Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

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.

Link to relevant study records

Referenceopen allclose all

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.

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.
Endpoint:
screening for reproductive / developmental toxicity
Remarks:
Expert Toxicological Opinion. IASON 2018
Data waiving:
exposure considerations
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. Please find in Conclusions and Executive summary for expert opinion.
Reason / purpose:
data waiving: supporting information
Conclusions:
There is no need to perform additional animal studies because ferrous slags behave toxicologically similar as natural mineral samples; no further action is required.
In conclusion, the experimental data demonstrate that there is no likely hazard due to ferrous slags. The registrants rely on data waiving for the specific endpoints ‘Toxicity to reproduction’, as it is justified in accordance with REACH requirements (Annexes VII-X, second column and/or Annex XI) of the REACH Regulation No 1907/2006 (refer to COMMISSION REGULATION (EC) No).
Executive summary:

Ferrous slags are solid UVCB substances (substances of Unknown or Variable composition, Complex reaction products or Biological materials) that resemble natural rocks found in terrestrial and sediment systems. The physicochemical properties are almost identical among ferrous slags, and their benign toxicological and ecotoxicological profiles are very similar. Similarities comprise also the mineralogical composition of the ferrous slags. Importantly, all mineral components of ferrous slags are present in natural rocks; no new component is introduced during steel processing. Ferrous slags demonstrate low extractability in water as metals in slag were found to be generally resistant to leaching. Ferrous slags are virtually free of hazardous fibres. Overall, ferrous slags can be considered artificial volcanic rocks.

The ‘Ferrous Slag Category’ comprises the following 5 slag types:

(1) ABS/GBS i.e., Slag, ferrous metal, blast furnace (air cooled or granulated),

(2) BOS i.e., Slag, steelmaking, converter (converter slag),

(3) EAF C i.e., Slag, steelmaking, elec. furnace (carbon steel production),

(4) EAF S i.e., Slag, steelmaking, elec. furnace (stainless/high alloy steel production), and

(5) SMS i.e., Slag, steelmaking. No significant hazard to environmental and ecological receptors has been anticipated for these slags.

The pathways of exposure quantitatively evaluated in this assessment were inhalation of suspended airborne ferrous slag particulates, incidental ingestion of ferrous slag, and dermal contact with ferrous slag.

From single-dose toxicity testing in animals via the oral, dermal and inhalation routes it can be concluded that ferrous slags are not acutely toxic. They do not need to be classified as oral, dermal and inhalation toxicants; neither a signal word nor hazard statement is required. Furthermore, ferrous slags exhibit no relevant irritant or sensitising potential, and does not show any mutagenic potential. Extensive testing in rat inhalation studies revealed that the biological responses to inhaled ferrous slag show no correlation to the course of pulmonary toxicity reported for amorphous silica (quartz); quartz dust served as positive control as it is well known to produce irreversible lung damage. Overall, ferrous slag in vivo data differ markedly from those reported for quartz in rats exposed at similar doses.

Supplemental in vitro testing also shows that ferrous slags, alike natural mineral samples, do not cause significant toxicity in cultured alveolar macrophages, nor does the slags induce major reactive oxygen species (ROS) formation and oxidative stress or trigger any inflammation in a biological system. On the contrary, the positive assay control quartz caused consistently evidence for an inflammation response in vitro associated with a significant secretion of the mature forms of pro-inflammatory cytokines from the cells, strong activation of the inflammasome pathway, and impaired phagocytosis functionality of alveolar macrophages.

Taken together the data generated in vivo and in vitro for ferrous slags it can be summarised that ferrous slags behave like natural rock, representing a rather inert category of UVCB substances. As expected biokinetics investigations in rats following inhalation exposure to high concentrations of ferrous slag particulates showed concentration-dependent lung burdens of persistent metals after inhalation exposure of rats to ferrous slags but there was no translocation to other organs of any metal investigated. The animal data suggest that the rat lung was able to get rid of the inhaled solid aerosol via physiological clearance mechanisms.

The toxicology programme for ferrous slags, as documented in the Chemical Safety Report (CSR) as part of the registration dossier of ferrous slags (CSR 2017), can be considered to fulfil the

information requirements for REACH (Registration, Evaluation, Authorisation and Restriction of Chemical substances) registration at the European Chemicals Agency (ECHA). There is sufficient, adequate and reliable information on hazardous properties for classification and risk assessment of ferrous slags.

The registrant makes use of Annex XI criteria regarding the scientific necessity of information, the technical possibility for testing, and exposure-based waiving to adapt the standard information requirements under REACH. Data waiving is justified for repeated oral dose toxicity testing and studies for toxicity to reproduction or developmental toxicity / teratogenicity in order to avoid unnecessary testing in vertebrate animals. These non-clinical studies are waived based on physico-chemical properties of ferrous slags that resemble natural rocks, mimicking the natural concentration of an element in the environment, and the low solubility in water, low extractability of components from ferrous slags, and lack of toxicological bioavailable fraction / systemic bioavailability of metals. Slag has been utilised in road construction for more than two centuries and wealth of humane experiences are available. Furthermore, ferrous slags have no PBT (persistent, bioaccumulative and toxic) or vPvB (very persistent and very bioaccumulative) properties. It is also of note that no toxicity effects of particular concern were observed in animal inhalation studies that is the likely route of human exposure, 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 toxicity can reliably be excluded.

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

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.

Effects on developmental toxicity

Description of key information
No evidence from acute tests or other data for developmental toxicity or teratogenicity.
Link to relevant study records

Referenceopen allclose all

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.
Reason / purpose:
data waiving: supporting information
Reason / purpose:
data waiving: supporting information
Reason / purpose:
data waiving: supporting information
Species:
other: not relevant. See justification for data waiving.
Key result
Abnormalities:
not specified
Key result
Developmental effects observed:
not specified
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.

