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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 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
Toxicity to reproduction
Administrative data
- Endpoint:
- screening for reproductive / developmental toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2007
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP and appropriate guidelines
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 007
- Report date:
- 2007
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Qualifier:
- according to guideline
- Guideline:
- other: EPA Health Effects Test Guidelines: OPPTS 870.3550 Reproduction/ Developmental Toxicity Screening test, July 2000
- Qualifier:
- according to guideline
- Guideline:
- other: TSCA test guidleine 40 CFR 799.9355 (comparable to OECD TG No. 421)
- GLP compliance:
- yes (incl. QA statement)
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
- Details on test material:
- 99.4% purity, DBM clear liquid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- A total of eighty animals (forty males and forty females) were accepted into the study. At the start of treatment, the males weighed 268 to 336g;
the females weighed 176 to 226g and were approximately eight weeks old.
Environmental conditions were continuously monitored by a computerised system and print-outs of hourly mean temperatures and humidities are included in the study records. The temperature and relative humidity controls were set to achieve target values of 21±2ºC and 55 ±15% respectively.
Administration / exposure
- Route of administration:
- oral: gavage
- Details on exposure:
- The test material was administered daily by gavage using a stainless steel cannula attached to a disposable plastic syringe. Control animals were treated in an identical manner with 4 polyethylene glycol 400.
- Details on mating procedure:
- Animals were paired on a 1 male: 1 female basis within each dose group, for a period of up to fourteen days. Cage tray-liners were checked each morning for the presence of ejected copulation plugs and each female was examined for the presence of a copulation plug in the vagina. A
vaginal smear was prepared for each female and the stage of the oestrous cycle or the presence of sperm was recorded. The presence of sperm within the vaginal smear and/or vaginal plug in situ was taken as positive evidence of mating (Day 0 of gestation) and the males were subsequently returned to their original holding cages (unless required for additional pairing). Mated females were housed individually during the period of gestation and lactation - Details on analytical verification of doses or concentrations:
- Samples were taken of each test material formulation and were analysed for concentration of Dibromomethane at Safepharm Analytical Laboratory. The results indicate that the prepared formulations were within ± 10% of the nominal concentration.
- Duration of treatment / exposure:
- 40 days (14 days premating, throughout mating, gestation, parturition and early lactation)
- Frequency of treatment:
- daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
50, 150, 500 mg/kg
Basis:
- No. of animals per sex per dose:
- Three groups each of 10 male and 10 female Sprague-Dawley Crl:CD® (SD) IGS BR strain rats
- Control animals:
- yes
- Details on study design:
- The test material was administered by gavage to three groups each of ten male and ten female Sprague-Dawley Crl:CD® (SD) IGS BR strain rats, for approximately forty days (to include a two week maturation phase, pairing, gestation and early lactation) at dose levels of 500, 150 and 50 mg/kg/day. A control group of ten males and ten females was similarly dosed with vehicle alone (Polyethylene glycol 400).
Clinical signs, bodyweight development, food and water consumption were monitored during the study.
Pairing of animals within each dose group was undertaken on a one male: one female basis on Day 15 of the study, with females subsequently being allowed to litter and rear their offspring to Day 5 of lactation.
During the lactation phase, daily clinical observations were performed on all surviving offspring, together with litter size, offspring weights and assessment of righting reflex.
Surviving males were terminated on Day 43 of the study, with all the surviving females and offspring being killed on Day 5 post partum. All animals were subjected to a gross necropsy examination and histopathological evaluation of reproductive tissues was performed.
Examinations
- Parental animals: Observations and examinations:
- All animals were examined for overt signs of toxicity, ill-health and behavioural change
immediately before and after dosing, and one and five hours after dosing, during the working
week. Animals were observed immediately before and after dosing, and one hour after dosing at
weekends (except for females during parturition where applicable). - Litter observations:
- On completion of parturition (Day 0 post partum), the number of live and dead offspring was recorded.
