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EC number: 931-219-8 | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Carcinogenicity
Administrative data
Description of key information
a long term carcinogenticty test carried out for AES fibres, no evidence of increased cancerous incidents occurred and as such the fibre is not considered carcinogenic. The results from the existing 90 day and 2 year inhalation studies for Alkaline Earth Silicate fibres linked to the short term bio-persistence study with the Potassium Alumino Silicate fibres provide reliable evidence as to the lack of toxic potential for Potassium Alumino Silicate fibres. This is supported by the lack of effect on the lungs of the rats used in the biopersistence studies. With this background we do not believe that further animal testing can be justified.
Key value for chemical safety assessment
Carcinogenicity: via inhalation route
Link to relevant study records
- Endpoint:
- carcinogenicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 24th May 1988 to 14th November 1990
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- GLP Compliant, no justifcataion for the dose used, which was assumed to be the MTD. read across study from AES fibres,the results from these existing 90 day and 2 year inhalation studies for Alkaline Earth Silicate fibres linked to the short term bio-persistence study with the Potassium Alumino Silicate fibres provide reliable evidence as to the lack of toxic potential for Potassium Alumino Silicate fibres. This is supported by the lack of effect on the lungs of the rats used in the biopersistence studies. With this background we do not believe that further animal testing can be justified.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 451 (Carcinogenicity Studies)
- Deviations:
- yes
- Principles of method if other than guideline:
- lifetime inhalation with serial sacrifice for inflammatory and fibrotic effects in lung
- GLP compliance:
- yes (incl. QA statement)
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Kingston, Stone Ridge, N.Y., USA
- Age at study initiation: 8 weeks
- Weight at study initiation: 130-150g
- Housing: during exposure and beginning of recovered, stainless steel wire cages, during major part of recovery period Macrolon Cages Type IV with standard softwood bedding
- Diet (e.g. ad libitum): pelleted standard Kliba 343, rat/mouse maintenance diet
- Water: ad libitum
- Acclimation period: 18 days from day of delivery
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12hrs
IN-LIFE DATES: From: 24th May 1988 To: 14th November 1990 - Route of administration:
- inhalation: aerosol
- Type of inhalation exposure (if applicable):
- nose only
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: flow -past nose-only design
- Method of holding animals in test chamber: makrolon tubes
- System of generating particulates/aerosols: fibres were aerosolised using a stepping motor and stainless steel brush to bring them into the tangential air stream, following aerosolisation the fibres passed through a Nickel63 charge neutraliser to reduce electrostatic charge
- Temperature, humidity, pressure in air chamber: 22degC, 30-70%
- Air flow rate: 0.9 litre/ airport/min
- Method of particle size determination: fibre size measurements carried out by SEM
TEST ATMOSPHERE
- Brief description of analytical method used: mass concentration (gravimetric), fibre number concentration, fibre size measurements and impactor sampling.
- Samples taken from breathing zone: yes - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- samples of the aerosol were collected on membrane filters , these were weighed for gravimetric analysis and fibres counted by SEM
- Duration of treatment / exposure:
- 104 week
- Frequency of treatment:
- 6hrs/day, 5days/week
- Post exposure period:
- 91 to 26 weeks depending on length of exposure see table 1 below for more details.
- Remarks:
- Doses / Concentrations:
29.93 mg/m3 ± 5.87
Basis:
analytical conc. - Remarks:
- Doses / Concentrations:
174 WHO f/ml ±72
Basis:
analytical conc. - Remarks:
- Doses / Concentrations:
47 fibres >20µm/ml ±23
Basis:
analytical conc. - No. of animals per sex per dose:
- 140
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- - Dose selection rationale: 30mg/m3 had been found to be the maximum tolerated dose for another fibre in a 56 day study, it was assumed that this dose was the MTD for all man-made fibres.