Endpoint:
developmental toxicity
Remarks:
CLP classification of reproductive/developmental 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 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
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
Species:
other: not relevant. See justification for data waiving.
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.
Endpoint:
developmental toxicity
Remarks:
Expert Toxicological Opinion. IASON 2018
Data waiving:
study waived due to provisions of other regulation
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
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.
Species:
other: not relevant. See justification for data waiving.
Conclusions:
There is no need to perform additional animal studies because ferrous slags behave toxicologically similar as natural mineral samples; no further action is required.
In conclusion, the experimental data demonstrate that there is no likely hazard due to ferrous slags. The registrants rely on data waiving for the specific endpoints ‘Toxicity/teratogenocity’, as it is justified in accordance with REACH requirements (Annexes VII-X, second column and/or Annex XI) of the REACH Regulation No 1907/2006 (refer to COMMISSION REGULATION (EC) No).
Executive summary:

Ferrous slags are solid UVCB substances (substances of Unknown or Variable composition, Complex reaction products or Biological materials) that resemble natural rocks found in terrestrial and sediment systems. The physicochemical properties are almost identical among ferrous slags, and their benign toxicological and ecotoxicological profiles are very similar. Similarities comprise also the mineralogical composition of the ferrous slags. Importantly, all mineral components of ferrous slags are present in natural rocks; no new component is introduced during steel processing. Ferrous slags demonstrate low extractability in water as metals in slag were found to be generally resistant to leaching. Ferrous slags are virtually free of hazardous fibres. Overall, ferrous slags can be considered artificial volcanic rocks.

The ‘Ferrous Slag Category’ comprises the following 5 slag types:

(1) ABS/GBS i.e., Slag, ferrous metal, blast furnace (air cooled or granulated),

(2) BOS i.e., Slag, steelmaking, converter (converter slag),

(3) EAF C i.e., Slag, steelmaking, elec. furnace (carbon steel production),

(4) EAF S i.e., Slag, steelmaking, elec. furnace (stainless/high alloy steel production), and

(5) SMS i.e., Slag, steelmaking. No significant hazard to environmental and ecological receptors has been anticipated for these slags.

The pathways of exposure quantitatively evaluated in this assessment were inhalation of suspended airborne ferrous slag particulates, incidental ingestion of ferrous slag, and dermal contact with ferrous slag.

From single-dose toxicity testing in animals via the oral, dermal and inhalation routes it can be concluded that ferrous slags are not acutely toxic. They do not need to be classified as oral, dermal and inhalation toxicants; neither a signal word nor hazard statement is required. Furthermore, ferrous slags exhibit no relevant irritant or sensitising potential, and does not show any mutagenic potential. Extensive testing in rat inhalation studies revealed that the biological responses to inhaled ferrous slag show no correlation to the course of pulmonary toxicity reported for amorphous silica (quartz); quartz dust served as positive control as it is well known to produce irreversible lung damage. Overall, ferrous slag in vivo data differ markedly from those reported for quartz in rats exposed at similar doses.

Supplemental in vitro testing also shows that ferrous slags, alike natural mineral samples, do not cause significant toxicity in cultured alveolar macrophages, nor does the slags induce major reactive oxygen species (ROS) formation and oxidative stress or trigger any inflammation in a biological system. On the contrary, the positive assay control quartz caused consistently evidence for an inflammation response in vitro associated with a significant secretion of the mature forms of pro-inflammatory cytokines from the cells, strong activation of the inflammasome pathway, and impaired phagocytosis functionality of alveolar macrophages.

Taken together the data generated in vivo and in vitro for ferrous slags it can be summarised that ferrous slags behave like natural rock, representing a rather inert category of UVCB substances. As expected biokinetics investigations in rats following inhalation exposure to high concentrations of ferrous slag particulates showed concentration-dependent lung burdens of persistent metals after inhalation exposure of rats to ferrous slags but there was no translocation to other organs of any metal investigated. The animal data suggest that the rat lung was able to get rid of the inhaled solid aerosol via physiological clearance mechanisms.

The toxicology programme for ferrous slags, as documented in the Chemical Safety Report (CSR) as part of the registration dossier of ferrous slags (CSR 2017), can be considered to fulfil the

information requirements for REACH (Registration, Evaluation, Authorisation and Restriction of Chemical substances) registration at the European Chemicals Agency (ECHA). There is sufficient, adequate and reliable information on hazardous properties for classification and risk assessment of ferrous slags.

The registrant makes use of Annex XI criteria regarding the scientific necessity of information, the technical possibility for testing, and exposure-based waiving to adapt the standard information requirements under REACH. Data waiving is justified for repeated oral dose toxicity testing and studies for toxicity to reproduction or developmental toxicity / teratogenicity in order to avoid unnecessary testing in vertebrate animals. These non-clinical studies are waived based on physico-chemical properties of ferrous slags that resemble natural rocks, mimicking the natural concentration of an element in the environment, and the low solubility in water, low extractability of components from ferrous slags, and lack of toxicological bioavailable fraction / systemic bioavailability of metals. Slag has been utilised in road construction for more than two centuries and wealth of humane experiences are available. Furthermore, ferrous slags have no PBT (persistent, bioaccumulative and toxic) or vPvB (very persistent and very bioaccumulative) properties. It is also of note that no toxicity effects of particular concern were observed in animal inhalation studies that is the likely route of human exposure, 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 toxicity can reliably be excluded.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Toxicity to reproduction: other studies

Description of key information

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

Justification for classification or non-classification

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.