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EC number: 939-253-5 | CAS number: 68424-85-1
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Bioaccumulation: terrestrial
Administrative data
- Endpoint:
- bioaccumulation: terrestrial
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- data waiving: supporting information
Reference
- Vapour pressure:
- 0.006 Pa
- at the temperature of:
- 25 °C
The vapour pressure was determined using the isothermal thermo gravimetric effusion method according to OECD Guideline 104, EU Method A.4 and EPA OPPTS 830.7950 (Brekelmans, 2012).
- Reason / purpose for cross-reference:
- data waiving: supporting information
Reference
- BCF (aquatic species):
- 79 L/kg ww
Given the ionic nature of the test substance and the available experimental and predicted BCF values indicates a low bioaccumulation potential. The experimental BCF value of 79 L/kg ww of the test substance has been considered further for hazard/risk assessment.
Study 1: A study was conducted to determine the aquatic bioaccumulation of the test substance, C12 -16 ADBAC (30.64% active; 98.9% radiolabeled purity) in Lepomis macrochirus (bluegill fish) under flow-through conditions, according to EPA OPP 165-4, in compliance with GLP. The blue gill fish were continuously exposed to a nominal concentration of 0.050 mg/L of the test substance (equivalent to a measured concentration of 0.076 mg/L) in well water for 35 days, followed by transfer of 35 fish into flowing uncontaminated water for a 21-d depuration period. Sampling was carried out on Days 0, 1, 3, 7, 9, 10, 14, 21, 23, 28 and 35 for the exposure period and Days 1, 3, 7, 10, 14 and 21 for the depuration period. Water samples were collected on Day 8 of the exposure period and Day 16 of the depuration for analytic determination of the test substance concentration. Radiometric analyses of the water and selected fish tissues revealed that the mean steady state bioconcentration factor (BCF) in the edible, non-edible and whole-body fish tissue during the 35 days of exposure to be 33, 160 and 79 L/kg. The half-life for non-edible tissue was attained between Days 14 and 21, while it could not be reached for the edible and whole-body fish tissues by the end of 21-d depuration period. By Day 21 of the depuration period, the 14C residues present on the last day of exposure in the edible, non-edible and whole-body fish tissues had been eliminated by 29, 60 and 44% respectively. Analysis of skin tissue after 35 d of exposure showed residue levels somewhat higher than those observed for edible tissue at the same sampling period, indicating that there is likely significant binding of 14C-ADBAC to the skins and scales of exposed bluegill, as expected behaviour of cationic surfactants. Under the study conditions, the whole body BCF of the test substance was determined to be 79, indicating low potential to bioaccumulate (Fackler, 1989).
Study 2: The Bioconcentration factor (BCF) value of test substance, C12 -16 ADBAC was predicted using regression-based and Arnot-Gobas BAF-BCF models of BCFBAF v3.02 program (EPI SuiteTMv4.11). The Arnot-Gobas method, takes into account mitigating factors, like growth dilution and metabolic biotransformations, therefore the BCF value using this method is generally considered to be more realistic or accurate. However, ionic, pigments and dyes, perfluorinated substances are currently excluded from the applicability domain of this model. In the case of the test substance, considering that it is a UVCB consisting of a mix of ionic (e.g., the quaternary ammonium salts) and non-ionic constituents (e.g., amines), the BCF values were predicted using the regression-based method for the ionic constituents and the Arnot-Gobas BAF-BCF method for the non-ionic constituents, using SMILES codes as the input parameter. The BCF values for the constituents ranged from 1.55 to 70.8 L/kg ww (log BCF: 0.19 to 1.85), indicating a low bioaccumulation potential. On comparing with domain descriptors, all constituents were found to meet the MW, log Kow and/or the maximum number of correction factor instances domain criteria as defined in the BCFBAF user guide of EPISuite. Further, given that the major constituents are structurally very similar and vary only in the carbon chain length, a weighted average value, which takes into account the percentage of the constituent in the substance, has been considered to dampen the errors in predictions (if any). Therefore, the weighted average BCF value was calculated as 69.62 L/Kg ww (Log BCF = 1.84). Overall, considering either the individual BCF predictions for the constituents or the weighted average values, the test substance is expected to have a low bioaccumulation potential. However, taking into consideration the model’s training set and validation set statistics and the fact that the training set only contains 61 ionic compounds, the BCF predictions for the individual constituents are considered to be reliable with moderate confidence.
Study 3: A study was conducted to determine the biomagnification (BMF) potential of the read across substance, C18 TMAC (purity 95%), following the principles of OECD TG 305. For the main study rainbow trout (Oncorhynchus mykiss) with an average weight of 5.42 g were fed test diets enriched with read across substance (23.6 mg/kg read across the substance in feed. The resulting treatment and one control group (each 40 animals) were tested simultaneously. The uptake phase of 14 days was followed by a depuration phase lasting 14 days. All animals were fed the non-spiked feed during the depuration phase. The concentrations of the read across substance in fish samples were determined by chemical analysis and all tissue concentrations were calculated based on a wet weight basis. Chemical analysis of the read across substance was performed by liquid chromatography with coupled mass spectrometry (LC-MS/MS). In the main study five animals of each group were sampled randomized 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. Biomagnification factor (BMF) and distribution factor were calculated based on the tissue concentrations measured at the end of the uptake phase. No mortality or abnormal behaviour of the test animals was observed during the main study. The experimental diets were accepted by the test animals and showed a decent digestibility as confirmed by the texture and appearance of the feces. One fish was euthanized at Day 25 due to injuries. The specific growth rates of the animals ranged from 1.95 to 2.71 %/d over the entire experiment. During the study, the feed conversion ratio (FCR) was 0.69 to 0.95. Fish were measured and weighed at the beginning of the experiment as well as at respective sampling time points to monitor growth and associated growth-dilution effects during the feeding study. Growth rate constants were determined separately for the uptake and depuration phases, for the treatments and the control group, using the ln-transformed weights of the fish. A subsequent parallel line analysis (PLA, as suggested by the OECD Guideline) resulted in no statistical differences between the uptake and the depuration phase among the treated groups with the read across substance. No statistically significant difference was detected with regard to the growth of the treated groups. Hence it was deduced that neither adverse nor toxic effects were caused by the enriched diets. As steady state seemed to be reached after 14 days of exposure, steady state biomagnification factors (BMFss) could be calculated as 0.02709 g/g, which showed that read across substance did not biomagnify after dietary exposure. In general, the GIT and the liver showed the highest values for the BMFk and BMFkg. The kinetic BMF (BMFk) and growth-corrected biomagnification factor (BMFkg) were calculated for the read across substance to be 0.0404 and 0.0463, respectively. Overall, it was concluded from the screening that ionization lowers the tendency of a chemical to bioaccumulate, compared to non-ionized chemicals. Aside from the well-known lipophobicity of ionized groups, fast depuration seems to be a major reason for the observed low biomagnification of ionic compounds, in particular anions. Fast depuration may happen due to rapid metabolism or conjugation of charged compounds, and future studies should test this hypothesis. Under the study conditions, the read across substance BMFss, BMFk and BMFkg values on whole body wet weight basis in rainbow trout were determined to be 0.02709, 0.0404 and 0.0463 g/g, respectively, suggesting low biomagnification potential (Schlechtriem, 2021). Based on the results of the read across study, a similar low biomagnification potential is expected for the test substance.