- Positive control:
- NIEHS Intermediate Length Chrysotile Asbestos - Plastibest-20
Dose: 10mg/m3 ± 3, WHO Fibres 10,600 f/ml ± 11,400 - Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily, prior and following exposure and once daily on non-exposure days
BODY WEIGHT: Yes
- Time schedule for examinations: Each animal was weighed once during the acclimation period, weekly during the first 13 weeks of exposure and at least monthly thereafter - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table in "any other information on materials and methods incl. tables")
HISTOPATHOLOGY: Yes (on all necropsied animals) - Other examinations:
- neoplastic tissues were sampled and sent frozen in liquid nitrogen to CIIT North Carolina 27709.
Special procedure for Lungs, examined under dissection microscope for detection and identification of small macroscopic lesions
lungs were inflated with formaldehyde photographed and sections taken for histopathology.
After sacrifices at 13, 26, 39 and 52 weeks lungs were instilled with Karnowski's fixative and sampled - Statistics:
- Body weight and organ weight were analysed using Dunnett test, age specific survival rates were calculated with Kaplan-Meier non-parametric estimates, statistical evaluations for the neoplastic lesion was performed according to Peto et al..
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY clinical signs were comparable in all groups including air controls in their nature, incidence, time of onset, severity and duration. Therefore they were considered not to be directly related to fibre exposure. The Kaplan Meier survivor function showed no intergroup difference reaching a statistical level of significance of 0.05, it was however shown that there was a marginally delayed mortality in the x607 exposure group during the second year of exposure and the initial part of the recovery period. This difference was considered to lie within the limits of normal biological variations and was assumed not to be treatment related. However it is not excluded that this may have a marginal influence on the incidence and/or intensity of some pathological changes.
BODY WEIGHT AND WEIGHT GAIN during the first year of exposure the mean body weight was minimally lower than the control group whereas body weight gain was marginally higher. during the second exposure year mean values were statistically higher than that of the controls, with the maximum mean body weight reached during the study being 2-3% higher than the control group and occurred approximately 10 weeks later. these differences are believed to essentially reflect the slightly delayed mortality of the x607 exposure group
ORGAN WEIGHTS lung and lung accessory lobe weights.
In the x607 group there was no relevant difference observed from the control group at any sacrifice time point, however in the positive control group (chrysotile exposed) the mean lung weight and the mean lung to body weight ratio were moderately to markedly higher than the controls at the same sacrifice time point, there was a trend to increasing difference from control values as the study progressed at least until the end of exposure.
HISTOPATHOLOGY: NON-NEOPLASTIC only cellular changes were seen in the rat lungs and these are typical of physiological response to inhaled dust, no fibrosis was seen and all effects regressed when exposure terminated, the maximum Wagner score did not exceed 2 see table 3
HISTOPATHOLOGY: NEOPLASTIC the tumours seen consisted of one adenoma and one adenocarcinoma, these are felt to be background for this strain of animal, see table 5 - Relevance of carcinogenic effects / potential:
- no carcinogenic effects were observed during this two year inhalation study
- Dose descriptor:
- NOAEC
- Effect level:
- > 174 other: WHO f./ml
- Based on:
- test mat.
- Sex:
- male
- Remarks on result:
- not determinable
- Remarks:
- no NOAEC identified. Effect type:carcinogenicity (migrated information)
- Conclusions:
- X607 was neither fibrogenic nor tumorigenic and induced only minimal lung cellularity that reversed after exposure was terminated.
- Executive summary:
Since X607 is an AES fibre this is key evidence for the importance of low bio-persistance and relates to the read across case in section 7.5.2 for using read across for the 90 day sub chronic inhalation study.
