sparingly soluble in water; soluble in acetic acid; freely soluble in
alcohol, benzene, ether; very soluble in carbon tetrachloride, toluene.
maximum allowable concentration: 0.1 mg/m3 (TLV-TWA) (ACGIH 1986)
TOCP is metabolized via three pathways. The first is the hydroxylation of one or more of the methyl groups, and the second is dearylation of the o-cresyl groups. The third is further oxidation of the hydroxymethyl to aldehyde and carboxylic acid. The hydroxylation step is critical because the hydroxymethyl TOCP is cyclized to form saligenin cyclic o-tolyl phosphate, the relatively unstable neurotoxic metabolite.
Saligenin cyclic o-tolyl phosphate (SCOTP) has been proposed as the active metabolite of tri-o-cresyl phosphate (TOCP), a neurotoxic organophosphate. TOCP is also toxic to the testis and SCOTP mimics some of this toxicity. The stability of SCOTP in vivo and its uptake by selected tissues has been measured. Total radioactivity and SCOTP-associated radioactivity were determined in male F-344 rats treated iv with 1 mg of [(14)C]-SCOTP/kg. The half-life of SCOTP in blood was 8.0 +/- 1.1 min. Testes, brain, and muscle had lower concentrations of [(14)C]-SCOTP-derived radioactivity than blood. Liver and kidney had higher concentrations of radioactivity than blood. HPLC analysis of liver, kidney, testes, and blood extracts showed that 2.8, 48, 11, and 18%, respectively, of the radioactivity present at 5 min was SCOTP. The amount of SCOTP declined rapidly, and at 30 min SCOTP could be detected only in kidney. It appears that SCOTP, although reactive, has sufficient stability to be transported from organ to organ. There is no evidence, however, of active uptake of SCOTP from blood by the testes. Evidence was obtained that SCOTP may act as an alkylating agent.
CBDP [2-(2-cresyl)-4H-1-3-2-benzodioxaphosphorin-2-oxide] is a toxic organophosphorus compound. It is generated in vivo from tri-ortho-cresyl phosphate (TOCP), a component of jet engine oil and hydraulic fluids. Exposure to TOCP was proven to occur on board aircraft by finding CBDP-derived phospho-butyrylcholinesterase in the blood of passengers. Adducts on BChE, however, do not explain the toxicity of CBDP. Critical target proteins of CBDP are yet to be identified. Our goal was to facilitate the search for the critical targets of CBDP by determining the range of amino acid residues capable of reacting with CBDP and characterizing the types of adducts formed. We used human albumin as a model protein. Mass spectral analysis of the tryptic digest of CBDP-treated human albumin revealed adducts on His-67, His-146, His-242, His-247, His-338, Tyr-138, Tyr-140, Lys-199, Lys-351, Lys-414, Lys-432, and Lys-525. Adducts formed on tyrosine residues were different from those formed on histidines and lysines. Tyrosines were organophosphorylated by CBDP, while histidine and lysine residues were alkylated. This is the first report of an organophosphorus compound with both phosphorylating and alkylating properties. The o-hydroxybenzyl adduct on histidine is novel. The ability of CBDP to form stable adducts on histidine, tyrosine, and lysine allows one to consider new mechanisms of toxicity from TOCP exposure.
The ability of bromine and rat liver microsomes (RLM) to convert organophosphorus (OP) protoxicants to esterase inhibitors was determined by measuring acetylcholinesterase (AChE) and neuropathy target esterase (NTE) inhibition. Species specific differences in susceptibility to esterase inhibition were determined by comparing the extent of esterase inhibition observed in human neuroblastoma cells and hen, bovine, and rodent brain homogenates. OP protoxicants examined included tri-o-tolyl phosphate (TOTP), O-ethyl O-p-nitrophenyl phenylphosphonothioate (EPN), leptophos, fenitrothion, fenthion, and malathion. Bromine activation resulted in greater AChE inhibition than that produced by RLM activation for equivalent concentrations of fenitrothion, malathion, and EPN. For EPN and leptophos, bromine activation resulted in greater inhibition of NTE than RLM. Only preincubation with RLM activated TOTP; resultant inhibition of AChE was less in hen brain (13 +/- 3%) than in neuroblastoma cells (73 +/- 1%) at 1x10-6 M. In contrast, 1x10-6 M RLM-activated TOTP produced more inhibition of hen brain NTE (89 +/- 6%) than NTE of human neuroblastoma cells (72 +/- 7%). Human neuroblastoma cells and brain homogenates from hens, the accepted animal model for study of OP-induced neurotoxicity, were relatively similar in sensitivity to esterase inhibition. Homogenates from hens were more sensitive to NTE inhibition induced by phenyl saligenin phosphate (PSP), an active congener of TOTP, than were homogenates from less susceptible species (mouse, rat, bovine). AChE of hen brain homogenates was also more sensitive than homogenates from other species to malaoxon, the active form of malathion.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A4；不可分类为人类致癌物。
A4; Not classifiable as a human carcinogen.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
暴露途径
这种物质可以通过吸入、皮肤接触和摄入被身体吸收。
The substance can be absorbed into the body by inhalation, through the skin and by ingestion.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
In cat studies, absorbed TOCP was widely distributed throughout the body, the highest concentration being found in the sciatic nerve, a target tissue. Other tissues with high concentration of TOCP and its metabolites were the liver, kidney, and gall bladder.
