Toxicological profiles - Methylene chloride

TOXICOLOGICAL PROFILE FOR METHYLENE CHLORIDE......Page 1
CONTENTS......Page 13
DISCLAIMER......Page 2
UPDATE STATEMENT......Page 3
FOREWORD......Page 5
QUICK REFERENCE FOR HEALTH CARE PROVIDERS......Page 7
CONTRIBUTORS......Page 9
PEER REVIEW......Page 11
LIST OF FIGURES......Page 17
LIST OF TABLES......Page 19
1.1 WHAT IS METHYLENE CHLORIDE?......Page 21
1.2 WHAT HAPPENS TO METHYLENE CHLORIDE WHEN IT ENTERS THE ENVIRONMENT?......Page 22
1.3 HOW MIGHT I BE EXPOSED TO METHYLENE CHLORIDE?......Page 23
1.5 HOW CAN METHYLENE CHLORIDE AFFECT MY HEALTH?......Page 24
1.6 HOW CAN METHYLENE CHLORIDE AFFECT CHILDREN?......Page 26
1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO METHYLENE CHLORIDE?......Page 27
1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO METHYLENE CHLORIDE?......Page 28
1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO PROTECT HUMAN HEALTH?......Page 29
1.10 WHERE CAN I GET MORE INFORMATION?......Page 31
2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE......Page 33
2.2.1.1 Death......Page 35
2.2.1.2 Systemic Effects......Page 50
2.2.1.3 Immunological and Lymphoreticular Effects......Page 55
2.2.1.4 Neurological Effects......Page 56
2.2.1.5 Reproductive Effects......Page 60
2.2.1.6 Developmental Effects......Page 62
2.2.1.7 Genotoxic Effects......Page 63
2.2.1.8 Cancer......Page 65
2.2.2.1 Death......Page 70
2.2.2.2 Systemic Effects......Page 71
2.2.2.5 Reproductive Effects......Page 80
2.2.2.8 Cancer......Page 81
2.2.3.2 Systemic Effects......Page 82
2.2.3.5 Reproductive Effects......Page 84
2.2.3.8 Cancer......Page 85
2.3 TOXICOKINETICS......Page 86
2.3.1.1 Inhalation Exposure......Page 87
2.3.1.2 Oral Exposure......Page 89
2.3.2.1 Inhalation Exposure......Page 90
2.3.2.2 Oral Exposure......Page 91
2.3.3 Metabolism......Page 92
2.3.4 Elimination and Excretion......Page 101
2.3.4.2 Oral Exposure......Page 102
2.3.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models......Page 103
2.3.5.1 Methylene Chloride PBPK Model Comparison......Page 104
2.3.5.2 Discussion of Methylene Chloride PBPK Models......Page 110
2.4.1 Pharmacokinetic Mechanisms......Page 132
2.4.2 Mechanisms of Toxicity......Page 134
2.4.3 Animal-to-Human Extrapolations......Page 141
2.5 RELEVANCE TO PUBLIC HEALTH......Page 143
2.7 CHILDREN’S SUSCEPTIBILITY......Page 161
2.8 BIOMARKERS OF EXPOSURE AND EFFECT......Page 165
2.8.1 Biomarkers Used to Identify or Quantify Exposure to Methylene Chloride......Page 166
2.8.2 Biomarkers Used to Characterize Effects Caused by Methylene Chloride......Page 168
2.9 INTERACTIONS WITH OTHER CHEMICALS......Page 169
2.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE......Page 171
2.11.1 Reducing Peak Absorption Following Exposure......Page 173
2.11.2 Reducing Body Burden......Page 174
2.11.3 Interfering with the Mechanism of Action for Toxic Effects......Page 175
2.12.1 Existing Information on Health Effects of Methylene Chloride......Page 176
2.12.2 Identification of Data Needs......Page 179
2.12.3 Ongoing Studies......Page 191
3.2 PHYSICAL AND CHEMICAL PROPERTIES......Page 193
4.1 PRODUCTION......Page 197
4.3 USE......Page 201
4.4 DISPOSAL......Page 202
5.2 RELEASES TO THE ENVIRONMENT......Page 204
5.2.1 Air......Page 210
5.2.2 Water......Page 211
5.2.3 Soil......Page 212
5.3.2.1 Air......Page 213
5.3.2.2 Water......Page 214
5.4.1 Air......Page 215
5.4.2 Water......Page 216
5.4.4 Other Environmental Media......Page 218
5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE......Page 219
5.6 EXPOSURES OF CHILDREN......Page 220
5.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES......Page 222
5.8.1 Identification of Data Needs......Page 224
5.8.2 Ongoing Studies......Page 228
6.1 BIOLOGICAL SAMPLES......Page 232
6.2 ENVIRONMENTAL SAMPLES......Page 233
6.3 ADEQUACY OF THE DATABASE......Page 239
6.3.1 Identification of Data Needs......Page 240
6.3.2 Ongoing Studies......Page 241
7. REGULATIONS AND ADVISORIES......Page 243
8. REFERENCES......Page 250
Case-Control Study......Page 304
Genotoxicity......Page 305
Malformations......Page 306
Pesticide......Page 307
Reference Dose (RfD)......Page 308
Threshold Limit Value (TLV)......Page 309
Xenobiotic......Page 310
ATSDR MINIMAL RISK LEVELS AND WORKSHEETS......Page 312
MINIMAL RISK LEVEL (MRL) WORKSHEET......Page 314
USER'S GUIDE......Page 324
ACRONYMS, ABBREVIATIONS, AND SYMBOLS......Page 332