Tris(2-ethylhexyl) phosphate

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

The study was comparable to modern international guideline requirements (OECD 305) but was not conducted in accordance with GLP (the study pre-dates GLP). The design of the study was sufficient to allow a BCF for uptake to be determined in a reliable fashion and in accordance with the OECD 305 guideline.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 305 C (Bioaccumulation: Test for the Degree of Bioconcentration in Fish)

Deviations:

not specified

GLP compliance:

not specified

Remarks:

Study pre-dates GLP

Radiolabelling:

no

Details on sampling:

Test water was analysed twice per week. Test fish analysis was performed every two weeks.

Vehicle:

yes

Details on preparation of test solutions, spiked fish food or sediment:

TEHP was dosed into the system to acheive 2 and 0.2 mg/L. Acetone was used at 200 and 20 mg/L as a solvent/ vehicle for TEHP.

Test organisms (species):

Cyprinus carpio

Details on test organisms:

Source: Kitamura fish farm, Yatsushiro-shi, Kumamoto
Lot No.: TFC 841029

For acclimatization to test conditions fish were kept under flow through conditions for 2 weeks after external disnifection using 0.005% terramycine powder aqueous solution for 24 hours. Acclimation prior to the study was at 25 ± 2 °C..

At the start of the study fish weighed about 20.3 g, were 9.2 cm long and had a lipid content of 5.1 %.

Route of exposure:

aqueous

Test type:

flow-through

Water / sediment media type:

natural water: freshwater

Total exposure / uptake duration:

>= 6 - <= 7 wk

Hardness:

Not reported (demineralized water)

Test temperature:

25 ± 2 °C

pH:

Not reported

Dissolved oxygen:

5.8- 7.5 mg/L

TOC:

Not reported

Salinity:

Not applicable

Details on test conditions:

Test vessels were glass tanks containing 100L of water, flow-rate was 582 L/d. Fish were fed pelleted carp food daily at a rate correspodning to 2 % of the total body weight of test fish in two daily portions. Fish were not fed on the day of sampling. Medium was demineralized water. Fish were placed in water where the fish stock density did not exceed 1 g fish per litre of water per day. Fish were washed before sampling. Fish weight was weighed before ananlysis. Fish were sampled on day 0 and at 2, 3, 4 & 6 weeks, n = 2 at each sampling point.

Nominal and measured concentrations:

Nominal 2 mg/L and 0.2 mg/L (acetone was dosed at 200 mg/L and 2 mg/L along with the test substance as a vehicle)

Details on estimation of bioconcentration:

BCF was calculated by comparison of the level of the substance in the fish and in the water. However it is not clear if a steady state was reached and no depuration was performed. Neither BCFss or BCFk can be properly calculated.

Key result

Conc. / dose:

0.2 mg/L

Temp.:

25 °C

Type:

BCF

Value:

>= 9.2 - <= 22 L/kg

Basis:

whole body w.w.

Remarks on result:

other: 6 weeks

Remarks:

Conc.in environment / dose:0.2 mg/L

Key result

Conc. / dose:

2 mg/L

Temp.:

25 °C

Type:

BCF

Value:

>= 2.4 - <= 6.5 L/kg

Basis:

whole body w.w.

Remarks on result:

other: 6 weeks

Remarks:

Conc.in environment / dose:2 mg/L

Table 1. Measured test item concentration (mg/L) in test system and % compared to nominal stated concnetration

Concentration	2 weeks (mg/L)	3 weeks (mg/L)	4 weeks (mg/L)	6 weeks (mg/L)
2 mg/L	2.07	2.05	2.02	2.02
% nominal	104	103	101	101
0.2 mg/L	0.19	0.19	0.19	0.19
% nominal	95.0	95.0	95.0	95.0

Results and discussions

Remarks: lipid-containing: 5.1 %

BCF values for fish of 2.4 -6.5 were calculated for the substance at a concentration of 2 mg/L in water; BCF values of 9.2 -22 were calculated for a concentration in water of 0.2 mg/L.

Validity criteria fulfilled:

not specified

Conclusions:

BCF values for fish of 2.4 - 6.5 were calculated for the substance at a concentration of 2 mg/L in water; BCF values of 9.2 - 22 were calculated for a concentration in water of 0.2 mg/L.

