Tris(methylphenyl) phosphate

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

other: Published study

Adequacy of study:

supporting study

Study period:

2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well-documented published study, however, no guideline was followed and no data on GLP compliance is provided.

Data source

Reference

Reference Type:

publication

Title:

Occupational exposure of air crews to tricresyl phosphate isomers and organophosphate flame retardants after fume events

Author:

Schindler BK; Weiss Y, Schutze A, Koslitz S, Broding HC, Bunger J, Bruning T

Year:

2012

Bibliographic source:

Arch Toxicol (2013) 87:645–648 DOI 10.1007/s00204-012-0978-0

Report date:

2012

Materials and methods

Type of study / information:

Assessment of metabolites in urine from personnel potentially exposed to Tricresylphosphate in aircraft cabin air.

Endpoint addressed:

other: Human biomonitoring for TCP in air cabin situations.

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

A total of 332 urine samples were collected from air crews, pilots and cabin crew members, after reported incidents of smoke/odour. The study was part of an occupational health examination
programme for pilots and cabin crew members. Quantification of three metabolites of tricresyl phosphate isomers—oo-, mm-, pp-dicresyl phosphate (DoCP, DmCP,DpCP)—as well as the dialkyl phosphate metabolites of tributyl phosphate (DBP), tris-(2-chloroethyl) phosphate (BCEP), tris-(2-chloroisopropyl) phosphate (BCPP) and triphenyl phosphate (DPP) in urine was undertaken.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Tricresylphosphate

IUPAC Name:

Tricresylphosphate

Test material form:

other: Not applicable. Metabolites from fume exposure where investigated.

Details on test material:

Not applicable. Metabolites from fume exposure where investigated.

Method

Ethical approval:

confirmed, but no further information available

Details on study design:

332 urine samples were collected from air crews, pilots and cabin crew members, after reported incidents of smoke/odour. Deuterium-labelled
internal standards were added to the urine samples. The analytes were separated from the urinary matrix using an ENV+ (crosslinked polystyrene divinylbenzene copolymer) solid-phase column.

After derivatisation with 2,3,4,5,6-pentafluorobenzylbromide, a second solid-phase extraction (PSA (silica material with ethylene diamine-Npropyl
moieties)-FL(Florisil)) was performed. The extracts were quantified after capillary gas chromatography using tandem mass spectrometry. LODs were 0.2 ug/l for DBP and DPP, 0.1 ug/l for BCEP and BCPP and 0.5 ug/l for DoCP, DmCP and DpCP.

Within-series and between-day imprecision were\10 % for all parameters. Spot urines of persons from the general population with no known occupational exposure to organophosphates were used as controls. In detail, these were 30 persons (16 female, 14 male, 11–68 years) for BCEP, DPP, DmCP and DpCP (and 25 persons (12 female, 13 male, 11–68 years) for
BCPP and DBP.
For statistical analysis, values below the LOD were set half the LOD. Differences between the two populations were calculated by the Mann–Whitney U test (Origin). The creatinine content of the urine samples was determined according to the method described by Larsen (1972).

Exposure assessment:

measured

Details on exposure:

As above. Exposures where monitored in air crews, pilots and cabin crew members, after reported incidents of smoke/odour.

Results and discussion

Results:

The results of human biomonitoring based on metabolite levels from the organophosphorus flame retardants are
summarised in Table 1 below. Creatinine levels of the urine samples were 0.05–3.98 g/l (median 0.74 g/l). The analytical method used in this study was sensitive enough to determine the levels of organophosphate metabolites in urine in the sub ug per litre range, which is also indicated by the high percentage of samples
None of the 332 urine samples contained metabolites of ooo-, oom- or oop-TCP. One urine sample contained m- and p-TCP metabolites close to the LOD (0.5 ug/l).

DoCP, DmCP and DpCP reflect the internal burden after exposure to nine out of ten possible tricresyl phosphate isomers.

With respect to 332 analysed samples, an occupational exposure of air crews to TCP isomers and particularly neurotoxic o-TCP after fume events was not evident.

Liyasova et al. (2011) measured phosphoserine adducts of butyrylcholinesterase in a semi-quantitative assay to assess o-TCP exposure in human plasma of 12 airplane passengers. Six out of 12 passengers were found positive for those adducts after completing a flight with butyrylcholinesterase adduct levels between 0.5 and 3 %. Six passengers were re-examined after three to seven months without any travel by airplane. None of these passengers presented adducts above the LOD (0.05 %). The measured phosphorylated butyrylcholinesterase adduct is known to be an ageing product of the adduct formed by the o-TCP metabolite
o-cresyl saligenin phosphate, but is not specific to o-TCP per se. The specific o-cresyl saligenin phosphate butyrylcholinesterase
adduct was not measured. As a consequence, it must remain questionable, if o-TCP is the only agent capable to form those adducts in man.
Currently, biological monitoring of dicresyl phosphate isomers in urine seems to be the only way to assess the individual exposure to TCP appropriately. Previous studies on air monitoring in aircrafts by Solbu et al. (2011) (no fume event) and Denola et al. (2011)
(including nine incidents of smoke/odour) reported levels of o-TCP in cabin air below the LOD, but the latter with total TCP up to 50 lg/m3, which is in good accordance with the results of ths study. Based on results and the failure of o-TCP detection in air during fume events, the reported health effects in air crews can hardly be attributed to o-TCP exposure.

Any other information on results incl. tables

Table 1 Metabolite levels of organophosphates in urines from air crews (n = 332) and controls from the general population (n = 30 for, DmCP and DpCP,

(Schindler et al.2009a,b)

	DmCP		DoCP		DpCP
	Air Crew	Controls	Air Crew	Controls	Air Crew	Controls
LOD [µg/l]	0.5	0.5	0.5	0.5	0.5	0.5
n[LOD (%)	0.3	0	0	0	0.3	0
Median (µg/l)	< 0.5	< 0.5	< 0.5	< 0.5	< 0.5	< 0.5
P95 (µg/l)	< 0.5	< 0.5	< 0.5	< 0.5	< 0.5	< 0.5
Max (µg/l)	0.62	< 0.5	< 0.5	< 0.5	0.55	< 0.5
p (Mann–Whitney U)	-	-	-	-	-	-

Applicant's summary and conclusion

Conclusions:

None of the 332 urine samples contained metabolites of ooo-, oom- or oop-TCP. One urine sample contained m- and p-TCP metabolites close to the LOD (0.5 ug/l). With respect to 332 analysed samples, an occupational exposure of air crews to TCP isomers and particularly neurotoxic o-TCP after fume events was not evident. Based on the results and the failure of o-TCP detection in air during fume events, the reported health effects in air crews can hardly be attributed to o-TCP exposure.

Executive summary:

None of the 332 urine samples contained metabolites of ooo-, oom- or oop-TCP. One urine sample contained m- and p-TCP metabolites close to the LOD (0.5 ug/l). With respect to 332 analysed samples, an occupational exposure of air crews to TCP isomers and particularly neurotoxic o-TCP after fume events was not evident. Based on the results and the failure of o-TCP detection in air during fume events, the reported health effects in air crews can hardly be attributed to o-TCP exposure.