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Long-term toxicity to fish

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Endpoint:
fish early-life stage toxicity
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint:
long-term toxicity to fish
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Study period:
2013
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The QSAR program is validated for the substance type (organosulphur).
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Guideline:
other: REACH guidance on QSARs R.6, May/June 2008
Principles of method if other than guideline:
Toxicity estimated using ECOSAR class (Thioureas) and Neutral Organic SAR (Baseline Toxicity).
Dose descriptor:
other: Chronic Value (ChV)
Effect conc.:
9.833 mg/L
Remarks on result:
other: ECOSAR Class (Thioureas). The toxicity value was determined from a predicted SAR using established acute-to-chronic ratios and ECOSAR regression techniques which are documented in the supporting Technical Reference Manual.
Dose descriptor:
other: Chronic Value (ChV)
Effect conc.:
3.517 mg/L
Remarks on result:
other: Neutral Organic SAR (Baseline Toxicity)
Details on results:
Thioureas :

For Fish and Daphnid Acute Toxicity Values: If the log Kow of the chemical is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

For Green Algae Acute Toxicity Values: If the log Kow of the chemical is greater than 6.4, or if the compound is solid and the EC50 exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

For All Chronic Toxicity Values: If the log Kow of the chemical is greater than 8.0, or if the compound is solid and the ChV exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.
Validity criteria fulfilled:
yes
Remarks:
QSAR validated for substance type (organosulphur).
Conclusions:
1,3-dihydro-4(or5)-methyl-2H-benimidazole-2-thione, zinc salt was estimated to have a Chronic Value (ChV) to fish of 9.833 mg/l using the ECOSAR Class (Thioureas) method and a ChV to fish of 3.517 mg/l using the Neutral Organic SAR (Baseline Toxicity) method.
Endpoint:
long-term toxicity to fish
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Study period:
2013
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The QSAR program is validated for the substance type (organosulphur).
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Guideline:
other: REACH guidance on QSARs R.6, May/June 2008
Principles of method if other than guideline:
Toxicity estimated using ECOSAR class (Thioureas) and Neutral Organic SAR (Baseline Toxicity).
Dose descriptor:
other: Chronic Value (ChV)
Effect conc.:
42.207 mg/L
Remarks on result:
other: ECOSAR Class (Thioureas). The toxicity value was determined from a predicted SAR using established acute-to-chronic ratios and ECOSAR regression techniques which are documented in the supporting Technical Reference Manual.
Dose descriptor:
other: Chronic Value (ChV)
Effect conc.:
12.086 mg/L
Remarks on result:
other: Neutral Organic SAR (Baseline Toxicity)
Details on results:
Thioureas :

For Fish and Daphnid Acute Toxicity Values: If the log Kow of the chemical is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

For Green Algae Acute Toxicity Values: If the log Kow of the chemical is greater than 6.4, or if the compound is solid and the EC50 exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.

For All Chronic Toxicity Values: If the log Kow of the chemical is greater than 8.0, or if the compound is solid and the ChV exceeds the water solubility by 10X, no effects at saturation are predicted for these endpoints.
Validity criteria fulfilled:
yes
Remarks:
QSAR validated for substance type (organosulphur).
Conclusions:
1,3-dihydro-5-methyl-2H-benzimidazole-2-thione was estimated to have a Chronic Value (ChV) to fish of 42.207 mg/l using the ECOSAR Class (Thioureas) method and a ChV to fish of 12.086 mg/l using the Neutral Organic SAR (Baseline Toxicity) method.
Endpoint:
fish early-life stage toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Refer to Section 13.2 for read-across justification.
Reason / purpose:
read-across source
Key result
Dose descriptor:
other: ChV
Effect conc.:
42.207 mg/L
Remarks on result:
ChV (chronic value, QSAR)
Remarks:
ECOSAR Class (Thioureas). The toxicity value was determined from a predicted SAR using established acute-to-chronic ratios and ECOSAR regression techniques which are documented in the supporting Technical Reference Manual.
Key result
Effect conc.:
12.086 mg/L
Remarks on result:
ChV (chronic value, QSAR)
Remarks:
Neutral Organic SAR (Baseline Toxicity)
Validity criteria fulfilled:
not specified
Conclusions:
The test item was estimated to have a Chronic Value (ChV) to fish of 42.207 mg/L using the ECOSAR Class (Thioureas) method and a ChV to fish of 12.086 mg/l using the Neutral Organic SAR (Baseline Toxicity) method.
Executive summary:

