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Aliphatic diketones: influence of dicarbonyl spacing on amine reactivity and toxicity.

Authors
Boekelheide-K; Anthony-DC; Giangaspero-F; Gottfried-MR; Graham-DG
Source
Chem Res Toxicol 1988 Jul; 1(4):200-203
NIOSHTIC No.
00184636
Abstract
A study was made of the chemical reactivity and in-vivo effects of the delta diketone, 2,6-heptanedione (13505345) and the epsilon diketone, 2,7-octanedione (1626091). The relative amine reactivities of 2,5-hexanedione (110134), a gamma diketone, 2,6- heptanedione, and 2,7-octanedione were determined by incubation with ovalbumin. 2,6-Heptanedione derivatized ovalbumin lysyl epsilon amines more rapidly than 2,5-hexanedione. However, 2,7-octanedione did not decrease the free amine concentration of ovalbumin during incubation, being essentially incapable of forming long lived adducts with amines under biologic conditions since this would require the development of a seven membered ring. The diketones were incubated with ovalbumin and tritium labeled lysine to compare their relative cross linking abilities. To assess in-vivo toxicity, rats were given daily intraperitoneal injections of 4 millimoles of 2,6-heptanedione/kilogram. Only three of seven survived and after 11 weeks they exhibited generalized wasting but no detectable neuropathy. Nor was there any significant difference in the weight of the testes of treated rats. In a second study 2,6-heptanedione was administered in the drinking water as a 1 percent solution for 7 weeks, followed by a 10 week period of 2 percent 2,6-heptanedione exposure for an average daily dose of 11.3 millimoles/kilogram. No mortality occurred and no clinical neurotoxicity was noted. Testes weight was normal. Intraperitoneal injection of 2,7-octadione produced severe local inflammation. In the one surviving rat no clinical signs of neurotoxicity were noted and testes weight was normal. The neurotoxic potency of the gamma diketones was clearly dependent on their rate of pyrrole formation, identifying cyclization as an essential step in the development of an injury.
Keywords
NIOSH-Publication; NIOSH-Grant; Laboratory-animals; Nervous-system-disorders; Testes; Reproductive-system-disorders; Metabolic-study; Carcinogenicity; Toxic-effects
Contact
Pathology and Lab Medicine Div. of Biology and Medicine Brown University, Box G Providence, RI 02912
CODEN
CRTOEC
CAS No.
13505-34-5; 1626-09-1; 110-13-4
Publication Date
19880701
Document Type
Other
Funding Amount
357615
Funding Type
Grant
Fiscal Year
1988
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-02191
Issue of Publication
4
ISSN
0893-228X
Priority Area
Reproductive-system-disorders
Source Name
Chemical Research in Toxicology
State
RI
Performing Organization
Brown University, Providence, Rhode Island
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