Triisobutyl phosphate

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

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:

QMRF and QPRF are attached as pdf file.

Principles of method if other than guideline:

Calculated with Catalogic v5.11.17 BCF base-line model v02.09.

Details on estimation of bioconcentration:

BASIS INFORMATION
- Measured/calculated logPow: calculated

BASIS FOR CALCULATION OF BCF
- Estimation software: BCF base-line model v02.09 of OASIS CATALOGIC v5.11.17

Key result

Type:

BCF

Value:

0.59 L/kg

Basis:

whole body w.w.

Calculation basis:

steady state

Remarks on result:

other: logBCF corrected L/kg wet: 0.59 +- 0.0914; all mitigating factors applied

Model domain similarity:

- Parametric domain: 100%

- Structural domain: 100%

- Mechanistic domain: 100%

Effects of mitigating factors on BCF:

Acids	0.0000
Metabolism	0.823
Phenols	0.0000
Size	0.1263
Water solubility	2.223E-003

The BCF base-line model estimates the corrected log BCF for the test substance at 0.95 L/kg ww.

Diameter information (values are given in Angstrom):

DiamMax Min value = 11.836 Å

DiamMax Max value = 13.753 Å

DiamMax Average = 12.913 Å

Conclusions:

Bioaccumulation is not to be expected.

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

Justification for type of information:

QMRF and QPRF are attached as pdf file.

Principles of method if other than guideline:

Estimation of BCF, BAF and biotransformation rate using BCFBAF v3.01

GLP compliance:

no

Test organisms (species):

other: fish

Details on estimation of bioconcentration:

BASIS FOR CALCULATION OF BCF
- Estimation software: KOWWIN v1.67
- Result based on calculated log Pow of: 3.6

Key result

Type:

BCF

Value:

64.15 L/kg

Basis:

whole body w.w.

Calculation basis:

steady state

Remarks on result:

other: Upper trophic, incl. biotransformation estimates; The substance is within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).

Type:

BCF

Value:

16.44 L/kg

Basis:

whole body w.w.

Calculation basis:

steady state

Remarks on result:

other: The substance is within the applicability domain of the BCFBAF submodel: Bioconcentration factor (BCF; Meylan et al., 1997/1999).

Type:

BCF

Value:

418.8 L/kg

Basis:

whole body w.w.

Calculation basis:

steady state

Remarks on result:

other: Upper trophic, incl. biotransformation rate of zero; The substance is within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).

Type:

BAF

Value:

64.15 L/kg

Basis:

whole body w.w.

Calculation basis:

steady state

Remarks on result:

other: Upper trophic, incl. biotransformation estimates; The substance is within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).

Type:

BAF

Basis:

not specified

Remarks on result:

other: Upper trophic, incl. biotransformation rate of zero; The substance is within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).

Details on kinetic parameters:

Biotransformation half-life (days): 0.1787
Biotransformation rate (kM, normalised to 10 g fish at 15 °C): 3.879
The substance is within the applicability domain of the BCFBAF submodel: Biotransformation rate in fish (kM; Arnot et al., 2008a/b).

Conclusions:

Bioaccumulation in fish is not to be expected.

Reference 3

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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

not GLP, no replication, purity not specified

Qualifier:

no guideline followed

Principles of method if other than guideline:

Bioconcentration tests with Oryzias latipes and Carassius auratus in a static water test system

GLP compliance:

no

Radiolabelling:

no

Details on sampling:

- Sampling intervals/frequency for test organisms:The concentration in water and in the fish were determined at various time intervals. At each sampling time, all the fish in one beaker were taken out and frozen until required for analysis.

Vehicle:

yes

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

PREPARATION AND APPLICATION OF TEST SOLUTION
- Method: The test chemical solutions were prepared by dilution of stock solution (1 g/L in acetone) with water to a concentrations of 3-4 mg/L.
- Chemical name of vehicle (organic solvent, emulsifier or dispersant): acetone
- Evidence of undissolved material (e.g. precipitate, surface film, etc): no

Test organisms (species):

other: Oryzias latipes and Carassius auratus

Details on test organisms:

TEST ORGANISM
- Common name: killifish
- Source: purchased from a market
- Weight at study initiation (mean and range, SD): 0.1 - 0.2 g
- Feeding during test
- Food type: TetraMin
- Frequency: once a day

- Common name: goldfish
- Source: purchased from a market
- Weight at study initiation (mean and range, SD): 0.8 - 2.8 g
- Feeding during test: no

ACCLIMATION
- Acclimation period: 10d
- Acclimation conditions (same as test or not): at 25 °C

Route of exposure:

aqueous

Test type:

static

Water / sediment media type:

natural water: freshwater

Total exposure / uptake duration:

96 h

Test temperature:

25 °C

Details on test conditions:

TEST SYSTEM
- Test vessel: 2L beakers
- Aeration: no
- No. of organisms per vessel: 10-20 killifish; 3-5 goldfish
- No. of vessels per concentration (replicates): 4

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: tap water dechlorinated by passage through an activated charcoal column
- Holding medium different from test medium: no

Nominal and measured concentrations:

Nominal: 3-4 mg/L

Reference substance (positive control):

no

Key result

Conc. / dose:

3 - 4 mg/L

Temp.:

25 °C

Type:

BCF

Value:

30 - 35

Basis:

whole body w.w.

