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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 690-995-3 | CAS number: 756-12-7
- 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
Endpoint summary
Administrative data
Description of key information
Repeat-dose oral and inhalation toxicity studies have been conducted on CAS# 756-12-7. The results of the studies are:
A 5 day inhalation study resulted in a repeat inhalation LC50 greater than 5,000 ppm.
A 28 day inhalation study resulted in a NOAEC of 3,000 ppm
Key value for chemical safety assessment
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 22 March 2011 to 04 October 2011
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study conducted under GLP conditions.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- yes
- Species:
- rat
- Strain:
- other: Sprague Dawley Crl:CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Inc., Raleigh, NC, USA
- Age at study initiation: Approx. 39 days old
- Weight at study initiation:
- Fasting period before study: None
- Housing: Individually in suspended cages.
- Diet (e.g. ad libitum): Certified Rodent LabDiet 5002 (meal) (PMI Nutrition International, LLC) provided ad libitum.
- Water (e.g. ad libitum): Reverse osmosis treated water provided ad libitum.
- Acclimation period: 19 days previous to treatment.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.3-22
- Humidity (%): 42.8-52.8
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light):12/12
IN-LIFE DATES: From: 22 March 2011 To: 20 May 2011 - Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: Air
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 1000 L stainless steel and glass whole-body inhalation exposure chamber. One chamber for each group
- Method of holding animals in test chamber: Animals were placed into exposure caging and placed into the chamber in the cage.
- Source and rate of air: HEPA and charcoal-filtered, temperature and humidity-controleed source.
- Method of conditioning air:
- System of generating particulates/aerosols: Vapor was generated by releasing test substance vapor from the orignial cylinder, heated to approximately 35 degrees Celsius.
- Temperature: 21.3-22 degrees Celsius.
-Humidity: 42.8-52.8% humidity
- Air flow rate:
- Air change rate: At least 12 to 15 air changes per hour.
- Treatment of exhaust air: HEPA and charcoal filter.
TEST ATMOSPHERE
- Brief description of analytical method used: Determined using a gas chromatogram. Samples collected from animal-breathing zone. Concentration in parts per million was calculated.
- Samples taken from breathing zone: yes - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Exposure concentrations were analyzed at 35-minute intervals using a gas chromatogram. Samples were collected from the approximate animal-breathing zone.
- Duration of treatment / exposure:
- 6 hours a day
- Frequency of treatment:
- 5 days a week, for 4 weeks.
- Remarks:
- Doses / Concentrations:
500, 1000, 3000 ppm
Basis:
analytical conc. - No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- - Dose selection rationale: Based on results from a previous actue inhalation study conducted at 10,000 and 20,000 ppm.
- Rationale for selecting satellite groups:
- Post-exposure recovery period in satellite groups: 2 week recovery period. - Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily, once in the morning and once in the afternoon.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Prior to exposure, during exposure (midpoint), and 0 to 1 hour following exposure.
BODY WEIGHT: Yes
- Time schedule for examinations: Recorded approximately weekly throughout the study starting during the pretest period.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption was recorded approximately weekly.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
- Time schedule for examinations:
OPHTHALMOSCOPIC EXAMINATION: No
- Time schedule for examinations:
- Dose groups that were examined:
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At primary necropsy (study day 26).
- Anaesthetic used for blood collection: Yes, isoflurane
- Animals fasted: Yes
- How many animals: 10 animals/sex/main study group and < or equal to 5 animals/sex in the control and 3000 ppm groups.
- Parameters checked in table appendix K were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At primary necropsy (study day 26).
- Animals fasted: Yes
- How many animals:10 animals/sex/main study group and < or equal to 5 animals/sex in the control and 3000 ppm groups.
- Parameters checked in table appendix K were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: At primary necropsy
- Metabolism cages used for collection of urine:No data
- Animals fasted: Yes
- Parameters checked in appendix K were examined.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: Prior to the initiation of exposure and during study week 3 (following 20 exposures.
- Dose groups that were examined: All
- Battery of functions tested: sensory activity / grip strength / motor activity / - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, Appendix K
HISTOPATHOLOGY: Yes, Appendix K - Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- 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
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY: No mortality occured. Yellow and/or red material on various body surfaces were noted in the 500, 1000, and 3000 ppm main study and satellite groups.
BODY WEIGHT AND WEIGHT GAIN: No treatment related effects.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No effects.
HAEMATOLOGY: No effects.
CLINICAL CHEMISTRY: Lower globulin and glucose levels with corresponding higher albumin/globulin (A/G) ratios noted in the 500, 1000, and 3000 ppm group males and females.
