[No public or meaningful name is available]

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2019

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

Acute dermal toxicity refers to those adverse effects occurring following a single dermal (skin) exposure to the substance within 24 h.
The aim was to estimate the acute toxicity by dermal route of target substance.

stimation of the biological activity (acute toxicity by dermal route)
The computational simulation was performed based on the read-across approach.The readacross is one of the so-called alternative test methods recommended by REACH, where the predictions are based on the experimental data available for the most similar compounds. The predictions were performed according to the Read-Across Assessment Framework (RAAF), which assumes six different risk assessment scenarios of chemical compounds.
Applied tool:
The OECD QSAR Toolbox, version 4.3
Procedure of analysis:
I. Profiling of the target substance in order to retrieve relevant information related to
mechanism of action and observed or simulated metabolites
II. Category (source compounds) search based on selected criteria:
a. analogues are aliphatic amines according to US-EPA New Chemical Categories
b. analogues are structurally similar to the target compound (similarity >20%)
c. analogues have the same alert “High level” according to the Cramer profile.
III. Data collection for the analogues (OECD Toolbox database/ECHA CHEM).
IV. Toxicity prediction for the target substance
V. Category consistency check in order to assess the quality of the prediction
Applied scenario:
Scenario 2
Toxicity prediction for the target substance:
This read-across is based on the fact that the organism is not exposed to common compounds but rather, as a result of similarity, to chemicals which have similar (eco)toxicological and fate properties.
The target substance is an organometallic compound containing manganese (Mn) centres, glycine (Gly) ligands. The metallic centres of the substance are linked by oxygen coordination bonds of the Gly ligands.
The target and source chemicals are classified as “Aliphatic amines” according to US-EPA New Chemical Categories and have the same “High level” alert responsible for the toxic effect based on the Cramer profiler. Moreover, analogue is structurally similar to the target compound in more than 20%. The sodium (2-aminoethyl)amino]ethanesulphonate was taken into account for the prediction.
The acute dermal toxicity for the source compound was performed according to:
Test guideline: OECD 402
Endpoint: LD50
Test organism: rat
The read-across prediction of the acute dermal toxicity for the target substance was performed based on the approach “one to one”.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Principles of method if other than guideline:

In order to meet regulatory needs, reliability of the predicted results should be assessed. In case of classic quantitative structure-activity relationships (QSAR) modelling, this idea can be realised by analysing, whether the predicted value is located within so-called applicability domain. The applicability domain is a theoretical region, defined by the range of toxicity values and structural descriptors for the training compounds, where the predictions may be considered as realistic ones. In a specific case of read-across, the assessment is performed based on the assessment of degree of similarity between the source and target compounds (in %). Moreover, the internal consistency of the group of source compounds (called „category” in OECD QSAR Toolbox nomenclature, independently which approach: analogue approach or category approach is used). The category consistency check could be based on the parameters describingthe structural similarity and/or properties as well as mechanistic similarity of the tested
compounds. For example, all members of the category (analogues as well as target substance) need to have the same functional groups and endpoint specific alerts.
In the case of read-across-based prediction of the acute dermal toxicity of the dehydrate manganese (II) glycine sulphate (VI), the read-across hypothesis considers that source and target compounds have the same structural features related to “Aliphatic amines” (US EPA New Chemical Categories) and have the same “High level” alert responsible for the toxic effect based on the Cramer profiler. Based on the Dice measure, the structural similarity between analogues and the target compound was higher than 20%. The sodium 2-[(2-aminoethyl)amino]ethanesulphonate was taken into account for the prediction.
Besides, the category consistency, the boundaries of the applicability domain are verified by the critical value of log KOW. In case of “one to one” approach, this criterium would be met only if source and target compounds are the same substance. Thus, information that “target chemical is out of domain” considering this criterium is not critical in this situation.
The structural similarity between the source (sodium 2-[(2-aminoethyl)amino]ethanesulphonate) and the target compound (Mn(Gly)SO4) equals to 27.3%.

GLP compliance:

no

Remarks:

QSAR

Test material

Test material information

Constituent 1

Reference substance name:

catena-((μ4-sulfato)-(μ2-glycinato)-manganese

Cas Number:

2087529-10-8

Molecular formula:

Mn(SO4)(C2H5NO2)

IUPAC Name:

catena-((μ4-sulfato)-(μ2-glycinato)-manganese

Test material form:

solid

Results and discussion

Effect levels

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute dermal toxicity for the target substance is predicted at level LD50 >= 2000 mg/kg

Executive summary:

The source and target compounds have the same structural features related to “Aliphatic amines” (US EPA New Chemical Categories) and have the same “High level” alert responsible for the toxic effect based on the Cramer profiler. The analogues search was performed assuming at least 20% structural similarity between the source and target substances. The toxicity prediction was performed based on the experimental data included in the OECD QSAR Toolbox. The sodium 2-[(2-aminoethyl)amino]ethanesulphonate would have similar structural features (organic functional groups) and cause similar toxic effect (Cramer profile) as well as the experimental data related to its acute dermal toxicity was available. Therefore, the prediction is based only on the sodium 2-[(2-aminoethyl)amino]ethanesulphonate.