Dinitrofenol – mieszanina izomerów. Dokumentacja proponowanych wartości dopuszczalnych wielkości narażenia zawodowego

Gralewicz, S.

Artykuł - szczegóły

Tytuł artykułu

Dinitrofenol – mieszanina izomerów. Dokumentacja proponowanych wartości dopuszczalnych wielkości narażenia zawodowego

Autorzy

Gralewicz S.

Treść / Zawartość

Pełne teksty:

Pobierz

Identyfikatory

Warianty tytułu

Dinitrophenol

Języki publikacji

Abstrakty

Dinitrofenol (DNP) – mieszanina izomerów: 2,3- DNP, 2,4- DNP i 2,6-DNP z przewagą 2,4-DNP, jest stosowany w produkcji barwników, kwasu pikrynowego i pikraminowego, wywoływaczy fotograficznych i materiałów wybuchowych oraz jako pestycyd w rolnictwie i sadownictwie. Dinitrofenol jest trucizną metaboliczną, a mechanizm jego działania toksycznego polega na rozprzęganiu fosforylacji oksydatywnej. Zawodowe narażenie na pary i pyły 2,4-DNP może wywoływać objawy wzmożonego metabolizmu. 2,4-DNP nie jest kancerogenem, nie wykazuje także działania genotoksycznego ani mutagennego. Za podstawę wyliczenia wartości NDS dla 2,4-DNP przyjęto wartość LOAEL dla skutków metabolicznych. Wartość ta u człowieka wynosi 1,2 mg/kg/dzień. W warunkach narażenia drogą oddechową taką dawkę pracownik może wchłonąć, gdy stężenie 2,4-DNP we wdychanym powietrzu wynosi 10,5 mg/m3. Przyjmując współczynnik niepewności równy 16 (2 dla różnic we wrażliwości osobniczej, 2 dla przejścia z wartości LOAEL do wartości NOAEL, 2 dla różnicy w sposobie narażenia i 2 dla ekstrapolacji z narażenia średnioterminowego do przewlekłego), to wyliczona wartość normatywu będzie wynosiła 0,66 mg/m3. W związku z powyższym proponuje się przyjęcie stężenia 0,5 mg/m3 za wartość NDS dla 2,4-DNP. Przyjmując, że 2,4-DNP jest najbardziej toksycznym izomerem dinitrofenolu oraz, że udział tego izomeru w dinitrofenolu – mieszaninie izomerów jest dominujący, proponujemy przyjęcie dla dinitrofenolu – mieszaniny również takiej samej wartości NDS jaką zaproponowano dla 2,4-DNP.

Dinitrophenol (DNP) is a mixture of 2,4-DNP and smaller amounts of 2,3-DNP and 2,6-DNP). It is a yellow, crystalline solid. DNP is used in synthesis of dyes, picric acid, picramic acid, wood preservatives, photographic developers, explosives, and insecticides. In the 1930s, 2,4-DNP was used as a weight-reducing drug. Short-term exposure to DNP may affect metabolism resulting in hyperthermia. High-level exposure may be fatal. The existing data concerning the health effects of 2,4-DNP oral exposure in humans indicate that the characteristic effects of 2,4-DNP for this route are: increased basal metabolic rate and perspiration, weight loss, a sensation of warmth, and – at higher dosage – increased heart and respiratory rate, and increased body temperature. Repeated or prolonged contact with the skin may cause dermatitis. Exposure to DNP may result in changes in the functional state of the peripheral nervous system, cardiovascular system and gastrointestinal system. It may also induce cataracts. Taking into account the results obtained in clinical studies on people ingesting 2,4-DNP (LOAEL for metabolic effects was 1.2 mg/kg/day), a concentration 0.5 mg of dinitrophenol/m3 is proposed as a maximum exposure limit (maximum admissible concentration) with a skin notation. With regard to systemic effects of DNP no STEL value has beeen established.

Słowa kluczowe

dinitrofenol fosforylacja oksydatywna metabolizm zaćma

dinitrophenol oxidative phosphorylation metabolism cataract

Wydawca

Centralny Instytut Ochrony Pracy - Państwowy Instytut Badawczy

Czasopismo

Podstawy i Metody Oceny Środowiska Pracy

Rocznik

2005

Tom

Nr 1 (43)

Strony

67--89

Opis fizyczny

Bibliogr. 85 poz., rys., tab.

