1-(N,N-bis(2-ethylhexyl)aminomethyl)-1,2,4-triazole

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

bioaccumulation in aquatic species, other

Remarks:

QSAR

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Principles of method if other than guideline:

Calculated with SRC BCFBAF v3.01

GLP compliance:

no

Radiolabelling:

no

Test organisms (species):

other: calculation

Details on estimation of bioconcentration:

BASIS INFORMATION
- Measured/calculated logPow: calculated

BASIS FOR CALCULATION OF BCF
- Estimation software: BCFBAF Program (v3.01) (part of EPI Suite v4.10)
- Result based on calculated log Pow of: 4.94 (EPI Suite v4.10)

Type:

BCF

Value:

3.16

Remarks on result:

other: log BCF: 0.5

Type:

BAF

Value:

0.915

Remarks on result:

other: log BAF: -0.04; Arnot-Gobas BAF method (including biotransformation rate estimates; upper trophic level)

Summary Results:

Log BCF (regression-based estimate): 0.50 (BCF = 3.16 L/kg wet-wt)

Biotransformation Half-Life (days) : 0.0918 (normalized to 10 g fish)

Log BAF (Arnot-Gobas upper trophic): -0.04 (BAF = 0.915 L/kg wet-wt)

 

Log Kow (experimental): -0.58

Log Kow used by BCF estimates: -0.58

 

Equation Used to Make BCF estimate:

Log BCF = 0.50

 

Correction(s):                   Value

Correction Factors Not Used for Log Kow < 1

 

Estimated Log BCF = 0.500 (BCF = 3.162 L/kg wet-wt)

Whole body primary biotransformation rate estimate for fish:
Type	Num	Log Biotransformation Fragment Description	Coeff	Value
Frag	1	Triazole ring	0.3225	0.3225
Frag	2	Aromatic-H	0.2664	0.5328
L Kow	*	Log Kow = -0.58 (KowWin estimate)	0.3073	-0.1783
MolWt	*	Molecular weight parameter		-0.1771
Const	*	Equation Constant		-1.5058
Result		Log Bio Half-Life (days)		-1.0371
Result		Bio Half-Life (days)		0.0918
Note		Bio Half-Life Normalized to 10 g fish at 15 deg C

Biotransformation Rate Constant:

kM (Rate Constant): 7.55 /day (10 gram fish)

kM (Rate Constant): 4.246 /day (100 gram fish)

kM (Rate Constant): 2.388 /day (1 kg fish)

kM (Rate Constant): 1.343 /day (10 kg fish)

 

Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates):

Estimated Log BCF (upper trophic) = -0.039 (BCF = 0.9151 L/kg wet-wt)

Estimated Log BAF (upper trophic) = -0.039 (BAF = 0.9151 L/kg wet-wt)

Estimated Log BCF (mid trophic)  = -0.023 (BCF = 0.9475 L/kg wet-wt)

Estimated Log BAF (mid trophic)  = -0.023 (BAF = 0.9475 L/kg wet-wt)

Estimated Log BCF (lower trophic) = -0.020 (BCF = 0.9545 L/kg wet-wt)

Estimated Log BAF (lower trophic) = -0.020 (BAF = 0.9545 L/kg wet-wt)

 

Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):

Estimated Log BCF (upper trophic) = -0.036 (BCF = 0.9211 L/kg wet-wt)

Estimated Log BAF (upper trophic) = -0.036 (BAF = 0.9215 L/kg wet-wt)

Reference 2

Endpoint:

bioaccumulation in aquatic species, other

Remarks:

QSAR

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

QSAR prediction

Principles of method if other than guideline:

T.E.S.T. is a toxicity estimation software tool. The program requires only the molecular structure of the test item, all other molecular descriptors which are required to estimate the toxicity are calculated within the tool itself. The molecular descriptors describe physical characteristics of the molecule (e.g. E-state values and E-state counts, constitutional descriptors, topological descriptors, walk and path counts, connectivity, information content, 2d autocorrelation, Burden
eigenvalue, molecular property (such as the octanol-water partition coefficient), Kappa, hydrogen bond acceptor/donor counts, molecular distance edge, and molecular fragment counts). Each of the available methods uses a different set of these descriptors to estimate the toxicity.
The bioaccumulation factor (BCF) was estimated using several available methods: hierarchical method; FDA method, single model method; group contribution method; nearest neighbor method; consensus method. The methods were validated using statistical external validation using separate training and test data sets.
The experimental data set was obtained from several different databases (Dimitrov et al., 2005; Arnot and Gobas, 2006; EURAS; Zhao, 2008). From the available data set containing 643 chemicals salts, mixtures and ambiguous compounds were removed. The final data set contained 598 chemicals.

