Triphenyl phosphite

PBT assessment

PBT assessment: overall result

Reference

Reference 1

Name:

Triphenyl Phosphite

Type of composition:

legal entity composition of the substance

State / form:

liquid

Reference substance:

Triphenyl Phosphite

Reference 2

Name:

Triphenyl Phosphite

Type of composition:

boundary composition of the substance

State / form:

liquid

Reference substance:

Triphenyl Phosphite

PBT status:

the substance is not PBT / vPvB

Justification:

Justification:

 

TPP is not classifiable as a PBT or a vPvB substance as it does not meet criteria for either persistence or bioaccumulation.

 

Persistence (P, vP)

 

Based upon weight of evidence, TPP does not meet the criteria for being either persistent or very persistent. The key supporting evidence includes 1) an OECD 301D study that unequivocally demonstrates that TPP is ready biodegradable when it is dosed in a bioavailable form and 2) a series of hydrolysis studies, in particular a recent OECD 111 study that shows hydrolysis of TPP to phenol occurs at rates more than 20 fold faster than the persistence criteria at pH 4, 7 and 9 at 12°C. 

 

TPP is a dense non-aqueous phase liquid, which because of its density and non-polar properties is heavier than water and exists as a separate physical phase when present in water at concentrations exceeding its water solubility estimated to be approximately 20 µg/L (EpiSuite). Given its hydrophobicity, its tendency is to minimize its contact with water by aggregating into a dense and stable bolus with a minimal surface to volume ratio, thereby preventing the vast majority of the mass from coming in direct contact with water. This same configuration also can result in a very slow equilibrium partitioning rate out of the bolus into the water and poor bioavailability to microorganisms. This physical behaviour is important to consider when interpreting hydrolysis and biodegradation studies used for evaluating persistence of TPP.

 

In a 301D ready biodegradation study conducted in 2003 (BC Research Inc. Project No. 2-11-0877D), 10 mg/L of TPP was pipetted onto a glass fibre filter that was added to the test media inoculated with effluent. Although the toxicity control indicated that the test material did not inhibit the inoculum, biodegradation was only 0.1% after 28 days. During the study, the test systems were gently inverted each day. In 2015, another 301D study (van Ginkel Study No. T15020C) was conducted using diluted activated sludge as an inoculum and a TPP concentration of 2 mg/L with the test substance dosed into the test media on silica gel. Silica gel provides a large surface area onto which the TPP could be dispersed increasing its bioavailability. In this study, over 60% biodegradation was achieved in a period of 6 days immediately following the attainment of 10% biodegradation and biodegradation reached 84% in 28 days indicating TPP is ready biodegradable.

 

The striking contrast in the two 301D test results could have been related to differences in the competency of the inocula or bioavailability of the test substance in the two studies, though the latter factor is much more likely. The importance of presenting an insoluble or sparingly soluble test substance in a way that promotes its bioavailability in a ready biodegradation test has long been recognized. Annex III of the OECD TG 301 discusses this issue and indicates that the use of silica gel matrices is seen as the preferred first option for increasing the bioavailability of insoluble test substances. The difference in results between the 2003 and 2015 studies is best explained by how the TPP was dosed. In the 2015 biodegradation test, a deliberate attempt was made to maximize the bioavailability and surface to volume ratio of the test material using silica gel resulting in rapid and extensive biodegradation of TPP. However, in the 2003 study, no attempt was made to achieve this condition and biodegradation was negligible. 

 

The lack of environmental persistence of TPP is further supported by its rapid and extensive hydrolysis. In 1973, Kovacset alreported that TPP had “striking hydrolytic sensitivity“. Moreover, practical experience has long indicated that TPP can rapidly hydrolyze in the presence in water resulting in a need to protect TPP from exposure to moisture during manufacture and handling.  Al-Lohedan et al (1991) reported a TPP half life of 1.1 hr at pH 1.3 in water with 20 -50% ethanol at 25° C. More recently, Reimer (2002; BC Research Study NoRAA10301 152) conducted hydrolysis studies of TPP in unbuffered deionized water (pH 6 -7) with 50% methanol and pH 9 buffer with 50% acetonitrile as a co-solvent at 22°C. Co-solvents were used to solubilize the TPP so it could be analyzed in the mixed aqueous phase. The results of this study indicated half lives of 0.5 hr in the deionized water and 14 hr in the pH 9 treatments, respectively. Importantly, these experiments indicated that concurrent with the disappearance and of parent TPP, there was an increase in the concentration of phenol. Notably, no other intermediates (i.e. diphenyl phosphite or monophenyl phosphite) were observed indicating that TPP hydrolyzed directly to phenol and phophorous acid.  While these intermediated may have been formed, their absence indicate that they did not accumulate and were extremely transient.

