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EC number: 200-824-2 | CAS number: 74-95-3
- 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:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Not performed according to known TG or GLP, but the study was well documented and scientifically accepted
Data source
Reference
- Reference Type:
- other: published data accessed
- Title:
- UNNAMED
- Author:
- US EPA
- Year:
- 2 010
- Bibliographic source:
- EPA Doc. No. 86-870001205, Fiche No. OTS0516108).
Materials and methods
- Principles of method if other than guideline:
- study was conducted using groups of 115 male and 15 female Sprague-Dawley rats and three male Beagle dogs exposed to 0, 25, 75, or 150 ppm (0, 178, 533, or 1066 mg/m3) of methylene bromide for 6 hours/day, 5 days/week, for a total of 62 or 63 exposures (rats) or 70 exposures (dogs) in approximately 90 days . After 58 exposure days, five rats/sex/level were sacrificed for cytogenetic analysis of bone marrow.
On the day after the last exposures, 10 rats/sex/level and all dogs were necropsied. The 100 remaining male rats were observed for up to 2 years following exposure. - GLP compliance:
- not specified
Test material
- Reference substance name:
- Dibromomethane
- EC Number:
- 200-824-2
- EC Name:
- Dibromomethane
- Cas Number:
- 74-95-3
- Molecular formula:
- CH2Br2
- IUPAC Name:
- dibromomethane
1
Test animals
- Species:
- other: rats and dogs
- Strain:
- other: Sprague Dowley and Beagles
- Sex:
- male/female
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- not specified
- Vehicle:
- not specified
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- 6hours/day 5 day/week
Doses / concentrations
- Remarks:
- 0 (control),25,75,150 ppm
- No. of animals per sex per dose:
- 115 males/group and 15 females/group
- Control animals:
- yes
- Details on study design:
- Treatment-related effects observed at the 90-day sacrifice were limited to the 0.53 and 1.07 mg/L exposure groups
A 2-year post-exposure holding period was implemented for 100 males/group. Endpoints included clinical signs, body weights, organ weights, hematology, urinalysis, clinical chemistry, cytogenetics, gross pathology, and histopathology
Examinations
- Observations and examinations performed and frequency:
- Endpoints that were evaluated during the exposure and observation parts of the study include clinical signs, body weight, hematology, and urinalysis indices (7 rats/sex/level, all dogs at termination of exposure, and 7 male rats/level after 1 year ofobservation) and clinical chemistry indices (10 rats/sex/level, all dogs at termination of exposure, and 10 male rats/level after 1 year of observation). The hematology determinations included red blood cell counts, hemoglobin concentration, packed
cell volume , and total and differential white blood cell counts. The urinalysis determinations included pH, protein, ketones, bilirubin, urobilinogen, and occult blood. The clinical chemistry determinations included blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Cytogenetic analyses were not performed because of inadequate slide preparation. Additional endpoints included plasma bromine/bromide levels at various time points and
blood carboxyhemoglobin (COHb) percentages. COHb was measured using an optical method. For each of these endpoints three rats/sex/level were evaluated preexposure and at 1, 3, 30, 41, 51, and 61 days of exposure. The authors did not specify whether the same or different animals were used for each measurement. All dogs were evaluated at similar time points. Complete gross necropsies and organ weight measurements (brain, heart, liver, kidneys, and testes) were performed on 10 rats/sex/level after 61or 62 exposures and all dogs after 70 exposures. Complete gross necropsies were also performed on 10 male rats/level at 1 and 2 years postexposure. Comprehensive histological examinations were performed in the 0- and
150-ppm groups after 90 days of exposure (Five rats/sex/level and all dogs) and at 1 year postexposure (five male rats/level). No histological examinations were performed during the observation period on male rats that died spontaneously, were killed in moribund condition, or were sacrificed after 2years. Histological examinations in the 25- and 75-ppm exposure groups were limited to the lungs, trachea, and bronchial lymph nodes in dogs after 90 days of exposure.
Results and discussion
Results of examinations
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- body weight decrease beginning on day 121 at the 1.07 mg/L exposure level.
(2 years post exposure group) - Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- increased blood percent carboxyhemoglobin saturations in both sexes.