References:
- Dimitrov, S., N. Dimitrova, T. Parkerton, M. Combers, M. Bonnell, and O. Mekenyan. 2005. Base-line model for identifying the bioaccumulation potential of chemicals. SAR and QSAR in Environmental Research 16:531-554.
- Arnot, J.A., and F.A.P.C. Gobas. 2006. A review of bioconcentration factor (BCF) and bioaccumulation factor (BAF) assessments for organic chemicals in aquatic organisms. Environ. Rev. 14:257-297.
- EURAS. Establishing a bioconcentration factor (BCF) Gold Standard Database. EURAS [cited 5/20/09]. Available from http://www.euras.be/eng/project.asp?ProjectId=92.
- Zhao, C.; Boriani, E.; Chana, A.; Roncaglioni, A.; Benfenati, E. 2008. A new hybrid system of QSAR models for predicting bioconcentration factors (BCF). Chemosphere 73:1701-1707.

GLP compliance:

no

Test organisms (species):

other: fish

Details on estimation of bioconcentration:

BASIS FOR CALCULATION OF BCF
- Estimation software: US EPA T.E.S.T. v4.0.1

Applied estimation methods:
- Hierarchical method : The toxicity for a given query compound is estimated using the weighted average of the predictions from several different cluster models.
- FDA method : The prediction for each test chemical is made using a new model that is fit to the chemicals that are most similar to the test compound. Each model is generated at runtime.
- Single model method : Predictions are made using a multilinear regression model that is fit to the training set (using molecular descriptors as independent variables).
- Group contribution method : Predictions are made using a multilinear regression model that is fit to the training set (using molecular fragment counts as independent variables).
- Nearest neighbor method : The predicted toxicity is estimated by taking an average of the 3 chemicals in the training set that are most similar to the test chemical.
- Consensus method : The predicted toxicity is estimated by taking an average of the predicted toxicities from the above QSAR methods (provided the predictions are within the respective applicability domains; recommended method by T.E.S.T. for providing the most accurate predictions).

Type:

BCF

Value:

0.89

Remarks on result:

other: method: consensus

Type:

other: log BCF

Value:

-0.05

Remarks on result:

other: method: consensus

Reference 3

Endpoint:

bioaccumulation in aquatic species, other

Remarks:

QSAR

Type of information:

calculation (if not (Q)SAR)

Remarks:

Migrated phrase: estimated by calculation

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Principles of method if other than guideline:

Calculated with Catalogic v5.11.2 BCF base-line model v02.05.

Details on estimation of bioconcentration:

BASIS INFORMATION
- Measured/calculated logPow: calculated

BASIS FOR CALCULATION OF BCF
- Estimation software: BCF base-line model v02.05 of OASIS CATALOGIC v5.11.2

Type:

BCF

Value:

13.39

Remarks on result:

other: log BCF: 1.267, all mitigating factors applied

Model domain similarity:

- Parametric domain: 100%

- Structural domain: 88.24% (11.76% unknown)

- Mechanistic domain: 100%

Effects of mitigating factors on BCF:

Acids	0.0000
Metabolism	2.8755
Phenols	0.0000
Size	0.3690
Water solubility	0.1108

The BCF base-line model estimates the log BCF for the test substance at 1.1267 (BCF 13.39).

Reference 4

Endpoint:

bioaccumulation in aquatic species, other

Remarks:

QSAR

Type of information:

calculation (if not (Q)SAR)

Remarks:

Migrated phrase: estimated by calculation

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Principles of method if other than guideline:

Calculated with SRC BCFBAF v3.01

GLP compliance:

no

Radiolabelling:

no

Test organisms (species):

other: calculation

Details on estimation of bioconcentration:

BASIS INFORMATION
- Measured/calculated logPow: calculated

BASIS FOR CALCULATION OF BCF
- Estimation software: BCFBAF Program (v3.01) (part of EPI Suite v4.10)
- Result based on calculated log Pow of: 4.94 (EPI Suite v4.10)

Type:

BCF

Value:

415

Remarks on result:

other: log BCF: 2.62

Type:

