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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Remarks:
Low toxicity – CLP classification of the ferrous slags based on toxicological data and physico-chemical properties
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance is of low toxicological activity (no evidence of toxicity seen in any of the tests available), it can be proven from toxicokinetic data that no systemic absorption occurs via relevant routes of exposure (e.g. plasma/blood concentrations below detection limit using a sensitive method and absence of the substance and of metabolites of the substance in urine, bile or exhaled air) and there is no or no significant human exposure
other:
Justification for type of information:
Scientific JUSTIFICATION in accordance with specific rules for adaption in Sections 3 of Annex XI of REACH, columns 2 in Annex X, endpoint 8.7
Low toxicity – CLP classification of the ferrous slags based on toxicological data and physico-chemical properties.
No evidence from acute tests or other data for any reproductive effect. No data available from studies dedicated especially to reproduction toxicity. As slags are similar to natural rock, no reporductive effects have to be expected. Additionally, for animal welfare, no study is recommended.
Cross-referenceopen allclose all
Reason / purpose:
data waiving: supporting information
Reference

No indication for reproductive/developmental toxicity, based on negative test results from available in vitro and in vivo mutagenicity studies.

No harmonised classification for reproductive/developmental toxicity for the components of the slags.

Endpoint conclusion:
no study available
Endpoint conclusion:
no study available
Endpoint conclusion:
no study available

Short description of key information:
No evidence from acute tests or other data for any reproductive effect. No data available from studies dedicated especially to reproduction toxicity. As slags are similar to natural rock, no reporductive effects have to be expected.

No evidence from acute tests or other data for developmental toxicity or teratogenicity.
Endpoint conclusion:
no study available
Endpoint conclusion:
no study available
Endpoint conclusion:
no study available

No indication for reproductive/developmental toxicity, based on negative test results from available in vitro and in vivo mutagenicity studies.

No indication for reproductive/developmental toxicity, based on negative test results from available in vitro and in vivo mutagenicity studies.

No harmonised classification for reproductive/developmental toxicity for the components of the slags.

The physico-chemical properties of ferrous slags are low solubility in water, low extractability of components from ferrous slags, and lack of toxicological bioavailable fraction/systemic bioavailability of metals. Furthermore, ferrous slags have no PBT (persistent, bioaccumulative and toxic) or vPvB (very persistent and very bioaccumulative) properties.

I the likely route of human exposure is inhalation and there is no toxicity effects of particular concern observed in animal inhalation studies, and results obtained from suitable in vitro studies demonstrate no certain dangerous property of ferrous slags.

Finally, previous risk assessments of slags provide sufficient supporting evidence that reproduction and developmental toxicity can reliably be excluded.

Reason / purpose:
data waiving: supporting information
Reference
Endpoint:
two-generation reproductive toxicity
Remarks:
Low toxicity – CLP classification of the ferrous slags based on toxicological data and physico-chemical properties
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because (i) the substance is of low toxicological activity (no evidence of toxicity seen in any of the tests available), (ii) it can be proven from toxicokinetic data that no systemic absorption occurs via relevant routes of exposure (e.g. plasma/blood concentrations below detection limit using a sensitive method and absence of the substance and of metabolites of the substance in urine, bile or exhaled air) and (iii) there is no or no significant human exposure
Justification for type of information:
Scientific JUSTIFICATION in accordance with specific rules for adaption in Sections 3 of Annex XI of REACH, columns 2 in Annex X, endpoint 8.7
Low toxicity – CLP classification of the ferrous slags based on toxicological data and physico-chemical properties.
see Executive summary for further information.
Reason / purpose:
data waiving: supporting information
Reproductive effects observed:
not specified
Conclusions:
All tests performed with ferrous slags were negative, and there is no indication, that any slag has any mutagenic or any relevant cytotoxic potential.
The ferrous slags are regarded as low toxicity based on available toxicological data in the summary below and do not refer to the ability to induce potential reproductive and/or developmental toxicity.
Executive summary:

In vitro gene mutation in bacteria/mammalian/ and cytogenicity or micronucleus formation refers to the ability of a substance to change and/or disrupt the genetic material (DNA) of bacteria/mammals/mammalian cells. If there is a positive result, the substance may cause gene mutagen in bacteria, mammals, cytogenicity or formation in mammalian cells of a micronucleus. It may also impact the genetic material in humans which in turn could lead to the development of cancer, affect reproduction or lead to an adverse health effect in offspring.

 

If there is a positive result in one or more in vitro tests, further mutagenicity studies in vivo must be considered to assess these types of effects, the possible concern for effects in humans needs to be further assessed in a living animal test system.In vivomutagenicity refers to the ability of a substance to damage the genetic material (DNA) of living mammals.

 

A reproductive and/or developmental toxic substance may affect fertility and can cause health effects in offspring after recurring contact. The exposure can occur by ingestion, inhalation, or skin contact.

If a substance is a reproductive and/or developmental toxicant, it may induce fertility problems, problems with the ability to reproduce and serious health effects in the offspring. A screening test for reproduction/developmental toxicity gives a first impression of possible problems with the ability to reproduce.

