Slags, granulated, resulting from plasma-enhanced gasification of non-hazardous municipal waste

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD 403, OECD 39 and 92/69/EEC

Deviations:

no

Principles of method if other than guideline:

This pilot study was carried out in accordance with OECD Guideline No. 403 (2009) {in regard to the exposure methodology and the criteria for dose selection}. More general procedures were considered in the study design as called for by OECD Guideline#39 (2009), and Directive 92/69/EEC testing guidelnes.

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Slags, ferrous metal, blast furnace

EC Number:

266-002-0

EC Name:

Slags, ferrous metal, blast furnace

Cas Number:

65996-69-2

IUPAC Name:

266-002-0

Constituent 2

Reference substance name:

GGBS (ground granulated blast furnace slag)

IUPAC Name:

GGBS (ground granulated blast furnace slag)

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

GGBS = Ground granulated slags, ferrous metal, blast furnace

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

Species: SPF-bred Wistar rats of the strain HsdCpb:WU from Laboratory animal breeder Harlan Nederland (NL), Kreuzelweg 53, 5960 AD Horst.
Acclimatization: at least 5 days before use.
Health status: Historical data is available. The breeding colony is routinely spot-checked for the main specific pathogens.Only healthy rats free of pathological signs will be used. Animals are not vaccinated or treated with anti-infective agents either before their arrival or during the acclimatization
or study periods.
Age and weight: approx. 2 months old. Weight range at the exposure day – males: 210 – 250 gram
Number and groups: 6 animals will be used in each group. There are for each concentration (0, 10, 250 mg/m³) and each postexposure day (1, 7, 28, 90) 2 groups, one for BAL & histopathology and one for kinetics.
Identification: individual color-marking and cage-labels.
Randomization: Prior to exposure, standard randomization procedure applied (computerized list of random numbers serves to assign animals at random to the treatment groups)
Animal housing: singly in Makrolon® Type IIIH cages (based on A. Spiegel and R. Gönnert, Zschr. Versuchstierkunde, 1, 38 (1961) and G. Meister, Zschr. Versuchstierkunde, 7, 144-153 (1965)). Cages are changed twice a week while unconsumed feed and water bottles are changed once per
week. The legal requirements of Directive 86/609 EEC were followed.
Bedding: Bedding consisted of type Lignocel BK 8-15 low-dust wood granulate from Rettenmaier. The wood granulate is randomly checked for harmful constituents at the request of the Laboratory Animal Services, Bayer HealthCare AG.
Temperature: 22 ± 3 °C
Relative humidity: 40 - 60 %,
Dark/light cycle : 12 h/12 h; artificial light from 6.00 a.m. to 6.00 p.m., light intensity: maximum 200 Lux
Ventilation: at least 10 air changes/h
Cleaning, disinfection, and pest control: The animal room is regularly cleaned and disinfected once a week with an aqueous solution of TEGOÒ 2000 VT25.
Pest control measures: Cleaning. Cockroach traps
Feeding: Ration consist of a standard fixed-formula diet (KLIBA 3883 = NAFAG 9441) pellets; PROVIMI KLIBA SA, 4303 Kaiseraugst, Switzerland) and tap water (drinking bottles). Both food and water is available ad libitum. The pelletized feed is contained in a rack in the stainless-steel wire cage
cover. Specification of ingredients and contaminants according to recommendations of GV SOLAS (August, 2001).
Water: Drinking quality municipality tap-water (current version of the Drinking Water Decree) is provided ad libitum in polycarbonate bottles containing approximately 300 ml (based on A. Spiegel and R. Gönnert, Zschr. Versuchstierkunde, 1, 38 (1961) and G. Meister, Zschr. Versuchstierkunde, 7, 144-153 (1965)).
Body weights: Body weights are recorded before exposure and 1, 3, 7 days and weekly thereafter. As a rule, for data evaluation, the exposure day is
defined as day 0 (relative).
Clinical observations: The appearance and behavior of each rat are examined carefully several times on the day of exposure and at least once daily thereafter. During the recovery period, if free from specific symptoms, the results of clinical observations were recorded once per week. Assessments from restraining tubes are made only if unequivocal signs occur (e.g. spasms, abnormal movements, and severe respiratory signs). Following exposure, observations are made and recorded systematically; individual records are maintained for each animal. Cage-side observations included, but are not limited to, changes in the skin and fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, and somatomotor activity and behavior pattern. Particular attention is directed to observation of tremors, convulsions, salivation, diarrhea, lethargy, somnolence and prostration. The time of death is recorded as precisely as possible, if applicable. Since these signs can only be assessed adequately from freely moving animals, no specific assessment is performed during exposure while animals are restrained.