This is further supported by the absence of bioaccumulation potential evidence observed in in the two toxicokinetic studies in mammals with the read across substance, C12-16 ADBAC (Selim, 1987 and Appelqvist, 2006). .
Also, the biocides assessment reports available from RMS Italy on Coco TMAC and C12-16 ADBAC, concluded the substances to show low potential for bioaccumulation, based on the results from the above study (Fackler, 1989) and an additional read across to DDAC for the Coco TM AC's assessment ((ECHA biocides assessment report, 2015, 2016).
Overall, given the ionic nature of the test substance and the available experimental and predicted BCF values indicates a low bioaccumulation potential. The experimental BCF value of 79 L/kg ww of the test substance has been considered further for hazard/risk assessment.
- Reason / purpose for cross-reference:
- data waiving: supporting information
Reference
- Half-life in soil:
- 17.1 d
- at the temperature of:
- 12 °C
Based on the most recent and radiolabelled aerobic biodegradation study in soil, the transformation of the C12 and C14 carbon chains of the test substance was considered to be rapid with DT50 values ranging from 2.2-28.7 days with the SFO model and 1.6 – 23.3 days with the FOMC model at 20°C. Further, in the biocides dossier, a weighted estimate of the DT50 value at 12°C was extrapolated for C12-16 ADBAC by assuming the highest allowable concentrations for the major chains. These calculations resulted in the estimated FOMC DT50 of 17.1 days at 12°C and SOF DT50 of 19.2 days at 12°C. The DT50 of 17.1 days at 12°C based on the biphasic model (FOMC) showing better visual fit and lower error was used further for risk assessment.
Therefore, in line with the biocides dossier, the DT50 of 17.1 days at 12°C based on the biphasic model (FOMC) also has been considered further for hazard/risk assessment.
Study 1:
A study was conducted to determine the aerobic transformation/dissipation in the soil of the test substance, C12 -16 ADBAC (radiochemical purity: 98.5%), according to the OECD Guideline 307, in compliance with GLP. Four different standard soils (LUFA 2.2, 2.3, 2.4 and 5M, field fresh sampled), varying in their organic carbon content, pH, clay content, cation exchange capacity and microbial biomass, were treated with [ring-U-14C] Benzalkonium chloride. Soil samples were incubated in the dark under aerobic conditions for up to 128 days under controlled laboratory conditions. After appropriate time intervals, soil samples were extracted, and the extracts were analysed for test substance and transformation products to calculate DT50 and DT90 values. The mineralization was determined by trapping and analysis of the evolved 14CO2. Non-extractable residues (NER) were determined after combustion of the extracted soil samples. The total radioactivity of the soil extracts, the extracted soil (NER) and evolved 14CO2 was determined by LSC. Test substance and transformation products in the soil extracts were analysed by LC-FSA (radio-HPLC). Evaluation of the transformation pathway was done by LC-HRMS.
Transformation of the C12 chain of the test substance [ring-U-14C]Benzalkonium chloride was rapid in all four soils. The transformation of the C14 chain started after a short adaptation phase but was thereafter rapid as well. Within 7 - 21 days the concentration of the C12 chain decreased from initially 67.2 – 69.6% of applied radioactivity (AR) to < 20 % of AR. The concentration of the C14 chain decreased from initially 23.8 – 24.6 % of AR to < 10 % of AR within 10 – 36 days. Formation of NER started directly after application of the test substance. Further formation of NER increased in parallel to the start of increased mineralisation, indicating that a major amount of NER is comprised by radioactivity incorporated in microbial biomass. At the test end, the biomass concentration was in the range of 1.46 – 2.62 % of soil organic carbon content in all four soils, indicating that viable microbial biomass was present throughout the incubation time. The mass balance was in the range 99.9 – 103.0 % at test start and 90.4 – 94.0 % at test end.
The predominant initial degradation step was the oxidative removal of the alkyl chain. Dimethylbenzylamine was determined as the major metabolite, the highest concentrations of dimethylbenzylamine were determined until Day 22, thereafter the concentrations deceased continuously until test end. Methylbenzylamine was transient and only present in traces. Benzylamine, a suspected metabolite, was not detected. Further metabolites containing partly degraded alkyl chains were all transient and were not detected or only <0.2 % of AR (soil 2.3) at the test end.
With regard to the kinetics, the transformation showed a slight bi-phasic pattern, therefore the ‘Single First Order Model’ (SFO) and the ‘First-Order Multi-Compartment Model’ (FOMC) were compared. Based on the visual fit and x2 error, the transformation of [ring-U-14C]Benzalkonium chloride met the requirements for both models well for all four soils. The calculated DT50 values with the Single-First-Order Model (SFO) for the dissipation of [ring-U-14C]Benzalkonium chloride were 2.2 – 8.7 days (C12 chain) and 6.1 – 28.7 days (C14 chain), the DT90 values were 7.2 – 28.8 (C12 chain) days and 20.2 – 95.4 days (C14 chain). The calculated DT50 values with the FOMC model for the dissipation of [ring-U-14C]Benzalkonium chloride were 1.6 – 7.2 days (C12 chain) and 5.5 – 23.3 days (C14 chain), the DT90 values were 15.0 – 48.8 days (C12 chain) and 35.8 – 164.3 days (C14 chain).
The test substance is predominantly C12-ADBAC and C14-ADBAC, with low to negligible amounts of C16-ADBAC. The chain length distribution is defined as follows:C12 (35-80%), C14 (20-55%), C16 (0-15%). C16-ADBAC was not included in this study because it is present in very low amounts; there are technical difficulties with having sufficient radioactivity for substances present in small amounts relative to other constituents. C16-ADBAC would be expected to degrade by the same route but at a slower rate than its C12 and C14 counterparts, as degradation rate tends to decrease with increasing chain lengths. Under the study conditions, transformations of both C12 and C14 carbon chains of the test substance were determined to be rapid in all four soils and the DT50 values were determined to be 2.2 – 8.7 days [C12 chain] and 6.1 – 28.7 days [C14 chain] with the SFO model and 1.6 – 7.2 days [C12 chain] and 5.5 – 23.3 days [C14 chain] with the FOMC modelat 20°C (Fiebig, 2019).
