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Long-term toxicity to fish

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Endpoint:
long-term toxicity to fish
Type of information:
calculation (if not (Q)SAR)
Remarks:
calculation
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The scientific validity of the (Q)SAR model has been established in accordance with the OECD Principles for (Q)SAR Model Validation. The data provided for in this study in conjunction with that of the in vivo study with the read-across chemical, provide a weight of evidence for the hazard endpoint that is sufficient for the purpose of classification and labelling and/or risk assessment.
Justification for type of information:
QSAR prediction
Principles of method if other than guideline:
ECOSAR v1.11
QMRF and QPRF are attached in IUCLID
GLP compliance:
not specified
Test organisms (species):
other: Fish
Test type:
other: Q(SAR)
Dose descriptor:
NOEC
Effect conc.:
4.14 mg/L
Nominal / measured:
estimated
Remarks on result:
other: NOEC was derived by dividing the ECOSAR modelled ChV (8.295 mg/L) by 2.

Supporting documentation are provided in the attached QPRF and QMRF.

Validity criteria fulfilled:
not applicable
Conclusions:
The estimated NOEC for fish is 4.14 mg/L. The data provided for in this study in conjunction with that of the in vivo study with the read-across chemical, provide a weight of evidence that fulfills the quality criteria (validity, reliability, repeatability).
Executive summary:

The NOEC to fish was estimated.A conservative approach for determining the NOEC is to divide the ECOSAR modeled ChV (8.295 mg/L) by 2. Therefore, the NOEC was estimated to be 4.14 mg/L.

Endpoint:
adult fish: sub(lethal) effects
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Lack of some information; e.g. No C of A available . Concentration tested is far below the water solubility limit and one cannot safely conclude about the real toxicity potential. The data provided for in this study in conjunction with that of the modeled data on the test substance, provide a weight of evidence for the hazard endpoint that is sufficient for the purpose of classification and labelling and/or risk assessment.
Justification for type of information:
see 13.2 for attached read across rationale
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 204 (Fish, Prolonged Toxicity Test: 14-day Study)
Deviations:
no
GLP compliance:
yes
Analytical monitoring:
yes
Details on sampling:
- Sampling method: HPLC
- Sample storage conditions before analysis: Not reported
Vehicle:
yes
Details on test solutions:
PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method: To prepare test solutions before starting exposure, the test substance was weighed using an electronic balance and the solvent was added. After thorough mixing, dilution water was added to make 1000 mL and an even stock test solution was prepared. The stock solution obtained was diluted as necessary with dilution water, and test solutions of nominal concentrations of 1.0, 1.8, 3.2, 5.6 and 10 mg/L were prepared.
- Eluate: dilution water (dechlorinated water, obtained by treating tap water supplied by the city of Takarazuka with activated carbon and thoroughly aerating after eliminating residual chlorine, etc.) was used. Major features of the dilution water included the hardness of 63.1 mg/L (converted to CaCO3) and the pH value of 8.1 and dimethylformamide
- Differential loading: N/A
- Controls: Yes, water control and water with solvent
- Chemical name of vehicle (organic solvent, emulsifier or dispersant): dimethylformamide
- Concentration of vehicle in test medium (stock solution and final test solution(s) including control(s)): 100 mg/L
- Evidence of undissolved material (e.g. precipitate, surface film, etc): None reported
Test organisms (species):
Oryzias latipes
Details on test organisms:
TEST ORGANISM
- Common name: orange killifish
- Strain: Not reported
- Source: Shiga Prefectural Nango Fisheries Center
- Age at study initiation (mean and range, SD): Not reported
- Length at study initiation (length definition, mean, range and SD): 2.0±0.5 cms
- Weight at study initiation (mean and range, SD): 0.10 - 0.21 g (mean 0.14g)
- Method of breeding: commercial
- Feeding during test
- Food type: Commercially obtained Tetramin Staple Food was given every day, feed was supplied at 2% of body weight determined at the beginning of exposure (adjusted depending on the number of fish); food was not given for 24 hours prior to exposure

ACCLIMATION
- Acclimation period: for at least 12 days
- Acclimation conditions (same as test or not): same as test
- Type and amount of food: Commercially obtained Tetramin Staple Food; amount not reported
- Feeding frequency: Not reported
- Health during acclimation (any mortality observed): None reported

QUARANTINE (wild caught) Not applicable
Test type:
flow-through
Water media type:
freshwater
Limit test:
no
Total exposure duration:
14 d
Post exposure observation period:
Not applicable
Hardness:
63.1 mg/L
Test temperature:
24±2°C
pH:
between 7.7 and 8.0
Dissolved oxygen:
between 7.1 and 8.0 mg/L
Salinity:
N/A
Nominal and measured concentrations:
Nominal: Control, solvent (vehicle) control, 1.0, 1.8, 3.2, 5.6 and 10 mg/L
Mean measured: Control, solvent (vehicle) control, <1-1, 1.7, 3.2, 5.6 and 9.9 mg/L
Details on test conditions:
TEST SYSTEM
- Test vessel:
- Type (delete if not applicable): open
- Material, size, headspace, fill volume: 5.0-L glass tank (inside dimension: about 21×16×23 cm)
- Aeration: None
- Type of flow-through (e.g. peristaltic or proportional diluter): Flow-through test system: A syringe-type micro-meter infusion pump (Model JP-V-W, Furue Science K.K.) was used to pump out the stock test solution, while a roller pump (Model RP-MRF, Furue Science K.K.) was used to pump out dilution water. The stock test solution and dilution water were stirred in the stirring vessel (300-mL glass, branched, conical flask) using a stirrer to obtain test solutions of designated concentrations. Obtained test solutions were allowed to flow into the test vessel and eliminated through a siphon tube.
- Renewal rate of test solution (frequency/flow rate): 1.8 mL/min
- No. of organisms per vessel: 10/block
- No. of vessels per concentration (replicates): 1
- No. of vessels per control (replicates): 1
- No. of vessels per vehicle control (replicates): 1
- Biomass loading rate: N/A