Executive summary:

The bioaccumulation of tris(2-ethylhexyl) phosphate from water was investigated in carp over a period of 6 weeks. BCF values for fish of 2.4 - 6.5 were calculated for the substance at a concentration of 2 mg/L in water; BCF values of 9.2 - 22 were calculated for a concentration in water of 0.2 mg/L.

Reference 2

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

Meylan, W.M., Howard, P.H., Boethling, R.S., Aronson, D., Printup, H., and Gouchie, S. (1999) Improved method for estimating bioconcentration/bioaccumulation factor from octanol/water partition coefficient. Environmental Toxicology and Chemistry 5, 261-272.

Specific details on test material used for the study:

SMILES: CCCCC(CC)COP(=O)(OCC(CC)CCCC)OCC(CC)CCCC

Key result

Type:

BCF

Value:

30.34 L/kg

Remarks on result:

other:

Remarks:

QSAR predicted value

BCFBAF predicted that tris(2 -ethylhexyl) phosphate has a BCF of 30.34 L/kg

Reference 3

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
Not applicable, QSAR run manually using Microsoft EXCEL

2. MODEL (incl. version number)
Dimitrov 2005 BCFmax model for identifying the bioaccumulation potential of chemicals

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Log Pow = 9.49 (KOWWIN)

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint:
Species: Fish
Endpoint: QMRF 2.4a. Bioconcentration BCF Fish
- Unambiguous algorithm: The approach for modelling bioaccumulation potential is based on a reference curve delineating the maximum empirically observed bioconcentration based on hydrophobicity. In fact, this is the highest logBCF (logBCFMax) which can be reached for a given logKOW value assuming that the molecules exhibit maximal bioavailability and are not metabolised. Theoretically, the base-line was justified by the model for multi-compartment diffusion:
log BCFmax = log(Know/(aKow + 1)^2n)+Fw)
where a and n are model parameters and Fw is the organism water content.
- Defined domain of applicability:
The domain of general parametric requirements included the range of variation of hydrophobicity (log KOW) and molecular weight (MW ) of chemicals in the training set. Respectively, chemicals with MW from 68 to 944 and log KOW in the range of 2.83 and 12.66 are assigned to belong to the domain of the general requirements. The structural component of the model domain is based on the structural similarity between chemicals in the training set which were correctly predicted by the model.
- Appropriate measures of goodness-of-fit and robustness and predictivity:
The relevant coefficients of determination for each divisional algorithm are as follows:
n = 511
SSR = 140
r2 = 0.84
S2 = 0.294
Refer to QMRF (Carson, 2018) for further information.
- Mechanistic interpretation:
The model is based on the relationship between the octanol/water partition coefficient and the bioconcentration factor of the training set.
Whilst octanol can be viewed as a reasonable surrogate phase for lipids and biological organisms, and thus the octanol/water partition coefficient acts as a screen for bioaccumulation, there is no mechanistic basis within this (Q)SAR for predicting BCF.

5. APPLICABILITY DOMAIN
- Descriptor domain: The log Pow was within the range of the applicability domain (2.83 - 12.66; actual = 9.49). The molecular weight of the substance was within the range of the applicability domain (68 - 944; actual = 434.6).
- Structural and mechanistic domains: The substance does not contain functional groups that were not present within the tratining set.
- Similarity with analogues in the training set: No suitable structural analogues were found. However, the substance still falls within the applicability domain of the model and the data derived from the model is considered to be appropriate. Further, there are substances similar (i.e. similar functional groups, moieties, molecular weight and Log KOW) to the target substance within the training set, and similar observations and relationships would be expected, making for appropriate interpolation
- Other considerations (as appropriate):
Not applicable