Further, in the biocides dossier, to account for the potential contribution of C16 ADBAC to the overall DT50 of ADBAC, a geometric mean of SFO and FOMC DT50s for C12 and C14 ADBAC in the four soils (as recommended in BPR Vol IV Part B and C) was calculated and converted to 12° using the following equation (DT50 (12°) = DT50 (20°) * e(0.08*(20-12)). This was followed by linear extrapolation of the geometric mean DT50s for C12 and C14 ADBAC, to estimate the DT50 for C16 ADBAC. See tables below:
SFO DT50s |
|
|
|
|
|
|
|
Soil |
2.2 |
2.3 |
2.4 |
5M |
Geo. Mean |
Adj. to 12° C |
|
C12 ADBAC |
2.2 |
3.3 |
6.2 |
8.7 |
4.4 |
8.4 |
|
C14 ADBAC |
6.1 |
8.9 |
12.9 |
28.7 |
11.9 |
22.6 |
|
C16 ADBAC |
-- |
-- |
-- |
-- |
-- |
36.7 |
FOMC DT50s |
|
|
|
|
|
|
|
Soil |
2.2 |
2.3 |
2.4 |
5M |
Geo. Mean |
Adj. to 12° C |
|
C12 ADBAC |
1.6 |
3.2 |
5.8 |
7.2 |
3.8 |
7.3 |
|
C14 ADBAC |
5.5 |
8.3 |
12.1 |
23.3 |
10.7 |
20.2 |
|
C16 ADBAC |
-- |
-- |
-- |
-- |
-- |
33.1 |
A weighted estimate of the DT50 of ADBAC (C12-C16) at 12°C was calculated by assuming the highest allowable concentrations of C14- and C16- ADBAC and the balance of C12-ADBAC (i.e., 12% C16, 52% C14 and 36% C12), which resulted in the following estimated DT50s:
SFO DT50 = 19.2d at 12°C; FOMC DT50 = 17.1d at 12°C
However, due to the relatively low levels of C16-ADBAC, the overall estimated DT50s were considered rather insensitive to the assumed DT50 for C16-ADBAC. The DT50 of 17.1 days at 12°C based on the biphasic model (FOMC) showing better visual fit and lower error was used further for risk assessment.
Study 2: A study was conducted to determine the aerobic biodegradation of the test substance, C12-16 ADBAC (50% active in water) in loamy soil, according to the US FDA Environmental Assessment Handbook, Technical Assistance Document 3.12 (1987). The study comprised two treatments: test and chemical blank control group, each with three replicates. The test substance was added into biometers at a concentration of 10 mg carbon per 50 g soil using appropriate amount of deionised water required for bringing the soils to 50-70% of the moisture capacity. Loam was added to the biometers after the test solutions to facilitate uniform moistening of the soils by capillary action. The test was then incubated at 22 ± 3°C and run for approximately 90 d. The side tube of the biometer contained 20 mL 0.2 M KOH for absorbing carbon dioxide produced by the microorganisms. The theoretical CO2 production of the test substance was calculated from its carbon content. The amounts of carbon dioxide were calculated by subtracting the mean carbon dioxide production in the test systems containing the test substance and the mean carbon dioxide production level in the control blank. Biodegradation was calculated as the ratio of experimental carbon dioxide production to theoretical carbon dioxide production [ThCO2P]. Under the study conditions, there was 64% degradation of the test substance after 70 days. This percentage of the theoretical carbon dioxide production presumes complete mineralization. The DT50 was estimated to be 40 days (van Ginkel, 1994).
Based on the most recent and radiolabelled aerobic biodegradation study in soil, the transformation of the C12 and C14 carbon chains of the test substance was considered to be rapid with DT50 values ranging from 2.2-28.7 days with the SFO model and 1.6 – 23.3 days with the FOMC model at 20°C. Further, in the biocides dossier, a weighted estimate of the DT50 value at 12°C was extrapolated for C12-16 ADBAC by assuming the highest allowable concentrations for the major chains. These calculations resulted in the estimated FOMC DT50 of 17.1 days at 12°C and SOF DT50 of 19.2 days at 12°C. The DT50 of 17.1 days at 12°C based on the biphasic model (FOMC) showing better visual fit and lower error was used further for risk assessment.
Therefore, in line with the biocides dossier, the DT50 of 17.1 days at 12°C based on the biphasic model (FOMC) also has been considered further for hazard/risk assessment.
- Reason / purpose for cross-reference:
- data waiving: supporting information
Reference
- Endpoint:
- biodegradation in water: sewage treatment simulation testing
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From January 17, 2007 to May 16, 2007
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 303 A (Simulation Test - Aerobic Sewage Treatment. A: Activated Sludge Units)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Radiolabelling:
- no
- Oxygen conditions:
- aerobic
- Inoculum or test system:
- activated sludge, domestic, non-adapted
- Details on inoculum:
- Nature: Activated sludge
Sampling site: Duiven, the Netherlands
Preparation of inoculum for exposure: Sludge was used upon arrival
Initial cell concentration: 3 g DW/L - Duration of test (contact time):
- 58 d
- Initial conc.:
- 49 mg/L
- Based on:
- test mat.
- Parameter followed for biodegradation estimation:
- other: non-pugeable organic carbon concentrations (NPOC)
- Details on study design:
- TEST SYSTEM:
- Test apparatus: The CAS test was performed in a Husmann-type units constructed of glass. The units consisted of an aeration vessel capable of holding 0.35 litre from which the liquor was passed continuously to a settler of 0.3 litre capacity. The domestic waste water liquor in a cooled vessel was supplied with a pump. The liquor passed through the aeration vessel and settler and treated effluent left the apparatus to be collected in a vessel.
Aeration was achieved through a capillary on the bottom of the aeration section at a rate of approximately 9 L/hour air.
- Number of units: Control and test unit
- Aeration device: Capillary on the bottom of the reactor
- Measuring equipment: The NPOC in acidified filtered samples were analysed in a TOC apparatus (Shimadzu, s‟Hertogenbosch, The Netherlands).
The chemical oxygen demand (COD) of the influent and effluent was determined by oxidation with an acid-dichromate mixture in which Cr6+ was reduced to Cr3+ (Hach Lange, Duesseldorf, Germany). The dissolved oxygen concentrations were determined electrochemically using an oxygen electrode (WTW Trioxmatic EO 200) and meter (WTW OXI 530) (Retsch, Ochten, The Netherlands).
The pH was measured using a Knick 765 calimatic pH meter (Elektronische Messgerate GmbH, Berlin, Germany). The temperature was measured with a Tegam thermometer Model 820 (Applikon, Schiedam, The Netherlands). The dry weight (DW) of the inoculum was determined by filtering the activated sludge over a pre weighed 12 µm Schleicher and Schüll filter. This filter was dried for 1.5 hours at 104°C and weighed after cooling. DW was calculated by subtracting the weighed filters and by dividing this difference by the filtered volume.
LC-MS/MS was used to analyse the parent compound.
