Registration Dossier

Diss Factsheets

Administrative data

Link to relevant study record(s)

Referenceopen allclose all

Endpoint:
basic toxicokinetics
Type of information:
other: Assessment from available information
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Objective of study:
toxicokinetics
Qualifier:
no guideline required

Acute studies

The substance, Slimes and Sludges, blast furnace and steelmaking, was applied to laboratory animals (rat, mouse, and rabbit) during studies with different way of entry into organism (e.g. stomach, respiratory tract - nose, skin and eye).

Only mild systemic effects - gibbous posture only 30 minutes after application and piloerection and increased response to stimuli 3 hours after application in all animals were described after single oral application of the dose level 2000 mg/kg of the substance to rats. Observed changes faded away till 24 hours after application of the test substance.

Common clinical abnormalities (increased respiratory rate, hunched posture, piloerrection and wet fur - till the 4th day after exposure) were noted after 4-hour nose exposure of the substance at the concentration of 5.12 mg/l.

After single application on skin of rabbit, no irritant or corrosive effects were observed. The substance is not irritant. No symptoms of systemic toxicity were observed in rabbits after application on skin.

Examination of eye after single application of substance to the conjunctival sac demonstrated, that Slimes and Sludges, blast furnace and steelmaking, is not irritating for eye of rabbit; the changes observed were reversible (redness and chemosis of conjunctivae and lacrimation - these changes faded away till the 2nd day of study). No corrosive effects were observed on eyes of rabbit and no clinical signs of systemic intoxication were detected. 

The substance, Slimes and Sludges, blast furnace and steelmaking, elicited negative response after topical application to the mouse ear in LLNA. No clinical signs of systemic intoxication were detected in study of sensitization.

Negative results in the micronucleus test after single per oral application indicate that, the test item Slimes and Sludges, blast furnace and steelmaking, does not produce micronuclei in immature erythrocytes in bone marrow of rat.

    

Long-term studies

The oral administration of the substance, Slimes and Sludges, blast furnace and steelmaking, to rats by gavage for a period of 28 consecutive days at dose levels 160, 400 and 1000 mg/kg/day affected haematological parameters. Parameters were significantly affected by treatment at the dose level 1000 mg/kg/day. The haematology examination detected significant irreversible effect on red blood cells parameters in both sexes of all treated groups - the increased value of hematocrit and haemoglobin were recorded in both sexes. Males showed the irreversible increased value of mean corpuscular volume and females showed the increased value of total erythrocyte count after application period.

The biochemical examination revealed significant differences in both sexes with a dose-related trend. A significantly decreased concentration of albumin together with dose-related decreased value of total protein was recorded in both sexes but markedly in males. Markedly decreased value of creatinine with dose-dependent manner was recorded in both sexes. The concentration of cholesterol was decreased at the highest dose of males and inorganic phosphorus was increased in all treated groups of females. After the recovery period, changes were recorded only in females: significantly decreased value of urea, increased concentration of cholesterol and insignificantly decreased activity of AST. These changes together with dose-dependent decreased weight of liver can be indications of affection of liver metabolism. Pathological examination revealed vacuolation of hepatocytes in most of males and females at the highest dose level. These changes are an indication for hepatocellular damage.

The biometry of organs also detected decreased weight of spleen in both sexes with dose-dependence in females.

The application of the test substance caused temporary colouring of the chyme and had negative effect on digestive tract.

In Reproduction/Developmental Toxicity Screening Test the following dose levels: 160, 400 and 1000 mg/kg/day were administered.

The negative influence of the test substance treatment expressed mainly at the highest dose level (limit dose): decreased body weight of parental females, impaired sperm quality of parental males and changes of microscopic structure of reproduction organs (testes) in parental males were observed.

The test substance administered at the highest dose level had negative influence on reproduction parameters of parental females (number of pregnant, number of females achieving pregnancy, average number of pups, sex ratio, average weight of litter, corpora lutea, implantation).

Durations of mating and pregnancy, average body weight and postnatal development of pups were unaffected by the test substance treatment.

