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EC number: 216-653-1 | CAS number: 1634-04-4
- 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
Immunotoxicity
Administrative data
- Endpoint:
- immunotoxicity: short-term inhalation
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Well reported study conducted under GLP and in compliance with relevant US EPA test guideline. Although study conclusions are clear, questionable relevance to toxicity assessment of MTBE makes Klimisch 2 appropriate.
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- publication
- Title:
- Health assessment of gasoline and fuel oxygenate vapors: Immunotoxicity evaluation
- Author:
- White Jr., K L et al
- Year:
- 2 014
- Bibliographic source:
- Regulatory Toxicology and Pharmacology 70 (2014) S43–S47
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.7800
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Basline gasoline vapour condensate (BGVC)
- IUPAC Name:
- Basline gasoline vapour condensate (BGVC)
- Reference substance name:
- Gasoline + MTBE vapour condensate (G/MTBE)
- IUPAC Name:
- Gasoline + MTBE vapour condensate (G/MTBE)
- Reference substance name:
- Gasoline + other oxygenates also investigated: not further described here
- IUPAC Name:
- Gasoline + other oxygenates also investigated: not further described here
- Test material form:
- other: vapours collected as condensates
- Details on test material:
- BGVC = vapour condensate collected from baseline gasoline (reformulated gasoline Summer baseline fuel meeting CAA section 211(k)(10)(B)(i) specification (40 CFR 79.55)).
G/MTBE = vapour condensate collected from baseline gasoline with MTBE added to create 2.7 wt% O2 content (corresponding to 14.9 vol% MTBE)
Constituent 1
Constituent 2
Constituent 3
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- Animals used in this investigation were satellite groups taken (after 4 weeks of exposure) from the subchronic inhalation toxicity study of Clark et al, Health assessment of gasoline and fuel oxygenate vapors: Subchronic inhalation toxicity. Regulatory Toxicology and Pharmacology 70 (2014) S18–S28 (paper summarised at section 7.5.2 of this dossier).
Administration / exposure
- Route of administration:
- inhalation: vapour
- Vehicle:
- other: air + nitrogen
- Details on exposure:
- Nitrogen was applied to the supplied containers of BGVC and G/MTBE vapour condensates to generate stable exposure concentrations of the test vapours (using a 3-way split flow to give test substance pressurisation, purge flow and vapourisation via a volatilisation chamber).
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Chamber concentrations were monitored:
- gravimetrically by measurement of chamber airflow and vapour condensate consumption
- during each exposure (4 times) by IR spectrophotometry of breathing zone samples
- by weekly GC analysis of charcoal tube collected control and test samples for determination of major components (at least 18) comprising 80 wt% or more of the tested vapour condensates
- by weekly particle size sampling and measurement to identify any aerosol present. - Duration of treatment / exposure:
- 6h/day, 5 days/week for 4 weeks (giving 20 exposures in total)
- Frequency of treatment:
- Daily as specified
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0 mg/cu.m vapour condensate (air control)
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
2050, 10148, 20234 mg/cum BGVC
Basis:
analytical conc.
Nominals 2000, 10000, 20000 mg/cu.m
- Remarks:
- Doses / Concentrations:
2029, 10099, 20242 mg/cu.m G/MTBE
Basis:
analytical conc.
Nominals 2000, 10000, 20000 mg/cu.m
- No. of animals per sex per dose:
- 10 females/group
- Control animals:
- yes, sham-exposed
- Details on study design:
- Nitrogen was applied to the supplied containers of BGVC and G/MTBE vapour condensates to generate stable exposure concentrations of the test vapours (using a 3-way split flow to give test substance pressurisation, purge flow and vapourisation via a volatilisation chamber).
Chamber concentrations were monitored:
- gravimetrically by measurement of chamber airflow and vapour condensate consumption
- during each exposure (4 times) by IR spectrophotometry of breathing zone samples
- by weekly GC analysis of charcoal tube collected control and test sample for determination of major components of the tested vapour condensates
- by weekly particle size sampling and measurement to identify any aerosol present.
Examinations
- Observations and clinical examinations performed and frequency:
- Observations related to immunotoxicology investigations only are detailed in the published paper.
- Sacrifice and pathology:
- Blood samples were taken for serum collection at termination (by CO2 inhalation). Thymuses were excised, weighed and preserved in addition to spleen collection.
4 days prior to termination, rats were given iv injections of sheep red blood cells (sRBC: 2 x 10E+08) for antigen sensitisation. Termination (1 day after last exposure) was followed by removal and weighing of spleens. These were then placed in balanced salt solution (EBSS with HEPES and gentamicin) and kept on ice for further processing. Single-cell (splenocyte) preparations were prepared using a laboratory blender, resuspended in balanced salts solution as before and diluted to the required cell densities. - Cell viabilities:
- Splenocyte viability was determined using propidium iodide and a flow cytometer.
- Humoral immunity examinations:
- Primary IgM response to sRBC was measured by the plaque assay (IgM antibody-forming cell response to the T-dependent antigen sheep erythrocytes) using the Jerne technique.