- Test performed in closed vessels due to significant volatility of TS: No
- Analytical parameter: NPOC (non purgeable organic carbon) removal and LC-MS/MS
TEST CONDITIONS:
- Composition of medium: Domestic wastewater contain organic compounds
- Additional substrate: No
- Test temperature: 19-21°C
- pH: 7.0 – 8.0
- Suspended solids concentration: 2 - 3 g/L
SAMPLING:
- At least two times a week for NPOC analysis and 5 times a week during the last week of the test for LC-MS/MS analysis.
STATISTICS:
- NPOC analyses in test and control unit were treated as paired observations. With paired observations an outlier test (Dixon) was performed. t–Statistics were used to determine the significance of the carbon removal. - Test performance:
- The performance of the control unit was checked (Day 14 and the last d of the test) by measuring the COD removal (Day 14 and the last d of the test) and the concentrations of ammonium and nitrite in the effluent (Day 14). At Day 14 the COD in the influent and effluent were 517 and 55 mg/L, respectively. At the last day the COD in the influent and effluent were 548 and 47 mg/L, respectively. The COD removal percentages were 89 and 91. The ammonium and nitrite concentrations in the effluent at Day 14 were <2.5 and <2.0 mg/L. These results demonstrate that the test is valid.
- Key result
- % Degr.:
- > 99.98
- Parameter:
- DOC removal
- Sampling time:
- 40 d
- Remarks on result:
- other: mean removal during Day 40-58
- Key result
- % Degr.:
- 0.016
- Parameter:
- other: via sorption
- Sampling time:
- 57 d
- Key result
- % Degr.:
- 0.023
- Parameter:
- other: via sorption
- Sampling time:
- 58 d
- Key result
- % Degr.:
- > 99.998
- Parameter:
- other: Total removal
- Sampling time:
- 58 d
- Key result
- % Degr.:
- ca. 0.02
- Parameter:
- other: Emission to sludge
- Sampling time:
- 58 d
- Key result
- % Degr.:
- ca. 99.978
- Parameter:
- other: degraded
- Sampling time:
- 58 d
- Remarks on result:
- other: (assessed based on total removal percentage of >99.998% after 58 days and percentage sorption to sludge of 0.02 % after 58 d)
- Transformation products:
- not measured
- Evaporation of parent compound:
- no
- Volatile metabolites:
- no
- Details on results:
- - From Day 40 to 58 samples were taken to assess a mean of the removal percentage with organic carbon concentrations. According to the Dixon test, there were no outliers during this period. Subsequently, all data were used in a t-statistic. The mean difference between the NPOC in the influent and effluent was 0.06 ± 1.18 mg/L (95 per cent confidence interval). The mean removal percentage calculated with this mean difference was 99.8 ± 3.5 (95 per cent confidence). This carbon removal is statistically not significant because the t-statistic (n = 15) did not exceed the critical value. The results therefore demonstrate that the continuous activated sludge system treating domestic waste water spiked with test substance removes the organic carbon of test substance (almost) completely from waste water. The high carbon removal percentages also demonstrate that recalcitrant water-soluble substances are not formed during the biodegradation process.
- During the last week of the test the parent compound in the effluent of the test unit was <10 µg/L corresponding to >99.98% removal. Analysis of the test substance present in the activated sludge demonstrated that ~99.98% of the test substance was removed by biodegradation.
- The performance of the control unit was checked (Day 14 and the last d of the test) by measuring the COD removal (Day 14 and the last d of the test) and the concentrations of ammonium and nitrite in the effluent (Day 14). At Day 14 the COD in the influent and effluent were 517 and 55 mg/L, respectively. At the last day the COD in the influent and effluent were 548 and 47 mg/L, respectively. The COD removal percentages were 89 and 91. The ammonium and nitrite concentrations in the effluent at Day 14 were <2.5 and <2.0 mg/L. These results demonstrate that the test is valid.
For details of results and graphs, please refer to the attachment under 'Attached background material'. - Validity criteria:
- (1) DOC or COD elimination in the control unit(s) is >80% after 2 weeks (2) biodegradation of the reference substance should be >90%. (3) the mean concentration in the effluents should be <1 mg/L ammonia-N and <2 mg/L nitrite-N.
- Observed value:
- (1) The COD removal percentages were 89 and 91% at Day 14 (2) the ammonium and nitrite concentrations in the effluent at Day 14 were <2.5 and <2.0 mg/L
- Validity criteria fulfilled:
- yes
- Remarks:
- Results of the reference substance has not been specified
- Conclusions:
- Under the study conditions, the test substance biodegrades almost completely in conventional biological waste water treatment plants.
- Executive summary:
A continuous activated sludge (CAS) study was conducted to determine the biodegradation of the test substance, C12-16 ADBAC (49.2% active in water), in domestic waste water according to OECD Guideline 303A, in compliance with GLP. In this study, the domestic waste microorganisms were exposed to the test substance, by spiking at a nominal influent concentration of 49 mg/L (36 mg/L carbon) for a period of 58 days. An additional unit fed only with the domestic wastewater was maintained as the control group. All samples were analysed for NPOC. A strong increase in the concentration of NPOC was noted on Day 2 in the test units. This was probably caused by toxicity of the test substance. The activated sludge acclimatised to the test substance within a few days, resulting in a decrease of the NPOC concentrations. After 3 weeks, very high carbon removal percentages were achieved. The mean removal percentage in the test unit assessed using a HLPC-MS/MS was determined to be 99.998%, indicating ultimate biodegradation. Removal of the test substance from the influent through adsorption onto sludge was only 0.023% on Day 58, showing that the main mechanism of elimination was biodegradation. Based on the results of the study, the test substance was removed from wastewater at a very high percentage (approximately 99.998%) in the continuous activated sludge test. Removal of the test substance from the influent through adsorption onto sludge was only 0.016 to 0.023% at two sampling times, demonstrating that the test substance was removed almost completely and biodegraded. This suggests that the test substance biodegrades almost completely in conventional biological wastewater treatment plants (Ginkel, 2007).
- Reason / purpose for cross-reference:
- data waiving: supporting information
Reference
- Bioaccumulation potential:
- low bioaccumulation potential
- Absorption rate - oral (%):
- 10
- Absorption rate - dermal (%):
- 10
- Absorption rate - inhalation (%):
- 50
Toxicokinetics data from studies conducted under in vitro and in vivo conditions suggests that the test substance, C12-16 ADBAC, has a low bioaccumulation potential and only a small fraction of the test substance is likely to be absorbed and distributed over the body. Therefore, a 10% absorption factor was considered for the chemical safety assessment for both oral as well as dermal routes as a worst-case approach even though with the most relevant and valid studies, a 1% dermal absorption would be a high estimate. An absorption of 100% was considered for the inhalation route.
