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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
Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.29 mg/m³
- Most sensitive endpoint:
- carcinogenicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 12.5
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 16.1 mg/m³
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 1
- Justification:
- A chronic study has been used
- AF for interspecies differences (allometric scaling):
- 1
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 5
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.91 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
- Hazard assessment conclusion:
- no DNEL required: short term exposure controlled by conditions for long-term
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
Carbon tetrachloride (CTC) is classified for acute dermal, oral and inhalation toxicity. Nevertheless animal studies failed to show a potential of acute toxicity by any route. Human case of poisoning are probably responsible for this classification since low amount of the substance were reported to be involved in human case of poisoning by ingestion. Nevertheless, the level of exposure for human fatal poisoning is very approximate and cannot be used as a point of departure for the derivation of a DNEL. Moreover, no acute oral exposure is expected for workers, and the derivation of long-term dermal and inhalation DNELs are supposed to prevent from acute exposure following the respective routes.
Occupational exposure to CTC occurs mainly by inhalation exposure, but may also occur by dermal exposure. For the inhalation route, DNELs have been derived from repeated dose toxicity studies as well as from developmental toxicity and fertility studies/
DNEL long-term for workers, inhalation, systemic toxicity
The approach is based on the recommendations given in the ECHAGuidance Document on Information Requirements and Chemical Safety Assessment, and inthe ECHA Practical Guide for Derivation of DNELs. The DNEL calculation has been taken from the updated CSR (2016).
Step 1: Selection of the relevant dose descriptor (starting point):
The combined chronic toxicity study/carcinogenicity study by Nagano et al. (2007b) is selected for the DNEL derivation. In this study, the inhalation NOAEL is 32 mg/m3 (5 ppm) based on liver effects in rats (especially liver fatty changes, increase of serum enzymes indicative of liver damage). This result is supported by the 90-day inhalation study (Nagano et al., 2007a) in which the NOAEL is 63 mg/m3 (10 ppm) based on liver fatty changes only.
Step 2: Correction of exposure duration and respiratory volume: total is 0.5025
Correction for activity driven differences in respiratory volume in workers compared to individuals at rest (6.7 m3/10 m3) and correction for an 8-hour duration exposure (6/8)
Step 3: Correction for life-time exposure: 1 (as a chronic study has been used)
Step 4: Use of assessment factors for inter- and intraspecies differences: total 12.5
Interspecies: 2.5 for remaining differences (for inhalation, no allometric scaling needed)
Intraspecies: 5 for workers
Using this approach, the DNEL long-term for workers, inhalation, systemic toxicity is calculated to be 1.29 mg/m3, which is equivalent to 0.2 ppm.
DNEL inhalation systemic, for workers based on reproductive toxicity studies
1.1. DNEL long-term derived from developmental toxicity study
A developmental toxicity study with inhalation exposure is available (Schwetz et al., 1974), which has been judged to beequivalent or similar to OECD Guideline 414 (OECD, 2011). In this study, a LOAEC of 2100 mg/m3(334 ppm) was found. If this LOAEC would be used to set a DNEL for long-term inhalation exposure, also taking into account the exposure duration of the study, the following DNEL would be obtained:
Step 1: Selection of the relevant dose descriptor (starting point):
According to the ECHA Guidance Documents, a factor of 3 needs to be applied to convert the LOAEC into an NOAEC. This results in an NOAEC (dose descriptor) of 700 mg/m3 (111 ppm).
Step 2: Correction of exposure duration and respiratory volume: total is 0.58625
Correction for activity driven differences in respiratory volume in workers compared to individuals at rest (6.7 m3/10 m3) and correction for an 8-hour duration exposure (7/8).
Step 3: Correction for life-time exposure: 6 (as a developmental toxicity study has been used)
Step 4: Use of assessment factors for inter- and intraspecies differences: total 12.5
Interspecies: 2.5 for remaining differences (for inhalation, no allometric scaling needed)
Intraspecies: 5 for workers
Using this conservative approach, the DNEL long-term for workers, inhalation based on a developmental toxicity study, is calculated to be 5.47 mg/m3, which is equivalent to 0.87 ppm.
