Evaluation of the hazards of industrial exposure to tricresyl phosphate:a review and interpretation of the literature

Abstract

Commercial tricresyl phosphate (TCP) is a heterogeneous mixture of isomers and aryl phosphate congeners, known for many years to induce delayed neurotoxicity (OPIDN) in humans and experimental animals. In the past the isomer tri-o-cresyl phosphate (TOCP) was thought to be the component primarily responsible for OPIDN. It is now clear that other constituents, particularly the mono-o-esters, are not only neurotoxic but also may be more potent than pure TOCP. As a generality, the toxicity potential of a particular brand of TCP is related to its content of o-phenolic residues, whereby the maximal potential is reached when o-phenolics are 33% of the mix. Historically, human TCP toxicity has resulted from inadvertent or intentional contamination of foodstuffs or beverages. TCP products with high ortho-residues synthesized by older manufacturing methods were involved in most of these cases, and were likely much more neurotoxic milligram for milligram than TOCP. Because of the great variability of TCP products, there are no conventional workplace exposure standards. Based upon data from the hen and cat, estimated human safe exposure rates for pure TOCP are estimated to be 2.5 mg/kg for a single dose, and 0.13 mg/kg/d for repetitive exposures. These levels may also be applied to TCP when o-methyl-phenyl, o-ethyl-phenyl, and o-xylenyl components are appropriately limited during manufacture such that the TCP product is less neurotoxic than TOCP. There have been relatively few reports of toxicity associated with the manufacture or use of TCP in commerce and industry. Low vapor pressures of the constituents preclude the presence of significant quantities of TCP vapor in the atmosphere. A lubricant or other formulation containing TCP may appear in the air as a mist. By these criteria the U.S. Petroleum Oil Mist exposure standard is protective when the formulation contains 4% or less of low ortho-TCP. Exposure calculations indicate that estimated safe levels are not likely to be exceeded in the well-regulated workplace. If it is of short duration, even a heavy fog of oil particulate may not exceed the 8-h-average inhalation exposure standard. Modern manufacturing practices tend to minimize the ortho content and thus the toxicity of TCP. Because individual TCP brands and synthesis methods vary, manufacturers should be consulted concerning the properties of their individual products.

Reply to the letter of Anderson J entitled “Comment on Schindler, BK; Weiss, T; Schütze, A; et al. Occupational exposure of air crews to tricresyl phosphate isomers and organophosphate flame retardants after fume events, Arch Toxicol (2013) 87:645–648”

“…Anyway, we agree with Ms. Andersons perception that "there is little if any ToCP in aviation oils." Furthermore, there is very little o-TCP as already quoted in our paper (<0.01 % according to Craig and Barth 1999).…”

“…Anyway, we agree with Ms. Andersons perception that "there is little if any ToCP in aviation oils." Furthermore, there is very little o-TCP as already quoted in our paper (<0.01 % according to Craig and Barth 1999).In her letter to the editor, it is pointed out that "the three urinary metabolites alone [used in our survey] are insufficient to characterize onboard exposure to TCPs …”

Tri-ortho-cresyl phosphate induces autophagy of rat spermatogonial stem cells

“…TOCP can induce neurotoxicity (Craig & Barth 1999, Zhang et al 2007 and immunotoxicity (Foil et al 1980, Brinkerhoff et al 1981 in animals. In addition, TOCP had adverse effects on male reproductive system.…”

“…Tricresyl phosphate (TCP) has been widely used as plastic softeners, plasticizers, jet oil additives, and flameretardants in industry, and tri-ortho-cresyl phosphate (TOCP) is one of the three isomers (i.e., o-, m-, or p-cresyl) (Craig & Barth 1999, Winder & Balouet 2002. Unlike most organophosphates (OPs) exerting their acute toxic effects by suppressing acetylcholinesterase, TOCP mainly induces a delayed neurodegenerative condition known as OP-induced delayed neuropathy (OPIDN), which affects both the central and the peripheral nerves in sensitive species such as humans and hens (Smith et al 1930, Emerick et al 2012, Song et al 2012.…”

“…It has been reported that TOCP can induce reproductive toxicology (Somkuti et al 1987a(Somkuti et al , 1991, besides neurotoxicity (Craig & Barth 1999, Zhang et al 2007 and immunotoxicity (Foil et al 1980, Brinkerhoff et al 1981 in animals. TOCP has been shown to decrease sperm density in the cauda epididymis, inhibit testicular enzyme activities, and disrupt the seminiferous epithelium in rats and mice (Somkuti et al 1987a, 1991, Chen et al 2012.…”