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EC number: 234-190-3 | CAS number: 10588-01-9
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 43 µg/m³
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: RAC-Note: “Application for Authorisation: Establishing a reference dose-response relationship for carcinogenicity of hexavalent chromium” RAC/27/2013/06 Rev.1, agreed on 4 December 2013 at RAC-27
- Overall assessment factor (AF):
- 37.5
- Dose descriptor starting point:
- LOAEL
- Value:
- 5.2 mg/kg bw/day
- Modified dose descriptor starting point:
- LOAEC
- Value:
- 1.6 mg/m³
- Explanation for the modification of the dose descriptor starting point:
For the derivation of DNELs for the oral, inhalation and dermal routes and the application of route-to-route extrapolation, the following route-specific absorption values for inhalation and dermal specified in the risk characterisation section of the EU RAR and taking into account the available ECHA guidance (lowest absorption value for the starting route and highest absorption value for the end route) have been used. No other relevant absorption values for the inhalation and dermal routes have been identified in the other reviews or publications.
For the oral route, the kinetic section of the EU RAR mentions a range of 2-9% of the dose being absorbed; the risk characterisation section of the EU RAR uses 5% and a value of 10% is mentioned in the original report of the carcinogenicity of chromate (ECHA/2011/01-SR-11). Taking a WoE (weight of evidence) approach, an oral absorption value of 5% would seem to be appropriate.
Oral: 5%
Inhalation: 30%
Dermal : 4%
- AF for dose response relationship:
- 3
- AF for differences in duration of exposure:
- 1
- Justification:
- In the Li et al (2001) study, the rats were treated for only 6 days. Therefore an AF to extrapolate to a long-term DNEL would seem appropriate. However, given that in a much longer exposure study (the sufficiently reliable 90 day study in rats by Chowdhury and Mitra,1995), a clear NOAEL of 7 mg Cr(VI) /kg bw/d was identified and a much higher LOAEL of 14 mg Cr(VI) /kg bw/d for 90 days was established, the RAC is of the opinion that, taking a WoE approach, an additional factor for duration extrapolation is not necessary. It should also be noted that there are several negative studies, including the reliable NTP studies where no effects were identified up to doses much higher than those at which effects have been reported in other studies.
- 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:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (respiratory tract)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- DMEL (Derived Minimum Effect Level)
- Value:
- 1 µg/m³
- Most sensitive endpoint:
- carcinogenicity
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (respiratory tract)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 43 µg/kg bw/day
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: RAC-Note: “Application for Authorisation: Establishing a reference dose-response relationship for carcinogenicity of hexavalent chromium” RAC/27/2013/06 Rev.1, agreed on 4 December 2013 at RAC-27
- Overall assessment factor (AF):
- 150
- Dose descriptor starting point:
- LOAEL
- Value:
- 5.2 mg/kg bw/day
- Modified dose descriptor starting point:
- LOAEL
- Value:
- 6.5 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
For the derivation of DNELs for the oral, inhalation and dermal routes and the application of route-to-route extrapolation, the following route-specific absorption values for inhalation and dermal specified in the risk characterisation section of the EU RAR and taking into account the available ECHA guidance (lowest absorption value for the starting route and highest absorption value for the end route) have been used. No other relevant absorption values for the inhalation and dermal routes have been identified in the other reviews or publications.
For the oral route, the kinetic section of the EU RAR mentions a range of 2-9% of the dose being absorbed; the risk characterisation section of the EU RAR uses 5% and a value of 10% is mentioned in the original report of the carcinogenicity of chromate (ECHA/2011/01-SR-11). Taking a WoE (weight of evidence) approach, an oral absorption value of 5% would seem to be appropriate.
Oral: 5%
Inhalation: 30%
Dermal : 4%
- AF for dose response relationship:
- 3
- AF for differences in duration of exposure:
- 1
- Justification:
- In the Li et al (2001) study, the rats were treated for only 6 days. Therefore an AF to extrapolate to a long-term DNEL would seem appropriate. However, given that in a much longer exposure study (the sufficiently reliable 90 day study in rats by Chowdhury and Mitra,1995), a clear NOAEL of 7 mg Cr(VI) /kg bw/d was identified and a much higher LOAEL of 14 mg Cr(VI) /kg bw/d for 90 days was established, the RAC is of the opinion that, taking a WoE approach, an additional factor for duration extrapolation is not necessary. It should also be noted that there are several negative studies, including the reliable NTP studies where no effects were identified up to doses much higher than those at which effects have been reported in other studies.
- AF for interspecies differences (allometric scaling):
- 4
- 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
- Most sensitive endpoint:
- acute toxicity
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - workers
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 11 µg/m³
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: RAC-Note: “Application for Authorisation: Establishing a reference dose-response relationship for carcinogenicity of hexavalent chromium” RAC/27/2013/06 Rev.1, agreed on 4 December 2013 at RAC-27
- Overall assessment factor (AF):
- 75
- Dose descriptor starting point:
- LOAEL
- Value:
- 5.2 mg/kg bw/day
- Modified dose descriptor starting point:
- LOAEC
- Value:
- 0.8 mg/m³
- Explanation for the modification of the dose descriptor starting point:
For the derivation of DNELs for the oral, inhalation and dermal routes and the application of route-to-route extrapolation, the following route-specific absorption values for inhalation and dermal specified in the risk characterisation section of the EU RAR and taking into account the available ECHA guidance (lowest absorption value for the starting route and highest absorption value for the end route) have been used. No other relevant absorption values for the inhalation and dermal routes have been identified in the other reviews or publications.
