Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 242-440-8 | CAS number: 18599-22-9
- 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
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Remarks:
- Two-week Inhalation Toxicity Study
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- December 4 2001 - December 10 2001
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Remarks:
- Study is well documented, but was not conducted according to national or international guidelines, and has a non-standard duration.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 003
- Report date:
- 2003
Materials and methods
- Principles of method if other than guideline:
- - Principle of test: The purpose of this study was to assess the potential subchronic toxicity of exposure to the test item
- Short description of test conditions: Young adult male rats (10 rats/exposure concentration) were exposed to atmospheres containing 0 or 1000 ppm of the test item for 6 hours per day, over a 2-week period for a total of 9 exposures.
- Parameters analysed / observed: Body weight was determined daily, and food consumption was determined weekly. Clinical signs of toxicity were monitored throughout the study. Blood and urine samples were collected at the end of the exposure period from 10 rats/concentration for evaluation of clinical pathology and urinalysis parameters. Additional blood samples were collected from each rat for determination of thyroid hormone concentrations. After the last exposure, 5 rats/concentration for each of the 3 test substances underwent gross necropsy. Selected tissues were processed for histopathology and examined. In addition, a liver sample was collected from each rat for determination of hepatic β-oxidation activity. After an approximate 2-week recovery period, blood and urine samples were collected from all surviving rats for evaluation of clinical pathlology and urinalysis parameters. All surviving rats underwent gross necropsy, and selected tissues were processed for histopathology and examined. - GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- 4-bromo-3,3,4,4-tetrafluorobut-1-ene
- EC Number:
- 242-440-8
- EC Name:
- 4-bromo-3,3,4,4-tetrafluorobut-1-ene
- Cas Number:
- 18599-22-9
- Molecular formula:
- C4H3BrF4
- IUPAC Name:
- 4-bromo-3,3,4,4-tetrafluorobut-1-ene
- Test material form:
- liquid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Crl:CD®(IGS)BR
- Details on species / strain selection:
- Rats have historically been used in safety evaluation studies for inhalation toxicity testing. The Crl:CD®(SD)IGS BR rat was selected based on consistently acceptable health status and on extensive experience with the strain at the testing laboratory.
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Inc. Raleigh, North Carolina.
- Females (if applicable) nulliparous and non-pregnant: N/A
- Age at study initiation: approximately 9 weeks old
- Weight at study initiation: 273 - 326 grams
- Fasting period before study:
- Housing: Rats were housed singly in stainless steel, wire-mesh cages suspended above cage boards.
- Diet (e.g. ad libitum): PMI Nutrition International, Inc. Certified Rodent LabDiet® 5002 was available ad libitum except during exposure and fasting periods prior to necropsy.
- Water (e.g. ad libitum): tap water was available ad libitum
- Acclimation period: 6 day quarantine
DETAILS OF FOOD AND WATER QUALITY:
Water samples were analyzed for total bacterial counts, and the presence of coliforms, lead, and other contaminants.
Feed samples were analyzed for total bacterial, spore, and fungal counts. The attending laboratory technician confirmed no conditions were present that affected the validity of the study.
Certified animal feed is guaranteed by the manufacturer to meet specified nutritional requirements and not to exceed stated maximum concentrations of key contaminants, including specified heavy metals, aflatoxin, chlorinated hydrocarbons, and organophosphates. The presence of these contaminants below the maximum concentration stated by the manufacturer would not be expected to impact the integrity of the study.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 1˚C
- Humidity (%): 50 ± 10%
- Air changes (per hr): Not provided.
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 10 December 2001 To: 04 January 2002
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: Air, and Nitrogen to sweep the vapor
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: All exposure chambers were constructed of stainless steel and glass (NYU style) with a nominal internal volume of 150 L, chosen so that the total body volume of the test animals did not exceed 5% of the chamber volume.