1.2. DNEL long-term derived from fertility studies
To estimate the DNEL inhalation long-term, based on potential fertility effects, a NOAEC-value of 630 mg/m3 (100 ppm) from a multi-generation study (Smyth et al,. 1936) and an inhalation study by Adams et al.(1952) has been used. If this NOAEC would be used to set a DNEL for long-term inhalation exposure, also taking the duration of this study into account, the following DNEL would be obtained:
Step 1: Selection of the relevant dose descriptor (starting point):
NOAEC is 630 mg/m3(= 100 ppm).
Step 2: Correction of exposure duration and respiratory volume: total is 0.5025
Correction for activity driven differences in respiratory volume in workers compared to individuals at rest (6.7 m3/10 m3) and correction for an 8-hour duration exposure (6/8)
Step 3: Correction for life-time exposure: 2 (as a sub-chronic type of study has been used)
Step 4: Use of assessment factors for inter- and intraspecies differences: total 12.5
Interspecies: 2.5 for remaining differences
Intraspecies: 5
Using this approach, the DNEL long-term for workers, inhalation, based on the existing fertility studies, is estimated to be 12.66 mg/m3, which is equivalent to 1.81 ppm.
If the oral study of Alumotet al. (1976) were taken into account for comparison, with a NOAEL of 10 mg/kg bw/day, the following calculation could be done:
Step 1: Selection of the relevant dose descriptor (starting point):
NOAEL is 10 mg/kg bw/day.
Step 2: Correction of activity and respiratory volume: 2.468
Correction for activity driven differences in respiratory volume in workers compared to individuals at rest (6.7 m3/10 m3) and correction for respiratory volume is 1/0.38. In addition, correction for 5 days exposure instead of 7 days is needed. No correction needed for absorption as carbon tetrachloride is readily absorbed by both routes of exposure.
Step 3: Correction for life-time exposure: 1 (2-year study)
Step 4: Use of assessment factors for inter- and intraspecies differences: total 12.5
Interspecies: 2.5 for remaining differences
Intraspecies: 5
The DNEL long-term for workers, inhalation, based on the existing oral fertility study, is estimated to be 1.974 mg/m3, which is equivalent to 0.32 ppm.
Conclusion for the inhalation route
The established DNELvalue (for workers) for systemic (liver) toxicity by inhalation is lower than those obtained when using NOAELs/NOAECs from reproductive and developmental toxicity studies. Thus,the DNEL based on liver toxicity will also be protective against potential reproductive effects.
Long term, systemic, dermal DNEL (workers)
It is proposed to proceed with a route to route extrapolation, from the inhalation DNEL value.
Dermal DNEL = (inhalatory DNEL x ABS inh-human / ABS dermal-human * 10)/70 where 10 is the respiratory volume of workers and 70 the body weight of worker; ABS inh-human = 100 %; ABS dermal-rat = 100 %
Long-term, systemic, dermal DNEL is 0.91 mg/kg
Local long-term dermal DNEL
In addition, an induction-specific DNEL was derived for skin sensitisation according to Guidance on information requirements and chemical safety assessment, Chapter R.8 (ECHA, May 2008) based on the EC3 value from an LLNA study (BAMM 2006). The EC3 value was reported to be 58 % w/v (14500 μg/cm²), indicative of a sensitiser of weak potency (ECETOC 2003). The EC3 value (in µg/cm2) can be considered as the NOAEL for induction, based on the Guidance on information requirements and chemical safety assessment, Chapter R.8.
Interspecies:
A number of other organizations were able to empirically show that the EC3 value (in µg/cm2) also closely correlates with the NOEL from human sensitization tests designed to confirm lack of induction (Api et al., 2006, Api et al., 2008, ECETOC TR87, 2003). Therefore, it seems appropriate to use the EC3, expressed as dose per skin area, as a surrogate for the human sensitisation threshold without the modification by uncertainty factors.
