Thirteen-week inhalation toxicity of N,N-dimethylformamide in F344/N rats and B6C3F1 mice

Toxicological Sciences

Volumn 72, Issue 2, 2003, Pages 347-358

  Lynch, D W ^a   Placke, M E ^b,c   Persing, R L ^c   Ryan, M J ^c  

^a NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH   (United States)

^b BATTELLE MEMORIAL INSTITUTE   (United States)

^c Battelle Columbus Lab   (United States)

Author keywords

13 week inhalation study; Centrilobular hepatocellular hypertrophy; Centrilobular hepatocellular necrosis; Dimethylformamide; DMF; Hepatotoxicity

Indexed keywords

ALANINE AMINOTRANSFERASE; BILE ACID; CHOLESTEROL; IDITOL DEHYDROGENASE; ISOCITRATE DEHYDROGENASE; N,N DIMETHYLFORMAMIDE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BILE ACID BLOOD LEVEL; BODY WEIGHT; CHOLESTEROL BLOOD LEVEL; CONCENTRATION RESPONSE; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME BLOOD LEVEL; FEMALE; HYPERTROPHY; LIVER INJURY; LIVER NECROSIS; LIVER TOXICITY; LIVER WEIGHT; MALE; MOUSE; MOUSE STRAIN; NONHUMAN; RAT; RAT STRAIN; SAMPLING; STATISTICAL ANALYSIS; STRAIN DIFFERENCE; TOXICITY TESTING;

ADMINISTRATION, INHALATION; ALANINE TRANSAMINASE; ANIMALS; BODY WEIGHT; CHOLESTEROL; DIMETHYLFORMAMIDE; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; ISOCITRATE DEHYDROGENASE; L-IDITOL 2-DEHYDROGENASE; LIVER; MALE; MICE; MICE, INBRED STRAINS; NECROSIS; NO-OBSERVED-ADVERSE-EFFECT LEVEL; ORGAN SIZE; RATS; RATS, INBRED F344; SOLVENTS;

ANIMALIA;

EID: 0037387813     PISSN: 10966080     EISSN: None     Source Type: Journal    
DOI: 10.1093/toxsci/kfg033     Document Type: Article

References (40)