Twórcy

autor

Gralewicz S.

Instytut Medycyny Pracy im. prof. dr. med. Jerzego Nofera 90-950 Łódź ul. św. Teresy 8

Bibliografia

1. ACGIH (1999) Threshold limit values for chemical substances and physical agents and biological exposure indices.
2. Anderson D., Styles J.A. (1978) The bacterial mutation test. Br. J. Cancer. 37, 924-930.
3. Bakke J.L., Lawrence N. (1965) Effect of dinitrophenol on pituitary-thyroid activity in the rat. Endocrinology 77, 382-389.
4. Bettman J.W. (1946) Experimental dinitrophenol cataract. Am. J. Ophtalmol. 29, 1388-1395.
5. Bouthwell R.K., Bosch D.K. (1959) The tumor-promoting action of phenol compounds for mouse skin. Cancer Res. 19, 413-424.
6. Branch S. i in. (1996) Supernumerary lumbar rib: manifestation of basic alteration in embryonic development of ribs. J. Apel. Toxicol. 16(2), 115-119.
7. Burke J.F., Whitehouse M.W. (1967) Concerning the differences in uncoupling activity of isomeric dinitrophenols. Biochem. Pharmacol. 16, 209-211.
8. Castor C.W., Beierwaltes W. (1956) Effect of 2,4-dinitrophenol on thyroid function in man. J. Clin Endocrinol. Metab. 16,1026-1031.
9. Chiu C.W. i in. (1978) Mutagenicity of some comercially available nitro compounds. Mutat. Res. 58, 11-22.
10. Davidson E.N., Shapiro M. (1934) Neutropenia following dinotrophenol with improvement after pentnucleotide and leucocyte cream. JAMA 103, 480-482.
11. De Flora S. (1981) Study of 106 organic and inorganic compounds in the Salmonella/microsome test. Carcinogenesis 2, 283-298.
12. Demerec M., Bertani G., Gibson J.E. (1951) A survey of chemicals for mutagenic action on E. coli. Am. Nat. 85, 119-136.
13. Dominguez S.E. i in. (1993) The effect of 2,4-dinitrophenol on the metabolic rate of bobwhite quail. Toxicol. Appl. Pharmacol. 123(2), 226-233.
14. Dow Chemical Co. (1940) Initial 8e submission: toxicity and health hazard of 2,4-dinitrophenol, dinitro-ortho-cresol, and dinitro-ortho-cyclohexyl phenol (final report) with letter dated 3/18/92 (sanitized). EPA/OPTS Public Files, Washington DC. Fiche 3 OPTS 0536148.
15. Dow Chemical Co. (1950) Initial 8e submission. The comparative acute oral toxicity of several dinitrophenols used in agriculture (final report) with cover letter dated 3/18/92 (sanitized). EPA/OPTS Public Files, Washington DC. Fiche 3 OPTS 0536145.
16. England P. i in. (1973) Increased thyroxine secretion following administration of dinitrophenol to rats. J. Physiol. (Lond) 229,33-49.
17. Eiseman J.L., Gehring P.J., Gibson J.E. (1972) In vitro metabolism of 2,4-dinitrophenol by rat livet homogenates. Toxicol. Appl. Pharmacol. 21, 275-285.
18. Eiseman J.L., Gehring P.J., Gibson J.E. (1974) Kinetics of in vitro reduction of 2,4-dinitrophenol by rat liver homogenates. Toxicol. Appl. Pharmacol. 27, 140-144.
19. EPA, Environmental Protection Agency (1994) Federal Register. 59 FR 15504.
20. Friedman M.A., Staub J. (1976) Inhibition of mouse testicular DNA synthesis by mutagens and carcinogens as a potential simple mammalian assay for mutagenesis. Mutat. Res. 37, 67-76.
21. Garner R.C., Nutman C.A. (1977) Testing of some azo dyes and their reduction products for mutagenicity using Salmonella typhimurium TA1538. Mutat. Res. 44, 9-19.
22. Garrett N.E., Lewtas J. (1983) Cellular toxicity in Chinese hamster ovary cell cultures. I. Analysis of cytotoxicity endpoints for twenty-nine priority pollutants. Environ. Res. 32, 455-465.