The available test results from following studies (in vitro and in vivo) are all negative:

  • in vitro gene mutation study in bacteria (Ames), OECD TG 471, EU TM B.13/14 (endpoint 7.6.1.1a – 7.6.1.1c, LAUS 2009)
  • in vitro gene mutation study in mammalian cells (gene mutation), OECD TG 476, EU TM B.17 (endpoint 7.6.2, Harlan 2009)
  • in vitro mammalian chromosome aberration test (Ames), OECD TG 473, EU TM B.10 (endpoint 7.6.1.3a, LAUS 2010)
  • in vitro gene mutation study in bacteria (Ames) OECD 471, EU TM B.13/14 (endpoint 7.6.1.101a-b, 7.6.2.101.a-b, Da Silva 2007)
  • in vivo mammalian erythrocyte micronucleus test, OECD 474, EU TM B12, (endpoint 7.6.1.101a-b, 7.6.2.101.a-b, Da Silva 2007)

The negative test results indicate there are no potential to induce damages/changes in the genetic material (DNA) of living mammals.

The exposures by ingestion and skin contact are considered as negligible (see further information in endpoint 7.2 and 7.3) and are not critical and/or relevant for this endpoint.

The exposure by inhalation was assessed as not acute toxic, supported by the test results from performed acute and short-term repeated inhalations studies.

Based on previous scientific considerations, no further testing for screening test for reproduction/developmental toxicity is required.

For further discussion, summary and test result for each endpoint below, kindly see the link (linked study/endpoint records) in Cross reference under Administrative data

Acute toxicity (oral, dermal and inhalation)

No acute toxicity of any routes, based on the conclusion of the following test results:

Oral: ABS, GBS, EAF C: OECD TG 401, rats: LD50 > 2000 mg/kg bw, BOS, SMS: OECD TG 423, rats: LD50 > 2000 mg/kg bw.

Inhalation: GGBS: OECD 403, rats: 4 h-LC50 >5235 mg/m³

Skin: BOS, SMS: rats OECD 402, rats: LD50 > 4000 mg/kg

Additional information (ABS): equal to oral intake. Slag leachtest fulfil the quality criteria of the German Federal Drinking Water Regulation. Conclusion: pose no risk to human health, when the criteria for drinking water is fullfil.

Irritation/Corrosion

Several in vitro and in vivo tests on ferrous slags demonstrate that these slags have no irritant and no corrosive potential to skin and eye.

Dermal absorption

From dermal toxicity testing with BOS and SMS, it is concluded, that no components of these UVCBs are taken up at relevant concentrations through the skin. Therefore this absorption of ferrous slag through the skin can be neglected including toxicokinetics.

Skin sensititation

ABS, EAF C, and EAF S are not sensitising when tested according to OECD 406 and NF EN ISO 10993-10 (February 2003) concerning biological evaluation of medical devices: Tests for irritation and delayed-type

hypersensitivity. BOS and SMS are not sensitising when tested according to OECD TG 406 Skin Sensitisation Test.

Carcinogenicity

There is no indication of carcinogenic potential of ferrous slags based on available data from literature.

Genotoxicity

Ferrous slags do not have any mutagenic potential and/or change/disrupt the DNA of bacteria and mammalian cells, assessed by the negative test results, performed by OECD 471, OECD 474 and OECD 476.

Reason / purpose:
data waiving: supporting information
Reference
Endpoint:
screening for reproductive / developmental toxicity
Remarks:
CLP classification of reproductive toxicity based on the constituent of the ferrous slags
Data waiving:
study waived due to provisions of other regulation
Justification for data waiving:
the study does not need to be conducted because (i) the substance is of low toxicological activity (no evidence of toxicity seen in any of the tests available), (ii) it can be proven from toxicokinetic data that no systemic absorption occurs via relevant routes of exposure (e.g. plasma/blood concentrations below detection limit using a sensitive method and absence of the substance and of metabolites of the substance in urine, bile or exhaled air) and (iii) there is no or no significant human exposure
Justification for type of information:
Scientific JUSTIFICATION in accordance with specific rules for adaption in Sections 3 of Annex XI of REACH, columns 2 in Annex X, endpoint 8.7
CLP classification of reproductive/developmental toxicity based on the constituent of the ferrous slags.

Based on the analytical information in section 1.4 on ferrous slags used in toxicological test/studies, the most frequent (>5%) elements in the slags are:
calcium, magnesium, aluminum, iron, silicon, manganese in oxidic compounds in mineral phases.
Other minor (<1%) constituents are barium, vanadium, fluoride, chromium and potassium. 

There is NO harmonized classification nor notified classification for reproductive/developmental toxicity for these components above, according to the Annex VI in CLP and the C&L Inventory. The elements are not considered as Known or presumed human reproductive toxicant, and/or suspected as such. Further, these are not classified and/or suspected as genotoxicity and/or carcinogen toxicity.
Reason / purpose:
data waiving: supporting information
Conclusions:
The ferrous slags are not classified as reproductive toxicity/developmental toxicity based on the constituents of the slags, according to the CLP harmonised and/or notified classification.

Data source

Materials and methods

Test animals

Species:
other: not relevant. See justification for data waiving.

Results and discussion

Results (fetuses)

Fetal abnormalities

Key result
Abnormalities:
not specified

Overall developmental toxicity

Key result
Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
No indication for reproductive/developmental toxicity, based on negative test results from available in vitro and in vivo mutagenicity studies.
No harmonised classification for reproductive/developmental toxicity.
Executive summary:

See endpoints 7.8.1 for further discussion and summary.