- Method of holding animals in test chamber: wire mesh cages
- Source and rate of air: Houseline air system, not rate provided
- Method of conditioning air: Not provided.
- System of generating vapor: heated glass flask with a Harvard Apparatus Model 22 Compact Infusion Pump
- Temperature, humidity, pressure in air chamber: 23 ± 2°C, relative humidity 50 ± 10%,
- Air flow rate: Not provided as separate value to air change rate.
- Air change rate: at least 12 air changes per hour
- Method of particle size determination: N/A
- Treatment of exhaust air: exhausted through a dry-ice cold trap, followed by an MSA charcoal/HEPA filter cartridge prior to discharge into the fume hood.
TEST ATMOSPHERE
- Brief description of analytical method used: The atmospheric concentration was determined at approximately 30-minute intervals by gas chromatography.
- Samples taken from breathing zone: yes, via sampling port.
VEHICLE (if applicable) - N/A - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Atmospheric concentration of the test substances was determined from a standard curve derived from gas standards. Standards were prepared prior to the first and sixth exposures, and were refrigerated during the remainder of the exposure days. Standards were prepared by injecting known volumes of test item liquid into bags that contained known volumes of air. Distribution of the test item in the test chambers was determined prior to initiation of the first exposure, and was found to be homogenous.
- Duration of treatment / exposure:
- 14 days
- Frequency of treatment:
- 9 exposures over 14 days
Doses / concentrationsopen allclose all
- Dose / conc.:
- 1 000 ppm
- Dose / conc.:
- 0 ppm
- No. of animals per sex per dose:
- 10 rats/exposure concentration
- Control animals:
- yes, sham-exposed
- Positive control:
- No
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Not specified
- Time schedule: N/A
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: before and after each exposure, with group clinical observations made during exposures.
BODY WEIGHT: Yes
- Time schedule for examinations: daily
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not specified
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Not specified
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified
HAEMATOLOGY: Yes
- Time schedule for collection of blood: 11 days after initiation of study
- Anaesthetic used for blood collection: light carbon dioxide anesthesia
- Animals fasted: Yes - overnight prior to collection
- How many animals: all animals in study
- Parameters checked in table [No.1] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: 11 days after initiation of study
- Animals fasted: Yes - overnight prior to collection
- How many animals: all animals in study
- Parameters checked in table [No.2] were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: 11 days after initiation of study
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters checked in table [No.3] were examined.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: prior to exposure, 3 times during each exposure, and after each exposure
- Dose groups that were examined: all animals in study
- Battery of functions tested: rats were checked for an alerting response to an auditory stimulus
IMMUNOLOGY: No
BRONCHOALVEOLAR LAVAGE FLUID (BALF): No
LUNG BURDEN: No
OTHER: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (see table 4 & 5) - Other examinations:
- THYROID FUNCTION: Blood was collected from all animals following the last exposure. Serum was prepared and stored between -65 and -85°C until analyzed for thyroid hormone concentrations. Serum thyroxine (T4), triiodothyronine (T3), and thyroid stimulating hormone (TSH) concentrations were measured using commercially available radioimmunoassay (RIA) kits.
β-OXIDATION ACTIVITY: The first 5 rats from each group had their livers removed, weighed, and then a portion was homogenized (1 gram tissue/4 mL buffer) in homogenization buffer (50 mM Tris-HCl, 50 mM Trizma-base, 0.25 M sucrose, and 5.4 mM EDTA, pH 7.4). Hepatic peroxisomes were prepared using differential centrifugation. The resulting peroxisomal pellets were resuspended in the homogenization buffer, aliquoted, and stored between -65 and -85˚C until analyzed for peroxisomal β-oxidation activity. The peroxisomal suspensions were diluted to a protein concentration of approximately 0.5 mg/mL. Peroxisomal β-oxidation activity was determined using [14C]palmitoyl CoA as the substrate. The protein content of the peroxisomes was determined before and after analysis by the Biorad method. Final rate calculations were made using the post-assay protein concentrations.
