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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 200-262-8 | CAS number: 56-23-5
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Accepable, well- documented publication which meets basic scientific principles
Data source
Reference
- Reference Type:
- publication
- Title:
- Uptake, distribution, and elimination of carbon tetrachloride in rat tissues following inhalation and ingestion exposures.
- Author:
- Sanzgiri UY, Srivatsan V, Muralidhara S, Dallas CE, Bruckner JV.
- Year:
- 1 997
- Bibliographic source:
- Toxicol Appl Pharmacol. vol. 143, no. 1, p. 120-9.
Materials and methods
- Objective of study:
- absorption
- distribution
- excretion
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- - Male Sprague-Dawley rats exposed to 1000 ppm CTC for 2 hr or to 179 mg/Kg bw CTC as a single oral bolus or or by constant gastric infusion over a period of 2 hr.
- GLP compliance:
- no
Test material
- Reference substance name:
- Carbon tetrachloride
- EC Number:
- 200-262-8
- EC Name:
- Carbon tetrachloride
- Cas Number:
- 56-23-5
- Molecular formula:
- CCl4
- IUPAC Name:
- tetrachloromethane
- Details on test material:
- - Name of test material (as cited in study report): carbon tetrachloride
- Physical state: liqid
- Analytical purity: Analytical-grade (99.9% pure)
- Lot/batch No.: not reported
- supplier: EM Science (EM Industries, Cherry Hill, NJ, U.S.A.)
- Stability under test conditions: stable
- Storage condition of test material: not reported
Constituent 1
- Radiolabelling:
- no
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Raleigh, NC, U.S.A.
- Age at study initiation: not reported
- Weight at study initiation: 325-375 g
- Fasting period before study: 18 hr prior to CTC exposure
- Housing: not reported
- Individual metabolism cages: no
- Diet (e.g. ad libitum): Purina Lab Chow 5001, St. Louis, MO, U.S.A., ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 1 wk
ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12
- other: room reported to be environmentally controled
Administration / exposure
- Route of administration:
- other: inhalation, oral: gavage, oral: gastric infusion
- Vehicle:
- other: inhalation: unchanged (no vehicle); gavage and gastric infusion: emulphor
- Details on exposure:
- inhalation exposure:
TYPE OF INHALATION EXPOSURE: whole body
GENERATION OF TEST ATMOSPHERE / CHAMPER DESCRIPTION
- Exposure apparatus: 1 m³ Rochester-type dynamic flow chamber
- Method of holding animals in test chamber: individual cages
- Source and rate of air: not reported
- Method of conditioning air: not reported
- System of generating particulates/aerosols: not applicable, substance is a volatile solvent
- Composition of vehicle (if applicable): no vehicle use in inhalation experiment
- Concentration of test material in vehicle (if applicable): not applicable
- Method of particle size determination: not applicable
- Treatment of exhaust air: not reported
TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: not applicable
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):
oral administration:
PREPARATION OF DOSING SOLUTIONS: 179 mg/Kg bw CTC,kg was administered per oral as an aqueous emulsion using 5% Emulphor in 0.9% saline,
in a volume of 5 ml/kg bw.
GAVAGE:
- administration: 179 mg/kg bw by gavage as a single oral bolus (5 mL/kg bw)
GASTRIC INFUSION:
- infusion installation: gastric cannula (PE-50 tubing), surgically implanted days prior to the exposure
- exposure: infusion of 5 mL/Kg bw solution (CTC in vehicle) with gastight syringes mounted on a Harvard microinfusion pump at a constant rate into the stomach (via the indwelling cannula) of each rat for 2 hr
VEHICLE
- Justification for use and choice of vehicle (if other than water): Emulphor ( a polyethoxylated vegetable oil is a common vehicle for volatine solvents
- Concentration in vehicle: 5% (v/v) in 0.9% (v/v) saline
- Amount of vehicle (if gavage): 250 µL/Kg bw (in 5 mL/kg bw water)
- Identity: Alkamuls
- Source: GAF Co. (New York, NY, U.S.A.)
