Sodium 3-(2H-benzotriazol-2-yl)-5-sec-butyl-4-hydroxybenzenesulfonate

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

bioaccumulation in aquatic species, other

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:

see attached QPRF, QPMF (attached justifications) and the WoE Justification attached in chapter 13.2

Principles of method if other than guideline:

Calculated with Catalogic vv5.14.1.5.BCF base-line model v.04.11

Details on estimation of bioconcentration:

BASIS INFORMATION
- Measured/calculated logPow: measured (measured see chapter 4.7 "Huntsman FC-88/1T)

BASIS FOR CALCULATION OF BCF
- Estimation software: BCF base-line model v.04.11of OASIS CATALOGIC v5.14.1.5

Type:

BCF

Value:

4.57 L/kg

Remarks on result:

other: 0.66 ± 0.0775 log(L/kg) wet; all mitigating factors applied

Applicability domain:

i Parameter domain:

Log(Kow):::
range = [ -6.34 .. 19.6 ]
calculated: -0.55 (In domain)MOL._WEIGHT
range = [ 16 .. 1180 ]Da
calculated: 369Da (In domain)
WaterSolubility_FR
range = [ 0 .. 1000000 ]mg/L
calculated: 23.6mg/L (In domain)

CONCLUSION:
The chemical fulfils the general properties requirements

ii. Structural fragment domain:
The following ACF are identified:
Fragments in correctly predicted training chemicals – 90.00%
Fragments in non-correctly predicted training chemicals – 0.00%
Fragments not present in the training chemicals – 10.00%

CONCLUSION: The chemical is out of the interpolation structural space

iii. Mechanistic domain:
The expected uptake mechanism of the target chemical is passive diffusion across biological
membranes.
CONCLUSION: The chemical is in the mechanistic domain of the model

d. Predicted value (model result):
0.66 ± 0.0775 log(L/kg) wet
Concomitant predictions :
logBCFmax = 0.980 log(L/kg) wet
relative mitigating effect of Acids= 0.0491
relative mitigating effect of Metabolism= 0.0576
relative mitigating effect of Phenols= 0.000
relative mitigating effect of Size3= 0.0356
relative mitigating effect of Watersolubility= 0.888
DiamMax Min value = 14.181 Å
DiamMax Max value = 16.022 Å
DiamMax Average = 15.022 Å

 

Reference 2

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:

guideline study with acceptable restrictions

Remarks:

GLP status unclear

Justification for type of information:

see attached WoE justification in chapter 13.2

Qualifier:

according to guideline

Guideline:

OECD Guideline 305 (Bioaccumulation in Fish: Aqueous and Dietary Exposure) -III: Dietary Exposure Bioaccumulation Fish Test

GLP compliance:

not specified

Specific details on test material used for the study:

- purity: 95%
- purchased from BOC Sciences

Radiolabelling:

no

Details on sampling:

Animals were sampled on day 7 and day 14 of the uptake phase and after 10 h, 24 h, 2 days, 3 days, 7 days and 14 days of depuration. At each time point, 5 fish were randomly taken from each test basin, immediately weighed, anesthetized in a water bath containing 150 mg/L MS 222 (Sigma Aldrich) and euthanized by a deep cut through the neck. Samplings were performed before feeding of the animals. The GIT was rinsed with ultra-pure water (UHQ) to remove remaining feed or feces. All tissue samples (n = 5) were weighed, shock frozen and stored at -20 °C until analyses. After each sampling, the remaining biomass in each basin was determined by weighing the complete group of fishes to adjust the daily feed ration.

Vehicle:

no

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

For preparation of the enriched test feed commercially available fish feed pellets (Inicio Plus® BioMar, Denmark) with a size of 1.1 mm were spiked according to the method described by Goeritz et al. An application solution of approximately 1.3 mg/mL was prepared in acetone. The experimental diet was spiked with a group of two anions (benzotriazole and tecloftalam). To ensure a homogenous distribution of the test items on the pellets the test solutions were applied via a solvent-inlet tube generating a spray and the pellets mixed thoroughly by rotation. Afterwards the applied ~ 5 mL solvent were removed by rotating the spiked feed under vacuum conditions (~350 mbar) for 10 min. Potential solvent residues were removed by evaporation during incubation in the fume hood overnight. Subsequently, the spiked feed pellets were coated with an alginate gel to avoid leaching of the test item during the feeding study. For this, 3.90 g of a 2 % sodium alginate solution (w/w) in UHQ was preheated to 100 °C and applied to 100 g of the spiked feed pellets. The bottle was shaken thoroughly, followed by the addition of 0.89 g CaCl2. The pellets were mixed until the pellets were completely coated with the alginate matrix. The control diet for feeding the control fish, was prepared in the same way, but without addition of IOCs in the spiking solution. Homogeneity and content of the IOCs in the spiked test diets were analysed directly after preparation in five representative feed samples from each batch. After the exposure phase of the feeding study, samples of the test diets were re-analysed to verify the stability of the test items.
-Recovery of test substance in feed at test end: 88.7%

