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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
2020
Reliability:
1 (reliable without restriction)
Justification for type of information:
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 pred
ictions 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 4.4
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. Analogue (source compound) search based on selected criteria:
a. analogue has the same structural features as the target compound according to:
i. Groups of elements profiler
ii. Chemical elements profiler
iii. Lipinski Rule Oasis profiler
b. analogue has the same alerts according to profiles:
i. Estrogen Binding Receptor
ii. OECD HPV Chemical Categories
iii. Substance type
III. Data collection for the analogues (OECD Toolbox database).
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 target and the source compounds are similar in terms of
their physicochemical, (eco)toxicological and fate properties. The target compound
and the source compounds exhibit similar toxicity effects due to the similarity according to the co
nsidered structural profilers (Group of elements profiler, Chemical of elements profiler,
Lipinski Rule Oasis profiler) expressed in 47,1% structural similarity, as well as consistent alerts
according to Estrogen Binding Receptor, OECD HPV Chemical Categories and
Substance type profilers. Based on the assumed analogue search criteria, one source compound has
been found: CoSO4.
The screening reproductive toxicity for the source compound was performed according to:
Test guideline: OECD 422
Endpoint: NOAEL
Test organism: rat
The read-across prediction of the screening reproductive toxicity for the target substance was
performed based on the approach one to one.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2020

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
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 consistencs of the group of source componnds (called categoris in OECD Toolbol
nomenclature, independently which approach: analogue approach or category approach is used).
The category consistency check could be based on the parameters describing the 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 reproductive toxicity of the iron (II) glycine sulphate
(VI) trihydrate, the read-across hypothesis considers that the target compound and the
source compounds exhibit similar toxicity effects due to the structural similarity. This readacross is
based on the fact that the target and the source compound are similar in terms of their
physicochemical, (eco)toxicological and fate properties. The test organism is exposed to compound,
which has the same structural features as the target compound according to
profilers: Groups of elements (Transition metalsNon-metals), Chemical elements (Group 16
Oxygen OGroup 16 Sulfur S) and Lipinski Rule Oasis (Bioavailable).
Structural similarity between the target and source compound is equal of [47.1%]. Both category
members exhibit consistent results according to Estrogen Binding Receptor, OECD
HPV Chemical Categories and Substance type profilers.
Besides, the category consistencies, the boundaries of the applicability domain are verified by the
critical value of the bioconcentration factor (BCF). In case of Fe(Gly)SO4x3H2O the BCF
is in the range of descriptor.

Test material

Constituent 1
Chemical structure
Reference substance name:
bis(λ⁴-iron(2+)) tetrakis(2-aminoacetate)
EC Number:
606-444-7
Cas Number:
20150-34-9
Molecular formula:
C4H8FeN2O4
IUPAC Name:
bis(λ⁴-iron(2+)) tetrakis(2-aminoacetate)
Test material form:
solid

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
no effects observed
Immunological findings:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Other effects:
no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed

Details on results (P0)

no effectn observed

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
ca. 0.5 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Remarks on result:
other: see remarks

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Sexual maturation:
no effects observed
Anogenital distance (AGD):
no effects observed
Nipple retention in male pups:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed
Other effects:
no effects observed

Developmental neurotoxicity (F1)

Behaviour (functional findings):
no effects observed

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
no effects observed

Details on results (F1)

no effect observed

Effect levels (F1)

Remarks on result:
not determinable due to absence of adverse toxic effects

Overall reproductive toxicity

Reproductive effects observed:
no

Applicant's summary and conclusion

Conclusions:
no classified (The screening reproductive toxicity for the target substance is predicted at level NOAEL= 0,5 mg/kg bdtwt/d)
Executive summary:

The prediction for the target compound is based on the structural similarity of category members.
The category members have the same toxicological properties due to common underlying mechanism after administration because of their high structural similarity. Both category members have the same structural features according to profilers: Groups of elements (Transition metals<AND>Non-metals),
Chemical elements (Group 16 - Oxygen O<AND>Group 16 - Sulfur S) and Lipinski Rule Oasis (Bioavailable). The toxicity prediction was performed based on the experimental data included in the OECD QSAR Toolbox.
Experimental data gathered for source substance was obtained with recommended OECD Guideline 422 and are considered as reliable without restriction.