Increased blood percent carboxyhemoglobin saturations were also seen in both sexes at 0.53 and 1.07 mg/L throughout the exposure period. - Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- increased liver weight in females
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Gross pathological examination of males exposed to 1.07 mg/L at the end of the 2-year post-exposure period revealed liver atrophy, decreased incidence of small red foci, and dark red foci visible in the liver; the study authors considered these lesions to be the result of spontaneous age-related processes.. All gross pathological (2-year observation) and histopathological (1-year observation) neoplastic and non-neoplastic observations were considered to be spontaneous in nature and unrelated to exposure.
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- No treatment-related histopathological effects were observed.(after 90 days)
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Remarks:
- rats
- Effect level:
- 0.18 mg/L air
- Sex:
- male/female
- Basis for effect level:
- other: increased blood percent carboxyhemoglobin saturations in both sexes during exposure and at termination of exposure
- Dose descriptor:
- LOAEL
- Remarks:
- rats
- Effect level:
- 0.53 mg/L air
- Sex:
- male/female
- Basis for effect level:
- other: increased blood percent carboxyhemoglobin saturations in both sexes during exposure and at termination of exposure
- Dose descriptor:
- NOAEL
- Remarks:
- dogs
- Effect level:
- 0.53 mg/L air
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: increased blood percent carboxyhemoglobin saturations in both sexes during exposure and at termination of exposure
- Remarks on result:
- other:
- Dose descriptor:
- LOAEL
- Remarks:
- dogs
- Effect level:
- 1.07 mg/L air
- Sex:
- male/female
- Basis for effect level:
- other: increased blood percent carboxyhemoglobin saturations in both sexes during exposure and at termination of exposure
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
There were no exposure-related changes in most of the endpoints in either species.
Dose-related increases in serum levels of free bromide ion and total bromine occurred at ≥25 ppm in the rats and dogs at all times of evaluation. There were no clinical signs of intoxication and no histopathological changes in both species. There was a slight increase in relative liver weight at the termination of the exposure period in female rats exposed to 75 pp(8.9% higher than controls,
p< 0.05) and 150 ppm (6.1% higher than controls, not statistically significant). Male rats that were exposedto ≥75 ppm showed an equivocal decrease in
body-weight gain during Study Days 121−361 in the postexposure observation period, but the decrease is not considered biologically significant.
Exposure to methylene bromide also caused increased blood COHb levels in both species as shown in Table 1. Increases in mean COHb percentages that were statistically significant (p< 0.05 compared to control group) occurred at ≥7
5 ppm methylene bromide; there was only one statistically significant increase at 25 ppm (after 61 exposures in females). However, due to the small group sizes (n= 2 or 3 rats/sex/level at each time point), the statistical tests performed
by the researchers had little power to detect an effect. Dogs were less sensitive than the rats, as
indicated by a small increase in percent COHb saturation relative to controls detectable only at 150 ppm (mean 6.0% increase at the only sampling time where the difference from the control mean was statistically significant). Regression analysis was performed by the researchers to
quantitatively assess the effect of increasing exposure concentration on percent COHb saturation. The analysis used pooled percentage COHb saturation values after 30 to 61 exposures; data for each concentration were pooled to improve the precision of analysis and because COHb percentages did not increase appreciably after more than 30 exposures. The slopes of the regression lines predicted that the average increase in percent COHb saturation (relative to
controls) in the animals repeatedly exposed to 25, 75, and 150 ppm would be 0.4, 1.2, and2.4%, respectively,in dogs, 2.6, 8.3, and16.5% in male rats , and 2.3, 6.8, and 13.5% in female rats.
Baseline COHb in untreated control animals was 2.8%.
Applicant's summary and conclusion
- Conclusions:
- Exposure related effects were not observed at any exposure level during the study. Body weights on all dogs were comparable to those of controls during the study. At necropsy, terminal body weights, organ weights, and organ to body weights ratio were comparable to controls. Haematological values in treated dogs were comparable to those of controls. Clinical chemistry values of exposed dogs were comparable to control dogs. All gross and histopathologic observations on control and treated dogs were considered spontaneous in nature, and not as a result of treatment. Among spontaneous lesions was a frequent occurrence of chronic inflammatory lesions of the lungs that varied in severity. In some animals, the lesions were clearly related to aspiration of food material, and in others typical of a parasitic infestation common in dogs. There was some discrepancy in values for bromide ions and for total bromides. The NOAEL was determined to be 75 ppm (based on elevatedcarboxyhemoglobin), and the LOAEL was set to 150 ppm.
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