RECOVERY CLINICAL PATHOLOGY:
Due to the presence of systemic toxicity, and alterations in clinical pathology parameters at the end of dosing, complete clinical pathology evaluations, excluding plasma fluoride, were performed at the end of the recovery period (test day 25). Blood was collected for plasma fluoride, but was not evaluated. - Statistics:
- Significance was judged at p < 0.05. Statistical parameters are described in table 7.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- There were no test substance-related effects for body weight or weight gain in males exposed to 1000 ppm. Males exposed to 1000 ppm of had significantly higher body weight gain during test days 4-7, and over the interval of test days 0-11. Since there were no adverse, test substance-related effects on organ weight or on the clinical condition of the animal, the higher weight gain for rats exposed to 1000 ppm was considered to be spurious. (Table 7)
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Description (incidence and severity):
- Males exposed to 1000 ppm had significantly higher food efficiency during test days 0-7 due to the significantly higher body weight gain during this interval. Since there were no adverse, test substance-related effects on organ weight or on the clinical condition of the animals, the higher weight gain and food efficiency for rats exposed to 1000 ppm were considered to be spurious. (Table 8)
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Rats exposed to 1000 ppm had minimally increased reticulocytes (group mean was 126% of control group mean) at test day 11. This change indicates a minimal increase in red cell turnover; however there was no effect on red cell mass parameters, so the changes were considered non-adverse. At test day 25 (after 14 days of recovery), reticulocytes in rats previously exposed to H-25111 were similar to control group values. Rats exposed to 1000 ppm had no other significant changes in hematology or coagulation. (Tables 9 & 10)
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- (Table 11)
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- There were no compound-related organ weight effects at either sacrifice in animals exposed to the test item
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Gross observations noted were sporadic across groups and were not test substance-related.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- There were no compound-related microscopic observations for the test item
Effect levels
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- > 1 000 ppm
- Based on:
- test mat.
- Sex:
- male
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Any other information on results incl. tables
- a Hepatic β-oxidation analyses were not performed on this animal.
- b Hepatic β-oxidation analyses for this animal was not reported due to missing identification on the sample tubes.
Table 7: Mean Body weights of male rats
Days on test | Mean body weight males (1000ppm) |
Exposure phase |
|
0 | 299.7 12.8 (10) |