 

While these previous studies showed rapid hydrolysis, they were not compliant with the OECD 111 guideline for multiple reasons including the pHs tested, the use of buffers for all treatments, the number of time points, and the use of high levels of co-solvent. The guideline allows at most 1% water miscible co-solvent to aid in the dissolution the test material. Consequently, a more standard OECD 111 was recently conducted (Wang and Schaefer 2017). Based upon the previous study showing that TPP hydrolyses directly to phenol, phenol release was used as the endpoint since it is highly soluble in water and would not require the use of high levels of co-solvent for its analysis. Preliminary studies were also conducted using different approaches for dosing TPP (Appendix V), sincejust as biodegradation of TPP could be affected by its physical state in the test so could its hydrolysis. The different dosing procedures examined included 1) adding the TPP to buffer using 1% acetone and vigorously agitating the test systems during incubation, 2) presenting the TPP as a thin film on the inner walls of the test vessels using a solvent and vigorously agitating the test systems during incubation and 3) applying the TPP to silica gel using solvent and incubating the test systems with gentle mixing. The most rapid and extensive hydrolysis was observed when TPP was dosed using silica gel. Since TPP had been visually observed dropping out of solution when added in a small volume of acetone to buffer solutions and subsequently aggregating into larger droplets, this likely explains the less rapid and less extensive hydrolysis observed in the first two treatments. Consequently, dosing with silica gel was used for the definitive hydrolysis study after verifying that TPP did not hydrolyse on silica gel in the absence of water.

 

In this definitive study, while parent TPP was observed in the chromatograms of some treatments, no other intermediates were present in agreement with the Reimer (2002) study. The hydrolytic half-lives of TPP at pH 7, which is the most relevant environmental pH, were 6.5 hrs at 20°C and 14.7 hrs at 12°C, which is considered the average temperature of EU surface waters. This measured half-life at 12°C (14.7 hr) was comparable to a 12.2 hr half-life at 12°C estimated from the 20°C data using the Arrhenius equation. The half-lives of TPP at pH 9 was 0.43 hrs and 21.9 hrs at pH 4 (20°C). Adjusting these half-lives to 12°C using theArrhenius equation resulted in half lives of 0.81 hrs at pH 9 and 41.0 hrs at pH 4.0. Notably, all these half-lives are much shorter than the half-life of 40 days used for establishing persistence in freshwater and estuarine water. In fact, the longesthalf-life at 12°C (1.7 days at pH 4) is more than 20 times shorter than the criteria for establishing persistence. 

 

Based upon these studies, TPP is expected to rapidly hydrolyse to phenol and phosphorous acid upon entering any aqueous environment. Hydrolysis may occur chemically or be accelerated enzymatically. Regardless, it will be very rapid and despite its mechanism of release, the resulting phenol will be rapidly biodegraded. Phenol is ready biodegradable and its biodegradation has been documented in a variety of environmental compartments relevant for a persistence assessment (European Chemical Bureau 2006).

 

Bioaccumulation (B, vB)

 

Although TPP has an estimated log K_owof 6.62, bioaccumulation is expected to be negligible due to its rapid hydrolysis when present in a bioavailable form in an aqueous setting. Furthermore, measuring a BCF or BAF in an OECD 305 study would not be practical due to TPP being hydrolytically unstable. The BCF model estimates for TPP are also of limited utility given the fact that hydrolysis of phosphite esters is not considered in the models. Given the rapid hydrolysis of TPP, the bioaccumulation potential of the hydrolysis products, phenol and phosphorous acid, were considered. Phenol has a log K_ow1.47, and phosphorous acid is a diproic acid with pK_as of 1.3 and 6.6 so it will be ionic at environmental pHs, Consequently, the metabolites are well below the screening criteria for being considered as bioaccumulative (B) or very bioaccumulative (vB). As such, it is concluded that TPP and its screening hydrolysis products do not meet the criteria for being B or vB.

 

Toxicity (T)

 

TPP is classified for both human health and environmental hazards. Phenol, TPP's primary hydrolysis product, is also classified for human health and the environment. As such, TPP is considered to meet the T criteria.

 

References:

 

BC Research Inc. 2003. Closed bottle test of Triphenyl Phosphite (CAS No. 101-02-0) using OECD Guideline 301D (Tox1002). BCRI Project No. 2-11-0877D.

 

Van Ginkel, CG. 2015.Biodegradability of triphenyl phosphite in the closed bottle test method (OECD TG 301). Akzo Nobel Study number T15020 C.

 

Kovacs, E. and Wolkober, Z. 1973. Effectivity of organic phosphites. J Polym Sci, Poly Symp No. 40, 73-8.

 

Al-Lohedan, HA. 1991. Micellar effects upon acid catalyzed hydrolysis of triphenyl phosphite. Phosphorus, Sulfur, Silicon Relat Elem 63(3-4), 261-71.

 

Reimer, GJ. 2002. Physical/Chemical Property of Triphenyl Phosphite (TPPi), CAS # 101-02-0: Hydrolytic Stability (OECD 111).BC Research Inc.Study NoRAA10301 152.

 

Wang, N and Schaefer, EC. 2017.Triphenyl phosphite: an evaluation of hydrolysis as a function of pH. EAG LaboratoriesProject Number: 835E-102.

 

European Chemicals Bureau. 2006. European Risk Assessment Report: Phenol (CAS No. 108-95-2).