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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 200-854-6 | CAS number: 75-25-2
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- publication
- Title:
- A teratological assessment of four trihalomethanes in the rat
- Author:
- Ruddick JA, Villeneuve DC, Chu I, Valli VE.
- Year:
- 1 983
- Bibliographic source:
- Journal of Environmental Science and Health, Part B 1983; 18(3):333-349
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- No guideline was provided in the study and the age of the study (1983) predates the OECD 414 guideline. The study does; however, cover many of the endpoints included in the OECD 414 guideline, although exposure covered days 6 to 15 of gestation rather than 5 to 15 specified in the OECD 414 guideline.
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Bromoform
- EC Number:
- 200-854-6
- EC Name:
- Bromoform
- Cas Number:
- 75-25-2
- Molecular formula:
- CHBr3
- IUPAC Name:
- tribromomethane
- Test material form:
- liquid
- Details on test material:
- - Name: Bromoform
- Source Aldrich Chemical Company, Milwaukee, Wisconsin.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Biobreeding Ltd., Montreal, Quebec.
- Age at study initiation: Not stated.
- Weight at study initiation: 150-175 g
- Fasting period before study: Not stated.
- Housing: Each female rat was caged individually following pairing with a sire.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2°C
- Humidity (%): 40-60%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hours light /12 hours dark
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- Pregnant rats were administered the test substance daily by oral intubation beginning on the 6th day of gestation and continuing until the 15th day of gestation.
- Analytical verification of doses or concentrations:
- no
- Details on mating procedure:
- Female rats were then paired overnight with a proven sire and the day on which sperm were seen in a vaginal smear was considered day 1 of gestation. The pregnant rats were then randomly divided into 4 groups (including the control) with each group having 15 rats.
- Duration of treatment / exposure:
- Rats were adminstered test substance from day 6 to day 15 day of gestation.
- Frequency of treatment:
- Daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- Vehicle Control
- Dose / conc.:
- 50 mg/kg bw/day (nominal)
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Dose / conc.:
- 200 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 15 rats per dose group.
- Control animals:
- yes, concurrent vehicle
Examinations
- Maternal examinations:
BODY WEIGHT: Yes
- Time schedule for examinations: The females were weighed on day 1 and days 6-15 of gestation as well as before and after caesarean section on day 22.
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 22
- Organs examined: Maternal rats were subject to gross pathological assessment and the liver, hear, brain spleen and one kidney were removed and weighed. The following tissue samples were taken from each animal and fixed: brain, heart, pituitary, thyroid, parathyroid, thymus, lungs, trachea and bronchi, bronchial node, liver, kidney, adrenal gland, spleen, skeleton muscle, peripheral nerve, salivary gland, skin, bone marrow, ovaries, uterus and bladder.
- OTHER EXAMINATIONS: Materal blood samples were taken fro haematology, blood chemistry. A liver sampels was taken following gross pathology for analysis of liver enzyme activiity.- Fetal examinations:
- At sacrifce on gestation day 22 foetuses were removed, weighed individually and examined for viability and external malformations.
Two pups from each dam were fixed in formalin for histological evaluation. Approximately two-thirds of the remaining live foetuses from each litter were placed in absolute ethanol for future staining of the skeleton with Alizarin red and subsequent examination for skeleton abnormalities. The rest of the foetuses were fixed in Bouin's fluid and studied for visceral changes. - Statistics:
- An analysis of variance was carried out on all measurements where applicable, and when a significant difference occurred (P<0.05), Duncan's Multiple Range Test (SPSS version 8.1) was applied to determine the group or groups that were different from the control.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
- Description (incidence and severity):
- No efffects on measured liver enzyme activity was reported (i.e. it was not positively stated that there had been no changes and it is assumed that no effects occurred).
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- effects observed, treatment-related
- Description (incidence and severity):
- There was some of evidence of dose related increase in sternebra aberrations and observations of interparietal anomalies in foetuses. These were considered to be caused by a foetal toxicity effect.