1 | 301.9 12.8 (10) |
2 | 311.6 15.2 (10) |
3 | 317.9 17.1 (10) |
4 | 326.1 16.5 (10) |
7 | 347.8 20.5 (10) |
8 | 250.8 21.2 (10) |
9 | 356.9 22.7 (10) |
10 | 361.2 23.7 (10) |
11 | 333.7 22.3 (10) |
Recovery Phase |
|
14 | 373.4 33.2 (5) |
18 | 401.7 40.2 (5) |
21 | 420.5 38.1 (5) |
25 | 404.3 47.9 (5) |
Table 8: Food Consumption
Animal # | Food Cons. g/anm/day Day 7 | Food Cons. g/anm/day Day 14 | Food Cons. g/anm/day Day 21 | Food Cons. g/anm/day Day 25 |
653804 | 16.8 |
|
|
|
653805 | 24.4 |
|
|
|
653806 | 28.6 |
|
|
|
653807 | 30.3 |
|
|
|
653808 | 24.6 |
|
|
|
653809 | 32.7 | 30.9 | 37.7 | 28.8 |
653810 | 27.5 | 20.0 | 23.3 | 12.9 |
653811 | 27.7 | 23.6 | 27.6 | 22.3 |
653812 | 30.8 | 26.6 | 31.5 | 23.0 |
653813 | 27.2 | 23.2 | 20.5 | 24.4 |
ABBREVIATIONS FOR HEMATOLOGY & CLINICAL CHEMISTRY:
General:
CS - clotted specimen
NT - not taken or not performed
QNS - quantity not sufficient for testing
> - greater than < - less than
Individual Hematology Values:
RBC - erythrocyte count
HGB - hemoglobin concentration HCT - hematocrit
MCV - mean corpuscular volume MCH - mean corpuscular hemoglobin
MCHC - mean corpuscular hemoglobin concentration RDW - red cell volume distribution width
RETIC - absolute reticulocyte count PLT - platelet count
WBC - total leukocyte count
ANEU - absolute neutrophils
ALYM - absolute lymphocytes
AMON - absolute monocytes
AEOS - absolute eosinophils
ABAS - absolute basophils
ALUC - absolute large unstained cells Poik - poikilocytosis
Poly - polychromasia
PLT MORPH - platelet morphology
CLSE - severe platelet clumping noted CLSL - slight platelet clumping noted
LPO - occasional large NAN - no abnormalities
Individual Coagulation Values:
PHEM - plasma hemolysis PLIP - plasma lipemia PICT - plasma icterus
platelets notednoted
PT - prothrombin time
APTT - activated partial thromboplastin time
Individual Serum and Plasma Chemistry Values:
SHEM - serum hemolysis SLIP - serum lipemia SICT - serum icterus
AST - aspartate aminotransferase ALT - alanine aminotransferase SDH - sorbitol dehydrogenase
ALKP - alkaline phosphatase BILI - total bilirubin
BUN - urea nitrogen CREA - creatinine CHOL - cholesterol TRIG - triglycerides GLUC - glucose
TP - total protein ALB - albumin
GLOB - globulin
CALC - calcium
IPHS - inorganic phosphorous
NA - sodium
K - potassium
CL - chloride
PHEM - plasma hemolysis from blood sample for fluoride determination PLIP - plasma lipemia from blood sample for fluoride determination PICT - plasma icterus from blood sample for fluoride determination PFLU - plasma fluoride
Table 9: Hematology
Male, Group IX - 1000 ppm - Day 11
Animal # | RBC X106/µL | HGB g/dL | HCT % | MCV fL | MCH pg | MCHC g/dL | RDW % | RETIC X103/µL | PLT X103/µL | WBC X103/µL | ANEU X103/µL |
653804 | 7.26 | 14.0 | 43.9 | 60.5 | 19.3 | 32.0 | 12.2 | 250.8 | 1322 | 15.30 | 2.14 |
653805 | 7.98 | 15.6 | 47.0 | 58.8 | 19.6 | 33.3 | 11.8 | 217.0 | 1091 | 08.90 | 1.39 |
653806 | 7.71 | 14.7 | 46.5 | 60.3 | 19.1 | 31.7 | 13.3 | 299.4 | 1143 | 11.70 | 1.64 |