Reference
Table 1: Fibre Concentrations and Dimensions
Concentration (mg/m3) |
Fibres (/ml) |
nonfibrous Particles/ml <3µm |
Dimensions (µm)b |
||||||||
Fibre |
Target |
Actual |
WHOa |
>20 µm Length |
Length |
Diameter |
|||||
A. Aerosol Averages of exposure period |
|||||||||||
Chronic Study, 2 years |
|||||||||||
x607 |
30 |
30 ± 6 |
174 ± 72 |
47 ± 23 |
117 ± 77 |
11 ± 4 |
0.9 ± 0.3 |
||||
RCF1 |
30 |
29 ± 6 |
187 ± 53 |
101 ± 15 |
307 ± 99 |
16 ± 3 |
0.8 ± 0.2 |
||||
Chrysotile |
10 |
10 ± 3 |
10,600 ± 11,400 |
0 |
0 |
1.2 ± 0.3 |
0.08 ± 0.01 |
||||
Deposition Study 6 h |
|||||||||||
x607 |
60 |
57 |
247 ± 7 |
46 ± 4 |
182 |
8 ± 2 |
0.9 ± 2 |
||||
RCF1 |
60 |
60 |
237 ± 7 |
69 ± 5 |
283 |
11 ± 3 |
1.0 ± 2 |
||||
B. Lung Burden following termination of exposure |
|||||||||||
Dimensions(µm)b |
Fibres (x103)c |
||||||||||
Fibre |
Length |
Diameter |
WHOa |
>20 µM |
|||||||
Chronic Study, 2 years |
|||||||||||
x607 |
6 ± 0.4 |
0.5 ± 0.02 |
187 ± 31 |
4 ± 4 |
|||||||
RCF1 |
8 ± 0.7 |
0.5 ± 0.05 |
275 ± 63 |
48 ± 10 |
|||||||
Chrysotile |
1.6 ± 0.2 |
0.07 ± 0.00 |
2800 ± 800 |
0 |
|||||||
Deposition Study 6 h |
|||||||||||
x607 |
7 ± 1.7 |
0.6 ± 1.6 |
24 ± 3 |
2.4 ± 0.3 |
|||||||
RCF1 |
8 ± 0.9 |
0.6 ± 1.8 |
9 ± 1 |
2.0 ± 0.3 |
|||||||
aWho Fibres are respirable fibres as defined by the World Health Organisation as being 5µmin length and >3µmin diameter and having a length/diameter ration >3.
bDimensions are the geometric mean of all (total) fibres±the geometric SD
cValues are means±SD per dry lung weight (n=6-10 animals) at termination of exposure
Table 2: Lung Burden after Exposure and after Exposure Plus Recovery
Exposure/recovery Weeks |
WHO (fibres/lungs) |
Fibres (>20 µm /lung) |
||||
Exposure (x106)a |
Recovery (x106)b |
Percent retained after recovery |
Exposure (x106)a |
Recovery (x106)b |
Percent retained after recovery |
|
X607 |
||||||
13/91 |
nd |
0.2 ± 0.1 |
nd |
nd |
0 |
0 |
26/78 |
nd |
0.7 ± 0.1 |
nd |
nd |
0 |
0 |
52/52 |
62 ± 6 |
2.0 ± 0.2 |
3 ± 0.3 |
1 ± 0.2 |
0.03 ± 0.03 |
6 ± 6 |
78/26 |
81 ± 4 |
13.3 ± 2 |
16 ± 2 |
2 ± 1.9 |
0 |
0 |
104/23 |
58 ± 6 |
15.0 ± 4 |
26 ± 7 |
1 ± 0.5 |
0.10 ± 0.03 |
8 ± 2 |
RCF1c |
||||||
13/91 |
39 ± 4 |
5.8 ± 2 |
15 ± 6 |
3 ± 0.6 |
0.16 ± 0.04 |
5 ± 1 |
26/78 |
56 ± 6 |
7.6 ± 3 |
14 ± 6 |
6 ± 1.0 |
0.32 ± 0.16 |
5 ± 3 |
52/52 |
119 ± 19 |
21.0 ± c |
18d |
20 ± 2.4 |
1.66 ± 0.00 |
8 ± 0 |
78/26 |
173 ± 51 |
87.7 ± 20 |
51 ± 11 |
21 ± 2.7 |
6.89 ± 2.54 |
33 ± 12 |
104/23 |
143 ± 10 |
61.0 ± 5 |
43 ± 4 |
25 ± 3.0 |
6.73 ± 1.20 |
27 ± 5 |
Chrysotilec |
||||||
13/0 |
250 ± 40 |
nd |
nd |
nd |
nd |
|
26/0 |
180 ± 83 |
nd |
nd |
nd |
nd |
|
52/0 |
1020 ± 178 |
nd |
nd |
nd |
nd |
|
78/0 |
853 ± 228 |
nd |
nd |
nd |
nd |
|
104/23 |
1600 ± 458 |
216 ± 60 |
14 ± 4 |
0 |
0 |
0 |
Note: nd, not done, no data. X607 lung samples were stored in liquid fixative causing lung fibres to degrade.