BAF

Value:

74 300

Remarks on result:

other: log BAF: 4.87; Arnot-Gobas BAF method (including biotransformation rate estimates; upper trophic level)

Summary Results:

Log BCF (regression-based estimate): 2.62 (BCF = 415 L/kg wet-wt)

Biotransformation Half-Life (days) : 14.9 (normalized to 10 g fish)

Log BAF (Arnot-Gobas upper trophic): 4.87 (BAF = 7.43e+004 L/kg wet-wt)

 

Log Kow (experimental): not available from database

Log Kow used by BCF estimates: 6.56

 

Equation Used to Make BCF estimate:

Log BCF = 0.6598 log Kow - 0.333 + Correction

 

Correction(s):                   Value

Alkyl chains (8+ -CH2- groups) -1.374

 

Estimated Log BCF = 2.618 (BCF = 415.2 L/kg wet-wt)

Whole body primary biotransformation rate estimate for fish:
Type	Num	Log Biotransformation Fragment Description	Coeff	Value
Frag	2	Linear C4 terminal chain [CCC-CH3]	0.0341	0.0682
Frag	1	Aliphatic amine [-NH2 or -NH-]	0.4067	0.4067
Frag	4	Methyl [-CH3]	0.2451	0.9804
Frag	10	-CH2- [linear]	0.0242	0.2419
Frag	2	-CH- [linear]	-0.1912	-0.3825
L Kow	*	Log Kow = 6.56 (KowWin estimate)	0.3073	2.0149
MolWt	*	Molecular weight parameter		-0.6192
Const	*	Equation Constant		-1.5058
Result		Log Bio Half-Life (days)		1.1734
Result		Bio Half-Life (days)		14.91
Note		Bio Half-Life Normalized to 10 g fish at 15 deg C

Biotransformation Rate Constant:

kM (Rate Constant): 0.04649 /day (10 gram fish)

kM (Rate Constant): 0.02615 /day (100 gram fish)

kM (Rate Constant): 0.0147 /day (1 kg fish)

kM (Rate Constant): 0.008268 /day (10 kg fish)

 

Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates):

Estimated Log BCF (upper trophic) = 3.477 (BCF = 3000 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 4.871 (BAF = 7.432e+004 L/kg wet-wt)

Estimated Log BCF (mid trophic)  = 3.620 (BCF = 4167 L/kg wet-wt)

Estimated Log BAF (mid trophic)  = 5.053 (BAF = 1.131e+005 L/kg wet-wt)

Estimated Log BCF (lower trophic) = 3.662 (BCF = 4591 L/kg wet-wt)

Estimated Log BAF (lower trophic) = 5.164 (BAF = 1.458e+005 L/kg wet-wt)

 

Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):

Estimated Log BCF (upper trophic) = 4.256 (BCF = 1.802e+004 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 6.879 (BAF = 7.57e+006 L/kg wet-wt)

Reference 5

Endpoint:

bioaccumulation in aquatic species, other

Remarks:

QSAR

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

QSAR prediction

Principles of method if other than guideline:

T.E.S.T. is a toxicity estimation software tool. The program requires only the molecular structure of the test item, all other molecular descriptors which are required to estimate the toxicity are calculated within the tool itself. The molecular descriptors describe physical characteristics of the molecule (e.g. E-state values and E-state counts, constitutional descriptors, topological descriptors, walk and path counts, connectivity, information content, 2d autocorrelation, Burden
eigenvalue, molecular property (such as the octanol-water partition coefficient), Kappa, hydrogen bond acceptor/donor counts, molecular distance edge, and molecular fragment counts). Each of the available methods uses a different set of these descriptors to estimate the toxicity.
The bioaccumulation factor (BCF) was estimated using several available methods: hierarchical method; FDA method, single model method; group contribution method; nearest neighbor method; consensus method. The methods were validated using statistical external validation using separate training and test data sets.
The experimental data set was obtained from several different databases (Dimitrov et al., 2005; Arnot and Gobas, 2006; EURAS; Zhao, 2008). From the available data set containing 643 chemicals salts, mixtures and ambiguous compounds were removed. The final data set contained 598 chemicals.