Calculation basis:

kinetic

Remarks on result:

other: Oryzias latipes

Key result

Conc. / dose:

3 - 4 mg/L

Temp.:

25 °C

Type:

BCF

Value:

6 - 11

Basis:

whole body w.w.

Calculation basis:

kinetic

Remarks on result:

other: Carassius auratus

The concentration of TBP in water were stable in the control breeding /(without fish) for 96h. TBP in the water containing killifish decreased rapidly compared with that in the water containing goldfish. The half-lives of TBP in the water containing killifish and goldfish were 58 hours and far more than 100 hours, respectively. The amount of TBP in the fish body varied with species. It appears that killifish absorb and metabolize TBP more actively than goldfish. Thus, the BCF of killifish was greater than of goldfish; however, in general the BCF of both fish was very low.

Validity criteria fulfilled:

not applicable

Reference 4

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

not GLP, no replication, purity not specified

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The source chemical is considered suitable for the analogue approach, as their chemical structure is very similar to that of the target substance and they share common functional groups. Both are triester of phosphate and isomers of butanol (Table 1): target substance = isobutanol; source substance = n-butanol. Based on additional similarity in physico-chemical properties, the read-across is considered justified by assuming comparable environmental behavior, metabolism (common break-down products) and mode-of-action.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The purity of the source substance was not indicated in the two studies used in this read across approach. However, it is mentioned that the test substance was purchased by a chemical trader (Wako), which at least assumes technical quality/ purity. Since the read across data are used in a read across approach only, the absence of specific purity data is considered to be acceptable.

3. ANALOGUE APPROACH JUSTIFICATION
[Summarise here based on available experimental data how these results verify that the read-across is justified]

4. DATA MATRIX
attached below

Reason / purpose for cross-reference:

read-across source

GLP compliance:

no

Radiolabelling:

no

Key result

Conc. / dose:

0.1 mg/L

Type:

BCF

Value:

27 L/kg

Basis:

whole body w.w.

Time of plateau:

24 h

Calculation basis:

steady state

Key result

Elimination:

yes

Parameter:

DT50

Depuration time (DT):

1.25 h

Reference 5

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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

not GLP, no replication, purity not specified

Qualifier:

no guideline followed

Principles of method if other than guideline:

Bioconcentration tests with Oryzias latipes in a continuous flow water test system

GLP compliance:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- purchased from Wako Pure Chem

Radiolabelling:

no

Details on sampling:

- Sampling intervals/frequency for test organisms: groups of 3-4 fish at various intervals

Vehicle:

yes

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

PREPARATION AND APPLICATION OF TEST SOLUTION
- Method: The test chemical solutions were prepared by dilution of stock solution (1 g/L in acetone) with water to suitable concentrations.
- Chemical name of vehicle (organic solvent, emulsifier or dispersant): acetone
- Evidence of undissolved material (e.g. precipitate, surface film, etc): no

Test organisms (species):

Oryzias latipes

Details on test organisms:

TEST ORGANISM
- Common name: killifish
- Source: purchased from a market
- Weight at study initiation (mean and range, SD): 0.1 - 0.2 g
- Feeding during test
- Food type: TetraMin
- Frequency: once a day

ACCLIMATION
- Acclimation period: 10d
- Acclimation conditions (same as test or not): at 25 °C

Route of exposure:

aqueous

Test type:

flow-through

Water / sediment media type:

natural water: freshwater

Total exposure / uptake duration:

38 d

Total depuration duration:

5 d

Test temperature:

25 °C

pH:

not specified

Dissolved oxygen:

not specified

Details on test conditions:

TEST SYSTEM
- Test vessel: 10 L aquarium
- Type of flow-through (e.g. peristaltic or proportional diluter): The test substance solution was supplied to the mixing equipment by a constant-flow micro pump E at a flow speed of 3.5 - 40 mL/h. In the mixing equipment, the test substance was diluted with water which was introduced via a tube pump at a flow speed of 1000-2000 mL/h.The diluted solution was poured into the aquarium.
- No. of organisms per vessel: 70 - 100

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: tap water dechlorinated by passage through an activated charcoal column
- Holding medium different from test medium: no

Nominal and measured concentrations:

Nominal: 0.1 mg/L

Reference substance (positive control):

no

Key result

Conc. / dose:

0.1 mg/L

Type:

BCF

Value:

27 L/kg

Basis:

whole body w.w.

Time of plateau:

24 h

Calculation basis:

steady state

Key result

Elimination:

yes

Parameter:

DT50

Depuration time (DT):

1.25 h

The concentration of TBP in water were mainteained almost constant (0.98 - 0.108 mg/L)

Validity criteria fulfilled:

not applicable

Conclusions:

The test substance was taken up rapidly by fish. and the concentration in the fish reached a constant level within only one day. The elimination was very fastindicating that the substance metabolises quickly after entering the body. Thus, the bioaccumulation potential is low.