Intraspecies:
It is recognized that a general DNEL must take into account that the threshold for skin sensitisation varies between individuals. This may be due to differences in parameters such as genetic effects, sensitive subpopulations, inherent barrier function, age, gender, and ethnicity (Api et al., 2008). Whereas the latter three are recognized to have some effect on the sensitisation threshold, it is generally recognized that genetic differences, the inherent barrier function and especially sensitive subpopulations play a major role (Api et al., 2008). The barrier function of the skin may be compromised which in turn may lead to a greater susceptibility of the individual. At the same time the barrier function is thought to be very similar from infancy to adulthood. The influence of the genetic setting is not well understood, however, may be plausible in the light of the immunological effect under consideration. The term sensitive subpopulations refers mostly to individuals who have previously been sensitised to other substances which may increase the susceptibility to further sensitizers (Api et al., 2006, Api et al., 2008). All of these effects make up the intraspecies factor, a factor of 10 is thought to adequately address the combined influence of these effects.
The DNEL for skin sensitisation was calculated to be 1450 µg/cm2/day= 1.45 mg/ cm2/day. Taking into account a hand surface of 960 cm2 and a body weight of 70 kg, the DNEL is 17.4 mg/kg bw, therefore much higher than the long-term systemic DNEL.
Api AM, Basketter DA, Cadby PA, Cano M-F, Graham E, Gerberick F, Griem P, McNamee P, Ryan CA, Safford B (2006). Dermal Sensitization Quantitative Risk Assessment (QRA) for fragrance ingredients. Technical dossier. March 15, 2006 (revised May 2006).
Api AM, Basketter, DA, Cadby PA, Cano M-F, Ellis G, Gerberick GF, Griem P, McNamee PM, Ryan CA, Safford R (2008). Dermal sensitization quantitative risk assessment (QRA) for fragrance ingredients.Reg Toxicol Pharmacol52: 3-23.
ECETOC (2003). Contact Sensitization: classification according to potency. Technical Report No. 87, April 2003.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.107 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 25
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 2.68 mg/m³
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 1
- Justification:
- A chronic study has been used
- AF for interspecies differences (allometric scaling):
- 2.5
- AF for other interspecies differences:
- 1
- AF for intraspecies differences:
- 10
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no DNEL required: short term exposure controlled by conditions for long-term
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
General population around factories is exposed to very low level of carbon tetrachloride (CTC) by inhalation, and is not exposed to CTC by dermal or oral. Nevertheless, long-term inhalation DNEL is calculated for general population.
CTC is classified for acute dermal, oral and inhalation toxicities. Nevertheless animal studies failed to show a potential of acute toxicity by any route. Human case of poisoning are probably responsible for this classification since low amount of the substance were reported to be involved in human case of poisoning by ingestion. Nevertheless, the level of exposure for human fatal poisoning is very approximate and can not be used as a point of departure for the derivation of a DNEL. Moreover, no acute exposure is expected for general population.
Long term, systemic, inhalation DNEL (general population)
The approach is based on the recommendations given in the ECHA Guidance Document on Information Requirements and Chemical Safety Assessment, and in the ECHA Practical Guide for Derivation of DNELs. The DNEL calculation has been taken from the updated CSR (2012).
Step 1: Selection of the relevant dose descriptor (starting point):
The combined chronic toxicity study/carcinogenicity study by Naganoet al.(2007b) is selected for the DNEL derivation. In this study, the inhalation NOAEL is 32 mg/m3 (5 ppm) based on liver effects in rats (especially liver fatty changes, increase of serum enzymes indicative of liver damage). This result is supported by the 90-day inhalation study (Nagano et al., 2007a) in which the NOAEL is 63 mg/m3 (10 ppm) based on liver fatty changes only.
Step 2: Correction of exposure duration and respiratory volume: total is 0.08375
Correction for activity driven differences in respiratory volume (6.7 m3/20 m3)
Correction for continuous exposure (6h/24 h).
Step 3: Correction for life-time exposure: 1 (as a chronic study has been used)
Step 4: Use of assessment factors for inter- and intraspecies differences: total 25
Interspecies: 2.5 for remaining differences (for inhalation, no allometric scaling needed)
Intraspecies: 10 for the general population
Using this approach, the DNEL long-term for the general population, inhalation, systemic toxicity is calculated to be 0.107 mg/m3, which is equivalent to 16.7 ppb.
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