The available data for the test substance on dermal absorption does not allow the quantification of the dose which was absorbed after dermal application. However, based on the radioactivity recovered at the skin application site after removal of the stratum corneum layers (6.5-8.7% of the dose) and the ionic nature of the test substance, it can be anticipated that the dermal absorption is not different from the oral one (10%). The primary effect involves disruption of the cytoplasmic membrane causing cell damage or lyses of the cell content. Due to adherence to negatively charged surfaces of the apolar alkyl chain, ADBAC substances will not easily pass biological membranes. Dermal uptake is therefore very limited at low, non-irritating concentrations.
ABSORPTION:
Oral absorption
Based on physicochemical properties:
According to REACH guidance document R7.C (May 2014), oral absorption is maximal for substances with molecular weight (MW) below 500. Water-soluble substances will readily dissolve into the gastrointestinal fluids; however, absorption of hydrophilic substances via passive diffusion may be limited by the rate at which the substance partitions out of the gastrointestinal fluid. Further, absorption by passive diffusion is higher at moderate log Kow values (between -1 and 4). If signs of systemic toxicity are seen after oral administration (other than those indicative of discomfort or lack of palatability of the test substance), then absorption has occurred.
C12-16 ADBACis an alkyl dimethyl benzyl ammonium chloride (ADBAC) type of cationic surfactant. It is a UVCB with majorly C12 to C16 alkyl chains with molecular weight ranging from 283.9 to 424.02 g/mol. The purified form of the substance is a crystalline, hygroscopic, sticky white solid. It has a moderate water solubility of 500-1000 mg/L at 20°C (based on CMC) and a low log Kow of 2.75 value, which was determined based on solubility ratios.
Based on the R7.C indicative criteria, together with the fact that the test substance is cationic with a strong adherence potential to the negatively charged surfaces of the membranes, suggests that it is not expected to easily pass biological membranes.
Based on experimental data on read across substances:
A study was conducted to determine the basic toxicokinetics of the test substance, C12-16 ADBAC (49.9% active in water with 99.4% radiolabelled purity), according to OECD Guideline 417, in compliance with GLP.In this study, Sprague-Dawley rats were treated with single and repeated oral doses (50 or 200 mg/kg bw) as well as a single dermal dose (1.5 or 15 mg/kg bw) of the radiolabelled test substance. Following single and/or repeated oral doses, the plasma, blood and organ radioactivity levels were essentially non-quantifiable, indicating a low oral bioavailability. The actual fraction of the oral dose absorbed was around 8% (urine and bile fractions). This was eliminated rapidly, essentially within a 48 to 72 h period. The majority of the oral dose was excreted in the faeces. At the high oral dose level only, quantifiable levels of radioactivity (2,386 to 23,442 ηg equivalent/g) were found in some central organs at 8 h post-dosing; otherwise, most of the dose was confined to the intestines, where their levels decreased over time and were all non-quantifiable by 168 h (i.e., 7 d). Only about 4% of the oral dose was eliminated in the bile in a 24 h period, of which about 30% during the first 3 h. Following a single dermal application, the plasma and blood radioactivity levels were non-quantifiable at nearly all time points. For the 1.5 mg/kg bw group, around 2 and 43% of the dose was eliminated in the urine and faeces, respectively, mostly within a 48-h period, suggesting that the dermal dose was highly absorbed via the skin. However, this apparent high absorption via the skin may have been due to the animal licking the test site. This is also supported by the finding that, after oral dosing, only about 4% was excreted via bile back to the intestine and 4% excreted via urine. If similar routes of excretion are expected for dermally absorbed doses, it would not be possible to find levels of 50% of applied doses in the intestine with only 2% excreted via urine. This indicates that about 50% of the dermally applied dose was taken up orally after all. According to the same oral kinetics, this leads to the 2% excretion in urine as indeed was observed. At 24 h post-dosing, most of the radioactivity was in the “stripped” skin (dermis/epidermis) application site (15.02/8.74% [male/female] and 33.8/24.2% of the dose for the high and low dose groups respectively) and intestines for both dose levels (5.76/8.32% and 5.61/7.79% of the dose for the high and low dose groups respectively), though some radioactivity was in the skin adjacent to the application site and minor traces were in the eyes (both most likely from cross-contamination due to grooming). At 168 h, levels in the application site of the individual animals of the low dose were 5.19 to 9.21% of the radioactive dose, suggesting the skin acted as a drug reservoir. In the stratum corneum of the application site, the levels of radioactivity were of similar magnitude in the different layers at each time point. For all tissues/organs, the radioactivity levels decreased over time. All data showed generally a low inter-animal variability. In addition, there was no evidence of gender differences. Under the study conditions and following oral administration the test substance was found to have limited absorption (ca. 10%), low distribution (below quantification limits within 4-7 d) and majorly excreted via faeces (ca. 80%). The results following dermal application are considered to be invalid, as the experiment suffered from design flaws, allowing for oral uptake from the skin after the 6 h exposure period (Appelqvist, 2006).
Further, a biocides assessment report available on the test substance by RMS Italy, concluded that the read across substance“is highly ionic and, therefore, it is expected not to be readily absorbed from the gastrointestinal tract or skin. The vast majority of the oral dose was excreted in the faeces (80%) as unabsorbed material (only about 4% of the oral dose was eliminated in the bile in a 24-hour period). The actual fraction of the oral dose absorbed was about 10%, based on the urinary mean value 3-4% (with a single peak value of 8.3%) and biliary excretion values (3.7-4.6%), as well as on the absence of residues in the carcass, as measured at 168 h. Excretion was rapid (within a 48 to 72-hour period). The radioactivity excreted in the urine was not associated with the parent compound, but with more polar metabolites which were not identified” (ECHA biocides assessment report, 2015).
