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EC number: 200-826-3 | CAS number: 74-97-5
- 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:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Test method equivalent or similar to OECD Guideline 413.
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 960
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- Deviations:
- yes
- Remarks:
- (Only two dose concentrations were tested in males).
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Bromochloromethane
- EC Number:
- 200-826-3
- EC Name:
- Bromochloromethane
- Cas Number:
- 74-97-5
- Molecular formula:
- CH2BrCl
- IUPAC Name:
- bromo(chloro)methane
- Details on test material:
- - Name of test material (as cited in study report): bromochloromethane
- Analytical purity: >99%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- not specified
- Sex:
- male/female
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: unchanged (no vehicle)
- Details on inhalation exposure:
- CHAMBER DESCRIPTION: 1700-liter capacity water-sealed chambers.
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 114 days
- Frequency of treatment:
- 7h/day, 5 days/week.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
400 ppm (females), 500 ppm (males and females) and 1000 ppm (males and females)
Basis:
nominal conc.
- No. of animals per sex per dose:
- 500 and 1000 ppm-dose groups: 20 animals/sex/group.
400 ppm-dose group: 10 females. - Control animals:
- yes, concurrent no treatment
- Details on study design:
- Since it was evident that female rats were the only group which was significantly affected by exposures to 500 ppm, it was deemed desirable to expose another group of female rats to 400 ppm to observe their response.
- Positive control:
- None
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
BODY WEIGHT: Yes
- Time schedule for examinations: The animals were weighed twice a week until it was evident that growth was essentially normal and once a week thereafter.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at study termination.
- Animals fasted: Yes.
- How many animals: on representative animals of the unexposed group and the 1000 ppm dose group.
- Parameters checked in table [No.3] were examined: RBC, WBC and differential count of Neutrophils, Lymphocytes, Monocytes and Eosinophils.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at study termination.
- Animals fasted: Yes
- How many animals: on representative animals of all dose groups and control groups.
- Parameters checked in table [No. 2] were examined: blood bromide, blood urea-nitrogen (BUN) and blood non-protein-nitrogen (NPN). - Sacrifice and pathology:
- SACRIFICE: all rats were fasted overnight and killed by decapitation the day following their last exposure.
GROSS PATHOLOGY: Yes (see table No. 1). After gross pathological examination was made, the lungs, heart, liver, kidney, spleen and testes were removed and weighed.
HISTOPATHOLOGY: Yes. Portions of the lungs, heart, liver, kidney, spleen, testes, pancreas and adrenals were examined microscopically. - Statistics:
- The "t" test was used to determine the significance of the organ weight differenes. A probability (P) of 0.05 or less was considered as significant.
Results and discussion
Results of examinations
- 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:
- no effects observed
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Bromide blood levels were elevated in males exposed at ≥500 ppm and females exposed at ≥ 400 ppm.
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Increase in weight of the liver in males exposed at ≥500 ppm and females exposed at ≥400 ppm.
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- In males and females exposed to 1000 ppm.
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Females in the ≥500 ppm groups and males in the 1000 ppm group.
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
Animals exposed to bromochloromethane were normal in appearance and activity.
BODY WEIGHT AND WEIGHT GAIN
The average body weight and growth of the exposed animals were normal.
HAEMATOLOGY
Hematological values were within normal limits.
CLINICAL CHEMISTRY
Blood bromide levels were elevated in females exposed to ≥400 ppm and in males exposed to ≥500 ppm.
ORGAN WEIGHTS
A small increase in weight of the liver was noted in males exposed to 500 ppm. Nevertheless, since no pathological changes were seen in the 500 ppm-dose group, it probably indicates that the organ was only under slight stress. The average liver weight in females exposed to 500 ppm was high. The average liver and kidney weights were elevaded in males and females exposed to 1000 ppm.
GROSS PATHOLOGY
Fatty and enlarged livers were seen grossly when female rats exposed to 1000 ppm were sacrified. Organs of exposed males appeared normal at autopsy.
HISTOPATHOLOGY: NON-NEOPLASTIC
A very slight proliferation of the bile duct epithelium with very slight portal fibrosis and inflammation was seen in males exposed to 1000 ppm. There was some cloudy swelling of the parenchymal cells in the midzonal areas spreading to the central areas of the lobule. Numerous parenchymal cells in the midzonal area and portal area contained many small vacuoles. Slight pathological changes were seen in females exposed to 500 ppm: bile duct epithelial proliferations and very slight portal fibrosis, together with occasional large and small vacuoles in parenchymal cells of the midzonal areas. Similar changes to those described for male rats were seen in females exposed to 1000 ppm, in addition of some portal fibrosis in the liver.
Effect levels
open allclose all
- Dose descriptor:
- NOAEC
- Effect level:
- 500 ppm
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: histopathology (pathological changes in the liver) (equiv. to 2645.88 mg/m3)
- Dose descriptor:
- NOAEC
- Effect level:
- 400 ppm
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: histopathology (pathological changes in the liver) (equiv. to 2116.71 mg/m3)
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table 1. Summary of Terminal Average Body and Organ Weights of Animals Receiving Repeated 7-Hour Exposures to Bromochloromethane (CH2BrCl).