Test organisms (species):

Oncorhynchus mykiss (previous name: Salmo gairdneri)

Details on test organisms:

TEST ORGANISM
- Common name: rainbow trout
- Source: purchased from Fischzucht Störk, Bad Saulgau, Germany)
- Age at study initiation (mean and range, SD): juvenile
- Weight at study initiation (mean and range, SD): 5.42 +- 1.14 g
- Feeding during test
- Food type: pellets
- Amount: 2% of their body weight/day.
- Frequency: daily

Route of exposure:

feed

Justification for method:

dietary exposure method used for following reason: lower membrane permeability of ionics and higher transepithelial resistance of the gills compared to the GIT

Test type:

flow-through

Water / sediment media type:

natural water: freshwater

Total exposure / uptake duration:

14 d

Total depuration duration:

14 d

Test temperature:

10.6 – 11.7 °C

pH:

7.2 – 7.5

Dissolved oxygen:

88.4 – 107 %; 8.63 – 9.94 mg/L

Details on test conditions:

TEST SYSTEM
- Test vessel: 80 L glass tanks filled with 75 L of copper reduced tap water
- Aeration: constantly
- Renewal rate of test solution (flow rate): 15.6 L/h
- No. of organisms per vessel: 40
- No. of vessels per concentration (replicates): 1
- No. of vessels per control / vehicle control (replicates): 1

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: copper free tap water
- Holding medium different from test medium: no
- Intervals of water quality measurement: Water temperature, oxygen content and pH were examined every other day. Nitrite, nitrate and ammonia concentrations in the test system were measured weekly.
- Intervals of test medium replacement: 5-fold water exchange per day

OTHER TEST CONDITIONS
- Photoperiod: 16:8 light -dark cycle
- For OECD 305 part III (dietary exposure fish bioaccumulation), overall daily feeding rate used in the study: the test animals were fed daily at a rate of 2 % of their body wet weight in compliance with the recommendation given by the feed manufacturer.

Nominal and measured concentrations:

Nominal: 0.00319 mg/g
Recovery: 88.7% at end of test (in fish feed)

Remarks on result:

not measured/tested

Remarks:

Lipid-normalized BMF value was not considered for the assessment, given that ionics such as the test substance does not primarily adsorb to lipids.

Key result

Conc. / dose:

0.003 mg/g food

Temp.:

11 °C

pH:

7.2

Type:

BMF

Value:

0.033 dimensionless

Basis:

whole body w.w.

Time of plateau:

14 d

Calculation basis:

kinetic, corrected for growth

Conc. / dose:

0.003 mg/g food

Temp.:

11 °C

pH:

7.3

Type:

BMF

Value:

0.033 dimensionless

Basis:

whole body w.w.

Time of plateau:

14 d

Calculation basis:

kinetic

Key result

Elimination:

yes

Parameter:

DT50

Depuration time (DT):

0.571 d

Details on kinetic parameters:

- Depuration rate constant k(e): 1.22/d

Details on results:

No mortality or abnormalities of the animals’ behavior were observed during the biomagnification study. The experimental diets were readily accepted by the experimental animals.

Homogeneity, content and stability of IOCs in fish feed
The homogenous distribution and the content of the test substance in the spiked experimental diet was confirmed directly after preparation by analysis of five individually processed replicates. The relative standard deviations of the concentrations were<10%, confirming the homogenous distribution of the test substance on the spiked feed. 

Spike recovery experiments
Mean recovery rate of the the test substance extracted from spiked fish compartments was 81.4% (GIT), 98.7% (liver) and 115% (carcass), respectively. 

Validity criteria fulfilled:

not specified

Conclusions:

The guideline study indicates that the test substance has a low potential for biomagnification.