aLung burdens for those animals euthanize within 24h of cessation of exposure
bLung burdens for animals that were exposed and then held in recovery for the number of weeks indicated in the column Exposure/recovery
cMast et all (1995)
donly one animal in the 52/52 exposure/recovery week RCF1 recovery group survived. Data for all other time points are averages of three to six animals ± SD
Table 3: Pulmonary Change: Mean Wagner Scorea
Exposure/Recovery (weeks) |
Air control (exposure only) |
X607 |
RCF1b |
Chrysotileb |
|||
Exposure |
Recovery |
Exposure |
Recovery |
Exposure |
Recovery |
||
13/91 |
1.3 |
2.0 |
1.3 |
3.5 |
3.0 |
4.0 |
nd |
26/78 |
1.0 |
2.0 |
1.0 |
4.0 |
4.0 |
4.0 |
nd |
39/65 |
1.0 |
2.3 |
1.0 |
4.0 |
4.0 |
4.0 |
nd |
52/52 |
1.0 |
3.0 |
2.5 |
4.0 |
4.0c |
4.0 |
nd |
65/nd |
1.0 |
3.0 |
nd |
4.0 |
nd |
nd |
nd |
78/26 |
1.0 |
3.0 |
2.0 |
4.3 |
4.0 |
4.0 |
nd |
104/23 |
1.0 |
2.8 |
2.7 |
4.0 |
4.5 |
4.0 |
4.0 |
Note: For exposure animals, n=3-6; for 104 ± 23 week time point, n=>10; for interim recovery groups; n=2-4 due to decreasing survivals. Nd, not done,
aScores according to Wagner, 1983. Scale 1, no lesion; 2, macrophage aggregation; 3, cellularity; 4 fibrosis (irreversible); 5, linking fibrosis
bMast et all (1995)
cScore of one surviving animal.
Table 4: Inflammation and Collagen Deposition in the Lung and Pleura during the Chronic Inhalation Study
Fibre |
Exposure/Recovery (weeks) |
Alveolar macrophage aggregationa |
Alveolar bronchiolizationa |
Microgranulationa |
Bronchioalveolar collagena |
Pleural collagena |
|||||
Exposure |
(+) Recovery |
Expos |
(+) Recov |
Expos |
(+) Recov |
Expos |
(+) Recov |
Expos |
(+) Recov |
||
X607 |
13/91 |
1.0 |
1.3 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
26/78 |
1.3 |
0.3 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
|
39/65 |
2.0 |
1.0 |
0.3 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
|
52/52 |
2.0 |
1.5 |
1.2 |
0.5 |
0.0 |
0.5 |
0.0 |
0.0 |
0.0 |
0.0 |
|
78/26 |
2.3 |
2.0 |
2.0 |
0.0 |
2.0 |
0.5 |
0.0 |
0.0 |
0.0 |
0.0 |
|
104/23 |
2.1 |
2.1 |
1.0 |
0.8 |
1.2 |
1.5 |
0.0 |
0.0 |
0.0 |
0.0 |
|
RCF1 |
13/91 |
2.0 |
0.5 |
1.0 |
0.5 |
2.0 |
0.0 |
0.7 |
0.5 |
0.0 |
0.0 |
26/78 |
2.7 |
2.0 |
2.0 |
1.3 |
2.0 |
1.0 |
1.7 |
1.3 |
0.0 |
0.7 |
|
39/65 |
3.0 |
2.0 |
2.7 |
1.0 |
2.7 |
2.0 |
2.7 |
2.0 |
1.0 |
0.5 |
|
52/52 |
3.0 |
2.0 |
2.3 |
2.0 |
2.5 |
2.0 |
2.2 |
2.0 |
1.5 |
1.0 |
|
78/26 |
3.0 |
2.5 |
2.7 |
1.8 |
2.3 |
2.0 |
2.3 |
2.3 |
1.0 |
0.5 |
|
104/23 |
3.0 |