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

clean air

Details on inhalation exposure:

Animal exposure and postexposure period: The test article will be dosed by inhalation. The exposure duration is 1 x 6 hours. The post exposure period is up to 13 weeks (depending on the timing of taking the bronchoalveolar lavage samples). Following time points: day(s) 1 (+/- 0), 7 (+/- 1), 28 (+/-3), 90 (+/-7 days tolerance)
Inhalation Chamber: An aluminum inhalation chamber with the following dimensions has to be used: inner diameter = 14 cm, outer diameter = 35 cm (two-chamber system), height = 25 cm (internal volume = about 3.8 l). If feasible, multiple segments of this chamber can be used, however, the respective air-flows have to be adapted to the larger chamber volume.
Optimization of respirability of aerosol (if applicable): In order to increase the efficiency of the generation of respirable particles and to prevent larger particles from entering the inhalation chamber, a pre-separator/baffle and/or elutriator/cyclone systems which favors the formation of fine particles is used.
Conditioning the compressed air: Compressed air is supplied by Boge compressors and is conditioned (i.e. freed from water, dust, and oil) automatically by a VIA compressed air dryer.
Inhalation chamber steady-state concentration: The test atmosphere generation conditions provide an adequate number of air exchanges per hour (approximately 200-times or more). Under such test conditions steady state is commonly attained within the first minute of exposure (t99% = 4.6 x
chamber volume/flow rate). The ratio between the air supplied and exhausted is chosen so that approximately 80-90% of the supplied air is removed via the exhaust system. The remainder provides adequate dead-space ventilation for the exposure tubes. At each exposure port a minimal air flow rate of 0.75 L/min must be provided.
Air flows: During the exposure period air-flows are monitored continuously and, if necessary, readjusted to the conditions required. Air-flows are measured with calibrated flow-meters and/or soap bubble meter (Gilibrator) and are checked for correct performance at regular intervals by other
equipment (e.g., spirometer).

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

6 h

Remarks on duration:

90 days post exposure observation

Concentrations:

Study groups
targeted concentration: animal-numbers
0 mg/m3: 1 - 48
10 mg/m3: 49 - 96
250 mg/m3: 97 - 144

No. of animals per sex per dose:

male: 48
female: 0

Control animals:

yes

Details on study design:

Analysis of particle-size distributions:
Sampling in the vicinity of the breathing zone, two samples per exposure.
ANDERSEN- or an AERAS low-pressure critical orifice cascade impactor. The individual impactor stages are covered by an adhesive stage coating (silicone spray) in order to prevent particle bounce and re-entrainment. If not advisable due to the specific conditions of the test coating can be omitted, or other measures may be taken.
Determined Mass Median Aerodynamic Diameter (MMAD)
Calculation of Geometric Standard Deviation (GSD): GSD = 84.1% mark / 50% mark.
To verify graphically that the aerosol is in fact unimodal and log-normally distributed the normalized mass per stage (fH') is evaluated as a histogram. Calculate the histogram
Calculate the log-normal mass distribution y'(Dae) = 1/Nf x y(Dae) as a function of the aerodynamic diameter

Statistics:

Necropsy findings: Fisher test after the R x C chi-squared test if required
Body weights: Means and single standard deviations, one-way ANOVA (vide infra)
Physiological data: ANOVA procedure (vide infra).
Calculation of the LC50: according to the method of Rosiello ROSIELLO, A.P., ESSIGMANN, J.M., and WOGAN, G.N. (1977). Rapid and Accurate Determination of the Median Lethal Dose (LD50) and its Error with Small Computer. J. Tox. and Environ. Health 3, pp. 797-809).
Analysis of variance (ANOVA): Checks for normal distribution of data by comparing the median and mean. The groups are compared at a confidence level of (1-a) = 95% (p = 0.05). The test for the between-group homogeneity of the variance employed Box's test if more than 2 study groups are compared with each other. If the above F-test shows a difference then a pair-wise post-hoc comparison is conducted (1- and 2-sided) using the Games and Howell modification of the Tukey-Kramer significance test.

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LC50

Effect level:

> 230.1 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

6 h

Mortality:

Substance-induced mortality did not occur at any exposure level.

Clinical signs:

other: All rats tolerated the exposure without effects considered to be test substance-induced.

Body weight:

Concentration-dependent effects on body weight were not observed.

Gross pathology:

No evidence of specific lung injury. Minor unspecific morphological changes in the lung at 230.1 mg/m³.

Other findings:

Biokinetics for metal tracer was determined in the lung. At the concentration of 230.1 mg/m³ and 10 mg'/m³ the amounts of silicon, vanadium and chromium were increased. The concentrations decreased over time, suggesting that these trace metals were pregressively eliminated from the lung. The elimination half-lives are comparable to clearance kinetics via alveolar marcophages known for inorganic dust having low solubility. There can be found no translocation to liver and kidneys.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

no classification required

Executive summary:

Overall, data suggests that there is no likely acute inhalation hazard due to GGBS. There were no deaths or clinical signs. No evidence of lung injury was seen. Minor reversible changes noted in BAL fluid indicative of macrophage-mediated particle clearance, increased organ weights of lung / in lung-associated lymph nodes and minor unspecific landings in lungs reflect the time-dependent physiological response of the body to inhaled mineral particulates of low solubility.