6. ADEQUACY OF THE RESULT
The prediction is adequate for the Classification and Labelling and PBT/vPvB of the substance as indicated in REACH Regulation (EC) 1907/2006: Annex XI Section 1.3 and Annex XIII.
The result should be considered in relation to corresponding information presented and in accordance with the tonnage driven information requirements of REACH Regulation (EC) 1907/2006 in a weight of evidence. Specifically:
i. The substance is not readily biodegradable and is considered as persistent in the absence of further information.
ii. The substance is not expected to bioaccumulate (predicted-BCF is significantly less than 2000). Further reference to REACH Regulation (EC) 1907/2006 Annex XIII section 1.1.2 - whilst acknowledging the screening criteria of log Kow = 4.5 is exceeded the predictions for BCF are an order of magnitude below the BCF = 2000 cut-off. The substance does not appear to have the potential to fulfil the bioaccumulative criteria. The constituents are equally significantly below the screening criteria cut-off BCF ≥ 500 as indicated in CLP Regulation (EC) 1272/2008: section 4.
iii. Substance experimental and predicted data does not demonstrate extreme acute aquatic toxicities (no adverse effects observed in available toxicity studies)
iv. The weight of evidence indicates the substance does not require classification for toxicity toward the environment.
v. The substance does not meet the Toxicity criteria in PBT assessment.
The assessment indicates that the prediction is adequate for the regulatory conclusion set out above. This conclusion is with due regard to REACH Article 25(1) and impact on the weight of evidence including new physicochemical, environmental fate and/or newly generated in vitro information.

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

S. Dimitrov , N. Dimitrova , T. Parkerton , M. Comber , M. Bonnell & O. Mekenyan (2005) Base-line model for identifying the bioaccumulation potential of chemicals, SAR and QSAR in Environmental Research, 16:6, 531-554, DOI: 10.1080/10659360500474623

Specific details on test material used for the study:

SMILES: CCCCC(CC)COP(=O)(OCC(CC)CCCC)OCC(CC)CCCC

Key result

Value:

336.6 L/kg

Remarks on result:

other: QSAR predicted value

The Dimitrov (2005) BCFmax model predicted that tris(2 -ethylhexyl) phosphate has a BCF of 336.6 L/kg.

Description of key information

BCF = <= 22 L/kg; OECD 305; Anon. (1985)

BCF = 30.34 L/kg; BCFBAF; Meylan et al., (1999)

BCF = 336.6 L/kg ; BCFmax; Dimitrov et al., (2005)

Key value for chemical safety assessment

BCF (aquatic species):

22 L/kg ww

Additional information

A bioaccumulation study in fish (OECD TG 305) is currently on-going in the framework of ECHA Compliance CHeck decision (CCH-D-2114465573-43-01/F).

Using a weight of evidence approach it has been demonstrated that the substance tris(2 -ethylhexyl) phosphate does not meet the criteria for a bioaccumulative substance, in accordance with Annex XIII of REACH.

 

In a study conducted equivalent to OECD 305 common carp (Cyprinus carpio) were exposed to two aqueous concentrations of tris(2-ethylhexyl) phosphate (0.2 and 2 mg/L) for 42 days.  Water solubility was aided by the use of suitable levels of acetone.  No significant uptake was shown after 42 days, so the study was terminated.  The maximum bioconcentration factor (BCF) determined in the study was 22 L/kg in the 0.2 mg/L dose group.  The range of BCF values determined throughout the study were 2.4 – 22 L/kg. Given the age of this study and some deficiencies compared to the most recent OECD 305 Guideline, the study has been assigned a Klimisch rating of 2 (reliable with restrictions). However, regardless of some relatively minor deficiencies from the current OECD 305 Guideline, the lack of significant uptake of TEHP over 42 days is a reliable indication of the bioaccumulating potential of this substance.

 

In support of the in vivo OECD 305 study, a series of BCF (Q)SARs were used in support of the conclusion drawn in the fish study. The following table summarises the results of the predicted BCF values.

 

Table 1. Bioconcentration factor (Q)SAR data for tris(2 -ethylhexyl) phosphate

(Q)SAR	BCF	Applicability Domain
BCFBAF (v3.01)	30.34 L/kg	in domain
BCFmax (Dimitrov et al., 2005)	336 L/kg	in domain

 

The weight-of-evidence, consisting of 3 reliable, discreet assessments of the BCF of tris(2-ethylhexyl) phosphate, indicate that the substance does not meet the criteria for B or vB (BCF is <2,000 L/kg).  This weight-of-evidence approach is consistent with ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R,7c, Section R.7.10.6. Integrated Testing Strategy for Aquatic Bioaccumulation, and Chapter R.11 PBT Assessment.