For the oral route, the kinetic section of the EU RAR mentions a range of 2-9% of the dose being absorbed; the risk characterisation section of the EU RAR uses 5% and a value of 10% is mentioned in the original report of the carcinogenicity of chromate (ECHA/2011/01-SR-11). Taking a WoE (weight of evidence) approach, an oral absorption value of 5% would seem to be appropriate.
Oral: 5%
Inhalation: 30%
Dermal : 4%
- AF for dose response relationship:
- 3
- AF for differences in duration of exposure:
- 1
- Justification:
- In the Li et al (2001) study, the rats were treated for only 6 days. Therefore an AF to extrapolate to a long-term DNEL would seem appropriate. However, given that in a much longer exposure study (the sufficiently reliable 90 day study in rats by Chowdhury and Mitra,1995), a clear NOAEL of 7 mg Cr(VI) /kg bw/d was identified and a much higher LOAEL of 14 mg Cr(VI) /kg bw/d for 90 days was established, the RAC is of the opinion that, taking a WoE approach, an additional factor for duration extrapolation is not necessary. It should also be noted that there are several negative studies, including the reliable NTP studies where no effects were identified up to doses much higher than those at which effects have been reported in other studies.
- AF for interspecies differences (allometric scaling):
- 1
- AF for other interspecies differences:
- 2.5
- 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:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (respiratory tract)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- DMEL (Derived Minimum Effect Level)
- Value:
- 0.001 µg/m³
- Most sensitive endpoint:
- carcinogenicity
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (respiratory tract)
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 22 µg/kg bw/day
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: RAC-Note: “Application for Authorisation: Establishing a reference dose-response relationship for carcinogenicity of hexavalent chromium” RAC/27/2013/06 Rev.1, agreed on 4 December 2013 at RAC-27
- Overall assessment factor (AF):
- 300
- Dose descriptor starting point:
- LOAEL
- Value:
- 5.2 mg/kg bw/day
- Modified dose descriptor starting point:
- LOAEL
- Value:
- 0.8 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
For the derivation of DNELs for the oral, inhalation and dermal routes and the application of route-to-route extrapolation, the following route-specific absorption values for inhalation and dermal specified in the risk characterisation section of the EU RAR and taking into account the available ECHA guidance (lowest absorption value for the starting route and highest absorption value for the end route) have been used. No other relevant absorption values for the inhalation and dermal routes have been identified in the other reviews or publications.
For the oral route, the kinetic section of the EU RAR mentions a range of 2-9% of the dose being absorbed; the risk characterisation section of the EU RAR uses 5% and a value of 10% is mentioned in the original report of the carcinogenicity of chromate (ECHA/2011/01-SR-11). Taking a WoE (weight of evidence) approach, an oral absorption value of 5% would seem to be appropriate.
Oral: 5%
Inhalation: 30%
Dermal : 4%
- AF for dose response relationship:
- 3
- AF for differences in duration of exposure:
- 1
- Justification:
- In the Li et al (2001) study, the rats were treated for only 6 days. Therefore an AF to extrapolate to a long-term DNEL would seem appropriate. However, given that in a much longer exposure study (the sufficiently reliable 90 day study in rats by Chowdhury and Mitra,1995), a clear NOAEL of 7 mg Cr(VI) /kg bw/d was identified and a much higher LOAEL of 14 mg Cr(VI) /kg bw/d for 90 days was established, the RAC is of the opinion that, taking a WoE approach, an additional factor for duration extrapolation is not necessary. It should also be noted that there are several negative studies, including the reliable NTP studies where no effects were identified up to doses much higher than those at which effects have been reported in other studies.
- AF for interspecies differences (allometric scaling):
- 4
- AF for other interspecies differences:
- 2.5
- 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
- Most sensitive endpoint:
- acute toxicity
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 17 µg/kg bw/day
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: RAC-Note: “Application for Authorisation: Establishing a reference dose-response relationship for carcinogenicity of hexavalent chromium” RAC/27/2013/06 Rev.1, agreed on 4 December 2013 at RAC-27
- Overall assessment factor (AF):
- 300
- Dose descriptor starting point:
- LOAEL
- Value:
- 5.2 mg/kg bw/day
- AF for dose response relationship:
- 3
- AF for differences in duration of exposure:
- 1
- Justification:
- In the Li et al (2001) study, the rats were treated for only 6 days. Therefore an AF to extrapolate to a long-term DNEL would seem appropriate. However, given that in a much longer exposure study (the sufficiently reliable 90 day study in rats by Chowdhury and Mitra,1995), a clear NOAEL of 7 mg Cr(VI) /kg bw/d was identified and a much higher LOAEL of 14 mg Cr(VI) /kg bw/d for 90 days was established, the RAC is of the opinion that, taking a WoE approach, an additional factor for duration extrapolation is not necessary. It should also be noted that there are several negative studies, including the reliable NTP studies where no effects were identified up to doses much higher than those at which effects have been reported in other studies.
- AF for interspecies differences (allometric scaling):
- 4
- AF for other interspecies differences:
- 2.5
- 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:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- acute toxicity
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - General Population
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