URINALYSIS: No effects.
NEUROBEHAVIOUR: No effects.
ORGAN WEIGHTS: Higher lung weights were noted in the 3000 ppm main study group at the primary necropsy and correlated with microscopic alteration of increased alveolar macrophages, increased BALT, and perivascular mononuclear cell infiltrates at 500 ppm and greater. Laryngeal epithelial degeneration at 3000 ppm and cecal hyperplasia at 500 ppm or greater were also noted. Lung and cecal alterations were partially recovered on study day 40, and the laryngeal alteration was fully recovered.
GROSS PATHOLOGY: No effects. - Dose descriptor:
- NOAEC
- Effect level:
- ca. 3 000 ppm (analytical)
- Sex:
- male/female
- Basis for effect level:
- other: overall effects
- Critical effects observed:
- not specified
- Conclusions:
- Tthe No-Observed-Adverse-Effect Concentration (NOAEC) was 3000 ppm of the test article in male and female rats exposed by whole-body inhalation for 6 hours/day, 5 days/week, for 4 weeks based on the reversibility of the test article-related effects.
- Executive summary:
The inhalation (vapor) toxicity potential of the test article (clear and colorless liquid, purity 99.98%) was evaluated in male and female Sprague-Dawley rats via whole-body inhalation for 6 hours/day, 5 days/week, for 4 weeks (20 total exposures). This study was performed in compliance with EPA GLP 40 CFR Part 792 (1989), OECD GLP C97 186 (1997), and Japanese MAFF GLP No. 3850 (1984). The study design was based on OECD Guideline 412 (2009). Main phase rats (10/sex/group) were exposed to filtered air (control) or filtered air containing 500 ppm, 1000 ppm, or 3000 ppm of the test article (equivalent doses were 5.44 mg/L, 10.88 mg/L, and 32.64 mg/L respectively), for 6 hour exposures, 5 days per week for 4 weeks (20 total exposures). Recovery rats (5/sex/group) were exposed to filtered air or 3000 ppm of the test article in the same manner to be followed for a 2 week recovery period after the exposure period. Satellite rats (5/sex/group) were exposed at 500 ppm, 1000 ppm, or 3000 ppm of the test article in the same manner as main phase rats. In all study animals, detailed physical examinations were preformed weekly, clinical observations were recorded daily, and body weights and food consumption were recorded weekly. A functional observational battery and motor activity tests were performed in all animals except the satellite rats at weeks 3 and 5 of the study. Main phase animals were necropsied on Day 26 and selected tissues were examined microscopically. In the satellite animals, necropsies were performed on Day 26 of the study and livers were collected for a peroxisome proliferation assay (PPAR). Necropsies were performed on the recovery group rats following the two week recovery period and selected tissues were examined microscopically. All animals survived. Test substance-related observations of yellow and/or red material on the body surface were noted in the 500, 1000, and 3000 ppm main study and satellite groups of animals. Test substance-related effects on serum chemistry parameters included lower globulin and glucose levels with corresponding higher albumin/globulin rations noted in 500, 1000, and 3000 ppm group male and female rats. These changes were considered non-adverse due to the small magnitude of the change being within historical parameters. Lung weights were higher in the 3000 ppm main study group at primary necropsy and correlated with increased alveolar macrophages, increased bronchial/bronchiolar associated lymphoid tissue (BALT), and perivascular mononuclear cell infiltrates at greater than or equal to 500 ppm. Laryngeal epithelial degeneration at 3000 ppm and cecal hyperplasia at greater than or equal to 500 ppm were observed. The lung and cecal alterations were found to be partially recovered on study day 40, and the laryngeal alteration was fully recovered. There also appeared to be a small sex difference in the rate of B-oxidation, but it did not appear to significantly induce peroxisomal proliferation. There were no toxicologically relevant changes in body weights, food consumption, FOB, hematology, coagulation or urinalysis parameters. In the female, the ovaries, uterus, cervix, and vagina were microscopically evaluated for changes in the estrous cycle, and a high incidence of diestrus was observed in the 3000 ppm group. All these tissues appeared normal, and consequently, the incidence of diestrus was considered normal. All other organs (weights and macroscopic observations) evaluated were considered to be not affected by the test substance. Based on the results of the study, the No-Observed-Adverse-Effect Concentration (NOAEC) was 3000 ppm of the test article in male and female rats exposed by whole-body inhalation for 6 hours/day, 5 days/week, for 4 weeks based on the reversibility of the test article-related effects.
