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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
64.68 µg/m³
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5 000
Dose descriptor starting point:
BMDL10
Value:
3.3 mg/kg bw/day
Modified dose descriptor starting point:
BMCL10
Value:
32.34 mg/m³
Explanation for the modification of the dose descriptor starting point:

The original point of departure was the BMDL10, calculated to be 3.3 mg/kg bw/day based upon tumour incidence in males rats in a 2 year drinking water study.

A scaling factor of 50% was applied for oral to inhalation route extrapolation, a body weight of 70 kg was assumed and a daily breathing rate of 10 cubic m per worker. A correction factor of 2.8 was also applied to account for the differences between occupational and lifetime exposure (7 days/5 days *52weeks/48weeks* 75 years/40years) =2.8.

3.3 mg/kg bw/day * 50% * 70 kg * 1/10 cubic meters * correction factor of 2.8= 32.34 mg/ cubic meter.

AF for dose response relationship:
10
Justification:
The BMDL10 is not a NOAEL
AF for differences in duration of exposure:
1
Justification:
chronic study
AF for interspecies differences (allometric scaling):
10
Justification:
standard factor in the Large Assessment Factor approach
AF for other interspecies differences:
1
Justification:
accounted for in the interspecies factor above
AF for intraspecies differences:
5
Justification:
default value in the Large Assessment Factor approach for workers
AF for the quality of the whole database:
1
Justification:
The carcinogenicity study was conducted according to modern guidelines
AF for remaining uncertainties:
10
Justification:
Default assessment factor for "Nature of Carcinogenic process" as per the Large Assessment Factor approach
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.2 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECETOC TR110
Overall assessment factor (AF):
90
Dose descriptor starting point:
NOAEC
Value:
554 mg/m³
Modified dose descriptor starting point:
other: LC50
Value:
660 mg/m³
Explanation for the modification of the dose descriptor starting point:

The dose descriptor starting point was the 4hr LC50 in rats of 660 mg/m3, this was modified in accordance with ECETOC guidance TR110 using a factor of 3 to estimate a non-lethal level that can be used as the basis for the point of departure for the DNEL derivation. The duration of exposure is corrected from 4 hours in rat to a 15 minute peak exposure in workers using Haber's rule where C^n x T = constant and n=3 for extrapolating to shorter time periods. (220mg/m^3)^3 x 4hrs = C^3 x 0.25 hrs C= 554 mg/m^3

AF for dose response relationship:
10
Justification:
The dose response curve for the substance is unknown, the AF is set to a default of 10
AF for interspecies differences (allometric scaling):
1
Justification:
Allommetric scaling is not applied for the inhalation route
AF for other interspecies differences:
3
Justification:
a default value of 3 is recommended in the ECETOC TR110 for remaining interspecies variability
AF for intraspecies differences:
3
Justification:
a default value of 3 is recommended in the ECETOC TR110 for remaining variability in workers
AF for the quality of the whole database:
1
Justification:
The overall quality of the database is robust
AF for remaining uncertainties:
1

Local effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
64.68 µg/m³
Most sensitive endpoint:
carcinogenicity
DNEL related information
DNEL derivation method:
other: The systemic long term inhalation DNEL is protective for long term local effects in terms of potential tumour induction
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
28.3 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: ECETOC TR110
Overall assessment factor (AF):
7.5
Dose descriptor starting point:
NOAEC
Value:
212 mg/m³
AF for dose response relationship:
1
Justification:
The dose descriptor is based upon the NOAEC of 80 ppm (212 mg/m^3) observed for tracheal irritation in a sub chronic rat inhalation study (6 hr/day). As irritation is a concentration dependent effect, time scaling is not neccessary to account for the difference between animal and worker exposure duration.
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling is not required for the inhalation route of exposure or local effects.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 is applied to account for potential quantitative differences in deposition, airflow patterns,
clearance rates and protective mechanisms between humans and animals and assuming that humans would be more sensitive than
animals to effects on the respiratory tract
AF for intraspecies differences:
3
Justification:
a default value of 3 is recommended in the ECETOC TR110 for remaining variability in workers
AF for the quality of the whole database:
1
Justification:
The overall quality of the database is robust
AF for remaining uncertainties:
1

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
18.48 µg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5 000
Dose descriptor starting point:
BMDL10
Value:
3.3 mg/kg bw/day
Modified dose descriptor starting point:
BMDL10
Value:
9.24 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The original point of departure was the BMDL10, calculated to be 3.3 mg/kg bw/day based upon tumour incidence in males rats in a 2 year drinking water study.

Default values of 50% dermal absorption (rat) ,drmal absorption (human) and oral absorption (rat) were assumed given the lack of Toxicokinetic data- these factors cancel themselves out when calculating the corrected Dermal BMDL10. A correction factor of 2.8 was also applied to account for the differences between occupational and lifetime exposure (7 days/5 days *52weeks/48weeks* 75 years/40years) =2.8.

3.3 mg/kg bw/day * correction factor of 2.8= 9.24 mg/kg bw/day.

AF for dose response relationship:
10
Justification:
The BMDL10 is not a NOAEL
AF for differences in duration of exposure:
1
Justification:
chronic study
AF for interspecies differences (allometric scaling):
10
Justification:
standard factor in the Large Assessment Factor approach
AF for other interspecies differences:
1
Justification:
accounted for in the interspecies factor above
AF for intraspecies differences:
5
Justification:
default value in the Large Assessment Factor approach for workers
AF for the quality of the whole database:
1
Justification:
The carcinogenicity study was conducted according to modern guidelines
AF for remaining uncertainties:
10
Justification:
Default assessment factor for "Nature of Carcinogenic process" as per the Large Assessment Factor
approach
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
18.48 µg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: The long term systemic DMEL is protective for the short term exposure

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation 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
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
AF for the quality of the whole database:
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

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