653807 | 7.80 | 14.3 | 45.1 | 57.8 | 18.4 | 31.8 | 12.4 | 246.8 | 1380 | 09.86 | 1.73 |
653808 | 7.90 | 15.4 | 46.9 | 59.4 | 19.4 | 32.7 | 12.1 | 248.2 | 1364 | 11.34 | 2.57 |
653809 | 6.82 | 14.5 | 44.1 | 64.6 | 21.2 | 32.8 | 13.0 | 256.0 | 1441 | 12.19 | 2.37 |
653810 | 7.71 | 14.8 | 45.6 | 59.2 | 19.2 | 32.4 | 12.5 | 214.9 | 1488 | 08.82 | 2.59 |
653811 | 7.45 | 14.6 | 45.4 | 60.9 | 19.6 | 32.2 | 12.0 | 245.4 | 1607 | 08.72 | 1.14 |
653812 | 7.97 | 15.1 | 47.1 | 69.1 | 19.0 | 32.2 | 13.2 | 250.4 | 1411 | 15.93 | 3.68 |
653813 | 7.78 | 15.3 | 48.6 | 62.5 | 19.6 | 31.4 | 12.2 | 283.0 | 1469 | 13.01 | 2.74 |
Male, Group IX - 1000 ppm - Day 25
Animal # | RBC X106/µL | HGB g/dL | HCT % | MCV fL | MCH pg | MCHC g/dL | RDW % | RETIC X103/µL | PLT X103/µL | WBC X103/µL | ANEU X103/µL |
653809 | 7.49 | 15.2 | 47.6 | 63.6 | 20.2 | 31.8 | 13.5 | 16.01 | 894 | 13.96 | 2.43 |
653810 | CS | CS | CS | CS | CS | CS | CS | CS | CS | CS | CS |
653811 | 7.46 | 14.2 | 45.2 | 60.5 | 19.0 | 31.4 | 12.8 | 221.2 | 1297 | 10.32 | 1.55 |
653812 | 8.14 | 14.9 | 48.1 | 59.0 | 18.3 | 31.0 | 13.1 | 213.1 | 1587 | 15.22 | 2.82 |
653813 | 7.82 | 15.3 | 49.0 | 62.7 | 19.6 | 31.3 | 13.0 | 223.9 | 1482 | 13.05 | 2.10 |
Male, Group IX - 1000 ppm - Day 11
Animal # | ALYM X103/µL | AMON X103/µL | AEOS X103/µL | ABAS X103/µL | ALUC X103/µL | Poik | Poly | PLT MORPH |
653804 | 12.45 | 0.36 | 0.09 | 0.13 | 0.12 | NAN | 1+ | NAN |
653805 | 7.01 | 0.20 | 0.11 | 0.10 | 0.08 | NAN | 1+ | NAN |
653806 | 9.45 | 0.21 | 0.12 | 0.17 | 0.11 | NAN | 1+ | NAN |
653807 | 7.75 | 0.20 | 0.07 | 0.05 | 0.06 | NAN | 2+ | NAN |
653808 | 8.43 | 0.13 | 0.06 | 0.09 | 0.07 | NAN | 1+ | NAN |
653809 | 9.40 | 0.18 | 0.11 | 0.06 | 0.07 | NAN | 2+ | NAN |
653810 | 5.87 | 0.24 | 0.06 | 0.03 | 0.04 | NAN | 1+ | NAN |
653811 | 7.21 | 0.18 | 0.10 | 0.04 | 0.05 | 1+ | 1+ | NAN |
653812 | 11.61 | 0.32 | 0.09 | 0.12 | 0.11 | 1+ | 1+ | NAN |
653813 | 9.70 | 0.19 | 0.20 | 0.09 | 0.08 | NAN | 2+ | NAN |
Male, Group IX - 1000 ppm - Day 25
Animal # | ALYM X103/µL | AMON X103/µL | AEOS X103/µL | ABAS X103/µL | ALUC X103/µL | Poik | Poly | PLT MORPH |
653809 | 10.85 | 0.32 | 0.13 | 0.11 | 0.11 | 1+ | 1+ | NAN |
653810 | CS | CS | CS | CS | CS | CS | CS | CS |
653811 | 8.35 | 0.20 | 0.08 | 0.07 | 0.07 | 1+ | 2+ | NAN |
653812 | 11.76 | 0.32 | 0.08 | 0.15 | 0.09 | 1+ | 1+ | NAN |
653813 | 10.32 | 0.30 | 0.11 | 0.13 | 0.10 | NAN | 1+ | NAN |
Table 10: Coagulation
Animal # | PHEM | PLIP | PICT | PT | APTT |
(sec) | (sec) | ||||
Male, Group IX - 1000 ppm - Day 11 | |||||
653804 | None | None | None | 15.4 | 17.7 |
653805 | None | None | None | 15.2 | 14.8 |
653806 | None | None | None | 15.3 | 19.9 |
653807 | None | None | None | 14.7 | 16.3 |
653808 | None | None | None | 14.7 | 17.7 |
Male, Group IX - 1000 ppm - Day 25 | |||||
653809 | None | None | None | 14.9 | 19.4 |
653810 | None | None | None | 15.5 | 19.1 |
653811 | None | None | None | 14.8 | 17.7 |
653812 | None | None | None | 14.6 | 22 |
653813 | None | None | None | 14.7 | 21 |
Table 11: Clinical Chemistry
Male, Group IX - 1000 ppm - Day 11
