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Titolo:
Organophosphate-induced delayed neurotoxicity of triarylphosphates
Autore:
Weiner, ML; Jortner, BS;
Indirizzi:
FMC Corp, Dept Toxicol, Princeton, NJ 08543 USA FMC Corp Princeton NJ USA08543 rp, Dept Toxicol, Princeton, NJ 08543 USA Virginia Tech, Virginia Maryland Reg Coll Vet Med, Lab Neurotoxic Studies,Blacksburg, VA 24061 USA Virginia Tech Blacksburg VA USA 24061 ic Studies,Blacksburg, VA 24061 USA
Titolo Testata:
NEUROTOXICOLOGY
fascicolo: 4, volume: 20, anno: 1999,
pagine: 653 - 673
SICI:
0161-813X(199908)20:4<653:ODNOT>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEUROPATHY TARGET ESTERASE; CRESYL PHOSPHATE TOCP; O-TOLYL PHOSPHATE; SUBCHRONIC NEUROTOXICITY; AXONAL DEGENERATION; SCIATIC-NERVE; HENS; POLYNEUROPATHY; NTE; PATHOGENESIS;
Keywords:
triaryl phosphate; organophosphates; organophosphate-induced delayed neurotoxicity; NTE- (Neuropathy target) esterase; TOCP- tri-ortho-cresyl phosphate;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
81
Recensione:
Indirizzi per estratti:
Indirizzo: Weiner, ML FMC Corp, Dept Toxicol, POB 8, Princeton, NJ 08543 USA FMC CorpPOB 8 Princeton NJ USA 08543 , Princeton, NJ 08543 USA
Citazione:
M.L. Weiner e B.S. Jortner, "Organophosphate-induced delayed neurotoxicity of triarylphosphates", NEUROTOXICO, 20(4), 1999, pp. 653-673

Abstract

This paper reviews the characteristics of organophosphate-induced delayed neurotoxicity, its mechanism, lesions, species sensitivities and structure activity-relationships as they relate to the class of compounds known as triaryl phosphates. The triaryl phosphates have been widely used in commerce for over thirty years as flame retardants in fluids and plastics. Concern has been raised regarding their potential to cause organophosphate-induced delayed neurotoxicity (OPIDN), due to structural similarities to the potent neurotoxicant, tri-ortho cresyl phosphate (TOCP). Based on research on manypure isomers, Johnson (1975a, 1975b) found that certain structural features are required for a triaryl phosphate to react with the enzyme, neuropathytarget enzyme (NTE), in a manner which induces OPIDN. Results of acute henOPIDN studies, the experimental model of choice, support his findings as regards the structure-activity relationships for commercial triaryl phosphates. Thus, standard acute hen OPIDN studies on triphenyl phosphate and butylated triaryl phosphates fail to demonstrate a potential to elicit OPIDN by these products after a single dose. Studies on the mixed isopropyl phenyl phosphates indicate that, while some are neurotoxic, they are much less potent than tricresyl phosphate (TCP) and TOCP in the induction of OPIDN. Most commercial isopropylated triaryl phosphates lacked the potential to induce acute OPIDN using a limit dose of 2000 mg/kg. Although in early studies these compounds appeared to be neurotoxic, they were generally tested at excessively high doses, often exceeding 10,000 mg/kg in acute hen OPIDN studies. In contrast to the isopropylated and butylated triaryl phosphate products,TCP, and especially its ortho substituted isomer, TOCP, were found to be neurotoxic in both acute and subchronic hen OPIDN studies. Recent advances in the synthesis of commercial TCP products have resulted in products with reduced neurotoxic potential McCormick et al, 1993. As an example, when 3% TCP in aviation oil was dosed acutely at 5000 mg/kg, or for 90 days at 1000 mg/kg/day, no delayed neurotoxicity was noted (Daughtrey et al., 1990, 1996). These data are indicative of the safety of these aviation lubricants at use levels currently employed. (C)1999 Inter Press, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 10:20:05