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water:Dechlorinated water, obtained by treating tap water supplied by the city of Takarazuka with activated carbon and thoroughly aerating after eliminating residual chlorine, etc., was used.
- Particulate matter: Not reported
- Metals: Not reported
- Pesticides: Not reported
- Chlorine: Not reported
- Alkalinity: Not reported
- Ca/mg ratio: Not reported
- Conductivity: Not reported
- Culture medium different from test medium: Not reported
- Intervals of water quality measurement: Not reported

OTHER TEST CONDITIONS
- Adjustment of pH: not reported
- Photoperiod: 16 hours light/8hours dark
- Light intensity: (room light, intensity not stated)

TEST CONCENTRATIONS
- Justification for using less concentrations than requested by guideline: N/A
- Range finding study
- Test concentrations: test solutions of nominal concentrations of 1.0, 1.8, 3.2, 5.6 and 10 mg/L were prepared. The highest test concentration was set at 10 mg/L since the 96-hr LC50 was found to be not less than 10 mg/L (Sumika Technos Report No.: EFA96001) in an acute toxicity study of the test substance in Oryzias latipes
Reference substance (positive control):
no
Duration:
14 d
Dose descriptor:
NOEC
Effect conc.:
>= 10 mg/L
Nominal / measured:
nominal
Conc. based on:
test mat.
Basis for effect:
mortality
Duration:
14 d
Dose descriptor:
NOEC
Effect conc.:
>= 10 mg/L
Nominal / measured:
nominal
Conc. based on:
test mat.
Basis for effect:
weight
Duration:
14 d
Dose descriptor:
NOEC
Effect conc.:
>= 10 mg/L
Nominal / measured:
nominal
Conc. based on:
test mat.
Basis for effect:
length
Duration:
14 d
Dose descriptor:
LC50
Effect conc.:
> 10 mg/L
Nominal / measured:
nominal
Conc. based on:
test mat.
Basis for effect:
mortality
Details on results:
- Observed effects at each concentration for each observation time: None
- Concentrations that produce lethal or other effects: [describe and attach graph showing effects with respect
to time] N/A
- Cumulative mortality at each concentration and for each recommended observation time if possible: one death at 10 mg/L observed on day 9; no further deaths were observed at any concentration
- Mortality in the controls: None
- Behavioural observation of the fish: None
- Effect concentrations exceeding solubility of substance in test medium: None reported
- Incidents in the course of the test which might have influenced the results: None reported
Validity criteria fulfilled:
yes
Conclusions:
When Oryzias latipes were exposed to varying concentrations of 2,2’-azobis (2-methylpropanitrile) over 14 days, the NOEC and LC50 of the test
substance was found to be > 10 mg/L. The study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
Executive summary:

A fish sub-acute toxicity study was conducted at Sumika Technos Corp, Japan to investigate the thresholds for lethal and other effects of the substance 2,2’-azobis (2-methylpropanitrile). The test type was a flow through study conducted to GLP and according to OECD Guideline 204 and involved exposing the species Oryzias latipes to the test substance dissolved in the water at nominal concentrations of 1.0, 1.8, 3.2, 5.6 and 10 mg/L over a 14 day period. The fish were observed over the test period for differences in weight, length, behaviour and mortality. At the end of the 14 day exposure period, the no overall effect concentration NOEC was found to be ≥10 mg/L and the LC50 (the 50% lethal concentration) was estimated to be >10 mg/L.

Description of key information

No measured long-term toxicity to fish study with the test substance is available. ECOSAR data for the test substance, along with a long-term fish study with 2,2’-azobis(isobutyronitrile) were used to fulfill the data gap for the test substance. The underlying hypothesis for using read-across is that based on the structural and functional group similarity, the presence of the nitrile group in both substances is likely driving aquatic toxicity. Additional documentation, provided within the IUCLID Assessment Reports section, supports the read-across approach.

Using a conservative approach, a NOEC of 4.14 mg/L was estimated by dividing the ECOSAR modelled ChV (8.295 mg/L) by 2. This value is supported by the measured data available for 2,2‘-azobis(isobutyronitrile). The 14-day NOEC in a flow-through study withOryzias latipes, based on mortality, weight, and length was ≥10 mg/L.

Key value for chemical safety assessment

EC10, LC10 or NOEC for freshwater fish:
4.14 mg/L

Additional information