SHEM | SLIP | SICT | AST | ALT | SDH | ALKP | BILI | BUN | CREA | CHOL | |
|
|
| U/L | U/L | U/L | U/L | mg/dL | mg/dL | mg/dL | mg/dL | |
|
|
|
|
|
|
|
|
|
|
| |
653804 | None | None | None | 101 | 48 | 23.1 | 228 | 0.1 | 15 | 0.27 | 58 |
653805 | None | None | None | 100 | 53 | 21.7 | 282 | 0.1 | 14 | 0.33 | 54 |
653806 | Trace | None | None | 105 | 40 | 16.3 | 181 | 0.1 | 14 | 0.32 | 79 |
653808 | None | None | None | 99 | 38 | 18.9 | 192 | 0.12 | 13 | 0.37 | 60 |
653809 | None | None | None | 94 | 46 | 18.8 | 274 | 0.14 | 17 | 0.32 | 47 |
653810 | None | None | None | 94 | 33 | 15 | 169 | 0.12 | 15 | 0.27 | 62 |
Male, Group IX - 1000 ppm H-25111 - Day 11 | ||||
PHEM | PLIP | PICT | PFLU (µg/mL) | |
653804 | None | None | None | 0.1 |
653805 | None | None | None | 0.1 |
653806 | None | None | None | 0.1 |
653807 | None | None | None | 0.1 |
653808 | None | None | None | 0.1 |
Male, Group IX - 1000 ppm - Day 25
Animal # | SHEM | SLIP | SICT | AST | ALT | SDH | ALKP | BILI | BUN | CREA | CHOL |
|
|
| U/L | U/L | U/L | U/L | mg/dL | mg/dL | mg/dL | mg/dL | |
653809 | TRACE | None | None | 90 | 42 | 18.1 | 214 | 0.1 | 14 | 0.29 | 43 |
653810 | TRACE | None | None | 86 | 40 | 15.2 | 153 | <0.10 | 17 | 0.3 | 52 |
653811 | TRACE | None | None | 82 | 32 | 13.9 | 186 | 0.1 | 15 | 0.36 | 79 |
653812 | TRACE | None | None | 82 | 34 | 16.1 | 120 | <0.10 | 12 | 0.33 | 99 |
653813 | TRACE | None | None | 80 | 28 | 17.3 | 195 | 0.11 | 15 | 0.36 | 59 |
Male, Group IX - 1000 ppm - Day 25
Animal # | TRIG | GLUC | TP | ALB | GLOB | CALC | IPHS | NA | K | CL |
mg/dL | mg/dL | g/dL | g/dL | g/dL | mg/dL | mg/dL | mmol/L | mmol/L | mmol/L | |
653809 | 42 | 103 | 6.5 | 4.0 | 2.5 | 11.0 | 9.6 | 144.6 | 5.46 | 98.1 |
653810 | 21 | 91 | 6.3 | 4.1 | 2.2 | 10.8 | 8.6 | 143.7 | 5.40 | 97.8 |
653811 | 27 | 103 | 6.5 | 4.1 | 2.4 | 11.0 | 9.2 | 146.1 | 3.08 | 101.9 |
653812 | 84 | 108 | 6.9 | 4.2 | 2.7 | 11.4 | 8.0 | 147.0 | 5.32 | 99.8 |
653813 | 37 | 95 | 6.6 | 4.4 | 2.2 | 10.7 | 8.4 | 147.7 | 6.02 | 102.3 |
Table 12: Thyroid Function & ß-Oxidation data
β-Oxidation | TSH | Triiodothyronine (T3) | Thyroxine (T4) | |
Animal # | (nmol/min-mg protein) | (ng/mL) | (ng/dL) | (ng/dL) |
653804 | 17.5 | 7.772 | 59.683 | 4.048 |
653805 | 16.5 | 4.469 | 85.695 | 4.993 |
653806 | 15.2 | 8.885 | 73.49 | 5.035 |
653807 | 15.4 | 5.779 | 79.156 | 3.696 |
653808 | 15.6 | 5.51 | 85.574 | 4.91 |
653809 | a | 7.656 | 64.098 | 5.141 |
653810 | a | 5.625 | 59.642 | 4.041 |
653811 | a | 4.586 | 70.28 | 4.89 |
653812 | a | 5.439 | 69.987 | 4.279 |
653813 | a | 5.285 | 83.285 | 4.765 |
FOOTNOTES:
Applicant's summary and conclusion
- Conclusions:
- Rats exposed to 1000 ppm test item had no adverse change in hematology, coagulation, clinical chemistry, urinalysis, or fluoride parameters. The only treatment-related, but non-adverse, change in rats exposed to 1000 ppm was a minimal increase in reticulocytes, without an effect on red cell mass. Therefore, under the conditions of this study and for the parameters measured, the no adverse effect level for male rats was 1000 ppm, the only exposure concentration administered.
