| Main Title |
In Vitro Metabolism in Rat, Mouse and Hamster Liver and Lung Fractions and in Human Liver Fractions with Methylene Chloride. |
| CORP Author |
Shell Oil Co., Houston, TX.; Environmental Protection Agency, Washington, DC. Office of Toxic Substances. |
| Year Published |
2000 |
| Report Number |
86-880000289 |
| Stock Number |
OTS0514367 |
| Additional Subjects |
Toxicology ;
Health effects ;
Methylene Chloride (75-09-2) ;
Pharmaco Kinetics ;
Mammals ;
Rats ;
In Vitro ;
Mice ;
Hamsters ;
Humans ;
Gavage ;
Toxic substances ;
Laboratory animals ;
CAS No 75-09-2
|
| Holdings |
| Library |
Call Number |
Additional Info |
Location |
Last
Modified |
Checkout
Status |
| NTIS |
OTS0514367 |
Some EPA libraries have a fiche copy filed under the call number shown. |
|
07/26/2022 |
|
| Collation |
33p |
| Abstract |
The metabolism of methylene chloride (75-09-2) was compared in vitro in liver and lung fractions of male B6C3F1 mice, Fischer 344 rats, Charles River Lake View hamsters, and 4 human accident victims (liver tissue only) to attempt to explain marked species specificity of tumorigenic response in these tissues. The cytochrome P450 and glutathione-S-transferase dependent pathways, respectively, of isolated microsomal and cytosolic fractions were assessed by carbon monoxide formation (cytochrome P450 pathway) and by formaldehyde production (glutathione-S- transferase pathway) after incubation of the tissues with methylene chloride. Cytochrome P450 biotransformation of methylene chloride to carbon monoxide in mouse and hamster lung and liver was significantly more efficient than that of rat or human (liver only). The rate of methylene chloride conversion to carbon monoxide via glutathione-S-transferase in the mouse liver (Vmax 36.4 nmoles/min/mg protein) markedly exceeded that of any other tissue, being 12 times more active than that of the rat (Vmax 2.9 nmoles/min/mg). Neither human nor hamster liver cytosolic fractions showed any detectable methylene chloride metabolism by this pathway, although positive controls confirmed viability of the system. Slight evidence of such metabolism was detected in mouse lung tissue (Vmax 0.15 nmoles/min/mg), but was barely perceived in that of rat or hamster (human lung was not available). In that known carcinogenicity correlates with methylene chloride metabolism by the glutathione pathway in experimental animals, but not the cytochrome P450 pathway, the relative inactivity of that pathway in humans suggests a low risk of methylene chloride-induced carcinogenicity. |
| Supplementary Notes |
The quality of the documents listed in the Office of Toxic Substances database may not meet usual NTIS standards but are included to further the opportunity for the scientific and technical community to locate materials which may not be available elsewhere. The content is the responsibility of OTS. Sponsored by Environmental Protection Agency, Washington, DC. Office of Toxic Substances. |
| Availability Notes |
Product reproduced from digital image. Order this product from NTIS by: phone at 1-800-553-NTIS (U.S. customers); (703)605-6000 (other countries); fax at (703)605-6900; and email at orders@ntis.gov. NTIS is located at 5285 Port Royal Road, Springfield, VA, 22161, USA. |
| PUB Date Free Form |
2000 |
| Category Codes |
57Y; 57U; 68G; 99; 44G |
| NTIS Prices |
PC A04/MF A04 |
| Document Type |
NT |
| Cataloging Source |
NTIS/MT |
| Control Number |
028801950 |
| Origin |
NTIS |
| Type |
CAT |