References:
- Dimitrov, S., N. Dimitrova, T. Parkerton, M. Combers, M. Bonnell, and O. Mekenyan. 2005. Base-line model for identifying the bioaccumulation potential of chemicals. SAR and QSAR in Environmental Research 16:531-554.
- Arnot, J.A., and F.A.P.C. Gobas. 2006. A review of bioconcentration factor (BCF) and bioaccumulation factor (BAF) assessments for organic chemicals in aquatic organisms. Environ. Rev. 14:257-297.
- EURAS. Establishing a bioconcentration factor (BCF) Gold Standard Database. EURAS [cited 5/20/09]. Available from http://www.euras.be/eng/project.asp?ProjectId=92.
- Zhao, C.; Boriani, E.; Chana, A.; Roncaglioni, A.; Benfenati, E. 2008. A new hybrid system of QSAR models for predicting bioconcentration factors (BCF). Chemosphere 73:1701-1707.

GLP compliance:

no

Test organisms (species):

other: fish

Details on estimation of bioconcentration:

BASIS FOR CALCULATION OF BCF
- Estimation software: US EPA T.E.S.T. v4.0.1

Applied estimation methods:
- Hierarchical method : The toxicity for a given query compound is estimated using the weighted average of the predictions from several different cluster models.
- FDA method : The prediction for each test chemical is made using a new model that is fit to the chemicals that are most similar to the test compound. Each model is generated at runtime.
- Single model method : Predictions are made using a multilinear regression model that is fit to the training set (using molecular descriptors as independent variables).
- Group contribution method : Predictions are made using a multilinear regression model that is fit to the training set (using molecular fragment counts as independent variables).
- Nearest neighbor method : The predicted toxicity is estimated by taking an average of the 3 chemicals in the training set that are most similar to the test chemical.
- Consensus method : The predicted toxicity is estimated by taking an average of the predicted toxicities from the above QSAR methods (provided the predictions are within the respective applicability domains; recommended method by T.E.S.T. for providing the most accurate predictions).

Type:

BCF

Value:

115.38

Remarks on result:

other: method: consensus

Type:

other: log BCF

Value:

2.06

Remarks on result:

other: method: consensus

Reference 6

Endpoint:

bioaccumulation in aquatic species, other

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

Qualifier:

no guideline available

Principles of method if other than guideline:

Static exposure in 30 l glass aquaria containing sea water (4 % salinity; 22-24°C)

GLP compliance:

no

Test organisms (species):

other: Peanaeus stylirostris (blue shrimp)

Route of exposure:

aqueous

Test type:

static

Water / sediment media type:

natural water: marine

Total exposure / uptake duration:

24 h

Test temperature:

22-24 °C

Salinity:

40 pro mille

Nominal and measured concentrations:

nominal: 0, 18,5 and 55,5 ppm

Type:

BCF

Value:

< 1 dimensionless

No extractable formaldehyde residues could be detected when analysed immediately after treatment. However during longer post-mortem storage up to 72 hours, significant amounts of extractable formaldehyde were produced biologically due to tissue decomposition.

Reference 7

Endpoint:

bioaccumulation in aquatic species, other

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:

However, the study was not conducted to determine a BCF of formaldehyde.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Aim of this study was to examine if residues of formaldehyde remain in edible fish tissue (muscle) after typicel anti-parasitical treatments in aquaculture.

GLP compliance:

no

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material (migrated information):
Not applicable

Radiolabelling:

no

Vehicle:

no

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

No data

Test organisms (species):

other:

Details on test organisms:

Fish species tested for formaldehyde residues were olive flounder (Paralichthys olivaceus), weighing between 86 and 105 g, and black rockfish (Sebastes schlegeli), weighing between 80 and 100 g.

Route of exposure:

aqueous

Test type:

flow-through

Water / sediment media type:

natural water: marine

Total exposure / uptake duration:

1 h

Hardness:

No data

Test temperature:

20°C

pH:

No data

Dissolved oxygen:

No data

TOC:

No data

Salinity:

No data

Details on test conditions:

Fish species tested for formaldehyde residues were olive flounder (Paralichthys olivaceus), weighing between 86 and 105 g, and black rockfish (Sebastes schlegeli), weighing between 80 and 100 g. Prior to the experiments fish were acclimated to laboratory conditions for 40 days in 400 L constant-flow seawater aquaria at 20 °C. Twenty-five fish were randomly assigned to each of the four treatments with 100 mg/L, 300 mg/L, 500 mg/L formalin and a control (treatments based on formaldehyde were 37 mg/L, 111 mg/L and 185 mg/L). As a test medium filtered seawater was used. After one hour of exposure, five fish per treatment were immediately sampled for formaldehyde analysis in muscle tissue. The remaining fish were transferred into clean water and five fish were then sampled at each sample date at 24, 48 and 72 hours post exposure. Aim of this study was to examine if residues of formaldehyde remain in edible fish tissue (muscle) after typicel anti-parasitical treatments in aquaculture.