23. Gatz E.E., Jones J.R. (1972) Haloperidol antagonism to the hypermetabolic effects of 2,4- -dinitrophenol (in vitro and in vivo correlation). W: Cellular biology and toxicity of anesthetics. Baltimore, MD.Wiliams and Wilking Co., 304-311; 1972.
24. Gautschi J.R., Kern R.M., Painter R.B. (1973) Modification of replicon operation in HeLa cells by 2,4-dinitrophenol. J. Mol. Biol. 80, 393-403.
25. Gehring P.J., Buerge J.F. (1969 a) The cataractogenic activity of 2,4-dinitrophenol in ducks and rabbits.Toxicol. Appl. Pharmacol. 14(3), 475-86.
26. Gehring P.J., Buerge J.F. (1969 b) The distribution of 2,4-dinitrophenol relative to its cataractogenic activity in ducklings and rabbits. Toxicol. Appl. Pharmacol. 15(3), 574-92.
27. Ghosh S., Paweletz N., Armas-Portella R. (1989) Post-metaphase mitotic events in cells treated with dinitrophenol. Indian J. Exp. Biol. 27, 317-323.
28. Gibson J.E. (1973) Teratology studies in mice with 2-sec-butyl-4,6-dinitrophenol (Dinoseb). Food Cosmet. Toxicol. 11, 31-43.
29. Gisclard J.B., Woodword M.M. (1946) 2,4-Dinitrophenol poissoning: a case report. J. Ind. Hyg. Toxicol. 28, 47-51.
30. Goldman A.S., Yakovac W.C. (1964) Salicylate intoxication and congenital anomalies. Arch. Environ. Health 8, 648-656.
31. Harvey D.G. (1959) On the metabolism of some aromatic dinitro compounds by different species of animal: Part III. The toxicity of the dinitrophenols, with a note on the effects of high environmental temperatures. J. Pharm. Prarmacol. 11, 462-474.
32. Heinemann B., Howard A.J. (1964) Induction of lambda-bacterial phage in Escherichia coli as a screening test for potential antitumor agents. Appl. Microbiol. 12, 234-239.
33. Hilton J., Walker M. (1977) DNA strand scission and its repair following exposure of cells to inhibitors of oxidative phosphorylaction. Biochem. Biophys. Res. Commun. 75, 909-914.
34. Hitch J.M., Schwartz W.F. (1936) Late, toxic results, including dermetitis exfoliative, from “slim” (dinitrophenol). JAMA 106, 2130-2132.
35. Horner W.D. (1942) Dinitrophenol and its relation to formation of cataracts. Arch. Ophtalmol. (Paris) 27, 1097-1121.
36. HSDB, Hazardous Substances Data Bank (May 1999).
37. Hunter E.S., Tugman J.A. (1993) Neural tube defects produced by inhibitors of mitochondrial metabolism in mouse embryos in vitro. Teratology 47(5), 410.
38. I ARC, International Agency for Research on Cancer (1993 a) IARC monographs on the evaluation of the carcinogenicity risk of chemicals to humans: 2-amino-4-nitrophenol 57, 161-176.
39. IARC, International Agency for Research on Cancer (1993 b) IARC monographs on the evaluation of the carcinogenicity risk of chemicals to humans: 2-amino-5-nitrophenol 57, 177-184.
40. Kaiser J.A. (1964) Studies on the toxicity of diisophenol (2,6-diiodo-4-nitrophenol) to dogs and rodents plus some comparison with 2,4-dinitrophenol. Toxicol. Apel. Pharmacol. 6, 232-244.
41. Kavlock R.J., Short R.D., Chernoff N. (1987) Further evaluation of an in vitro teratology screen. Teratogenesis Carcino. Mutagen. 7, 7-16.
42. Kawai A. i in. (1987) Mutagenicity of aliphatic and aromatic nitro compounds, industrial materials and related compounds. Japn. J. Ind. Health 29, 34-54.