For each litter the following was recorded:
i) Number of offspring born
ii) Number and sex of offspring alive recorded daily and reported on Day 1 and 4 post partum
iii) Clinical condition of offspring from birth to Day 4 post partum
iv) Individual offspring and litter weights on Day 1 and 4 post partum - Postmortem examinations (parental animals):
- Adult males and females were killed by intravenous overdose of sodium pentobarbitone followed by exsanguination. Surviving males and a single female that failed to mate were killed on Day 43 of the study. One female that failed to litter was killed on Day 27 post coitum. Females that showed total litter loss were killed on the day the last offspring was found dead. Surviving females were killed on Day 5 of lactation. Surviving offspring were terminated via intracardiac overdose of sodium pentobarbitone at Day 5 of age.
All adult animals and offspring, including those dying during the study, were subjected to a full external and internal examination, and any macroscopic abnormalities were recorded.
In addition, the corpora lutea of all ovaries from pregnant females were counted at necropsy. The uterine implantation sites were counted. The procedure was enhanced (where necessary) by staining the uteri with a 1% ammonium polysulphide solution. - Statistics:
- Data were assessed for dose response relationships by linear regression analysis, followed by one way analysis of variance (ANOVA) incorporating Levene’s test for homogeneity of variance.
Where variances were shown to be homogenous, pairwise comparisons were conducted using Dunnett’s test. Where Levene’s test showed unequal variances the data were analysed using nonparametric methods: Kruskal-Wallis ANOVA and Mann-Whitney ‘U’ test.
Non-parametric methods were used to analyse implantation loss, offspring sex ratio and landmark developmental markers.
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- There were no significant treatment-related clinical signs of toxicity observed at 50, 150 or 500 mg/kg/day.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- At 500 mg/kg/day,lower bodyweight gain was apparent for females during gestation, compared to control, but this was considered to be a consequence of the lower litter size at this dosage. No similar effects were apparent for animals at 50 or 150 mg/kg/day
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- At 500 mg/kg/day,lower bodyweight gain was apparent for females during gestation, compared to control, but this was considered to be a consequence of the lower litter size at this dosage. No similar effects were apparent for animals at 50 or 150 mg/kg/day
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- Microscopic examination of adult reproductive tissues did not reveal any treatment-related effects at dosages of 50, 150 or 500 mg/kg/day.
Details on results (P0)
Litter responses At 500 mg/kg bw/day, litter size was lower than control on Day 1 due to increased post-implantation loss; this loss probably representing death of the offspring in utero. In addition, one female at this dosage was considered to have lost her litter in-utero. No similar treatment
related effects were apparent at 50 or 150 mg/kg bw/day.
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Effect level:
- 150 other: mg/kg
- Sex:
- male/female
Results: F1 generation
General toxicity (F1)
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- Necropsy findings among adult animals and their offspring did not indicate any effect of maternal treatment at dosages of 50, 150 or 500 mg/kg/day.
- Histopathological findings:
- no effects observed
- Description (incidence and severity):
- Microscopic examination of adult reproductive tissues did not reveal any treatment-related effects at dosages of 50, 150 or 500 mg/kg/day.
Details on results (F1)
Effect levels (F1)
- Dose descriptor:
- NOEL
- Generation:
- F1
- Effect level:
- 150 other: mg/kg
- Sex:
- male/female
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Treatment with dibromomethane at 500 mg/kg bw/day was associated with effect on mating performance and a reduction in litter size at birth, most probably due to increase in in-utero mortality. The ‘No Observed Adverse Effect Level’ (NOAEL) for reproduction observed in this study was considered to be 150 mg/kg/day.
- Executive summary:
Oral (Gavage) Reproduction/Development Toxicity Screening Test in the Rat (Dhinsa and Fulcher 2007) was conducted under GLP standards and in accordance with OECD TG for Testing of Chemicals No.421. (adopted 27 July 1996) and EPA Health Effects Test Guidelines: OPPTS 870.3550 (July 2000). The study was identified as a key study (klimisch rating 1).