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:

QMRF and QPRF are attached.
See the attached WoE justification

Principles of method if other than guideline:

Calculation based on BCFBAF v3.01, Estimation Programs Interface Suite™ for Microsoft® Windows v 4.10. US EPA, United States Environmental Protection Agency, Washington, DC, USA.

GLP compliance:

no

Test organisms (species):

other: fish

Route of exposure:

aqueous

Test type:

other: calculation

Water / sediment media type:

natural water: freshwater

Details on estimation of bioconcentration:

BASIS FOR CALCULATION OF BCF
- Estimation software: BCFBAF v3.01
- Result based on calculated log Pow of: 2.29 (KOWWIN v1.68)

Key result

Type:

BCF

Value:

0.953 L/kg

Basis:

whole body w.w.

Calculation basis:

steady state

Remarks on result:

other: Mid 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).

BCFBAF Program (v3.01) Results:
==============================
SMILES : c32c(cccc3)nn(c1c(O)c(C(C)CC)cc(S(=O)(O)O)c1)n2

CHEM : sodium 3-(2H-benzotriazol-2-yl)-5-sec-butyl-4-hydroxybenzenesulfonate
MOL FOR: C16 H19 N3 O4 S1
MOL WT : 349.41
--------------------------------- BCFBAF v3.01 --------------------------------
Summary Results:
Log BCF (regression-based estimate): 0.50 (BCF = 3.16 L/kg wet-wt)
Biotransformation Half-Life (days) : 0.0146 (normalized to 10 g fish)
Log BAF (Arnot-Gobas upper trophic): -0.04 (BAF = 0.916 L/kg wet-wt)
Log Kow (experimental): not available from database
Log Kow used by BCF estimates: -0.24 (user entered)
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 | Aromatic alcohol [-OH] | -0.4727 | -0.4727
Frag | 1 | Alkyl substituent on aromatic ring | 0.1781 | 0.1781
Frag | 1 | Triazole Ring | 0.3225 | 0.3225
Frag | 1 | Aromatic-CH | -0.4629 | -0.4629
Frag | 6 | Aromatic-H | 0.2664 | 1.5983
Frag | 2 | Methyl [-CH3] | 0.2451 | 0.4902
Frag | 1 | -CH2- [linear] | 0.0242 | 0.0242
Frag | 1 | Number of fused 6-carbon aromatic rings | -0.5779 | -0.5779
Frag | 1 | Number of fused 5-carbon aromatic rings | 0.0000 | 0.0000
Frag | 1 | Benzene | -0.4277 | -0.4277
L Kow| * | Log Kow = -0.24 (user-entered ) | 0.3073 | -0.0738
MolWt| * | Molecular Weight Parameter | | -0.8960
Const| * | Equation Constant | | -1.5371
============+============================================+=========+=========
RESULT | LOG Bio Half-Life (days) | | -1.8348
RESULT | Bio Half-Life (days) | | 0.01463
NOTE | Bio Half-Life Normalized to 10 g fish at 15 deg C |
============+============================================+=========+=========
Biotransformation Rate Constant:
kM (Rate Constant): 47.39 /day (10 gram fish)
kM (Rate Constant): 26.65 /day (100 gram fish)
kM (Rate Constant): 14.98 /day (1 kg fish)
kM (Rate Constant): 8.427 /day (10 kg fish)
Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates):
Estimated Log BCF (upper trophic) = -0.038 (BCF = 0.9156 L/kg wet-wt)
Estimated Log BAF (upper trophic) = -0.038 (BAF = 0.9156 L/kg wet-wt)
Estimated Log BCF (mid trophic) = -0.021 (BCF = 0.9534 L/kg wet-wt)
Estimated Log BAF (mid trophic) = -0.021 (BAF = 0.9534 L/kg wet-wt)
Estimated Log BCF (lower trophic) = -0.017 (BCF = 0.9613 L/kg wet-wt)
Estimated Log BAF (lower trophic) = -0.017 (BAF = 0.9613 L/kg wet-wt)
Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):
Estimated Log BCF (upper trophic) = -0.020 (BCF = 0.9546 L/kg wet-wt)
Estimated Log BAF (upper trophic) = -0.020 (BAF = 0.9553 L/kg wet-wt)

Validity criteria fulfilled:

yes

Conclusions:

The substance does not bioaccumulate in fish.

Description of key information

A weight of evidence approach was chosen to assess the bioaccumulation potential of Tinogard HS. A detailed justification is attached in chapter 13.2.