43. Kleinhofs A., Smith J.A. (1976) Effect of excision repair on azide-induced mutagenesis. Mutat. Res. 41, 233-240.
44. Levij I.S., Rubin D. (1975) Inhibition by 2,4-dinitrophenol of 9,10-dimethyl-1,2-benzantracene carcinogenesis in the hamster cheek pouch. Oncology 31, 334-337.
45. Limaye D.A., Shaikh Z.A. (1999) Cytotoxicity of cadmium and characteristics of its transport in cardiomyocytes. Toxicol. Apel. Pharmacol. 154, 59-66.
46. Linsinger G. i in. (1999) Uncouplers of oxidative phosphorylation can enhance a fas death signal. Mol. Cell. Biol. 19, 3299-3311.
47. Loomis W.F., Lippmann F. (1948) Reversible inhibition of the coupling between phosphorylation and oxidation. J. Biol. Chem. 173, 807-808.
48. Matzger E. (1934) Can sensitivity to dinitrophenol be determined by skin tests? JAMA 103, 253.
49. Maayan M.L. (1968) Effect of dinitrophenol on thyroid responses to thyreotropin. Endocrinology 83, 938-944.
50. Mitra A.B., Manna G.K. (1971) Effect of some phenolic compounds on chromosomes of bone marrow cells in mice. Indian J. ed. Res. 59, 1442-1447.
51. Miyagawa S. (1977) Differential effects of continuous and short time treatment with 2,4-dinitrophenol on the cell cycle of mouse L cells. Tokushima J. Ex. Med. 24, 147-154.
52. Murphy S.D. (1986) Toxic effects of pesticides: dinitrophenols. Casarett and Doull’s toxicology. New York, Macmillan Publishing Co. 555-556.
53. Murray i in.(1995) W: Biochemia Harpera. Wyd. III. Warszawa, Wydawnictwo Lekarskie PZWL.
54. Nadler J.E. (1935) Peripheral neuritis caused by prolonged use of dinitrophenol. JAMA 195,12-13.
55. Nakamura S. i in. (1987) SOS-inducing activity of chemical carcinogens and mutagens in Salmonella typhimurium TA1535/pSK1002, Examination with 151 chemicals. Mutat. Res. 192, 239-246.
56. Nishihata T. i in. (1988) Protective effect of salicylate against 2,4-dinitrophenol-induced protein-thiol loss in the samll intestine of rats. J. Pharm. Pharmacol. 40, 516-518.
57. Ogino S., Yasukura K. (1957) Biochemical studies on cataracts. VI. Production of cataracts in guinea pigs with dinitrophenol. Am. J. Ophtalmol. 43, 936-946.
58. Parker V.H. (1952) Enzymic reduction of 2,4-dinitrophenol by rat-tissue homogenates. Biochem. J. 51, 363-370.
59. Perkins R.G. (1919) A study of the munition intoxications in France. Public. Health Rep. 34, 2335- 2374.
60. Probst G.S. i in. (1981) Chemically induced unscheduled DNA synthesis in primary rat hepatocyte cultures: a comparison with bacterial mutagenicity using 218 compounds. Environ. Mutagen. 3, 11-32.
61. Pugsley L.I. (1935) The effect of 2,4-dinitrophenol upon calcium, creatine, and creatinine excretion in the rat. Biochem. J. 29, 2247.
62. Richard A.M. i in. (1991) Structure-activity study of paracetamol analogues: inhibition of replicative DNA synthesis in V79 chinesse hamster cells. Chem. Res. Toxicol. 4, 151-156.
63. Robert T.A., Hagardorn A.N. (1983) Analysis and kinetics of 2,4-dinitrophenol in tissues by capillary gas chromatography-mass spectrometry. J. Chromatogr. 276, 77-84.
64. Robert T.A., Hagardorn A.N. (1985) Plasma levels and kinetic disposition of 2,4-dinitrophenol and its metabolites 2-amino-4-nitrophenol and 4-amino-2-nitrophenol in the mouse. J. Chromatogr. 45, 177-186.
65. Saransaari P., Oja S.S. (1999) Mechanisms of D-aspartate release under ischemic conditions in mouse hippocampal slices. Neurochem. Res. 24, 1009-1016.