In a one-to-one read-across approach, the substance 1,3-dihydro-4(or 5)-methyl-2H-benzimidazole-2-thione (source substance) is considered appropriate for direct read-across (one-to-one) to zinc 4-methyl-2-thioxo-2,3-dihydrobenzimidazol-1-ide 7-methyl-2-thioxo-2,3-dihydrobenzimidazol-1-ide (target substance) for the endpoint long-term toxicity to fish. In conclusion, the test item was estimated to have a Chronic Value (ChV) to fish of 42.207 mg/L using the ECOSAR Class (Thioureas) method and a ChV to fish of 12.086 mg/l using the Neutral Organic SAR (Baseline Toxicity) method. A full justification for the read-across approach is presented in IUCLID Section 13.2.

Description of key information

Key Study/waiver:

According to column 2 of Reach Annex VII-X, a long-term ecotoxicity study should be proposed by the registrant if the chemical safety assessment indicates the need to further investigate the effects on those organisms. For the risk characterisation of the aquatic compartment, a PNEC has been derived on the basis of three acute aquatic toxicity data and two chronic toxicity studies on the most sensitive trophic levels, as well as the consideration of the bioaccumulative potential. According to the CSA, the risk characterisation yields a PEC/PNEC ratio smaller than 1. Further testing is therefore not necessary as the risk is sufficiently described based on the already available data.

As such there is no key value for use in the chemical safety assessment

Supporting studies:

Long-term toxicity to fish (QSAR) Chronic toxicity value (ChV) = 3.517 mg/L; ECOSAR v1.0; ECOSAR (2013)

Long-term toxicity to fish (QSAR) ChV = 12.086 mg/L; ECOSAR v1.0; ECOSAR (2013) (data from read-across substance 1,3-dihydro-4(or 5)-methyl-2H-benzimidazole-2-thione, used in a one-to-one approach)

Key value for chemical safety assessment

Additional information

Waiver:

According to column 2 of Reach Annex VII-X, a long-term ecotoxicity study should be proposed by the registrant if the chemical safety assessment indicates the need to further investigate the effects on those organisms. For the risk characterisation of the aquatic compartment, a PNEC has been derived on the basis of three acute aquatic toxicity data and two chronic toxicity studies on the most sensitive trophic levels, as well as the consideration of the bioaccumulative potential. According to the CSA, the risk characterisation yields a PEC/PNEC ratio smaller than 1. Further testing is therefore not necessary as the risk is sufficiently described based on the already available data.

Supporting studies:

Long term toxicity to fish data were generated using the United States (US) Environmental Protection Agency (EPA) Ecological Structure Activity Relationships (ECOSAR) v1.0 tool. ECOSAR is validated for organosulphates, a chemical class which includes the read-across substance MB2 (CAS Number 27231-36-3), and is structurally similar to ZMB2 (CAS Number 61617-00-3).

ECOSAR QSAR data are used to address the following endpoints: 

  • Long-term toxicity to fish.

In addition, ECOSAR data were generated for endpoints for which testing data are also available, for comparison purposes. ECOSAR results were within 1 degree of magnitude when compared to study data and significantly similar to results from testing data. Due to this consistency, the ECOSAR QSAR model was considered to provide reliable results for the long-term toxicity to fish endpoint.

ZMB2 was estimated to have a Chronic Value (ChV) to fish of 9.833 mg/l using the ECOSAR Class (Thioureas) method, and a ChV to fish of 3.517 mg/l using the Neutral Organic SAR (Baseline Toxicity) method (ECOSAR, 2013).

The read across substance, MB2, was estimated to have a Chronic Value (ChV) to fish of 42.207 mg/l using the ECOSAR Class (Thioureas) method, and a ChV to fish of 12.086 mg/l using the Neutral Organic SAR (Baseline Toxicity) method

(ECOSAR, 2013).

Discussion:

ChV results for both ZMB2 and the read-across substance MB2 both show that fish is expected to be the least sensitive species in during chronic aquatic toxicty tests. This is echoed in the acute testing results, the fish NOEC is 2.1 mg/l (Safepharm Laboratories, 2003) and the acute Daphnia magna NOEC is 0.47 mg/L (Safepharm, 2003).

As the endpoint is waived there is no key value for the chemical safety assessment, however, the QSAR results will be used to support the hazard assessment of the substance.