Conclusions:
Interpretation of results (migrated information): other: see Conclusions
Only mild systemic effects were described after single oral application of the dose level 2000 mg/kg of the substance to rats. Observed changes faded away till 24 hours after application of the test substance.
Common clinical abnormalities were noted after 4-hour nose exposure of the substance at the concentration of 5.12 mg/l.
After single application on skin of rabbit, no irritant or corrosive effects were observed. The substance is not irritant. No symptoms of systemic toxicity were observed in rabbits after application on skin.
Examination of eye after single application of substance to the conjunctival sac demonstrated, that Slimes and Sludges, blast furnace and steelmaking, is not irritating for eye of rabbit; the changes observed were reversible. No corrosive effects were observed on eyes of rabbit and no clinical signs of systemic intoxication were detected.
The test substance elicited negative response after topical application to the mouse ear in LLNA. No clinical signs of systemic intoxication were detected in study of sensitization.
The oral administration of the test substance to rats by gavage for a period of 28 consecutive days at dose levels 160, 400 and 1000 mg/kg/day affected haematological parameters. Parameters were significantly affected by treatment at the dose level 1000 mg/kg/day. The haematology examination detected significant irreversible effect on red blood cells parameters in both sexes of all treated groups. The biochemical examination revealed significant differences in both sexes with a dose-related trend. Dose-dependent decreased weight of liver can be indications of affection of liver metabolism. Pathological examination revealed vacuolation of hepatocytes in most of males and females at the highest dose level. These changes are an indication for hepatocellular damage. The biometry of organs also detected decreased weight of spleen in both sexes with dose-dependence in females. The application of the test substance caused negative effect on digestive tract.
In Reproduction/Developmental Toxicity Screening Test the following dose levels: 160, 400 and 1000 mg/kg/day were administered. The negative influence of the test substance treatment expressed mainly at the highest dose level (limit dose) was observed. The test substance administered at the highest dose level had negative influence on reproduction parameters of parental females. Durations of mating and pregnancy, average body weight and postnatal development of pups were unaffected by the test substance treatment.
Executive summary:

Evaluation of toxicokinetics of the substance Slimes and Sludges, blast furnace and steelmaking was performed. Evaluation of toxicokinetics of the substance is required according to the section 8.8.1 of Annex VII to the Directive (EC) No. 1907/2006 (REACH).

Slimes and Sludges, blast furnace and steelmaking is the complex product of oxides and elements. The main components of the test substance are the following: Fe total (54.29 % - mainly as oxides) and CaO (10.17 %).

The evaluation of toxicokinetics of the test substance was performed according to experimental data from the testing of Slimes and Sludges, blast furnace and steelmaking at CETA - VUOS.

The data used for the evaluation originated from three sources:

- Experimental data of toxicological tests (unpublished)

- Literature data obtained from internet

- Data from toxicological databases - free and commercial     

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Deviations:
not specified
GLP compliance:
not specified
Radiolabelling:
no
Species:
other: In vitro method
Details on test animals or test system and environmental conditions:
not applicable
Type of coverage:
other: In vitro method
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: B+B Agro, Cíneves, Czech Republic
- Type of skin: sheet of pork skin from both sides of the backbone (cca 40 x 70 cm)
- Preparative technique: subcutaneous fat was removed using electrical knife and blunt butcher knife; skin was shaved by electrical shaver, washed with lukewarm water and let to dry
- Membrane integrity check: standard 1% solution of caffeine in ethanol / water (3:7) was applied 20 µl per skin preparation, two skin preparations in each run; determined values (30.9 - 37.0 % penetration) falls into the range of historical data (29.4 - 40.2 %) and thus quality of skin was acceptable
- Storage conditions: skin was divided into disc-shaped pieces (diameter 5 cm), which were stored in vacuum bags with designated date of preparation and frozen (-18°C); prior to testing (2-3 hours) the skin preparations were defrozen on air at laboratory temperature
- Justification of species, anatomical site and preparative technique: according to Council Regulation (EC) No. 440/2008 skin from many mammalian species can be used, the structure and characteristics of porcine skin are similar to human skin

