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EC number: 900-600-0 | CAS number: -
- Life Cycle description
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- Endpoint summary
- Appearance / physical state / colour
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- Particle size distribution (Granulometry)
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- Endpoint summary
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- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
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- Toxicological Summary
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- Acute Toxicity
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- Repeated dose toxicity
- Genetic toxicity
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- Specific investigations
- Exposure related observations in humans
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- 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
- Dose descriptor starting point:
- NOAEC
- Value:
- 32 mg/m³
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 16.1 mg/m³
- Explanation for the modification of the dose descriptor starting point:
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)
Correction for an 8-hour duration exposure in human (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.
- AF for dose response relationship:
- 1
- Justification:
- Combined chronic toxicity study/carcinogenicity study in rats exposed by inhalation
- AF for differences in duration of exposure:
- 1
- Justification:
- Combined chronic toxicity study/carcinogenicity study
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Rats exposed by inhalation
- AF for other interspecies differences:
- 2.5
- Justification:
- Remaining uncertainties
- AF for intraspecies differences:
- 5
- Justification:
- Workers
- AF for the quality of the whole database:
- 1
- Justification:
- The whole databse meets the quality required for a REACH dossier
- AF for remaining uncertainties:
- 1
- Justification:
- Not applicable
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:
- 0.184 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 12.5
- Dose descriptor starting point:
- NOAEC
- Value:
- 32 mg/m³
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 2.3 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
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 0.184 mg/kg bw/d
- AF for dose response relationship:
- 1
- Justification:
- Combined chronic toxicity study/carcinogenicity study in rats exposed by inhalation
- AF for differences in duration of exposure:
- 1
- Justification:
- Combined chronic toxicity study/carcinogenicity study in rats exposed by inhalation
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Rtas exposed by inhalation
- AF for other interspecies differences:
- 2.5
- Justification:
- Remaining uncertainties
- AF for intraspecies differences:
- 5
- Justification:
- Worker
- AF for the quality of the whole database:
- 1
- Justification:
- The whole database meets the quality required for REACH dossier
- AF for remaining uncertainties:
- 1
- Justification:
- No further remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
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 0.184 mg/kg bw/d
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
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 25
- Dose descriptor starting point:
- NOAEC
- Value:
- 32 mg/m³
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 2.68 mg/m³
- Explanation for the modification of the dose descriptor starting point:
DNEL long-term for general population, 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 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: 0.08375
Correction for activity driven differences in respiratory volume (6.7 m3% 20 m3)
Correction for an 24-hour duration exposure in human (6/24)
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 general population
Using this approach, the DNEL long-term for general population, inhalation, systemic toxicity is calculated to be 0.01072 mg/m3.
- AF for dose response relationship:
- 1
- Justification:
- Combined chronic toxicity study/carcinogenicity study in rats exposed by inhalation
- AF for differences in duration of exposure:
- 1
- Justification:
- Combined chronic toxicity study/carcinogenicity study
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Rats exposed by inhalation
- AF for other interspecies differences:
- 2.5
- Justification:
- Remaining uncertainties
- AF for intraspecies differences:
- 10
- Justification:
- General population
- AF for the quality of the whole database:
- 1
- Justification:
- The whole databse meets the quality required for a REACH dossier
- AF for remaining uncertainties:
- 2.5
- Justification:
- No remaining uncertainties
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 hazard identified
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
- Value:
- 0.508 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 25
- Dose descriptor starting point:
- NOAEC
- Value:
- 32 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 12.7 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
For general population, the exposure time is 24 hrs per day, 7 days per week for lifetime (75 years).
The selected value (sel. POD) of 32 mg/m3 is adjusted accordingly (corr. POD = sel. POD x 0.288 m3/kg bw x 6 hrs/24 hrs x 5 days/7 days) resulting in corrected points of departure (corr. POD) of 12.7 mg/kg bw/d.
- AF for dose response relationship:
- 1
- Justification:
- Combined chronic toxicity study/carcinogenicity study in rats exposed by inhalation
- AF for differences in duration of exposure:
- 1
- Justification:
- Combined chronic toxicity study/carcinogenicity study
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Rats exposed by inhalation
- AF for other interspecies differences:
- 2.5
- Justification:
- Remaining uncertainties
- AF for intraspecies differences:
- 10
- Justification:
- General population
- AF for the quality of the whole database:
- 1
- Justification:
- The whole database meets the quality required for REACH dossier
- AF for remaining uncertainties:
- 1
- Justification:
- No further remaining uncertainties
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
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.