- Executive summary:
Introduction
The purpose of this study was to assess the potential subchronic toxicity of exposure to the test item in adult rats. Young adult male Crl:CD®(IGS)BR rats (10 rats/exposure concentration) were exposed to atmospheres containing 1000 ppm test item for 6 hours per day, over a 2-week period for a total of 9 exposures.
Observations
Body weight was determined daily, and food consumption was determined weekly. Clinical signs of toxicity were monitored throughout the study. Blood and urine samples were collected at the end of the exposure period from 10 rats/concentration for evaluation of clinical pathology and urinalysis parameters. Additional blood samples were collected from each rat for determination of thyroid hormone concentrations. After the last exposure, 5 rats/concentration for each of the 3 test substances underwent gross necropsy. Selected tissues were processed for histopathology and examined. In addition, a liver sample was collected from each rat for determination of hepatic β-oxidation activity. After an approximate 2-week recovery period, blood and urine samples were collected from all surviving rats for evaluation of clinical pathlology and urinalysis parameters. All surviving rats underwent gross necropsy, and selected tissues were processed for histopathology and examined.
Results
There were no test substance-related, toxicologically significant effects on body weight, weight gain, food consumption, food efficiency, or clinical signs of toxicity in males exposed to the test item at 1000 ppm.
Exposed animals had no adverse changes in hematology, coagulation, clinical chemistry, urinalysis, or fluoride parameters. The only treatment-related, but non-adverse, change was a minimal increase in reticulocytes, without an effect on red cell mass.
There were no test substance related effects on organ weights or tissue morphology.
Test substance related changes in thyroid homeostasis were observed. Serum T3 and T4 concentrations were significantly decreased in rats following exposure. However, serum TSH was not affected. While these alterations suggest that the test item may be capable of modulating thyroid hormone homeostasis, these alterations may be transient effects since thyroid weight and histopathology were not affected.
Hepatic β-oxidation activity was similar to control in exposed rats.
Conclusions
The no-observed-effect level (NOEL) for this study is defined as the highest dose at which toxicologically important effects attributable to the test substance were not detected. Thus for this study, the NOEL is equivalent to the NOEL as defined by the United States Environmental Protection Agency (1985), and the no-observed-adverse effect level (NOAEL) as defined by the European Union (1994). Under the conditions of the study, the NOEL for the test item was 1000 ppm, the highest concentration tested.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.