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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
Screening reproductive toxicity describes the effect of a test chemical on male or female reproductive performers.
The aim was to estimate the screening reproductive toxicity of target substance.
2.7.1 Estimation of the biological activity (screening reproductive toxicity)
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 4.4
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 (Appendix 1.7B).
II. Analogue (source compound) search based on selected criteria:
a. analogue dissociates similarly like the target compound (dissociation simulator)
b. analogue has the same structural features as the target compound according to:
i. Groups of elements
ii. Chemical elements profiler (subcategorization)
III. Data collection for the analogues (OECD Toolbox database/ECHA CHEM).
IV. Toxicity prediction for the target substance based on the worst-case scenario
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 their structural similarity.
The target substance is an organometallic compound containing calcium (Ca) centres, glycine (Gly) ligands. The metallic centres of the substance are linked by oxygen coordination bonds of the Gly ligands. The target compound and the source compounds exhibit similar toxicity effects due to the structural similarity. The prediction was performed basing on the source compound, which was found similar with the target compound due to similarities within the groups of elements (non-metals and alkaline earth groups) as well as chemical elements of their structures. The overall structural similarity to the target compound is in range of [50-60%].
Calcium carbonate is used as the source compound to predict the screening reproductive
toxicity.
The screening reproductive toxicity for the source compound was performed according to:
Test guideline: OECD 422
Endpoint: NOEL
Test organism: rat
The read-across prediction of the acute inhalation toxicity the target substance was performed based on the "one to one" approach. Compound used as source compound for prediction is presented in Table 5.

Table 5 Source compounds for the screening reproductive toxicity
No. CAS Name NOEL Test guideline
1. 471-34-1 calcium carbonate 1000 mg/kg bdwt/d OECD 422

Data source

Reference
Title:
Unnamed
Year:
2020
Report date:
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 consistency of the group of source compounds (called "category" in OECD Toolbox 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 screening reproductive toxicity of the calcium glycine (1:2) monohydrate, the read-across hypothesis considers that source and target compounds are similar in terms of their physicochemical, (eco)toxicological and fate properties.
The prediction for the target compound is based on the structural similarity of category members. All category members have the same structural features according to the structure similarity profilers: Groups of elements (Non-MetalsAlkaline Earth) and Chemical elements (Group 16 - Oxygen OGroup 14 - Carbon CGroup 15 - Nitrogen
NGroup 2- Alkaline Earth Be,Mg,Ca,Sr,Ba,Ra). The target compound and the source compounds exhibit similar toxicity effects due to their structural similarity. Additionally, all category members exhibit similar values of selected calculated physicochemical parameters.
Moreover, the category consistencies, the boundaries of the applicability domain are verified by the value of the bioconcentration factor (BCF). In case of calcium glycine (1:2) monohydrate, the BCF is in the range of descriptor (the same value). The structural similarity between the source (calcium carbonate) and target (calcium glycine (1:2) monohydrate) is 50% .

Test material

Constituent 1
Chemical structure
Reference substance name:
Calcium glycinate (1:2)
EC Number:
252-809-5
EC Name:
Calcium glycinate (1:2)
Cas Number:
35947-07-0
Molecular formula:
(C4H10N2O5Ca)n)
IUPAC Name:
catena (q3-glycinato-(q2-glycinato)-aqua-calcium)
Test material form:
solid: crystalline

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:
NOEL
Effect level:
ca. 1 000 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 NOEL = 1000 mg/kg bdtwt/d)
Executive summary:

The source and the target compound have similar toxicological properties due to common underlying mechanism after administration because of their high structural similarity. The prediction for the target compound in based on the "one-to-one" approach. The target compound (calcium carbonate) has the same structural features as source compound according to similarities within the groups of elements well as chemical elements of their structures. The overall structural similarity of the source compound to the target is 50%. Additionally, within
the repeated dose category of endpoints, the source compound toxicity has been identified to be similar (>1000mg/kg bdwt/d) for the 90-day oral toxicity test (OECD 408). The toxicity prediction was performed based on the experimental data included in the OECD QSAR Toolbox. Experimental data gathered for source substance were obtained with recommended OECD Guideline 422 and are considered as reliable without restriction and are characterized by a value of 1000mg/kg bdwt/d.