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Registration Dossier
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EC number: 278-388-8 | CAS number: 76199-85-4
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 4.93 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 75
- Dose descriptor starting point:
- NOAEL
- Value:
- 300 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 370.26 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Test substance-related systemic effects were reported in a prenatal developmental toxicity study with gavage (OECD TG 414 with rats) and in a reproduction/developmental toxicity screening test (OECD TG 421) . A NOAEL of 300 mg/kg bw/day for general systemic or maternal toxicity, respectively, was established. These effects can most likely be attributed to the partially soluble impurity of the particle, designated as “Halbkondensat CO-HK” (see "Specific investigations", IUCLID chapter 7.9.4.). Thus, a worker-DNEL long-term for inhalation route - systemic is derived from the oral NOAEL for general systemic toxicity of 300 mg/kg bw/day, obtained from the reproduction/developmental toxicity screening test (OECD 421) in rats.
The NOAECcorr. is calculated as follows:
- respiration rate of rat = 0.38 m3 in 8h
- route-specific rate of absorption = 50%/100%
- experimental exposure time = 7 days/week
- exposure time worker = 5 days/week
- standard respiratory volume human = 6.7 m3/8h
- worker respiratory volume (light activity) = 10 m3/8h
--> modified dose descriptor (corrected inhalatory NOAEC) = 300 mg/kg bw/d * (1/0.38 m3/kg/bw) * (50% / 100 %) * (7 d/wk / 5 d/wk) * (6.7 m3/person(8h) / 10 m3/person(8h) = 370.26 mg/m3.
The DNEL is calculated as follows:
- AF Dose-Response Relationship = 1 (NOAEL)
- AF Differences in Duration of Exposure = 6 (subacute study)
- AF Interspecies Differences (Allometric scaling) = 1 (omitted if inhalation DNEL)
- AF Other Interspecies Differences = 2.5 (Default)
- AF Intraspecies Differences = 5 (Default factor for worker)
- AF Quality of the whole database = 1 (Default factor, good quality)
- AF Remaining Uncertainties = 1 (Default factor)
--> systemic DNEL, long-term inhalative, worker = corrected inhalatory NOAEC (370.26 mg/m3) / product of assessment factors (75) = 4.93 mg/m3
- AF for dose response relationship:
- 1
- Justification:
- ECHA REACH Guidance: Starting point for DNEL calculations a NOAEL, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 6
- Justification:
- ECHA REACH Guidance: Default factor needed for extrapolation from subacute to chronic exposure.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- ECHA REACH Guidance: No additional factor needed for inhalation DNELs.
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA REACH Guidance: Default factor.
- AF for intraspecies differences:
- 5
- Justification:
- ECHA REACH Guidance: Default factor for worker.
- AF for the quality of the whole database:
- 1
- Justification:
- ECHA REACH Guidance: The quality of the whole data base is considered to be sufficient.
- AF for remaining uncertainties:
- 1
- Justification:
- ECHA REACH Guidance: Default factor.
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:
- 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
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
Based on all the available data, the test substance is not subject to classification and labeling requirements under the current EU regulation ( Regulation (EC) No. 1272/2008.)
The LD50 for acute oral exposure is greater than 5000 mg/kg bw. For acute inhalative exposure the LC50 is greater than 5.42 mg dust/L air. The test substance is not irritating to skin and eyes and has no skin sensitizing potential. All in vitro and in vivo genetic toxicity studies with the test substance and the analogous test substance CAS 36888-99-0 were negative.