1. ACGIH (2001). Documentation of the Threshold Limit Values for Chemical Substances, 7th ed., Vol. I. American Conference of Governmental Industrial Hygienists, Cincinnati, OH.
2. Arena, N., Santa-Cruz, G., Alia, E. F., Baldus, M., Corgiolu, T., and Alia, E. E. (1982). Structural and ultrastructural changes in the myocardia of rabbits exposed to dimethylformamide vapors. Soc. Ital. Biol. Sper. 58, 1496-1501 (In Italian).
3. Brondeau, M. T., Bonnet, P., Guenier, J. P., and De Ceaurriz, J. (1983). Short-term inhalation test for evaluating industrial hepatotoxicants in rats. Toxicol. Lett. 19, 139-146.
4. Clayton, J. W., Barnes, J. R., Hood, D. B., and Schepers, G. W. H. (1963). The inhalation toxicity of dimethylformamide (DMF). J. Am. Ind. Hyg. Assoc. 24, 144-154.
5. Craig, D. K., Weir, R. J., Wagner, W., and Groth, D. (1984). Subchronic inhalation toxicity of dimethylformamide in rats and mice. Drug Chem. Toxicol. 7, 551-571.
6. Dunn, O. J. (1964). Multiple comparisons using rank sums. Technometrics 6, 241-252.
7. Dunnett, W. (1955). A multiple comparison procedure for comparing several treatments with a control. J. Am. Stat. Assoc. 50, 1095-1121.
8. Du Pont (1986). Dimethylformamide (DMF). Properties, Uses, Storage and Handling. E. I. Du Pont de Nemours, Wilmington, DE.
9. Fiorito, A., Larese, F., Molinari, S., and Zanin, T. (1997). Liver function alterations in synthetic leather workers exposed to dimethylformamide. Am. J. Ind. Med. 32, 255-260.
10. Germanova, A. L., Khalepo, A. I., Aviova, G. G., Anvaer, L. P., Khoroshilova, N. V., Maltseva, N. M., and Migukina, N. V. (1979). Adaptive reaction to monotonous and intermittent action of dimethylformamide. Toksikol. Nov. Prom. Khim. Veschestv. 15, 69-76; 145-150 (In Russian).
11. Hundley, S. G., Lieder, P. H., Valentine, R., Malley, L. A., and Kennedy, G. L., Jr. (1993a). Dimethylformamide pharmacokinetics following inhalation exposures to rats and mice. Drug Chem. Toxicol. 16, 21-52.
12. Hundley, S. G., McCooey, K. T., Lieder, P. H., Hurtt, M. E., and Kennedy, G. L., Jr. (1993b). Dimethylformamide pharmacokinetics following inhalation exposure in monkeys. Drug Chem. Toxicol. 16, 53-79.
13. Hurtt, M. E., Placke, M. E., Killinger, J. M., Singer, A. W., and Kennedy, G. L., Jr. (1992). 13-week inhalation toxicity study of dimethylformamide (DMF) in cynomolgus monkeys. Fundam. Appl. Toxicol. 18, 596-601.
14. Jonckheere, A. R. (1954). A distribution free k-sample test against ordered alternatives. Biometrika 41, 133-145.
15. Kennedy, G. L., Jr. (1986). Biological effects of acetamide, formamide, and their monomethyl and dimethyl derivatives. Crit. Rev. Toxicol. 17, 129-182.
16. Kennedy, G. L., Jr. (2001). Biological effects of acetamide, formamide, and their monomethyl and dimethyl derivatives: An update. Crit. Rev. Toxicol. 31, 139-222.
17. Kennedy, G. L., Jr., and Sherman, H. (1986). Acute and subchronic toxicity of dimethylformamide and dimethylacetamide following various routes of administration. Drug Chem. Toxicol. 9, 147-170.
18. Korsrud, G. O., Grice, H. G., Goodman, T. K., Knipfel, J. E., and McLaughlan, J. M. (1973). Sensitivity of several serum enzymes for the detection of thioacetamide-, dimethylnitrosamine-, and diethanolamine-induced liver damage in rats. Toxicol. Appl. Pharmacol. 26, 299-313.
19. Malley, L. A., Slone, T. W., Jr., Vanpept, C., Elliott, G. S., Ross, P. E., Stadler, J. C., and Kennedy, G. L., Jr. (1994). Chronic toxicity/oncogenicity of dimethylformamide in rats and mice following inhalation exposure. Fundam. Appl. Toxicol. 23, 268-279.
20. Maronpot, R. R., and Boorman, G. A. (1982). Interpretation of rodent hepatocellular proliferative alterations and hepatocellular tumors in chemical safety assessment. Toxicol. Pathol. 10, 71-80.
21. Marsella, J. A. (1994). "Dimethylformamide" under "Formic acid and derivatives." In Kirk-Othmer Encyclopedia of Chemical Technology, 4th ed. (J. I. Kroschwitz and M. Howe-Grant, Eds.), Vol. 11, pp. 967-976. John Wiley & Sons, New York.
22. Massmann, W. (1956). Toxicological investigations on dimethylformamide. Br. J. Indust. Med. 13, 51-54.
23. Morrison, D.F. (1976). Multivariate Statistical Methods, pp. 170-179. McGraw Hill, New York.
24. Morrissey, R. E., Schwetz, B. A., Lamb, J. C., IV, Ross, M. C., Teague, J. L., and Morris, R. W. (1988). Evaluation of rodent sperm, vaginal cytology, and reproductive organ weight data from National Toxicology Program 13-week studies. Fundam. Appl. Toxicol. 11, 343-358.
25. Mraz, J., Cross, H., Gescher, A., Threadgill, M. D., and Flek, J. (1989). Differences between rodents and humans in the metabolic toxification of N,N-dimethyformamide. Toxicol. Appl. Pharmacol. 98, 507-516.
26. NTP (1992). NTP Technical Report on the Toxicity Studies of N,N-Dimethylformamide in F344/N Rats and B6C3F1 Mice. NTP Tox 22. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, NC.
27. OSHA (1989). 29 CFR Part 1910. Air Contaminants; Final Rule. U.S. Department of Labor. 54 Fed. Regist. 2332-2983.
28. Potter, H. P. (1973). Dimethylformamide-induced abdominal pain and liver injury. Arch. Environ. Health 27, 340-341.
29. Redlich, C. A., Beckett, W. S., Sparer, J., Barwick, K. W., Riely, C. A., Miller, H., Sigal, S. L., Shalat, S. L., and Cullen, M. R. (1988). Liver disease associated with occupational exposure to the solvent dimethylformamide. Ann. Int. Med. 108, 680-686.
30. Redlich, C. A., West, B. A., Fleming, L., True, L. D., Cullen, M. R., and Riely, C. A. (1990). Clinical and pathological characteristics of hepatotoxicity associated with occupational exposure to dimethylformamide. Gastroenterology 99, 748-757.
31. Roure, M. B., Lambert, A. M., Cour, C., Bonnet, P., and Saillenfait, A. M. (1996). Hepatotoxicity of N,N-dimethylformamide in rats following intra-peritoneal or inhalation routes of administration. J. Appl. Toxicol. 16, 265-267.
32. Santa-Cruz, G. M., and Maccioni, A. (1978). Experimental studies on the toxicity of dimethylformamide: Myocardial changes from prolonged inhalation in the rat. Boll. Soc. Ital. Biol. Sper. 54, 1717-1722 (In Italian).
33. Scailteur, V., and Lauwerys, R. R. (1987). Dimethylformamide (DMF) hepatotoxicity. Toxicology 43, 231-238.
34. Shirley, E. (1977). A non-parametric equivalent of Williams' test for contrasting increased dose levels of a treatment. Biometrics 33, 386-389.
35. Smyth, H. F., and Carpenter, C. P. (1948). Further experience with the range finding test in the industrial toxicology laboratory. J. Ind. Hyg. Toxicol. 30, 63-68.
36. Tanaka, K. I. (1971). Toxicity of dimethylformamide (DMF) to the young female rat. Int. Arch. Arbeitsmed. 28, 95-105.
37. Travlos, G. S., Morris, R. W., Elwell, M. R., Duke, A., Rosenblum, S., and Thompson, M. B. (1996). Frequency and relationships of clinical chemistry and liver and kidney histopathology findings in 13-week toxicity studies in rats. Toxicology 107, 17-29.
38. Trochimowicz, H. J., Kennedy, G. L. Jr., and Krivanek, N. D. (1994). Heterocyclic and miscellaneous nitrogen compounds. In Patty's Industrial Hygiene and Toxicology, 4th ed. (G. D. Clayton and F. E. Clayton, Eds.), Vol. II, Part E Toxicology, pp. 3285-3521. John Wiley & Sons, New York.
39. Williams, D. A. (1971). A test for differences between treatment means when several dose levels are compared with a zero dose control. Biometrics 27, 103-117.
40. Williams, D. A. (1972). The comparison of several dose levels with a zero dose control. Biometrics 28, 519-531.