2.9 |
2.0 |
2.9 |
2.0 |
1.9 |
2.3 |
2.4 |
0.5 |
1.3 |
|
Chrysotile Asbestos |
13/91 |
2.0 |
-b |
1.7 |
2.0 |
1.0 |
0.0 |
||||
26/78 |
2.0 |
2.0 |
2.0 |
2.0 |
0.0 |
||||||
39/65 |
2.0 |
2.0 |
2.0 |
2.3 |
1.0 |
||||||
52/52 |
2.0 |
2.0 |
2.3 |
2.2 |
0.2 |
||||||
78/26 |
2.0 |
2.0 |
2.0 |
2.3 |
0.0 |
||||||
104/23 |
2.7 |
2.5 |
2.7 |
2.4 |
2.0 |
1.9 |
2.7 |
2.7 |
0.0 |
0.0 |
Note: Level of severity of lesions observed at time points during 2 year exposure period and 6 month recovery period was graded as follows: Grade 0, normal; 1, minimal; 2, mild; 3, moderate; 4, marked; 5, massive. Each grade is a mean of 3-10 animals. Boldface values are scores of 2 or higher
aExpos. Indicates animals had exposure but not recovery time: recov. Indicates animals had exposure + recovery
bRecovery data for chrysotile pathology was determined for 12 month exposure/6 month recovery only
Table 5: Pulmonary and Mesothelial Proliferative Lesions during the Chronic Inhalation Study
Exposure |
nb |
Hyperplasia (bronchioalveolar)a |
Lung Cancera |
Mesothelioma (pleural)a |
||
Adenoma |
Carcinoma |
Total lung cancers |
||||
Air |
130 |
5 (3.8) |
2 (1.5) |
0 |
2 (1.5) |
0 |
x607 |
121 |
6 (4.9) |
1 (0.8) |
1 (0.8) |
3 (1.6) |
0 |
RCF1c |
118 |
17 (14.0) |
8 (6.6) |
7 (5.6) |
15 (12.4) |
2 (1.7) |
Chrysotilec |
69 |
13 (18.8) |
6 (8.7) |
6 (8.7) |
12 (17.4) |
1 (1.4) |
Note: Values in boldface are significantly different from air controls
aValues are the total number of X. Values in parentheses are percentages
bNumber of animals at risk for tumour formation (at risk defined as surviving until at least the 12 month time point, after first tumour appeared)
cMast et al (1995b)
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
Justification for classification or non-classification
no evidence of carcinogenicity by read across in conjunction with low bio-persistence testing according to note Q criteria.
Additional information
read across from 2 year inhalation study carried out on AES Fibres. The 2 year inhalation studies for Alkaline Earth Silicate fibres linked to the short term bio-persistence study with the Potassium Alumino Silicate fibres provide reliable evidence as to the lack of toxic potential for Potassium Alumino Silicate fibres. This is supported by the lack of effect on the lungs of the rats used in the biopersistence studies. With this background we do not believe that further animal testing can be justified.
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