Others <PIM9.5>American astronauts on the Apollo - Soyuz mission were briefly exposed by accident to nitrogen dioxide. Elevated urinary levels of hydroxylysine glycosides suggested collagen breakdown in the pulmonary parenchyma (Ellenhorn & Barceloux, 1988).</PIM9.5> <A NAME = "EndSectionTitle:9.5 Others"></A><A NAME = "SectionTitle:9.6 Summary"></A>9.6 Summary <A NAME = "EndSectionTitle:9.6 Summary"></A><A NAME = "EndPartTitle:9. CLINICAL EFFECTS"></A><A NAME = "PartTitle:10. MANAGEMENT"></A>10. MANAGEMENT <A NAME = "SectionTitle:10.1 General principles"></A>10.1 General principles <PIM10.1>Remove the patient from the source of exposure.<NL> Establish an adequate airway and maintain respiration.<NL> Give oxygen and assisted ventilation if necessary.<NL> Remove secretions.<NL> Advise strict bed rest.<NL> Asymptomatic patients should be kept under observation for up to 72 hours.</PIM10.1> <A NAME = "EndSectionTitle:10.1 General principles"></A><A NAME = "SectionTitle:10.2 Life supportive procedures and symptomatic treatment"></A>10.2 Life supportive procedures and symptomatic treatment <PIM10.2>Establish an adequate airway and respiration. Remove frothy exudate from respiratory tract. Give oxygen for dyspnoea and cyanosis. If severe pulmonary oedema is present, assisted ventilation may be needed.<NL> <NL> Give normal saline or plasma expanders intravenously or blood transfusion to maintain adequate perfusion pressure.<NL> <NL> Do frequent sputum cultures. Treat infection with appropriate antibiotics.<NL> <NL> Correct acid-base abnormalities.<NL> <NL> If pulmonary oedema is not present, ensure a urine output of at least 1500 ml daily by giving adequate fluids. <NL> <NL> If symptoms of irritation or bronchospasm occur give a bronchodilator such as salbutamol by nebulizer.<NL> <NL> Give methylprednisolone 20 to 80 mg orally or intravenously. Repeat daily for 8 weeks before gradually decreasing the dose (Haddad and Winchester, 1990).</PIM10.2> <A NAME = "EndSectionTitle:10.2 Life supportive procedures and symptomatic treatment"></A><A NAME = "SectionTitle:10.3 Decontamination"></A>10.3 Decontamination <PIM10.3>Eye contact:<NL> Irrigate exposed eyes with copious amounts of water.</PIM10.3> <A NAME = "EndSectionTitle:10.3 Decontamination"></A><A NAME = "SectionTitle:10.4 Enhanced elimination"></A>10.4 Enhanced elimination <PIM10.4>Not relevant</PIM10.4> <A NAME = "EndSectionTitle:10.4 Enhanced elimination"></A><A NAME = "SectionTitle:10.5 Antidote treatment"></A>10.5 Antidote treatment <A NAME = "SubSectionTitle:10.5.1 Adults"></A>10.5.1 Adults <PIM10.5.1>No specific antidote.</PIM10.5.1> <A NAME = ":10.5.1 Adults"></A><A NAME = "SubSectionTitle:10.5.2 Children"></A>10.5.2 Children <PIM10.5.2>No specific antidote.</PIM10.5.2> <A NAME = ":10.5.2 Children"></A><A NAME = "EndSectionTitle:10.5 Antidote treatment"></A><A NAME = "SectionTitle:10.6 Management discussion"></A>10.6 Management discussion <PIM10.6>For bronchospasm, atropine, epinephrine, expectorants, and sedative drugs are ineffective and harmful (Gosselin et al., 1984).<NL> <NL> Patients must be followed-up for at least 6 weeks since relapses can occur.<NL> <NL> Asymptomatic patients could be discharged after 24 to 36 hours of observation but they should be followed up within several weeks to assess pulmonary status.</PIM10.6> <A NAME = "EndSectionTitle:10.6 Management discussion"></A><A NAME = "EndPartTitle:10. MANAGEMENT"></A><A NAME = "PartTitle:11. ILLUSTRATIVE CASES"></A>11. ILLUSTRATIVE CASES <A NAME = "SectionTitle:11.1 Case reports from literature"></A>11.1 Case reports from literature <PIM11.1>Cough, dyspnoea at rest and on exertion, chest pain, headache, haemoptysis and weakness were the symptoms reported by 116 people exposed to fumes from a malfunctioning engine (Hedberg et al., 1989).