hexyl nitrite

Short-term toxicity to aquatic invertebrates

Administrative data

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

21/09/2020

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

1. SOFTWARE : QSAR

2. MODEL (incl. version number) : Model 4.0.4 Molcode Ltd.

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL : 3D Mol file used for prediction

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF or providing a link]
- Defined endpoint: OECD Principle 1
REACH C.2.; QSAR 3.1
Acute toxicity to Daphnia magna (48h)
Test name: Short-term Toxicity testing on Invertebrates (preferred Daphnia) OECD 202 Daphnia immobilization test.
Acute toxicity for Daphnia (water flea) is expressed as the median effective concentration EC50 (LC50). This is the concentration which immobilizes 50% of the Daphnia in a test batch within 48h. Those animals which are not able to swim within 15 seconds after gentle agitation of the test batch are considered to be immobile.
- Unambiguous algorithm: OECD Principle 2
a. Model or submodel name: Linear QSAR Model for Acute toxicity for Daphnia magna -LC50 (48h)
b. Model version: 12.05.2010
c. Reference to QMRF: JRC Q19-10-30-299, enclosed separately
d. Predicted value (model result): Log(LC50) = -4.48; LC50 = 7.51E6 mg/L.; Category = “No Category”
- Defined domain of applicability: OECD Principle 3
i. descriptor domain:
ii. structural fragment domain:
iii. mechanism domain: Hexyl nitrite is considered to be in the same mechanistic domain as the molecules in the training set as it is structurally similar to the model compounds.
iv. metabolic domain, if relevant: Hexyl nitrite is considered to be in the same metabolic domain as the molecules in the training set of the model due to the structural similarity.
- Appropriate measures of goodness-of-fit and robustness and predictivity: OECD principle 4
The source experimental data for the model originate from different labs and different experiment series, as they are represented in the US EPA database, adding to uncertainty, however, careful data analysis, previous (and present) successful modeling add to the consistence of the data. The significant dataset size (~300) statistical quality (RMS, correlation coefficients etc.) of the model supports reliable predictions within the margins of the experimental error. The similarity of the analogues together with the correct estimates supports potential prediction consistency.
Considering the dataset size, model statistical quality and prediction reliability, a reliability score (Klimisch score) “2” could be assigned to the present prediction.
The prediction reliability is estimated as 85 %.
- Mechanistic interpretation: OECD Principle 5
The toxicity baseline (as it is usually modeled by logP) is defined here with combination of "Molecular weight", "Average Bonding Information content (order 2)", "HPSA Polar (AM1) part of SASA" and " min(#HA, #HD) (AM1)". "Molecular weight" defines generally the mass and size of the structure; "Average Bonding Information content (order 2)" accounts the bonding complexity, i.e. aromatic, single, double, triple bonds, where also taking into account a heteroatoms; "HPSA Polar (AM1) part of SASA" shows the amount of polar surface area; and "min(#HA, #HD) (AM1)" counts the hydrogen bondi ng. All these descriptors affect more or less hydrophobicity - the baseline. Indirectly they are also related with other mode of action (like polar narcosis). For instance, heteroatoms, polar surface area and hydrogen bonding are important factors for different MOA. Specifically "HOMO - LUMO energy gap (AM1)" is defining the electronic hardness of molecules and is an important descriptor to define t he deviation from baselin.
5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
- Descriptor domain: All descriptor values for Hexyl nitrite fall in the applicability domain (training set value ±30%).
- Structural domains: H exyl nitrite is structurally relatively similar to the model compounds. The training set contains compounds of similar size to the studied molecule.
- Mechanism domain: Hexyl nitrite is considered to be in the same mechanistic domain as the molecules in the training set as it is structurally similar to the model compounds.
- Similarity with analogues in the training set:
The experimental acute toxicity values for compounds of similar functionalities are somewhat scattered in the toxicity scales depending on the molecular size and other functionalities. The structural analogues are relatively similar to the studied compound, covering all the chemical features. The descriptor values of the analogues are close to those of the studied compound. The analogues are con sidered to be within the same mechanistic domain. All the analogues are very well estimated within the model. The following aspects have been considered for the selection and analysis
of structural analogues:
Presence and number of common functional groups;
Presence and relevance of non-common functional groups;
Similarity of the ‘core structure’ apart from the (non-)common functional groups;
Potential differences due to reactivity;
Potential differences due to steric hindrance;
Presence of structural alerts;
Position of the double bonds;
Presence of stereoisomers.
- Other considerations (as appropriate):

6. ADEQUACY OF THE RESULT
6.1 Regulatory purpose:
The present prediction may be used for preparing the REACH Joint Registration Dossier on the Substance(s) for submission to the European Chemicals Agency (“ECHA”) as required by Regulation (EC) N° 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals ("REAC H") and as required by Bi ocide Product Directive 98/8/EC ("98/8/EC").
6.2 Approach for regulatory interpretation of the model result
The predicted result has been presented in the formats directly usable for the intended regulatory purposes, both the numeric value and the transferred (regulatory) scale values have been presented.
6.3 Outcome
See section 3.2(e) for the classification of the prediction in light of the regulatory purpose described in 4.1.
6.4 Conclusion
Considering the above, the predicted result can be considered adequate for the regulatory conclusion described in 4.1.]

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

GLP compliance:

yes

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

liquid

Sampling and analysis

Analytical monitoring:

no

Test solutions

Vehicle:

no

Test organisms

Test organisms (species):

Daphnia magna

Study design

Test type:

not specified

Water media type:

not specified

Limit test:

no

Total exposure duration:

48 h

Test conditions

Reference substance (positive control):

no

Results and discussion

Effect concentrations

Key result

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

ca. 7 510 g/L

Nominal / measured:

nominal

Conc. based on:

not specified

Basis for effect:

not specified

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

Following the “hazardous to the aquatic environment” categories defining the respective categories according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) the studied compound falls to the "No Category" (LC50 > 100.0 mg/l). This allows considering the toxicity as practically non-toxic.

Executive summary:

Predicted value (model result):

Log(LC₅₀) = -4.48

LC₅₀ = 7.51E6 mg/l

Following the "Hazardous to the aquatic environment" categories defining the perspective categories according to the GHS:

Category	Acute 1	Acute 2	Acute 3	No Category
LC50 (mg/l)	LC50 ≤ 1.0	1.0 < LC50≤ 10	10 < LC50 ≤ 100	LC50 > 100

On the above scale, the studied compound falls to the "No Category" classification. This allows considering the toxicity as practically non-toxic.