In another study conducted according to EPA OPP 85-1, Sprague-Dawley rats (10 animals per sex per group) were treated with radiolabelled test substance, C12-16 ADBAC (30% active in water with 99.4% radiolabelled purity).Sprague-Dawley rats (10 animals per sex per group) were treated with a radiolabelled test substance. The study was conducted in four phases: a single low dose (10 mg/kg); a single high dose (50 mg/kg); a 14-d repeated dietary exposure with non-radiolabelled test substance (100 ppm) and a single low dose of radiolabelled (14C) test substance (10 mg/kg); and single intravenous dose (10 mg/kg). Following the single doses or the last dietary dose, urine and faeces were collected for 7 d. A preliminary study had indicated that insignificant 14CO2 was generated. Tissues, urine and faeces were collected and analysed for radioactivity and faeces were analysed by TLC, HPLC and MS for metabolites and parent compound. Following oral administration, radiolabelled test substance was rapidly absorbed, although in very limited amounts, consistent with its highly ionic nature. Residual 14C in tissues was negligible after administration by gavage both after single and repeated dosing, indicating low potential for bioaccumulation. After i.v. administration a higher amount of radioactivity (30−35%) was found as residue in the tissues. About 6−8% of orally administered test substance is excreted in the urine whereas, 87−98% was found in the faeces. Since no data on bile duct-cannulated rats are available, it was not possible to conclude if this radioactivity accounts exclusively for the unabsorbed test substance or not. However, the i.v. experiment showed that 20−30% was excreted in the urine and 44-55% in the faeces, suggesting that both the kidney and liver are capable of excreting test substance once absorbed and that absorption is higher than the % found in the urine after oral administration. Based on the urinary mean value 3-4% (with a single peak value of 8.3%) and biliary excretion values (3.7-4.6%), as well as on the absence of residues in the carcass, as measured at 168 h, it can be expected that the test substance absorption through the g.i. tract is about 10% (a conclusion not included in the study report; as assessed by the Italian Rapporteur Member state in the biocides dossier; ECHA biocides assessment report, 2015). Less than 50% of the orally administered test substance was found to be metabolised to side-chain oxidation products. Given the limited absorption of the test substance, the four major metabolites identified were expected to be at least partially formed in the gut of rats, apparently by microflora. No significant difference in metabolism between male and female rats or among the dosing regimens was observed. Repeated dosing did not alter the uptake, distribution or metabolism of test substance. Under the conditions of the study, the test substance was found to have limited absorption (ca. 10%; due to its ionic nature), negligible distribution (no bioaccumulation), and majorly excreted majorly via faeces (87-98%) following oral administration. However, following i.v. administration, it was found to be widely distributed (30-35%) in tissues and excreted both via faeces (40-55%) and urine (20-30%). Four major metabolites were identified, formed via oxidation of the alkyl chain (Selim, 1987).
Further, the biocides assessment report concluded that“the oral absorption can be considered to be approximately 10%, based on the 5-8% of the C12-16-ADBAC administered dose eliminated via urine and tissue residues (less than 1% of the administered dose 7 days after single and repeated oral dosing). More than 90% is excreted in the faeces and the pattern did not change after repeated doses. Although it was not possible to discriminate between unabsorbed/absorbed material, based on the chemical nature of the test substance, it can be anticipated that about 90% is present in faeces as unabsorbed material. The majority of C12-16-ADBAC metabolism is expected to be carried out by intestinal flora; the metabolites, which account for less than 60% of the administered dose, include hydroxyl- and hydroxyketo- derivatives of the dodecyl, tetradecyl and hexadecyl chains. No metabolite accounted for more than 10% of the total administered dose”(ECHA biocides assessment report, 2015).
Assessment from biocides assessment report available on the test substance:
As indicated above the biocides assessment reports available on the read-across substance C12-16 ADBAC indicated that given its ionic nature, C12-16 ADBAC was not expected to be readily absorbed from the gastrointestinal tract or skin. And based on the results from thein vivostudies with rats andin vitrostudies with human skin, an oral and dermal absorption value of 10% could be considered at non-corrosive concentrations (ECHA biocides assessment report, 2015).
Conclusion:Overall, based on the available weight of evidence information, the test substance at non-corrosive concentrations can be expected to overall have low absorption potential through the oral route. Therefore, in line with the biocide assessment report and as a conservative approach a maximum oral absorption value of 10% can be considered for risk assessment.
Dermal absorption
Based on physicochemical properties:
According to REACH guidance document R7.C (ECHA, 2017), dermal absorption is maximal for substances having MW below 100 together with log Kow values ranging between 2 and 3 and water solubility in the range of 100-10,000 mg/L. Substances with MW above 500 are considered to be too large to penetrate skin. Further, dermal uptake is likely to be low for substances with log Kow values <0 or <-1, as they are not likely to be sufficiently lipophilic to cross the stratum corneum (SC). Similarly, substances with water solubility below 1 mg/L are also likely to have low dermal uptake, as the substances must be sufficiently soluble in water to partition from the SC into the epidermis.
The test substance is a crystalline, hygroscopic, sticky white solid with an MW exceeding 100 g/mol, moderate water solubility and an estimated log Kow above 2.This together with the fact that the test substance is cationic with a strong adherence potential to the negatively charged surfaces, suggests that the test substance at non-corrosive concentrations is likely to have a low penetration potential through the skin.
At higher corrosive concentrations although there is a likelihood of exposure to the test substance due to disruption of the barrier properties of the skin, the likelihood of occurrence of these cases is expected to be minimal due to the required risk management measures and self-limiting nature of the hazard. Therefore, this scenario has not been considered further for toxicokinetic assessment.
Based on QSAR predictions:
The two well-known parameters often used to characterise percutaneous penetration potential of substances are the dermal permeability coefficient (Kp[1]) and maximum flux (Jmax). Kp reflects the speed with which a chemical penetrates across SC and Jmax represents the rate of penetration at steady state of an amount of permeant after application over a given area of SC. Out of the two, although Kp is more widely used in percutaneous absorption studies as a measure of solute penetration into the skin. However, it is not a practical parameter because for a given solute, the value of Kp depends on the vehicle used to deliver the solute. Hence, Jmax i.e., the flux attained at the solubility of the solute in the vehicle is considered as the more useful parameter to assess dermal penetration potential as it is vehicle independent (Robert and Walters, 2007).
In the absence of experimental data, Jmax can be calculated by multiplying the estimated water solubility (using WATERNT v.1.02) with the Kp values from DERMWIN v2.02 application of EPI Suite v4.11. The calculated Jmax values for the different carbon chains of the UVCB substance was determined to be range between 5.00E-07 to 8.50E-05 μg/cm2/h, leading to a weighted average value of 5.07E-06 μg/cm2/h. As per Kroeset al.,2004 and Shenet al. 2014, the default dermal absorption for substances with Jmax ≤0.1 μg/cm2/h can be considered to be less than 10%. Based on this, the test substance can be predicted to have low absorption potential through the dermal route.
Based on experimental data:
Following a single dermal application of the test substance, C12-16 ADBAC in the Appelqvist (2006) study, the plasma and blood radioactivity levels were non-quantifiable at nearly all time-points. For the 1.5 mg/kg bw group, around 2 and 43% of the dose was eliminated in the urine and faeces, respectively, mostly within a 48-h period, suggesting that the dermal dose was highly absorbed via the skin. However, this apparent high absorption via the skin may have been due to the animal licking the test site. This was also supported with the finding that, after oral dosing, only about 4% was excreted via bile back to the intestine and 4% excreted via urine. If similar routes of excretion are expected for dermally absorbed doses, it would not be possible to find levels of 50% of applied doses in intestine with only 2% excreted via urine. This indicates that about 50% of the dermally applied dose was taken up orally after all. Excretion in urine (2%) following dermal exposure was similar to that following oral exposure. At 24 h post-dosing, most of the radioactivity was in the “stripped” skin (dermis/epidermis) application site (15.02/8.74% [male/female] and 33.8/24.2% of the dose for the high and low dose groups respectively) and intestines for both dose levels (5.76/8.32% and 5.61/7.79% of the dose for the high and low dose groups respectively), though some radioactivity was in the skin adjacent to the application site and minor traces were in the eyes (both most likely from cross-contamination due to grooming). At 168 h, levels in the application site of the individual animals of the low dose were 5.19 to 9.21% of the radioactive dose, suggesting the skin acted as a drug reservoir. In the stratum corneum of the application site, the levels of radioactivity were of similar magnitude in the different layers at each time-point. For all tissues/organs, the radioactivity levels decreased over time. All data showed generally a low inter-animal variability. In addition, there was no evidence of gender differences (Appelqvist, 2006). Further, the biocides assessment report concluded that “The available data on BKC dermal absorption do not allow to quantify exactly the % of the dose which was absorbed after dermal application. However, due to the radioactivity recovered at the skin application site after removal of the stratum corneum layers (6.5-8.7% of the dose) and the ionic nature of the test item, it can be anticipated that the dermal absorption is not different from the oral one (10% at non corrosive concentration)”(ECHA biocides assessment report, 2015).