- Duration and frequency of treatment / exposure:
- - inhalation: once for 2 h
- gavage: single oral bolus dose
- gastric infusion: once for 2 h
Doses / concentrations
- Remarks:
- Doses / Concentrations:
- inhalation: 1000 ppm (= 6.4 g/m³)
- gavage: 179 mg/Kg bw in 5 mL/Kg bw
- gastric infusion: 179 mg/Kg bw in 5 mL/Kg bw
- No. of animals per sex per dose / concentration:
- - inhalation: 25
- gavage: 45
- gastric infusion: 50 - Control animals:
- no
- Positive control reference chemical:
- no
- Details on study design:
- - Dose selection rationale:
The total systemically absorbed dose in rats inhaling 1000 ppm CTC for 2 hr was determined to be 179 mgkg bw. The procedure of Dallas et al. (Dallas, C. E., Bruckner, J. V., Maedgen, J. L., and Weir, F. W. (1986). A method for direct measurement of systemic uptake and elimination of volatile organics in small animals. J. Pharmacol. Methods 16,239-250. Dallas, C. E., Ramanathan, R., Muralidhara, S., Gallo, J. M., and Bruckner, J. V. (1989). The uptake and elimination of l,l,l-trichloroethane during and following inhalation exposures in rats. Toxicol. Appl. Pharmacol. 98, 385-397.) was utilized to measure CTC uptake in individual rats inhaling through a miniaturized one-way breathing valve. The minute volume and inhaled and exhaled CCI, concentrations were monitored for 2 hr. Subtraction of the quantity of CC1, exhaled from the quantity of CCI, inhaled yielded the amount of CC1, absorbed during each sampling period. Summing these quantities over time yielded the cumulative uptake, or total dose of the chemical absorbed over 2 hr (i.e., 179 mgkg).
Therefore 179 mg/Kg bw was chosen to be the adequate dose for the gavage and the gastric infusion experiments
- Animals were terminated at selected time intervals during and postexposure and tissues (liver, kidney, lung, brain, fat, skeletal muscle, spleen, heart, and GI tract) removed for measurement of their CTC content by headspace gas chromatography - Details on dosing and sampling:
- PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: see experimental desidn for details
- Time and frequency of sampling:
inhalation: 0, 120, 240, 480, 1440 min post start of exposure
gavage: 0, 5, 15, 60, 120, 240 480, 720 1080 and 1440 min post exposure
gastric infusion: 30, 60, 120, 150, 180, 360, 450, 720, 1080, 1440 min post start of exposure
METABOLITE CHARACTERISATION STUDIES
only the parent compound (=test item) was analyzed
- Method type(s) for identification GC
- Limits of detection and quantification: 1 ng
- see experimental design for details
Results and discussion
- Preliminary studies:
- none
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- CTC is readily absorbed via the gastro intestinal tract: Liver levels were highest at 1 min post dosing, but declined quite rapidly thereafter.
see table 1 for details - Details on distribution in tissues:
- CTC is readily distributed via the blood circulation: Maximum CTC concentrations in most tissues other than liver were reached 5 to 15 min postdosing. CTC uptake and elimination in fat tissue were considerably slower than in other tissues leading to much higher CTC levels in fat. Cmax, CLmax and AUC values were comparable for tissues other than fat and liver.
see table 1 for details
- Details on excretion:
- mainly via exhalation and partly via metabolism
Toxicokinetic parameters
- Toxicokinetic parameters:
- other: CTC is absorbed readily from the gastrointestinal and respiratory tracts, and more slowly through the skin. It is distributed to all major organs, with highest concentrations in the fat, liver, bone marrow, adrenals, blood, brain, spinal cord, and kidney.