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 07 December 2009 to 11 December 2009
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study not conducted under GLP conditions, but followed sound scientific methods.
- Qualifier:
- according to guideline
- Guideline:
- other: Conducted according to custom 3M protocol
- Principles of method if other than guideline:
- 4 male rats were whole body exposed to the test article at 5,000 ppm (v/v) for 6 hours per day on five consecutive days. Clinical observations were recorded continuously during each exposure. Gross necropsies were conducted immediately after the last exposure on day 5.
- GLP compliance:
- no
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 191-199 grams
- Fasting period before study:No data
- Housing: All animals were double-housed in standard solid bottom cages after each exposure.
- Diet (e.g. ad libitum): harlan Teklad Rat/Mouse 2018 Diet (Harlan Teklad, Madison, WI) ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: No data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.6-23.9
- Humidity (%): 30-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 07 December 2009 To: 11 December 2009 - Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: unchanged (no vehicle)
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 40 liter test chamber
- Method of holding animals in test chamber: No data
- Source and rate of air: No data
- Method of conditioning air: No data
- System of generating particulates/aerosols:
- Temperature, humidity, pressure in air chamber: Temp: 20.6-23.9 degrees Celsius, Humidity: 37-93%
TEST ATMOSPHERE
- Brief description of analytical method used: No data
- Samples taken from breathing zone: No data - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 6 hour exposure once daily, for 5 consecutive days
- Frequency of treatment:
- Daily for 5 consecutive days.
- Remarks:
- Doses / Concentrations:
5000 ppm (v/v)
Basis:
nominal conc. - No. of animals per sex per dose:
- 4 male rats were dosed at 5000 ppm
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- - Dose selection rationale: 4 hour acute inhalation LC50 was found to be > 10000 ppm in a previous study.
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Continuously during exposure..
DETAILED CLINICAL OBSERVATIONS No data
BODY WEIGHT: Yes
- Time schedule for examinations: Prior to exposure each day
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: No
-CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At necropsy
- Animals fasted: No data
- How many animals: 8 males (4 treatment, 4 control)
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: No - Statistics:
- A Student's T-Test was used to calculate statistical significance between control and test animal data
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- 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:
- not examined
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY: No abnormal clinical signs or mortality occurred.
BODY WEIGHT AND WEIGHT GAIN: Treated animals had lower mean body weight gain.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
FOOD EFFICIENCY
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study)
OPHTHALMOSCOPIC EXAMINATION
HAEMATOLOGY
CLINICAL CHEMISTRY: Treated rats had statistically significantly higher albumin, sodium, and A/G ratios while serum cholesterol, calcium, chloride, LDH, and globulin results were statistically significantly lower than controls.
URINALYSIS
NEUROBEHAVIOUR
ORGAN WEIGHTS: Treated rats had higher mean liver weights than controls - Dose descriptor:
- other: 5 Day Inhalation LC50
- Effect level:
- > 5 000 ppm
- Sex:
- male
- Basis for effect level:
- other: No mortality occurred during the study.
- Critical effects observed:
- not specified
- Conclusions:
- Based on the results of this study, the 5-day repeat inhalation LC50 of the test article is greater than 5,000 ppm.
- Executive summary:
This study evaluated the inhalation toxicity potential of the test article (supplied as liquid, 99.67% pure) in male Sprague-Dawley rats after 5 daily whole body repeat inhalation exposures. This study was performed according to a custom 3M protocol and was not intended to comply with GLP guidelines. Rats (4 males) were exposed whole body to the test article at atmospheric concentrations of 5,000 ppm (v/v) for 6 hours per day on five consecutive days. Clinical observations were recorded continuously during each exposure period. Gross necropsies were conducted immediately after the last exposure on Day 5. Blood chemistry analysis was performed on serum samples. No abnormalities were noted in any of the animals during the study. All animals were active and appeared normal after removal from the chamber at the end of each exposure. Compared to controls, test article-treated rats had statistically significant increases in the following serum chemistry values: albumin, sodium, and A/G ratio; there were statistically significant decreases in cholesterol, calcium, chloride, LDH, and globulin. The test article-treated rats, when compared to control rats, had lower mean body weight gain and higher mean liver weights. Although there were evidences of changes in calcium, sodium, and chloride levels in serum, however, there was no change in kidney weights and there is no other indication of kidney toxicity. Based on the results of this study, the 5-day repeat inhalation LC50 of the test article is greater than 5,000 ppm.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
Additional information
Justification for classification or non-classification
The results of these tests do not meet the requirement to classify CAS# 756-12-7 as dangerous.
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.