66. Sax N.I., Lewis R.J. (1987) Havley’s condensed chemical dictionary. 11 ed. New York, Van Nostrand Reinhold, 421.
67. Seiler J.P. (1981) Testicular DNA synthesis inhibition: an in vivo system for the detection of mutagenic and carcinogenic chemicals. Toxicol. Environ. Chem. 3, 239-249.
68. Simkins S. (1937 a) Dinitrophenol and dessicated thyroid in the treatment of obesity: a comprehensive clinical and laboratory study. JAMA 108, 2110-2117.
69. Simkins S. (1937 b) Dinitrophenol and dessicated thyroid in the treatment of obesity: a comprehensive clinical and laboratory study. JAMA 108, 2193-2199.
70. Spencer H.C. i in. (1948) Toxicological studies on laboratory animals of certain alkyldinitrophenols used in agriculture. J. Ind. Hyg. Toxicol. 30, 10-28.
71. Stenback F., Garcia H. (1975) Studies on the modifying effect of dimethyl sulfoxide and other chemicals on experimental skin tumor induction. Ann NY, Acad. Sci. 243, 209-227.
72. Swenberg J.A., Petzold G.L., Harbach P.R. (1976) In vitro DNA damage/alkaline elution assay for predicting carcinogenic potencial. Biochem. Biophys. Res. Commun. 72, 732-738.
73. Tainter M.L. (1938) Growth, life-span, and food intake of white rats fed dinitrophenol throughout life. J. Pharmacol. Exp. Ther. 63, 51057.
74. Tainter M.L., Borley W.E. (1938) Influence of vitamins and dinitrophenol on the production of experimental cataract. Arch. Ophtalmol. 20, 30-36.
75. Tainter M.L., Cutting W.C. (1933) Miscellaneous actions of dinitrophenol. Repeated administrations, antidotes, fatal doses, antiseptic tests and actions of some isomers. J. Pharmacol. Exp. Ther. 49, 187- 209.
76. Tainter M.L. i in. (1934) Di-nitrophenol. Studies of blood, urine, and tissue of dogs on continued medication and after acute fatal poisoning. Arch. Pathol. 18, 881.
77. Tainter M.L., Stockton A.B., Cutting W.C. (1935) Dinitrophenol in the treatment of obesity. Final report. JAMA 105, 332-337.
78. Tainter M.L., Wood D.A. (1934) A case of fatal dinitrophenol poisoning. JAMA 102, 1147.
79. Thompson J.G. i in. (2000) Effects of inhibitors and uncouplers of oxidative phosphorylation during compaction and blastulation of bovine embryos cultured in vitro. J. Reprod. Fertil. 118, 47-55.
80. TPD, Toxicological Profile for Dinitrophenols (August 1995) U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry.
81. Toyomizu M. i in. (1992) Research note: effect of 2,4-dinitrophenol on growth and body composition of broilers. Pult. Sci. 71, 10-96-1100.
82. Van der Voet G.B., van Ginkel M.F., de Wolff F.A. (1989) Intestinal absorption of aluminum in rats: stimulation by nitric acid and inhibition by dinitrophenol. Toxicol. Appl. Pharmacol. 99, 90-97.
83. Videla L., Israel Y. (1970) Facts that modify the metabolism of ethanol in rat liver and adaptive changes produced by its chronic administration. Biochem. J. 118, 275-281.
84. Wilkins J.N., Mayer S.E., Vanderlaan W.P. (1974) The effects of hypothyroidism and 2,4- -dinitrophenol on growth hormone synthesys. Endocrinology 95, 1259-1267.
85. Wulf L.M.R., Emge L.A., Bravo F. (1935) Some effects of alpha-dinitrophenol on pregnancy in the white rat. Proc. Soc. Exp. Biol. Med. 32, 678-680.

Typ dokumentu

Bibliografia

Identyfikator YADDA

bwmeta1.element.baztech-2571e4ad-87f9-45c4-b48e-5fcedbad6105