Specie |
Sex |
Group |
Ratio of survival |
Final average body weight, g |
Organ Weights, g/100 g body weight |
|||||
Lung |
Heart |
Liver |
Kidney |
Spleen |
Testes |
|||||
Rat |
M |
Unexposed control |
19/20 |
341 |
0.55 |
0.31 |
2.46 |
0.68 |
0.29 |
0.87 |
M |
1000 ppm |
17/20 |
306 |
0.56 |
0.32 |
3.20d |
0.75d |
0.32 |
0.85 |
|
M |
500 ppm |
17/20 |
300 |
0.56 |
0.34 |
2.77d |
0.69 |
0.32 |
0.82 |
|
F |
Unexposed control |
17/20 |
203 |
0.73 |
0.37 |
2.67 |
0.71 |
0.36 |
|
|
F |
1000 ppm |
19/20 |
206 |
0.70 |
0.38 |
3.65d |
0.82d |
0.35 |
|
|
F |
500 ppm |
19/20 |
210 |
0.70 |
0.38 |
3.05d |
0.75 |
0.38 |
|
|
F |
Unexposed control |
12/12 |
215 |
0.64 |
0.39 |
2.70 |
0.76 |
0.28 |
|
|
F |
Air exposed control |
12/12 |
220 |
0.64 |
0.34 |
2.77 |
0.75 |
0.32 |
|
|
F |
400 ppm |
9/10 |
232 |
0.63 |
0.38 |
2.98bb |
0.78 |
0.25 |
|
Probability values (P): a = P > 0.05; b = P = 0.01-0.05; bb = P ≈ 0.045; c = P = 0.001-0.01; d = P < 0.001.
Table 2. Summary of Average Blood Bromide, Blood Urea-Nitrogen and Blood Non-Protein-Nitrogen Levels in Animals Exposed Repeatedly to the Vapours of Bromochloromethane in Air.
Specie |
Sex |
Months on exposure, day bled |
Vapour conc. (ppm) |
Blood Bromide |
Blood Nitrogen |
||||
No. of animals |
Mg Br-/ 100 ml |
Analytical method |
No. of animals |
Urea N |
Total NPN |
||||
mg/100 ml |
mg/100 ml |
||||||||
Rat |
M |
4 Thurs. |
0 |
3 |
8 |
W |
2 |
14.8 |
|
M |
4 Thurs. |
1000 |
3 |
122 |
W |
2 |
13.9 |
|
|
M |
4 Thurs. |
500 |
3 |
88 |
W |
2 |
16.0 |
|
|
F |
4 Fri. |
0 |
3 |
5 |
W |
2 |
15.2 |
|
|
F |
4 Fri. |
1000 |
3 |
122 |
W |
2 |
15.9 |
|
|
F |
4 Fri. |
500 |
3 |
83 |
W |
2 |
18.7 |
|
|
F |
6 Wed. |
0 |
3 |
0.9 |
S |
8 |
20.8 |
48 |
|
F |
6 Wed. |
400 |
3 |
73 |
S |
3 |
12.9 |
47 |
*Analytical method for blood bromide:
W Wuth’s: Hepler, O.E., Manual of Clinical Laboratory Methods, Charles C Thomas, Springfield, Illinois, 1951.
S Shrader’s: Shrader, S.A., et al., Ind. Eng. Chem. Anal. Ed. 14:1 (1942).
Table 3. Average Terminal Hematological Values for Animals Receiving Repeated 7-Hour Exposures to Bromochloromethane.
Treatment |
Sex |
No. of animals |
RBC x 106 |
WBC x 103 |
Differential Count (%) |
|||
Neutrophils |
Lymphocytes |
Monocytes |
Eosinophils |
|||||
Unexposed control |
F |
5 |
8.8 |
16.9 |
14.2 |
82.9 |
0.4 |
3.0 |
1000 ppm |
F |
10 |
8.7 |
14.4 |
18.9 |
79.5 |
1.0 |
1.5 |
Applicant's summary and conclusion
- Conclusions:
- On the basis of the pathological changes observed in the liver, the inhalative NOAEC of bromochloromethane was established to be 500 ppm (2645.88 mg/m3) for males and 400 ppm (2116.71 mg/m3) for females.
- Executive summary:
20 male and 20 female rats were exposed in 114 days to 500 and 1000 ppm. The exposures were for seven hours per day and given five days a week. Since it was evident that female rats were the only group which was significantly affected by exposures to 500 ppm, a 400 ppm-dose group was including only females was added. A fourth group was maintained in the animal quarters at all times as unexposed controls. The animals were weighed twice a week until it was evident that growth was essentially normal and once a week thereafter. Terminal hematological examinations were made on representative animals and all rats were subjected to gross pathological and histopathological examinations. Exposed animals were normal in appearance, activity and growth. Hematological values were within normal limits as were BUN levels. Blood bromide levels were found elevated in females exposed to ≥400 ppm and in males exposed to ≥500 ppm. Pathological changes in the liver were seen in males exposed to 1000 ppm of bromochloromethane: it was seen a very slight proliferation of the bile duct epithelium with very slight portal fibrosis and inflammation. Besides, there was some cloudy swelling of the parenchymal cells in the midzonal areas spreading to the central areas of the lobule and numerous parenchymal cells in the midzonal area and portal area contained many small vacuoles. Pathological changes in the liver were seen at a lower dose-level in females: females exposed to 500 ppm showed bile duct epithelial proliferations and very slight portal fibrosis, together with occasional large and small vacuoles in parenchymal cells of the midzonal areas. Similar changes to those described for male rats were seen in females exposed to 1000 ppm, in addition of some portal fibrosis in the liver. On the basis of the pathological changes observed in the liver, the NOAEC was established to be 500 ppm (or 2645.88 mg/m3) for males and 400 ppm (or 2116.71 mg/m3) for females.
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