<NL> <NL> A chemist exposed to nitrogen dioxide (nitrous fumes) had cough and slight headache only. Twelve hours later he was awakened with dyspnoea and cough. On admission to hospital soon after, he had severe acute pulmonary oedema. He was discharged on the 7th day. On the 20th day after exposure he was readmitted with dyspnoea, coughing and sweating. He required intermittent positive pressure ventilation. He was treated with corticosteroids and discharged 28 days later (Milne, 1969). </PIM11.1> <A NAME = "EndSectionTitle:11.1 Case reports from literature"></A><A NAME = "EndPartTitle:11. ILLUSTRATIVE CASES"></A><A NAME = "PartTitle:12. ADDITIONAL INFORMATION"></A>12. ADDITIONAL INFORMATION <A NAME = "SectionTitle:12.1 Specific preventive measures"></A>12.1 Specific preventive measures <PIM12.1>Exposure to oxides of nitrogen at workplace should be avoided by appropriate storage of chemicals and by following proper safety standards.</PIM12.1> <A NAME = "EndSectionTitle:12.1 Specific preventive measures"></A><A NAME = "SectionTitle:12.2 Other"></A>12.2 Other <PIM12.2>No data available.</PIM12.2> <A NAME = "EndSectionTitle:12.2 Other"></A><A NAME = "EndPartTitle:12. ADDITIONAL INFORMATION"></A><A NAME = "PartTitle:13. REFERENCES"></A>13. REFERENCES <PIM13.>American Conference of Governmental Industrial Hygienists Inc. (1986).Documentation of the threshold limit values and biological exposure indices.5th Edition.Cincinnati, Ohio. 435 - 436.<NL> <NL> Budavari S ed. (1996) The Merck Index: an encyclopedia of chemicals, drugs, and biologicals, Rahway, New Jersey, Merck and Co. Inc.<NL> <NL> Cotlon FA, Wilkinson G ed. (1980) Advanced Inorganic Chemistry, U.S.A., John Wiley and Sons Inc.<NL> <NL> Dreishbach RH, Robertson WO ed (1987) Handbook of Poisoning: Prevention, Diagnosis and TreatmentLos Altos, Appleton & Lange. p 202.<NL> <NL> Ellenhorn MJ & Barceloux DG ed (1988). Medical Toxicology. New York, Elsevier Science Publishing Company, Inc. p 876. <NL> <NL> Gosselin RE, Smith RP, Hodge HC ed.(1984) Clinical Toxicology of Commercial Products. Baltimore, Williams and Wilkins. p III 319- 326.<NL> <NL> Guidotti TL (1978). The higher oxides of nitrogen: inhalation toxicology. Environmental Research 15:43-72<NL> <NL> Haddad LM and Winchester JF ed. (1990)Clinical management of poisoning and drug overdose 2nd Edition.W.B. Saunders Company, Philadelphia 1272 - 1280.<NL> <NL> Horvath SM (1980) Nitrogen dioxide, pulmonary function and respiratory disease. Bull. N.Y. Acid. Med. 56 (9): 835 - 846.<NL> <NL> NIOSH: Criteria for a Recommended Standard - Oxides of nitrogen (1976).DHEW Pub. No (NIOSH) 76 - 149.<NL> <NL> Hedberg K, Hedberg CW, Iber C, et al (1989) An outbreak of nitrogen dioxide induced respiratory illness among ice hockey players. JAMA, 262 (21): 3014 - 3017<NL> <NL> Lee JD ed. (1964) Concise Inorganic chemistry, 2nd Edition, Great Britain, William Clowes & Sons Ltd. pp. 115 - 119.<NL> <NL> Mellor JW ed. (1967) Mellor's Comprehensive Treatise on Inorganic and theoretical chemistry.Volume VIII Supplement II Nitrogen Part II. London, Longmans Green Co. Ltd. pp 189 - 195.<NL> <NL> Milne JEH (1969) Nitrogen dioxide inhalation and bronchiolitis obliterans. J. Occupational Medicine 11: 538 - 547.<NL> <NL> WHO (1977). Environmental Health Criteria 4. Oxides of nitrogen. World Health Organisation. Geneva, Switzerland.</PIM13.> <A NAME = "EndPartTitle:13. REFERENCES"></A><A NAME = "PartTitle:14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESSES"></A>14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESSES <PIM14.>Author(s): Dr. Ravindra Fernando & Miss. Deepthi Widyaratne<NL> National Poisons Information Centre<NL> Faculty of Medicine<NL> Kynsey Road<NL> Colombo 8<NL> Sri Lanka.<NL> <NL> Date: January 1992<NL> <NL> Peer Review: London, United Kingdom, September 1992<NL> <NL> Editor: M.Ruse (IPCS, May, 1999)</PIM14.> <A NAME = "EndPartTitle:14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESSES"></A> </PRE> <script src="/scripts/google_analytics.js" type="text/javascript"></script> </BODY> <PRE> </PRE> <PRE> See Also: <A HREF="../../eintro/eintro/abreviat.htm">Toxicological Abbreviations</A> <A HREF="../../jecfa/jecmono/40abcj32.htm">Nitrogen oxides (FAO Nutrition Meetings Report Series 40abc)</A> <A HREF="../../jecfa/jeceval/jec_1705.htm">NITROGEN OXIDES (JECFA Evaluation)</A> </PRE> </HTML>

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Nitrogen pentoxide (PIM 283)