An in vitro study was conducted to determine the rate and extent of dermal absorption of the test substance, C12-16 ADBAC (80.5% active; >99% radiolabelled purity), according to OECD Guideline 428, in compliance with GLP. The study was conducted with radiolabelled test substance at 0.03% and 0.3% concentrations, which was topically applied over split-thickness human skin membranes mounted into flow-through diffusion cells. Receptor fluid was pumped underneath the skin at a flow rate of 1.5 mL/hour. The skin surface temperature was maintained at approximately 32°C. A barrier integrity test using tritiated water was performed and any skin sample exhibiting a permeability coefficient (kp) greater than 2.5 x 10-3 cm/h were excluded from subsequent absorption measurements. The 14C- radiolabelled test substance was applied at an application rate of 10 mg/cm2. Absorption was assessed by collecting receptor fluid in hourly intervals from 0-6 h post-dose and then in 2-hourly intervals from 6-24 h post-dose. At 24 h post-dose, the exposure was terminated by washing and drying the skin. The stratum corneum was then removed from the skin by 20 successive tape strips. All samples were analysed by liquid scintillation counting. Under the conditions of the study, the mean absorbed dose and mean dermal deliveries were determined to be 0.05% (0.01 ηg equiv. /cm2) and 2.22% (0.07 ηg equivalent/cm2) of the applied dose for the low concentration test preparation, respectively, and 0.03% (0.01 ηg equivalent /cm2) and 2.16% (0.67 ηg equivalent/cm2) of the applied dose for the high concentration test preparation, respectively. The stratum corneum acted as a barrier to absorption, with the mean total unabsorbed doses (recovered in skin wash, tissue swabs, pipette tips, cell wash, stratum corneum and unexposed skin) of 96.80 and 94.68% of the applied dose for the low and high concentration test preparations, respectively. The maximum fluxes for the low and high doses were 0.12 ηg equivalent /cm2/h and 0.74 ηg equivalent /cm2/h, respectively, at 2 h (Roper, 2006).Based on literature evidence, substances with Jmax ≤ 0.1μg/cm2/h, can be expected to have low skin penetration potential and can be assigned a default skin absorption of <10% (Shenet al., 2014, Kroeset al.,2004). Further, the dermal absorption of the test substance was concluded in its biocides assessment report (by RMS Italy) to be 8.3%, which was obtained by summing up the radioactivity present in the receptor fluid (0.05%), at the application site (after 20 consecutive tape stripping procedures) and the one present in tape strips (n°6-20) (ECHA biocides assessment report, 2015).
Another in vitro study was conducted to determine the dermal absorption of the test substance, C12 -16 ADBAC (25.5% active in water; radiochemical purity: >98%) according to a method comparable to OECD Guideline 427, in compliance with GLP. The dermal absorption and excretion study was conducted in rats following application of 0.4 mL of a 0.77% w/w solution of the test substance over approximately 20 cm2 of shaved skin, under a gauze patch for 72 h. After a single topical application of radio-labelled test substance, the total amount of radioactive substance was 16% in males (urine 0.8%, faeces about 9.9% and carcass about 5.3%) and 14% in females (urine about 0.7%, faeces about 6.1% and carcass about 7.0%). This was equivalent to a total mass of 24 µg equivalents (males) and 21 µg equivalents (females) absorbed per cm2(after a dose of approximately 3 mg). Most of the radio-labelled test substance (62.6%, males; 63.2%, females) was found in both the treated (48.0%, males; 45.1%, females) and the untreated (14.6%, males; 18.1%, females) skin after 72 h. The radioactive substance in the untreated skin may have been due to surface migration of the applied material from the perimeter of the treated area. The overall recoveries of radioactivity were acceptable for the experimental objectives of quantifying the absorption of radio-labelled test substance after a single dermal application. Under the study conditions, the findings indicate that the dermal absorption of the test substance is limited and most of the absorbed test substance is excreted in the faeces (Hallifax, 1991).
Additionally, a publication of Blank (1964) was identified which reported an in vitro study evaluating the dermal penetration of the test substance, C12-16 ADBAC (purity not specified) in normal excised human skin. From un-buffered aqueous solutions of the test substance ranging in concentration from 0.005 (1.7 ppm) to 0.1 M (34 ppm), no measurable amount penetrated the dermis of excised human skin within periods of 1 to 3 d at temperatures between 23 and 35°C. Lowering the pH of the contact solution up to pH 1.3 had no influence. However, at pH 10.5 to 12, the test substance could be recovered from the skin. At these levels, electrical conductivity indicated damage to the cutaneous barrier. Similarly, pre-treatment of skin at that pH caused damage to the skin and resulted in penetration of the test substance upon subsequent contact to test solutions. Also, damaging the skin by repeated stripping of the stratum corneum with pressure-sensitive tape resulted in penetration into the skin when stripped more than 10 times (Blank, 1964).
A corneal penetration was identified from literature sources, where single or multiple drops of radiolabelled test substance, C12 -16 ADBAC (0.03% radiolabelled purity) was instilled on the cornea of rabbits to determine the corneal penetration. The test substance was found in the palpebral and bulbar conjunctiva, corneal epithelium, stroma and endothelium. Single-drop administration resulted in high tissue levels in the anterior ocular tissues that were retained for up to 120 h. Multiple-drop administration led to accumulation in the epithelium to a greater degree than any other tissue. However, at no time did the test substance appear in the aqueous humour or any other tissue besides cornea and exposed conjunctivae (Green, 1986).
Assessment from biocides assessment report available on the test substance:
As indicated above the biocides assessment reports available on the test substance C12-16 ADBAC indicated that given its ionic nature, C12-16 ADBAC was not expected to be readily absorbed from the gastrointestinal tract or skin. And based on the results from thein vivostudies with rats andin vitrostudies with human skin, an oral and dermal absorption value of 10% could be considered at non-corrosive concentrations (ECHA biocides assessment report, 2015).