Nominal and measured concentrations:

Nominal concentrations: 37 mg/L, 111 mg/L, 185 mg/L formaldehyde and a control

Reference substance (positive control):

no

Type:

BCF

Value:

< 1

Calculation basis:

other: calculated from water and tissue concentration

Remarks on result:

other: No data on steady

Elimination:

not specified

Remarks on result:

not measured/tested

Details on kinetic parameters:

- Uptake rate constant (k1): No data
- Depuration (loss) rate constant (k2): No data. 24 hours post exposure tissue formaldehyde concentrations returned to normal levels.

Metabolites:

No data

Results with reference substance (positive control):

Not applicable

Details on results:

- Mortality of test organisms: No mortality occurred
- Behavioural abnormalities: No data on behavioural responses

Bioconcentration factor (BCF):
No data given in the publication.
Under the assumption that steady-state conditions had already been reached after one hour of exposure, BCFs can be calculated as follows:
BCF = concentration in fish (mg/g) / concentration in water (mg/L)
Using that equation results in BCF values between 0.000003 and 0.000004. These values, however, remain unreliable.

Reported statistics:

Student's t-test

All data refer to fish muscle tissue.

Formaldehyde concentration (µg/g) in the fillet tissue of olive flounder after exposure to 100, 300 and 500 mg/l of formalin for 1 h
(mean ± S.E.; n = 5):

	Time after exposure (h)
	0	24	48	72
Control	0.8 ± 0.1	0.8 ± 0.1	0.9 ± 0.04	0.9 ± 0.02
100 mg/l	0.8 ± 0.1	0.7 ± 0.1	0.8 ± 0.1	0.9 ± 0.02
300 mg/l	1.2 ± 0.2	0.8 ± 0.3	0.9 ± 0.2	0.7 ± 0.2
500 mg/l	1.6 ± 0.2^*	0.8 ± 0.1	1.0 ± 0.1	0.8 ± 0.1

^*Significant difference at p 0.05 using Student's t-test to compare between control and treated groups at each sampling times.

Formaldehyde concentration (µg/g) in the fillet tissue of black rockfish after exposure to 100, 300 and 500 mg/l of formalin for 1 h
(mean ± S.E.; n = 5):

	Time after exposure (h)
	0	24	48	72
Control	0.9 ± 0.1	0.9 ± 0.1	0.8 ± 0.1	0.9 ± 0.2
100 mg/l	1.0 ± 0.1	0.8 ± 0.1	0.9 ± 0.04	0.8 ± 0.1
300 mg/l	1.2 ± 0.1	0.9 ± 0.1	0.8 ± 0.1	0.7 ± 0.1
500 mg/l	1.4 ± 0.1^*	1.1 ± 0.2	0.9 ± 0.1	0.8 ± 0.1

^*Significant difference at p 0.05 using Student's t-test to compare between control and treated groups at each sampling times.

In neither of the two test species a bioaccumulation potential was found for formaldehyde. This is supported by the estimation of bioconcentration using log P_ow (cf. 4.7).

Conclusions:

Despite the deficiencies of the test, it can be concluded that formaldehyde has no bioconcentration potential in fish. Food-chain accumulation and secondary poisoning can thus be excluded.

Executive summary:

Immediately after one hour of exposure towards formaldehyde at a concentration of 185 mg/L, formaldehyde levels in muscle tissue were elevated by 0.5 to 0.8 µg/g freshweight in both species. After 24 hours levels had returned to control levels.

Log P_OW  = 0.35

BCF = 0.000004 (unreliable)
Uptake rate constant: no data
Depuration rate constant: no data
DT₅₀: no data

Estimation of bioconcentration 
Experimental data from the present study and a low log P_ow value indicate that formaldehyde does not bioconcentrate in fish. Consequently, secondary poisoning due to food-chain accumulation can be excluded.