Reference 6

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

not GLP, no replication, purity not specified

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The source chemical is considered suitable for the analogue approach, as their chemical structure is very similar to that of the target substance and they share common functional groups. Both are triester of phosphate and isomers of butanol (Table 1): target substance = isobutanol; source substance = n-butanol. Based on additional similarity in physico-chemical properties, the read-across is considered justified by assuming comparable environmental behavior, metabolism (common break-down products) and mode-of-action.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The purity of the source substance was not indicated in the two studies used in this read across approach. However, it is mentioned that the test substance was purchased by a chemical trader (Wako), which at least assumes technical quality/ purity. Since the read across data are used in a read across approach only, the absence of specific purity data is considered to be acceptable.

3. ANALOGUE APPROACH JUSTIFICATION
[Summarise here based on available experimental data how these results verify that the read-across is justified]

4. DATA MATRIX
attached below

Reason / purpose for cross-reference:

read-across source

Key result

Conc. / dose:

3 - 4 mg/L

Temp.:

25 °C

Type:

BCF

Value:

30 - 35

Basis:

whole body w.w.

Calculation basis:

kinetic

Remarks on result:

other: Oryzias latipes

Key result

Conc. / dose:

3 - 4 mg/L

Temp.:

25 °C

Type:

BCF

Value:

6 - 11

Basis:

whole body w.w.

Calculation basis:

kinetic

Remarks on result:

other: Carassius auratus

Description of key information

Triisobutyl phosphate does not bioaccumulate in aquatic or sediment organisms.

Additional information

No GLP guideline study according to OECD 305 is available to assess the bioaccumulation potential of Triisobutyl phosphate (CAS 126-71-6, TiBP). Therefore, all available related data is combined in a Weight of Evidence (WoE), which is in accordance to the REACh Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2, to cover the data requirements of Regulation (EC) No. 1907/2007 Annex IX and X (ECHA guidance section R.7.11.5.3, page 121).

As part of the WoE approach and in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 Grouping of substances, a read-across to Tributyl phosphate (CAS 126-73-8, TBP) was conducted. Target and source substance are structurally almost identical only slightly differing in the alkyl moiety, which is branched (isobutyl) in the target and linear (butyl) in the source substance. Since this difference does not have a significant effect on the physico-chemical properties of the substances. Thus, both substances share the same metabolism and environmental fate. Two publications are available investigating the bioaccumulation potential of Tributyl phosphate (CAS 126-73-8; TBP). Both are well documented studies, which meet generally accepted scientific principles and are thus considered to be reliable and acceptable for the bioaccumulation assessment. The studies investigated the absorption and elimination of TBP in killifish (O. latipes) and goldfish (C. auratus) under static (96h) as well as killifish (O. latipes) under flow-through (38d) conditions (Sasaki et al. 1981, 1982). The static absorption studies showed low BCF values of 30-25 for killifish and 6-11 for goldfish after 96h. This low bioaccumulation potential was confirmed in a 38d flow through test with killifish, which resulted in a BCF value of 27. TBP was taken up rapidly by fish and the concentration in the fish reached a constant level within only one day. The elimination was very fast (DT50 = 1.25h). This indicates that TBP metabolizes quickly after entering the body. Consequently, the bioaccumulation potential of TBP and TiBP is low. These results are supported by valid QSAR calculations for TiBP using BCFBAF v3.01 and Catalogic BCF baseline model v2.9. Calculated BCF value range between 0.59 and 418.8. Both QSAR models clearly indicate metabolism as main mitigation factor. There are various publications available in the literature, which confirm the very fast metabolism of TiBP (and TBP) in organisms. For instance, Sasaki et al. (1984) studied the metabolism of TBP by rat liver homogenate. Rat liver microsomes were observed to possess enzymes decomposing TBP in the presence of NADPH quickly. TBP was either hydroxylated by CYP [TBP-OH, TBP-(OH)2] or catalyzed by phosphotrieesterases to Dibutyl phosphate (DBP) and excreted via the urine. Hydroxylation and, to a lower degree, phosphorylation dominated metabolism in the earthworm Perionyx excavates (Wang et al. 2018).  

Based on these data the bioaccumulation of Triisobutyl phosphate (CAS 126-71-6) in aquatic organisms is considered to be negligible. Therefore, and due to animal welfare reasons, no confirmatory animal test according to OECD 305 is deemed necessary.  

 

References

Sasaki K, Suzuki T, Takeda M, Uchiyama M. 1984.Metabolism of phosphoric acid triesters by rat liver homogenate. Bull Environ Contam Toxicol 33: 281-288.

Wang L, Huang X, Laserna AKC, Li SFY. 2018.Metabolism of tri-n-butyl phosphate in earthworm Perionyx excavatus. Environ Poll 234: 389-395