Dermal absorption of TOCP in humans appears to be at least an order of magnitude faster than that in dogs. Significant dermal absorption also appears to occur in cats. Oral absorption of the compound has been reported in rabbits. There is no direct information on absorption via the inhalation route.
Tri-o-cresyl phosphate (TOCP) is used commercially as a plasticizer and flame retardant. The disposition, metabolism, elimination and transplacental uptake of [phenyl-U-(14)C]TOCP and/or its metabolites, in pregnant and non-pregnant mice, were examined. Pregnant (18th-day gestation) and non-pregnant, ICR mice were given an i.v. dose of [(14)C]TOCP (557 uCi kg-1; Specified activity 4.83 uCi mumol-1). At various time intervals (1, 24, 48 and 72 hr) the animals were processed for whole-body autoradiography (WBA). Over 72 hr the non-pregnant mice excreted 55% of the (14)C in the urine and 9% in the feces, while excretion in the urine and feces by the pregnant mice was 50% and 9% of the total dose, respectively. The WBA and its computer-assisted image analysis indicated extensive distribution of the (14)C label originally dosed as [(14)C]TOCP in pregnant mice and their fetuses. The retention of radioactivity in organs such as lung, spleen, gall-bladder and liver of mother and its fetuses suggest that these are the target sites of TOCP toxicity. The distribution in non-pregnant and pregnant mice and in the fetal tissues followed a similar pattern in uptake and retention until 72 hr. Brain and spinal cord had the least amount of [(14)C]TOCP. This finding may support reports that explain the insensitivity of the mice towards organophosphate-induced delayed neurotoxicity (OPIDN) of TOCP.
申请人：Commissariat a L'Energie Atomique et aux Energies Alternatives
公开号：US20170240485A1
公开（公告）日：2017-08-24
The invention relates to a method for (I) producing a carboxylic ester of formula (I). Said method comprises the steps of: a) bringing an organosilane/borane of formula Si or B into contact with CO
2
, in the presence of a catalyst and an electrophilic compound of formula (III), the groups R
1
, R
2
, R
3
, R
4
, R
5
, Y, and M′ being as defined in claim 1; and optionally b) recovering the compound of formula (I) produced.
Palladium-Catalyzed C(sp<sup>2</sup>)–N Bond Cross-Coupling with Triaryl Phosphates
作者：Zicong Chen、Xiangmeng Chen、Chau Ming So
DOI：10.1021/acs.joc.9b00703
日期：2019.5.17
The first general palladium-catalyzed amination of aryl phosphates is described. The combination of MorDalPhos with [Pd(π-cinnamyl)Cl]2 enables the amination of electron-rich, electron-neutral, and electron-poor aryl phosphates with a board range of aromatic, aliphatic, and heterocyclic amines. Common functional groups such as ether, keto, ester, and nitrile show an excellent compatibility in this
[EN] HEMI-AMINAL ETHERS AND THIOETHERS OF N-ALKENYL CYCLIC COMPOUNDS<br/>[FR] ÉTHERS ET THIOÉTHERS HÉMIAMINAUX DE COMPOSÉS CYCLIQUES N-ALCÉNYLIQUES
申请人：ISP INVESTMENTS INC
公开号：WO2014116560A1
公开（公告）日：2014-07-31
Described herein are hemi-aminal ethers and thioethers of N-alkenyl cyclic compounds that may be produced through a reaction comprising: (A) at least one first reactant represented by a structure (I), wherein X is a functionalized or unfunctionalized C1-C5 alkylene group optionally having one or more heteroatoms, and each R1, R2, and R3 is independently selected from the group consisting of hydrogen and functionalized and unfunctionalized alkyl groups optionally having one or more heteroatoms, and (B) at least one second reactant having at least one hydroxyl moiety or thiol moiety. The hemi-aminal ethers and thioethers of N-alkenyl cyclic compounds may comprise a polymerizable moiety, in which case they may be left as-is or used to create homopolymers or non-homopolymers, or they may not comprise a polymerizable moiety. A wide variety of formulations may be created using the hemi-aminal ethers and thioethers of N-alkenyl cyclic compounds, including personal care, oilfield, and construction formulations.
Industrially important triaryl phosphites, traditionally prepared from PCl3, have been synthesized by a diphenyl diselenide-catalyzed one-step procedure involving white phosphorus and phenols, which provides a halogen- and transition metal-free way to these compounds. Subsequent oxidation of triaryl phosphites produces triaryl phosphates and triaryl thiophosphates. Phosphorotrithioates are also prepared
The invention comprises lubricating compositions and hydraulic fluids containing N,N′-diaryl-o-phenylenediamine compounds that impart good levels of oxidation inhibition in the lubricants and hydraulic fluids. The invention further comprises a method of making N,N′-diaryl-o-phenylenediamine compounds.