PRINCIPLES OF ASSAY
- Diffusion cell: static Franz diffusion cells consisted of a donor chamber (in the form of a glass cap with an opening in the center) and receptor chamber (double bottom glass cell, diameter cca 2 cm, volume cca 5 ml); the system was placed on a magnetic stirrer set for 310 rpm
- Receptor fluid: 0.9% NaCl, 1% bovine albumin, 0.05% Gentamicin in deionised water
- Static system: yes
- Exposure duration: 24 hours
- Test temperature: 34°C
- Reference substance(s): caffeine
- Negative control: distilled water
Signs and symptoms of toxicity:
not examined
Remarks:
not applicable
Dermal irritation:
not examined
Remarks:
not applicable
Absorption in different matrices:
see Slimes and Sludges - Dermal Absorpotion - Results.pdf in Attached background material
Total recovery:
see Slimes and Sludges - Dermal Absorpotion - Results.pdf in Attached background material
Key result
Remarks on result:
other: Under the test conditions of the in vitro skin absorption method, the elements contained in the test item do not significantly penetrate into the deeper skin layers and receptor fluid, thus excluding the possibility of systemic exposure.

see Slimes and Sludges - Dermal Absorpotion - Results.pdf in Attached background material

Conclusions:
Under the test conditions of the in vitro skin absorption method, the elements contained in the test item do not significantly penetrate into the deeper skin layers and receptor fluid, thus excluding the possibility of systemic exposure.

Description of key information

Short description of key information on bioaccumulation potential result: 
Evaluation of toxicokinetics of the substance Slimes and Sludges, blast furnace and steelmaking was performed. Evaluation of toxicokinetics of the substance is required according to the 8.8.1 of Annex VII to the Directive (EC) No. 1907/2006 (REACH).
The data used for the evaluation originated from three sources:
- Experimental data of toxicological tests (unpublished)
- Literature data obtained from internet
- Data from toxicological databases - free and commercial

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

The substance, Slimes and Sludges, blast furnace and steelmaking, was applied to laboratory animals (rat, mouse, and rabbit) during studies with different way of entry into organism (e.g. stomach, respiratory tract - nose, skin and eye).

Only mild systemic effects were described after single oral application of the dose level 2000 mg/kg of the substance to rats. Observed changes faded away till 24 hours after application of the test substance.

Common clinical abnormalities were noted after 4-hour nose exposure of the substance at the concentration of 5.12 mg/l.

After single application on skin of rabbit, no irritant or corrosive effects were observed. The substance is not irritant. No symptoms of systemic toxicity were observed in rabbits after application on skin.

Examination of eye after single application of substance to the conjunctival sac demonstrated, that Slimes and Sludges, blast furnace and steelmaking, is not irritating for eye of rabbit; the changes observed were reversible. No corrosive effects were observed on eyes of rabbit and no clinical signs of systemic intoxication were detected. 

The test substance elicited negative response after topical application to the mouse ear in LLNA. No clinical signs of systemic intoxication were detected in study of sensitization.

The oral administration of the test substance to rats by gavage for a period of 28 consecutive days at dose levels 160, 400 and 1000 mg/kg/day affected haematological parameters. Parameters were significantly affected by treatment at the dose level 1000 mg/kg/day. The haematology examination detected significant irreversible effect on red blood cells parameters in both sexes of all treated groups. The biochemical examination revealed significant differences in both sexes with a dose-related trend. Dose-dependent decreased weight of liver can be indications of affection of liver metabolism. Pathological examination revealed vacuolation of hepatocytes in most of males and females at the highest dose level. These changes are an indication for hepatocellular damage. The biometry of organs also detected decreased weight of spleen in both sexes with dose-dependence in females. The application of the test substance caused negative effect on digestive tract.

In Reproduction/Developmental Toxicity Screening Test the following dose levels: 160, 400 and 1000 mg/kg/day were administered. The negative influence of the test substance treatment expressed mainly at the highest dose level (limit dose) was observed. The test substance administered at the highest dose level had negative influence on reproduction parameters of parental females. Durations of mating and pregnancy, average body weight and postnatal development of pups were unaffected by the test substance treatment.