- Changes in pregnancy duration:
- not specified
- Changes in number of pregnant:
- no effects observed
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- 200 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: No effects observed in maternal animals.
Maternal abnormalities
- Key result
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Reduction in number of live offspring:
- effects observed, treatment-related
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- not examined
- External malformations:
- effects observed, treatment-related
- Skeletal malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- There was some of evidence of dose related increase in sternebra aberrations and observations of interparietal anomalies in foetuses. These were considered to be caused by foetal toxic and not indicative of teratogenicity.
- Visceral malformations:
- no effects observed
- Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- Mild hilar dilation was observed in the kidneys of some treated foetuses but this was considered to spontaneous in nature.
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- other: Evidence of foetal toxicity.
Fetal abnormalities
- Key result
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Key result
- Developmental effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- The test substance was not considered teratogenic to Sprague-Dawley rats. The study No Observed Effect Level (NOEL) for teratogenicity was 200 mg/kg bw/day (highest dose administered). There was some evidence of a foetal toxicity caused by the test substance. The study No Observed Adverse Effect Level (NOAEL) for foetal toxicity was considered to be 100 mg/kg bw/day.
- Executive summary:
Introduction
The teratogenic potential of the test substance toSprague-Dawley ratswas assessed using a study design that pre-dated the OCED 414 guideline, but which nevertheless covered many of the endpoints included in the guideline.
Method
Test substance was administered in corn oil by gavage to pregnant Sprague-Dawley rats from day 6 to day 15 of gestation at doses of 50, 100 or 200 mg/kg/day. A control group was administered corn oil only. Each group consisted of 15 rats and each rat was housed individually with free access to food and water.
On day 22 of gestation rates sacrificed and their viscera including the uteri were examined for pathological changes. The foetuses were removed, weighed individually and examined for viability and external malformations. Two pups from each dam were fixed in formalin for histological evaluation. Approximately two-thirds of the remaining live foetuses from each litter were placed in absolute ethanol for future staining of the skeleton with Alizarin red and subsequent examination for skeleton abnormalities. The rest of the foetuses were fixed in Bouin's fluid and studied for visceral changes.
Maternal rats were subject to gross pathological assessment and the liver, hear, brain spleen and one kidney were removed and weighed. The following tissue samples were taken from each animal and fixed: brain, heart, pituitary, thyroid, parathyroid, thymus, lungs, trachea and bronchi, bronchial node, liver, kidney, adrenal gland, spleen, skeleton muscle, peripheral nerve, salivary gland, skin, bone marrow, ovaries, uterus and bladder.
Maternal blood samples were taken for haematological and clinical chemistry assessments.
Following gross pathological examination a liver sample was taken from maternal animals for liver protein aniline hydroxylase (AH) and aminopyrine demethylase (APDM) activity.
Results
Body and Organ Weights: There were no effects on maternal weight, liver, kidney or spleen weights resulting from treatment with test substance.
Foetal effects: There were no effects or litter size, incidence of resorptions, foetal weight or incidence of visceral anomalies resulting from treatment with test substance.
Histopathology: There were no dose related histological, changes in mother or foetuses resulting from treatment with test substance.
Haematology: Maternal haematological parameters assessed showed no affects from treatment with test substance.
Clinical Chemistry: Maternal clinical chemistry parameters assessed showed no affects from treatment with test substance.
Liver Enzymes: Maternal liver enzyme parameters assessed showed no affects from treatment with test substance.
Foetal toxicity: There was some of evidence of dose related increase in sternebra aberrations and observations of interparietal anomalies in foetuses at 100 and 200 mg/kg bw/day. These were considered to be the result of a foetal toxicity effect and not teratogenicity related.
Conclusion
The test substance was not considered teratogenic to Sprague-Dawley rats. The study No Observed Effect Level (NOEL) for teratogenicity was 200 mg/kg bw/day (highest dose administered).
There was some evidence of a foetal toxicity caused by the test substance. The study No Observed Adverse Effect Level (NOAEL) for foetal toxicity was considered to be 100 mg/kg bw/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.