Reference 8

Endpoint:

bioaccumulation in aquatic species, other

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

Qualifier:

no guideline available

Principles of method if other than guideline:

static exposure followed by different depuration periods

GLP compliance:

no

Test organisms (species):

other: various fish species

Route of exposure:

aqueous

Test type:

static

Water / sediment media type:

natural water: freshwater

Total exposure / uptake duration:

>= 1 - <= 3 h

Total depuration duration:

<= 24 h

Type:

BCF

Value:

< 1 dimensionless

No formaldehyde was detected in the muscle, liver or blood plasma (detection limit : 5 µg/g fish tissue, recovery 36-62% with fish tissue)

Reference 9

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

abstract

Qualifier:

no guideline available

Principles of method if other than guideline:

other

GLP compliance:

no

Test organisms (species):

Cyprinus carpio

Details on results:

Results showed that formaldehyde in the muscle increased in the first samples after being exposed to various formalin treatments, and the level of formalin in treated fish was significantly higher than that of the control group. Furthermore, formaldehyde in the muscle of the fish at 30 and 20°C treated with 25 ppm for the long-term exposure reached a peak at 24 and 48 h, respectively. However, the formaldehyde concentrations of treated fish gradually decreased before returning to the background level after 144 h in each group.

No BCF values reported

Reference 10

Endpoint:

bioaccumulation in aquatic species, other

Remarks:

QSAR

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Principles of method if other than guideline:

Calculated with Catalogic v5.11.2 BCF base-line model v02.05.

Details on estimation of bioconcentration:

BASIS INFORMATION
- Measured/calculated logPow: calculated

BASIS FOR CALCULATION OF BCF
- Estimation software: BCF base-line model v02.05 of OASIS CATALOGIC v5.11.2

Type:

BCF

Value:

5.09

Remarks on result:

other: log BCF: , all mitigating factors applied

Model domain similarity:

- Parametric domain: 100%

- Structural domain: 73.91% (26.09% unknown)

- Mechanistic domain: 100%

Effects of mitigating factors on BCF:

Acids	0.0000
Metabolism	2.9376
Phenols	0.0000
Size	0.0000
Water solubility	0.2546

The BCF base-line model estimates the log BCF for the test substance at 0.7068 (BCF 5.09).

Reference 11

Endpoint:

bioaccumulation in aquatic species, other

Remarks:

QSAR

Type of information:

calculation (if not (Q)SAR)

Remarks:

Migrated phrase: estimated by calculation

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Principles of method if other than guideline:

Calculated with SRC BCFBAF v3.01

GLP compliance:

no

Radiolabelling:

no

Test organisms (species):

other: calculation

Details on estimation of bioconcentration:

BASIS INFORMATION
- Measured/calculated logPow: calculated

BASIS FOR CALCULATION OF BCF
- Estimation software: BCFBAF Program (v3.01) (part of EPI Suite v4.10)
- Result based on calculated log Pow of: 4.94 (EPI Suite v4.10)

Type:

BCF

Value:

117 L/kg

Remarks on result:

other: log BCF: 2.07

Type:

BAF

Value:

1 070 L/kg

Remarks on result:

other: log BAF: 3.03; Arnot-Gobas BAF method (including biotransformation rate estimates; upper trophic level)

Summary Results:

Log BCF (regression-based estimate): 2.07 (BCF = 117 L/kg wet-wt)

Biotransformation Half-Life (days) : 2.5 (normalized to 10 g fish)

Log BAF (Arnot-Gobas upper trophic): 3.03 (BAF = 1.07e+003 L/kg wet-wt)

 

Log Kow (experimental): not available from database

Log Kow used by BCF estimates: 5.72

 

Equation Used to Make BCF estimate:

Log BCF = 0.6598 log Kow - 0.333 + Correction

 

Correction(s):                   Value

Alkyl chains (8+ -CH2- groups) -1.374

 

Estimated Log BCF = 2.067 (BCF = 116.7 L/kg wet-wt)

Whole body primary biotransformation rate estimate for fish:
Type	Num	Log Biotransformation Fragment Description	Coeff	Value
Frag	2	Linear C4 terminal chain [CCC-CH3]	0.0341	0.0682
Frag	1	Tertiary amine	-0.7829	-0.7829
Frag	1	Triazole ring	0.3225	0.3225
Frag	2	Aromatic-H	0.2664	0.5328
Frag	4	Methyl [-CH3]	0.2451	0.9804
Frag	11	-CH2- [linear]	0.0242	0.2661
Frag	2	-CH- [linear]	-0.1912	-0.3825
L Kow	*	Log Kow = 5.72 (KowWin estimate)	0.3073	1.7581
MolWt	*	Molecular weight parameter		-0.8271
Const	*	Equation Constant		-1.5058
Result		Log Bio Half-Life (days)		0.3985
Result		Bio Half-Life (days)		2.503
Note		Bio Half-Life Normalized to 10 g fish at 15 deg C

