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Link to relevant study record(s)

Description of key information

Key value for chemical safety assessment

Absorption rate - oral (%):
80
Absorption rate - dermal (%):
40

Additional information

Hazards identified by EU Risk Assessment in May 2008:

"After oral administration, there were indications of <100% absorption, when oral and i.v. dosing were compared. It is quite difficult to estimate the percent oral absorption. However, it appears from the available information that oral absorption is at least 75%, and may be slightly higher (based on the Minegishi data, and supported by the Stauffer data). Therefore, 80% oral absorption will be taken forward to risk characterisation.

After oral administration, Cmax in plasma was reached in 0.5 to 2 hours and 5.7 hours in tissues. Tissue radioactivity concentrations were dose and administration route-dependent (oral and intravenous). Although tissue/blood ratios over 7 days were > 1 for liver, kidney, lung and adipose tissue, absolute concentrations were low and the bioaccumulation potential was considered minimal. TCPP is extensively metabolised and accounted for 2% of urinary or faecal radioactivity after oral administration. Metabolites identified in urine and faeces, in order of abundance, were 0,0-[Bis(1-chloro-2-propyl)]-0-(2-propionic acid)phosphate, bis(1-chloro-2-propyl)monophosphoric acid and 1-chloro-2-propanol. Elimination of TCPP from plasma and tissues was biphasic. The average terminal plasma t½ was 48.7 hours. The longest tissue t½ was recorded in adipose tissue (up to 103.4 hours). Urinary and faecal excretion of radioactivity was dose and administration route-dependent (oral and intravenous), and occurred quite rapidly. The observed biliary/faecal excretion ratio is indicative of enterohepatic recirculation. In a separate in vitro comparative metabolism study with 14C-TCPP, TCEP and TDCP, TCPP was metabolised to 89 and 61% respectively in rat liver S9 mix and liver slices. An in vitro percutaneous absorption study using human skin membranes was conducted to determine the absorption following topical application of [14C]-TCPP. The skin membranes were exposed to TCPP for 8 hours, mimicking a normal working day. The mean total absorption was 22.7 %, 13.6 % and 3.7 %, for doses 0.002, 0.1 and 1 mg/cm2, respectively. The total absorption value of 23% is taken forward to risk characterisation for scenarios where there is exposure to "neat" TCPP. A second in vitro study was conducted to determine the percentage of TCPP absorbed across the skin resulting from manual handling of flexible PUR foam containing TCPP. The skin membranes were exposed to the target concentrations of TCPP in artificial sweat for a period of 8 hours, mimicking a normal working day. It was determined that the total mean absorptions were 33.3% and 38.1% for the low and high doses of TCPP respectively. Therefore, with respect to risk characterisation, 40% dermal absorption will be taken forward for those scenarios where there is exposure due to handling of foam containing TCPP, i.e. Scenario 3 "Cutting of flexible PUR foam", Scenario 4 "Production of rebounded PUR foam and Scenario 8 Use of rigid PUR foam".

No toxicokinetic data is available for the inhalation routes at present. For this route, and in line with the TGD, 100% absorption is assumed."

Updated relevant information (March 2018):

A hydroxylated human metabolite of TCPP was found in the urine of the Australian population, i.e. 1-hydroxy-2-propyl bis (1-chloro-2-propyl)phosphate (Van den Eede et al. (2015).

The updated risk assessment for TCPP follows the most recent and relevant ECHA Guidance Documents. As such, only one DNEL (or qualitative assessment) is derived for each type of hazard based on the lowest and most relevant NOAEL/LOAEL or qualitatively, on the most relevant critical effect for the route and exposure duration.

The experimentally derived value of 80% oral absorption and the worst-case dermal absorption rate of 40% will be taken forward to risk characterisation.