Metabolite characterisation studies
- Metabolites identified:
- no
Any other information on results incl. tables
- Table 1: pharmacokinetics of CTC in tissues of rats following the different applications
Inhalation (1000 ppm for 2 h) |
|||||
Tissue |
t1/2 (min) |
AUC (0 – 1440 min) (µg × min/mL) |
Clapp (mL/min/kg) |
Cmax (µg/g) |
Tmax (min) |
Liver |
249 |
2,823 |
63 |
20 |
30 |
Kidney |
204 |
3,064 |
58 |
25 |
30 |
Lung |
226 |
2,952 |
61 |
24 |
30 |
Brain |
248 |
3,255 |
55 |
28 |
30 |
Fat |
665 |
230,699 |
0.8 |
1506 |
240 |
Heart |
274 |
2,571 |
70 |
18 |
30 |
Muscle |
218 |
3,248 |
55 |
18 |
30 |
GI tract |
224 |
1,139 |
158 |
20 |
30 |
Spleen |
273 |
2,035 |
88 |
13 |
30 |
Gavage (179 mg/Kg bw, single oral dose) |
|||||
Tissue |
t1/2 (min) |
AUC (0 – 1440 min) (µg × min/mL) |
Clapp (mL/min/kg) |
Cmax (µg/g) |
Tmax (min) |
Liver |
323 |
1,023 |
175 |
58 |
1 |
Kidney |
278 |
3,029 |
59 |
14 |
5 |
Lung |
442 |
2,908 |
62 |
10 |
15 |
Brain |
313 |
4,223 |
42 |
15 |
15 |
Fat |
780 |
235,471 |
0.8 |
246 |
120 |
Heart |
490 |
2,747 |
65 |
10 |
5 |
Muscle |
649 |
4,117 |
43 |
7 |
60 |
Spleen |
472 |
4,096 |
44 |
12 |
5 |
Gastric infusion |
|||||
Tissue |
t1/2 (min) |
AUC (0 – 1440 min) (µg × min/mL) |
Clapp (mL/min/kg) |
Cmax (µg/g) |
Tmax (min) |
Liver |
269 |
149 |
1,198 |
0.5 |
120 |
Kidney |
190 |
800 |
224 |
4 |
120 |
Lung |
249 |
2,842 |
72 |
6 |
180 |
Brain |
250 |
2,683 |
67 |
10 |
150 |
Fat |
358 |
165,983 |
1 |
179 |
360 |
Heart |
216 |
1,900 |
94 |
8 |
120 |
Muscle |
262 |
2,164 |
83 |
10 |
150 |
Spleen |
208 |
1,660 |
108 |
6 |
150 |
tmax calculated from start of exposure
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): no bioaccumulation potential based on study results (liver, kidney, lung, brain, fat, skeletal muscle, spleen, heart, and GI tract)
Very low bioaccumulation potential. - Executive summary:
The study (Sanzgiri 1997) describes the uptake, the distribution and the elimination of CTC in rats after exposure through 3 different routes (inhalation, 1000 ppm, 2 h; gavage, 179 mL/Kg bw single bolus dose; gastric infusion, 179 mg/Kg bw within 2 h). The study is not conducted according to an official guideline.
The pharmacokinetic properties of CTC were analyzed by treating male Sprague-Dawle rats with either 1000 ppm CTC for 2 hr by inhalation, by a single oral dose of 179mg/Kg bw via gavage and by a constant gastric infusion over a period of 2 hr also with totally 179 mg/Kg bw. Animals were terminated at selected time intervals during and post exposure and tissues (liver, kidney, lung, brain, fat, skeletal muscle, spleen, heart, and GI tract) removed for measurement of their CTC content by headspace gas chromatography. By gavage maximal tissue concentrations were reached fastest followed by inhalation and then gastric infusion. In all routes the distribution of CTC was comparable for all tissues except for liver after gavage, where higher levels were attained faster than by the other two routes.
Concentrations in fat tissues were found to reach much higher levels than any other tissue regardless of the route while the kinetics of absorption as well as the release of CTC was much slower in fat than in all other tissues. In general the total tissue concentrations over time (AUC (0 – infinity)) were comparable between inhalation and gavage and lower in gastric infusion. Compared to inhalation, lower tissue levels after gastric infusion (same exposure period) are due to first pass elimination in the latter route (exhalation and metabolism + excretion through the liver). This elimination works more efficient when continuous low concentrations are absorbed as in gastric infusion as compared to a fast peaking absorption after single bolus exposure via gavage. This explains the differences between the two moral routes. In summary the absorption and desorption of CTC is fast for all tissues except for fat. Absorption of identical amounts of CTC via inhalation and gavage are comparable. The absorption after a single bolus dose via gavage is higher than after gastric infusion as the first pass elimination is overloaded. Therefore gavage is a worst case scenario for assessment of risks of CTC contaminations in food and drinking water.
Due to the low elimination half life of CTC in the tissues low to no bioaccumulation potential for CTC is expected.
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.