Spleen cell suspension (0.1 ml) was added to Guinea pig complement + sRBc (each 25 microlitres) in 0.5 ml warm agar, plated and incubated (36-38C, 3h). Plaques were counted, taking counts from tested dilutions giving 100-300 plaques/plate. Splenocyte counts , cells/spleen and Antibody-Forming Cells/10E+06 spleen cells were determined. Since each observed plaque is generated from a single IgM antibody-producing B cell, AFC/spleen can be calculated. Resultant data were expressed as specific activity (AFC/10E+06 spleen cells) and total
spleen activity (AFC/spleen); following US NTP immunotoxicology assay practice, the plaque-forming assay results were not adjusted for spleen cell viability. - Specific cell-mediated immunity:
- Not directly evaluated
- Non-specific cell-mediated immunity:
- Not directly evaluated
- Positive control:
- Rats of the positive control group were injected intraperitoneally with cyclophosphamide (50 mg/kg) daily for 4 days prior to termination.
- Statistics:
- Data were tested for homogeneity of variance (Bartlett’s Chi Square Test), then homogeneous data were analysed by parametric 1-way ANOVAR). When significant differences were seen, test groups were compared to air controls using Dunnett’s t Test. Nonhomogeneous data were evaluated using non-parametric ANOVAR. When significant differences were seen, test groups and controls were compared using the Gehan-Wilcoxon Test. Jonckheere’s Test was used to test for exposure-related trends across control and test groups. Positive controls were compared to the air control group using Student’s t Test (evidence of decreased immune response, p<0.05 being required for study validity).
Results and discussion
Results of examinations
- Clinical signs:
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- terminal bodyweights unaffected by treatment
- 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
- Gross pathological findings:
- not specified
- Details on results:
- Results of the plaque assays revealed no effect of inhalation exposure to BGVC or G/MTBE on IgM antibody-forming cell response .
Specific immunotoxic examinations
- Cell viabilities:
- not specified
- Humoral immunity examinations:
- no effects observed
- Description (incidence and severity):
- IgM antibody-forming cell responses did not differ between rats exposed to BGVC or G/MTBE and the air controls, whether evaluated as specific (AFC/10E+06 spleen cells) or as total spleen activity (AFC/spleen). No treatment-related trend was seen.
- Specific cell-mediated immunity:
- not examined
- Non-specific cell-mediated immunity:
- not examined
- Other functional activity assays:
- not examined
- Other findings:
- no effects observed
- Description (incidence and severity):
- Terminal spleen and thymus weights unaffected, except in positive control group
Any other information on results incl. tables
Plaque assay (IgM AFC response to T-dependent sheep erythrocyte antigen) and body/organ weight results
|
BGVC (mg/cu.m) |
G/MTBE (mg/cu.m) |
||||||||
|
0 (Air control) |
2000 |
10000 |
20000 |
CP pos control |
0 (Air control) |
2000 |
10000 |
20000 |
CP pos control |
Body weight (g) |
247.8 |
258 |
250 |
245.7 |
224.4* |
248.3 |
265.9 |
242.5 |
254.8 |
231.3 |
Spleen weight (mg) |
615 |
647 |
600 |
675 |
265* |
646 |
637 |
574 |
651 |
283* |
Spleen cells (x10E+07) |
53.18 |
62.26 |
55.82 |
57.96 |
9.69* |
72.09 |
76.52 |
65.13 |
76.28 |
10.65* |
IgM AFC (1) |
1639 |
1540 |
1687 |
1175 |
3* |
1646 |
1128 |
1490 |
1680 |
0* |
IgM AFC (2) |
880 |
980 |
903 |
685 (3) |
0* |
1162 |
887 |
966 |
1245 |
0* |
(1) IgM antibody-forming cell response/10E+06 spleen cells
(2) IgM antibody-forming cell response/spleen x10E+03
(3) Group mean excludes a single, rejected value (outlier)
CP pos control = cyclophosphamide positive control group (dose 50 mg/kg/day for last 4 days)
* significantly different from air control, p<0.01
Applicant's summary and conclusion
- Conclusions:
- In this study, subacute inhalation exposure of female rats to BGVC or G/MTBE vapour condensates did not significantly change their humoral immune response, as determined by the plaque assay (IgM antibody-forming cell response to T-dependent antigen sheep erythrocytes). Spleen weight, spleen cell number and IgM antibody production (expressed in terms of specific activity or total spleen activity) were unaffected by these exposures, at concentrations up to 50% of the lower explosion limits of the test materials. Also, the presence of MTBE in G/MTBE did not significantly alter the measured humoral immune response to the baseline gasoline vapour condensate (BGVC) alone.
- Executive summary:
Exposure of female rats to BGVC or G/MTBE vapour condensates (6 h/day, 5 days/ week over 4 weeks) did not alter humoral immune response as determined by IgM antibody-forming cell response to T-dependent antigen sheep erythrocytes. Spleen weight, spleen cell number and IgM antibody production (expressed in terms of specific activity or total spleen activity) were unaffected. Inclusion of the MTBE in G/MTBE did not significantly alter the measured humoral immune response to the baseline gasoline vapour condensate (BGVC) alone.
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