Biotransformation Rate Constant:

kM (Rate Constant): 0.2769 /day (10 gram fish)

kM (Rate Constant): 0.1557 /day (100 gram fish)

kM (Rate Constant): 0.08756 /day (1 kg fish)

kM (Rate Constant): 0.04924 /day (10 kg fish)

 

Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates):

Estimated Log BCF (upper trophic) = 2.962 (BCF = 916.2 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 3.028 (BAF = 1066 L/kg wet-wt)

Estimated Log BCF (mid trophic)  = 3.093 (BCF = 1239 L/kg wet-wt)

Estimated Log BAF (mid trophic)  = 3.359 (BAF = 2286 L/kg wet-wt)

Estimated Log BCF (lower trophic) = 3.132 (BCF = 1355 L/kg wet-wt)

Estimated Log BAF (lower trophic) = 3.653 (BAF = 4496 L/kg wet-wt)

 

Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):

Estimated Log BCF (upper trophic) = 4.270 (BCF = 1.861e+004 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 6.095 (BAF = 1.245e+006 L/kg wet-wt)

Reference 12

Endpoint:

bioaccumulation in aquatic species, other

Remarks:

QSAR

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Principles of method if other than guideline:

T.E.S.T. is a toxicity estimation software tool. The program requires only the molecular structure of the test item, all other molecular descriptors which are required to estimate the toxicity are calculated within the tool itself. The molecular descriptors describe physical characteristics of the molecule (e.g. E-state values and E-state counts, constitutional descriptors, topological descriptors, walk and path counts, connectivity, information content, 2d autocorrelation, Burden
eigenvalue, molecular property (such as the octanol-water partition coefficient), Kappa, hydrogen bond acceptor/donor counts, molecular distance edge, and molecular fragment counts). Each of the available methods uses a different set of these descriptors to estimate the toxicity.
The bioaccumulation factor (BCF) was estimated using several available methods: hierarchical method; FDA method, single model method; group contribution method; nearest neighbor method; consensus method. The methods were validated using statistical external validation using separate training and test data sets.
The experimental data set was obtained from several different databases (Dimitrov et al., 2005; Arnot and Gobas, 2006; EURAS; Zhao, 2008). From the available data set containing 643 chemicals salts, mixtures and ambiguous compounds were removed. The final data set contained 598 chemicals.

References:
- Dimitrov, S., N. Dimitrova, T. Parkerton, M. Combers, M. Bonnell, and O. Mekenyan. 2005. Base-line model for identifying the bioaccumulation potential of chemicals. SAR and QSAR in Environmental Research 16:531-554.
- Arnot, J.A., and F.A.P.C. Gobas. 2006. A review of bioconcentration factor (BCF) and bioaccumulation factor (BAF) assessments for organic chemicals in aquatic organisms. Environ. Rev. 14:257-297.
- EURAS. Establishing a bioconcentration factor (BCF) Gold Standard Database. EURAS [cited 5/20/09]. Available from http://www.euras.be/eng/project.asp?ProjectId=92.
- Zhao, C.; Boriani, E.; Chana, A.; Roncaglioni, A.; Benfenati, E. 2008. A new hybrid system of QSAR models for predicting bioconcentration factors (BCF). Chemosphere 73:1701-1707.

GLP compliance:

no

Test organisms (species):

other: fish

Details on estimation of bioconcentration:

BASIS FOR CALCULATION OF BCF
- Estimation software: US EPA T.E.S.T. v4.0.1

Applied estimation methods:
- Hierarchical method : The toxicity for a given query compound is estimated using the weighted average of the predictions from several different cluster models.
- FDA method : The prediction for each test chemical is made using a new model that is fit to the chemicals that are most similar to the test compound. Each model is generated at runtime.
- Single model method : Predictions are made using a multilinear regression model that is fit to the training set (using molecular descriptors as independent variables).
- Group contribution method : Predictions are made using a multilinear regression model that is fit to the training set (using molecular fragment counts as independent variables).
- Nearest neighbor method : The predicted toxicity is estimated by taking an average of the 3 chemicals in the training set that are most similar to the test chemical.
- Consensus method : The predicted toxicity is estimated by taking an average of the predicted toxicities from the above QSAR methods (provided the predictions are within the respective applicability domains; recommended method by T.E.S.T. for providing the most accurate predictions).