The test material (99.4% purity, dibromomethane) was administered by gavage to three groups each of 10 male and 10 female Sprague-Dawley Crl:CD® (SD) IGS BR strain rats, at dose levels of 50, 150 and 500 mg/kg/day, for approximately forty days (two week maturation phase, pairing of maximum 14 days, gestation and early lactation).
A control group was similarly dosed with vehicle only (Polyethylene Glycol 400).
Clinical signs, bodyweight development, food and water consumption were monitored during the study. Animals were paired one male:one female on day 15 of the study, with females subsequently being allowed to litter and rear their offspring to day 5 of lactation.
During the lactation phase, daily clinical observations were performed on all surviving offspring, together with litter size, offspring weights and assessment of righting reflex.
Surviving males were terminated on Day 43 of the study, with all surviving females and offspring being killed on Day 5post partum. All animals were subjected to a gross necropsy examination and histopathological evaluation of reproductive tissues was performed.
Effects on Fertility
Mortality: One male, receiving 500 mg/kg bw/day, was killedin extremison Day 2 of the study and one control female was found dead on Day 4 of the study; neither of these deaths were considered to be a consequence of treatment.
Clinical Observation: There were no significant treatment related-clinical signs of toxicity observed at 50, 150 or 500 mg/kg bw/day.
Bodyweights:At 500 mg/kg bw/day, lower bodyweight gain was apparent for females during gestation, compared to control, but this was considered to be a consequence of the lower litter size at this dosage. No similar effects were apparent for animals at 50 or 150 mg/kg bw/day.
Food consumption and food conversion efficiency:At 500 mg/kg bw/day, lower food conversion efficiency was apparent for females during gestation, compared to control, reflecting the lower weight gain observed during this phase of the study. Food intake was lower during lactation and was attributed to the lower physiological demand on parent females due to the smaller litter size. No similar effects were apparent for animals at 50 or 150 mg/kg bw/day.
Mating performance, fertility and gestation length:At 500 mg/kg bw/day, there was a clear increase in pre-coital interval, compared with control, with only four females mating during the first four days of pairing. Copulation plug count was generally lower than control, but fertility was not adversely affected with 8/ 10 females achieving pregnancy. Gestation length of these females tended to be longer than control, possibly influenced by lower litter size. At 50 or 150 mg/kg bw/day, mating performance, fertility and gestation length were considered to be unaffected by treatment.
Litter responses:at 500 mg/kg bw/day, litter size was lower than control on Day 1 due to increased post-implantation loss; this loss probably representing death of the offspringin-utero.In addition, one female at this dosage was considered to have lost her litterin-utero. No similar treatment related effects were apparent for animals at 50 or 150 mg/kg bw/day.
At 50 or 150 mg/kg bw/day, offspring bodyweight on day 1 and subsequent survival, growth and development to Day 4 were unaffected by maternal treatment; lower litter weights at 500 mg/kg bw/day reflected the lower litter size. One control female and one female receiving 500 mg/kg bw/day showed total litter loss on Day 1post partum.
Necropsy:Necropsy findings among adult animals and their offspring did not indicate any effect of maternal treatment at dosages of 50, 150 or 500 mg/kg bw/day.
Organ weight:At 500 mg/kg bw/day, males showed lower absolute and bodyweight-relative epididymal testes weights compared to control. At 150 mg/kg bw/day, absolute and bodyweight-relative testes weights were also lower than control. In the absence of any treatment-related histopathological effects at 500 mg/kg bw/day, these differences in male reproductive organ weights were considered to be of equivocal toxicological significance.
Histopathology: Microscopic examination of adult reproductive tissues did not reveal any treatment related effects at dosages of 50, 150 or 500 mg/kg bw/day.
Conclusion: Treatment with dibromomethane at 500 mg/kg bw/day was associated with effect on mating performance and a reduction in litter size at birth, most probably due to increase inin-uteromortality. The ‘No Observed Adverse Effect Level’ (NOAEL) for reproduction observed in this study was considered to be 150 mg/kg/day.
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.