 Based on the very low log Pow (-0.24) and molecular properties the substance is not expected to accumulate in organisms. This is confirmed by a valid QSAR calculations using BCFBAF v3.01, which showed BCF values of 0.9534 L/kg (Arnot & Gobas mid trophic, including biotransformation) and OASIS Catalogic base-line model v.04.11, which predicted a BCF of 4.57 L/kg. As well as a BMF value of 0.0334 experimentally determined for a structurally similar benzotriazole derivate.

Key value for chemical safety assessment

BCF (aquatic species):

4.57 L/kg ww

BMF in fish (dimensionless):

0.033

Additional information

QSAR data evaluating the bioaccumulation potential of sodium 3-H(2H-benzotriazol-2-yl)-5-sec-butyl-4-hydroxybenzenesulfonate (CAS 92484-48-5) as well as a dietary exposure study with the structurally similar substance 3-(3-(2H-benzo[d][1,2,3]triazol-2-yl)-5-(tertbutyl)-4-hydroxyphenyl)-propanoic acid (CAS 84268-36-0) are available. No reliable study regarding bioaccumulation was available for sodium 3-H(2H-benzotriazol-2-yl)-5-sec-butyl-4-hydroxybenzenesulfonate (CAS 92484-48-5). Therefore, to conclude on the bioaccumulation potential of the test substance, all available and relevant data are combined in a Weight of Evidence (WoE) approach, which is in accordance to 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 VIII.

Based on the physical-chemical characteristics of sodium 3-H(2H-benzotriazol-2-yl)-5-sec-butyl-4-hydroxybenzenesulfonate, particularly high water solubility, very low octanol-water partition coefficient (log Kow = -0.24 at pH 6.1) and vapor pressure, very little absorption of this ingredient is expected from dermal exposures. In addition to the physico-chemical properties a fragment based QSAR analysis indicates a low bioaccumulation potential of sodium 3-H(2H-benzotriazol-2-yl)-5-sec-butyl-4-hydroxybenzenesulfonate. Both models (BCFBAF v.3.01, Arnot & Gobas mid trophic; Catalgoic base-line model v.04.11) calculated very low bioconcentration factors of 0.9534 L/kg whole body w.w. and 4.57 L/kg whole body w.w. confirming that a significant direct uptake via the aqueous phase is not to be expected.

Mueller et al. (2020) examined the dietary ingestions of six substances including the structurally similar substance (3-(3-(2H-benzo[d][1,2,3]triazol-2-yl)-5-(tertbutyl)-4-hydroxyphenyl)-propanoic acid (CAS 84268-36-0). The study was performed according to OECD guideline 305 combined with organ-specific analysis using juvenile rainbow trout (O. mykiss) as test organisms. The fish were fed three test diets supplemented with the test substances for 14 days at a rate of 2% of their body weight. The accumulation phase was followed by a 14-day depuration phase. Biomagnification could not be demonstrated for any of the substances tested. For benzotriazole (3-(3-(2H-benzo[d][1,2,3]triazol-2-yl)-5-(tertbutyl)-4-hydroxyphenyl)-propanoic acid the growth-corrected depuration rate k2g was 1.24 d-1 and the depuration half-life calculated from k2g amounted to 0.571 indicating rapid excretion. The growth-corrected kinetic biomagnification factor (BMF) was 0.0334, which is well below the proposed threshold values for biomagnification of 1 and 0.1 indicating a slow uptake and rapid depuration. Hence, dietary uptake can be considered very low while excretion is expected to be rapid through both urine and feces.

In conclusion, 3-H(2H-benzotriazol-2-yl)-5-sec-butyl-4-hydroxybenzenesulfonate possess a low potential for bioconcentration based on the physico-chemical properties, such as low log Kow (- 0.24), ionization in water, molecular size and the BCF values calculated using BCFBAF v.3.01 and Catalogic v5.14.1.5. Dietary uptake can also be considered very low while excretion is expected to be rapid through both urine and feces as demonstrated by the suitable read across substance (3-(3-(2H-benzo[d][1,2,3]triazol-2-yl)-5-(tertbutyl)-4-hydroxyphenyl)-propanoic acid (CAS 84269-36-0).

Armitage JM et al (2017) Assessing the bioaccumulation potential of ionizable organic compounds: Current knowledge and research priorities. Environ Toxicol Chem 36(4):882–897. https ://doi.org/10.1002/etc.3680