Type:

BCF

Value:

32.58

Remarks on result:

other: method: consensus

Type:

other: log BCF

Value:

1.51

Remarks on result:

other: method: consensus

Description of key information

No significant accummulation in organisms from the substance or its degradation products is expected.

Additional information

Evaluation for the original substance (EC no. 401 -280 -0)

No studies on the bioaccumulative potential for the original substance are available. Therefore, three different QSAR calculations have been performed.

1. Catalogic v5.11.2, BCF base-line model v02.05:

BCF = 5.09 L/kg (all mitigating factors applied). The molecule was in the structural domain by 73.91 %.

2. US EPA T.E.S.T. v4.0.1:

BCF = 32.58

3. US EPA EPISuite v4.10, BCFBAFv3.01:

BCF = 117 L/kg wet-wt

Hydrolysis products:

Evaluation for bis(2 -ethylhexyl)amine

No studies on the bioaccumulative potential for that degradation product are available. Therefore, three different QSAR calculations have been performed.

1. Catalogic v5.11.2, BCF base-line model v02.05:

BCF = 13.39 L/kg (all mitigating factors applied). The molecule was in the structural domain by 88.24 %.

2. US EPA T.E.S.T. v4.0.1:

BCF = 115.38

3. US EPA EPISuite v4.10, BCFBAFv3.01:

BCF = 415 L/kg wet-wt

Due to the results of the QSAR calculations, significant accumulation in organisms is not to be expected for the degradation product bis(2 -ethylhexyl)amine.

Evaluation for 1H-1,2,4 -triazole

No studies on the bioaccumulative potential for that degradation product are available. Therefore, two different QSAR calculations have been performed. The structure was not in the structural domain of Catalogic, hence, no further calculations have been performed with this tool.

1. US EPA T.E.S.T. v4.0.1:

BCF = 0.89

2. US EPA EPISuite v4.10, BCFBAFv3.01:

BCF = 3.16 L/kg wet-wt

Due to the results of the QSAR calculations, significant accumulation in organisms is not to be expected for the degradation product 1H-1,2,4 -triazole.

Evaluation for formaldehyde

In tests on different fish species and a shrimp no bioaccumulation of formaldehyde was observed.

One recent study on marine fish is available in which tissue formaldehyde levels after exposure to formaldehyde were investigated (Jung 2001). Elevated formaldehyde levels in muscle tissue (by 0.8 µg/g wet weight) were found only directly after a one-hour treatment at 185 mg/L, but not after a 24-hour or longer depuration period. The results indicate that there is no bioaccumulation in fish.

Based on the physical-chemical properties a BCF can be calculated. According to TGD (EC 2003, part II, chapter 3, p. 126) a BCF_fish for substances with a log Pow < 6 can be calculated using the following QSAR developed by Veith et al. (1979):
log BCF_fish = 0.85 · log Pow – 0.7
Applying the experimentally derived log Pow for formaldehyde of 0.35 (Hansch et al., 1995) results in
log BCF_fish (formaldehyde) = 0.85 · 0.35 – 0.7
log BCF_fish (formaldehyde) = – 0.403
BCF_fish (formaldehyde) = 0.396
As measured data are limited, default values can be used for deriving a BMF according to TGD (EC 2003, part II, chapter 3, p. 127).
Applying the experimentally derived log Pow for formaldehyde of 0.35 (Hansch et al. 1995) and the BCF_fish estimated above results in
BMF (formaldehyde) = 1.
Due to the result, formaldehyde is not expected to accumulate in biota.
Additionally, different tests show no significant concentrations of formaldehyde in fish.

In tests on 4 fish species, no formaldehyde was detected in the muscle, liver or blood plasma (Sills 1979).

In a test on a marine shrimp, no extractable formaldehyde residues could be detected when analysed immediately after treatment (Hose 1980). However during longer post-mortem storage up to 72 hours, significant amounts of extractable formaldehyde were produced biologically due to tissue decomposition.

In conclusion, none of the identified degradation products are expected to significantly accumulate in organisms.