Notably, test substance-related systemic effects were reported in a prenatal developmental toxicity study with gavage (OECD TG 414 with rats) and in a reproduction/developmental toxicity screening test (OECD TG 421) . A NOAEL of 300 mg/kg bw/day for general systemic or maternal toxicity, respectively, was established. These effects can most likely be attributed to the partially soluble impurity of the particle, designated as “Halbkondensat CO-HK” (see "Specific investigations", IUCLID chapter 7.9.4.). Thus, a DNEL for systemic effects after long-term inhalation was calculated for the workers.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.48 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 150
- Dose descriptor starting point:
- NOAEL
- Value:
- 300 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 222.22 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Test substance-related systemic effects were reported in a prenatal developmental toxicity study with gavage (OECD TG 414 with rats) and in a reproduction/developmental toxicity screening test (OECD TG 421) . A NOAEL of 300 mg/kg bw/day for general systemic or maternal toxicity, respectively, was established. These effects can most likely be attributed to the partially soluble impurity of the particle, designated as “Halbkondensat CO-HK” (see "Specific investigations", IUCLID chapter 7.9.4.). Thus, a general population-DNEL long-term for inhalation route - systemic is derived from the oral NOAEL for general systemic toxicity of 300 mg/kg bw/day, obtained from the reproduction/developmental toxicity screening test (OECD 421) in rats.
The NOAECcorr. is calculated as follows:
- respiration rate of rat = 1.35 m3 in 24h
- route-specific rate of absorption = 50%/100%
--> modified dose descriptor (corrected inhalatory NOAEC) = 300 mg/kg bw/d * (1/1.35 m3/kg/bw) * (50% / 100 %) = 222.22 mg/m3.
The DNEL is calculated as follows:
- AF Dose-Response Relationship = 1 (NOAEL)
- AF Differences in Duration of Exposure = 6 (subacute study)
- AF Interspecies Differences (Allometric scaling) = 1 (omitted if inhalation DNEL)
- AF Other Interspecies Differences = 2.5 (Default)
- AF Intraspecies Differences = 10 (Default factor for general population)
- AF Quality of the whole database = 1 (Default factor, good quality)
- AF Remaining Uncertainties = 1 (Default factor)
--> systemic DNEL, long-term inhalative, general population = corrected inhalatory NOAEC (222.22 mg/m3) / product of assessment factors (150) = 1.48 mg/m3
- AF for dose response relationship:
- 1
- Justification:
- ECHA REACH Guidance: Starting point for DNEL calculations a NOAEL, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 6
- Justification:
- ECHA REACH Guidance: Default factor needed for extrapolation from subacute to chronic exposure.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- ECHA REACH Guidance: No additional factor needed for inhalation DNELs.
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA REACH Guidance: Default factor.
- AF for intraspecies differences:
- 10
- Justification:
- ECHA REACH Guidance: Default factor for general population.
- AF for the quality of the whole database:
- 1
- Justification:
- ECHA REACH Guidance: The quality of the whole data base is considered to be sufficient.
- AF for remaining uncertainties:
- 1
- Justification:
- ECHA REACH Guidance: Default factor.
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:
- DNEL (Derived No Effect Level)
- Value:
- 0.5 mg/kg bw/day
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 600
- Dose descriptor starting point:
- NOAEL
- Value:
- 300 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 300 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
no correction needed
- AF for dose response relationship:
- 1
- Justification:
- ECHA REACH Guidance: Starting point for DNEL calculations a NOAEL, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 6
- Justification:
- ECHA REACH Guidance: Default factor needed for extrapolation from subacute to chronic exposure.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- ECHA REACH Guidance: Extrapolation needed from rat to human.
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA REACH Guidance: Default factor.
- AF for intraspecies differences:
- 10
- Justification:
- ECHA REACH Guidance: Default factor for general population.
- AF for the quality of the whole database:
- 1
- Justification:
- ECHA REACH Guidance: The quality of the whole data base is considered to be sufficient.
- AF for remaining uncertainties:
- 1
- Justification:
- ECHA REACH Guidance: Default factor.
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
Test substance-related systemic effects were reported in a prenatal developmental toxicity study with gavage (OECD TG 414 with rats). A NOAEL of 300 mg/kg bw/day for maternal toxicity was established. Moreover, in a reproduction/developmental toxicity screening study (OECD TG 421), the NOAEL for general systemic toxicity was determined to be 300 mg/kg bw/day. These systemic effects can most likely be attributed to the partially soluble impurity of the particle, designated as “Halbkondensat CO-HK” (see "Specific investigations", IUCLID chapter 7.9.4.). Thus, a DNEL for systemic effects after long-term inhalation and oral exposure for the general population was calculated.
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