Conclusion:Overall, based on all the available weight of evidence information, the test substance at non-corrosive concentrations can be expected to have a low absorption potential absorption through the dermal route. As a conservative approach and in line with the biocide assessment report a maximum dermal absorption value of 10% can be considered for risk assessment.
Inhalation absorption
Based on physicochemical properties:
According to REACH guidance document R7.C (ECHA, 2017), inhalation absorption is maximal for substances with VP >25 KPa, particle size (<100 μm), low water solubility and moderate log Kow values (between -1 and 4). Very hydrophilic substances may be retained within the mucus and not available for absorption.
The test substance, because of its crystalline, hygroscopic, sticky white solid physical state and relatively low vapour pressure of < 5.8E-3 Pa at 25°C, will not be available as vapours for inhalation under ambient conditions. Therefore, the substance will neither be available for inhalation as vapours nor as aerosols. In the case of spraying applications, coarse droplets would be formed which typically settle on the ground and result in a very lower inhalable or respirable fraction. Of the inhalable fraction, due to the droplet size and the moderate water solubility, almost all droplets are likely to be retained in the mucus and will not be available to reach the deeper lungs. The deposited droplets in the upper respiratory tract are expected to be absorbed in a relatively slower rate compared to the deeper lungs due to differences in vascularity. Some amounts of these deposited droplets are also expected to be transported to the pharynx and swallowed via the ciliary mucosal escalator. Therefore, the systemic uptake of the test substance via the respiratory route can be considered to be similar to the oral route.
Conclusion: Based on all the available weight of evidence information, together with the fact that the test substance is cationic with an adherence potential to the negatively charged surfaces, the test substance at non-corrosive concentrations can be expected to have a low to moderate absorption potential through the inhalation route, depending on the droplet size. Therefore, a value of 50% can be considered for the risk assessment.
.
METABOLISM:
Based on experimental data on test substances:
As discussed in the Selim, 1987 study, less than 50% of the orally administered C12-16 ADBAC is metabolised to side-chain oxidation products. Given the limited absorption of the test substance, the four major metabolites identified may be at least partially formed in the gut of rats, apparently by microflora. The metabolites, which account for less than 60% of the administered dose, include hydroxyl- and hydroxy keto- derivatives of the dodecyl, tetradecyl and hexadecyl chains. No metabolite accounted for more than 10% of the total administered dose. No significant difference in metabolism between male and female rats or among the dosing regimens was observed. Repeated dosing did not alter the uptake, distribution or metabolism of the test substance (Selim, 1987).
Based on QSAR modelling:
The OECD Toolbox (v.4.4.1) and FAME 3were used to predict the first metabolic reaction, since the rat liver S9 metabolism simulator performs predictions for salts, while SMARTCyp and MetaPrint2D are not powered enough for this type of substance. The second simulator of the OECD Toolbox (in vivorat metabolism simulator) was not used as it does not consistently perform predictions for salts. As per the rat liver S9 metabolism simulator, the major constituents are primarily predicted to undergo ω or ω-1 aliphatic hydroxylation reactions. Similar results were found with FAME 3 metabolism simulation tool (which currently covers only CYP metabolism). See the table in the CSR for the reaction sites. For further details, refer to the read-across justification.
Overall, similar reactive sites were predicted for other TMACs and ADBACs from the category.
Conclusion:Based on all the available weight of evidence information, the test substance is considered to be primarily metabolised by alkyl chain hydroxylation, which is carried out by the intestinal flora.
DISTRIBUTION
Based on physico-chemical properties:
According to REACH guidance document R7.C (ECHA, 2017), the smaller the molecule, the wider the distribution. Small water-soluble molecules and ions will diffuse through aqueous channels and pores, although the rate of diffusion for very hydrophilic molecules will be limited. Further, if the molecule is lipophilic (log P >0), it is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues. Identification of the target organs in repeated dose studies is also indicative of the extent of distribution.
Generally given the ionic nature of the test substance, the test substance is not likely to readily partition across the blood membranes into the different organs, leading to an overall low distribution potential. Moreover, even if the test substance distributes to a certain extent, it is not expected to bioaccumulate based on the experimentalBCF values of C12-16 ADBAC(see section 4.3 of the CSR).
Based on experimental data on read across substances:
As discussed above, in the Appelqvist, 2006 study, quantifiable levels of radioactivity (2,386 to 23,442 ηg equivalent/g) were found in some central organs at 8 h post-dosing at 200 mg/kg bw; otherwise, the vast majority of the dose was confined to the intestines, where their levels decreased over time and were all non-quantifiable by 168 h (i.e., 7 d). In the Selim, 1987 study, residual 14C in tissues was negligible after administration by gavage both after single and repeated dosing, indicating low potential for bioaccumulation. However, following i.v. administration, it was found to be widely distributed (30-35%) in tissues (Selim, 1987).
A couple of studies were also identified from literature sources (Bogs, 1971; Cutler, 1970):
The Bogs (1971) article reported a study evaluating the distribution of the test substance, C12-16 ADBAC (purity not specified) inside the body of rabbits, cats and dogs. A single high dose (approximately 1 mL of 15% solution of the test substance in water/kg bw of animals, which is equal to about 10 times the lethal dose) was administered by oral, rectal and intramuscular route. Within a few minutes, the animals died, and the test substance concentrations were measured locally at the sites of dosing, in blood, liver and kidneys. It was concluded that only a small fraction is absorbed and distributed in the body. Less than 1.5% of the applied dose was found in the organ investigated (sites of dosing, blood, liver and kidneys), of which the major part was found in the liver (Bogs, 1971).
The Cutler (1970) article reported studies conducted in rat and Beagle dogs, which compared the application of test substance, C12 -16 ADBAC (purity not specified) in both milk and water as vehicle. Rats received 50 and 100 mg/kg bw/day for 12 weeks, and dogs 12.5, 25 and 50 mg/kg bw/day for 52 weeks. Depression in weight gain was observed in rat receiving 100 mg/kg bw/day in the water, but not in milk. Mortality occurred in dogs at 25 and 50 mg/kg bw/day in the water, but not in milk. The 12.5 mg/kg bw/day dose level was well tolerated (Cutler, 1970).
Conclusion:Based on all the available weight of evidence information, the test substance is expected to have a low distribution and bioaccumulation potential.
EXCRETION:
Based on physicochemical properties:
Given the expected low absorption potential of the test substance which is due to its ionic nature and physico-chemical properties, it can be expected to be primarily excreted through faeces.
Based on experimental data on read across substances:
Based on the evidence from the available oral studies (Appelqvist, 2006; and Selim, 1987), the test substance is primarily expected in faeces (>90%) and less via urine (<10%).
Conclusion:Based on all the available weight of evidence information, the test substance is expected to be primarily excreted via faeces.
[1] Log Kp = -2.80 + 0.66 log kow – 0.0056 MW
Data source
Materials and methods
Results and discussion
Applicant's summary and conclusion
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