Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
DNEL (Derived No Effect Level)
Value:
30.4 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):
25
Dose descriptor starting point:
NOAEL
Explanation for the modification of the dose descriptor starting point:

See derivation in section summary

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
A factor of 2 is used for subchronic to chronic durations
AF for interspecies differences (allometric scaling):
1
Justification:
No value due to inhalation route
AF for other interspecies differences:
2.5
Justification:
standard value
AF for intraspecies differences:
5
Justification:
Standard Value
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:
2.8 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Explanation for the modification of the dose descriptor starting point:

See calculations in section summary below

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Starndard value for subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
standard value
AF for other interspecies differences:
2.5
Justification:
standard value
AF for intraspecies differences:
5
Justification:
standard value
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

There is an extensive database for CHDM.  The existing DNEL was based on 90-day rat studies, and there was also a rat developmental toxicity study available.  The initial DNEL was based on systemic toxicity from the rat 90-day study.

The 2019 update to the CHDM dossier takes into account the addition of an extended 1-generation reproductive study. In that study, there was no affect on systemic or developmental toxicity at the highest dose of 700 mg/kg/day.

As the initial DNEL was based on the NOAEL of 479 mg/kg/day, that value will continue to be used for the starting point of the DNEL.  One adjustment that will be made to the previous calculation will be the removal of the adjustment factor of 3 for the adequacy of the database with the addition of the extended 1-generation study.

There is a slight, but non-significant decrease in the DNEL values as the previous version used ECETOC values which are no longer supported by ECHA.

 

DNEL Derivation

 

Inhalation DNEL:  The long-term systemic DNEL was calculated by taking the rat NOAEL from the 90 day study of 479 mg/kg/day and adjusting it to an inhalation dose by dividing by 0.38 m3/kg-BW. Oral bioavailability is corrected to 90% based on the available TK data. Workers are corrected for light work by correcting respiration from 6.7 m3/day to 10 m3/day. The correction values used are:

               Intraspecies:                                    5 for worker, 10 for general population

               Remaining interspecies:               2.5

               Subchronic to chronic study:      2

               

               Calculations:

                               Worker:  NOAEL 479 mg/kg * 1kg/0.38 m3BW (8 hr) = 1260.52 m3/kg-day.

                               Correct for 90% bioavailability = 1260.52 m3/kg-day *0.9 = 1134.46 m3/kg-day

                               Correct for light work = 1134.46 m3/kg-day * 0.67 = 760.08 m3/kg-day

                               Apply total correction factors of 25 = 760.08 m3/kg-day /25 =30.4 m3/kg-day

 

General population:  NOAEL 479 mg/kg * 1kg/1.15 m3/kg BW (24 hr) = 416.52 m3/kg-day.

                               Correct for 90% bioavailability = 416.52 m3/kg-day *0.9 = 374.86 m3/kg-day

                               Apply total correction factors of 50 = 374.86 m3/kg-day /50 =7.5 m3/kg-day

 

 

Oral/Dermal DNEL: The long-term systemic DNEL was calculated by taking the rat NOAEL from the 90 day study of 479 mg/kg/day and adjusting it for oral bioavailability by correcting to 90% based on the available TK data. Workers are corrected for light work by correcting respiration from 6.7 m3/day to 10 m3/day. The correction values used are:

               Intraspecies:                                    5 for worker, 10 for general population

               Remaining interspecies:               2.5

               Subchronic to chronic study:      2

               Allometric scaling:                           4

               

               Calculations:

                               Worker:  NOAEL 479 mg/kg

                               Correct for 90% bioavailability = 479 mg/kg-day *0.9 = 431.1 mg/kg-day

                               Correct for light work = 431.1 mg/kg-day * 0.67 = 288.83 mg/kg-day

                               Apply total correction factors of 100 = 760.08 m3/kg-day /100 =2.88 mg/kg-day

 

                               General Population: NOAEL 479 mg/kg

                               Correct for 90% bioavailability = 479 mg/kg-day *0.9 = 431.1 mg/kg-day

                               Apply total correction factors of 200 = 760.08 m3/kg-day /200 =1.44 mg/kg-day

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.5 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):
50
Explanation for the modification of the dose descriptor starting point:

See the section summary below for calculations

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
standard value for subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric correction for inhalation
AF for other interspecies differences:
2.5
Justification:
standard value
AF for intraspecies differences:
10
Justification:
standard value
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:
DNEL (Derived No Effect Level)
Value:
1.44 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Explanation for the modification of the dose descriptor starting point:

The calculations are in the section summary below

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
standard value for subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
standard value
AF for other interspecies differences:
2.5
Justification:
standard value
AF for intraspecies differences:
10
Justification:
standard value
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.44 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Explanation for the modification of the dose descriptor starting point:

The calculations are in the section summary below

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
standard value for subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
standard value
AF for other interspecies differences:
2.5
Justification:
standard value
AF for intraspecies differences:
10
Justification:
standard value
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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

There is an extensive database for CHDM.  The existing DNEL was based on 90-day rat studies, and there was also a rat developmental toxicity study available.  The initial DNEL was based on systemic toxicity from the rat 90-day study.

The 2019 update to the CHDM dossier takes into account the addition of an extended 1-generation reproductive study. In that study, there was no affect on systemic or developmental toxicity at the highest dose of 700 mg/kg/day.

As the initial DNEL was based on the NOAEL of 479 mg/kg/day, that value will continue to be used for the starting point of the DNEL.  One adjustment that will be made to the previous calculation will be the removal of the adjustment factor of 3 for the adequacy of the database with the addition of the extended 1-generation study.

There is a slight, but non-significant decrease in the DNEL values as the previous version used ECETOC values which are no longer supported by ECHA.

 

DNEL Derivation

 

Inhalation DNEL:  The long-term systemic DNEL was calculated by taking the rat NOAEL from the 90 day study of 479 mg/kg/day and adjusting it to an inhalation dose by dividing by 0.38 m3/kg-BW. Oral bioavailability is corrected to 90% based on the available TK data. Workers are corrected for light work by correcting respiration from 6.7 m3/day to 10 m3/day. The correction values used are:

               Intraspecies:                                    5 for worker, 10 for general population

               Remaining interspecies:               2.5

               Subchronic to chronic study:      2

               

               Calculations:

                               Worker:  NOAEL 479 mg/kg * 1kg/0.38 m3BW (8 hr) = 1260.52 m3/kg-day.

                               Correct for 90% bioavailability = 1260.52 m3/kg-day *0.9 = 1134.46 m3/kg-day

                               Correct for light work = 1134.46 m3/kg-day * 0.67 = 760.08 m3/kg-day

                               Apply total correction factors of 25 = 760.08 m3/kg-day /25 =30.4 m3/kg-day

 

General population:  NOAEL 479 mg/kg * 1kg/1.15 m3/kg BW (24 hr) = 416.52 m3/kg-day.

                               Correct for 90% bioavailability = 416.52 m3/kg-day *0.9 = 374.86 m3/kg-day

                               Apply total correction factors of 50 = 374.86 m3/kg-day /50 =7.5 m3/kg-day

 

 

Oral/Dermal DNEL: The long-term systemic DNEL was calculated by taking the rat NOAEL from the 90 day study of 479 mg/kg/day and adjusting it for oral bioavailability by correcting to 90% based on the available TK data. Workers are corrected for light work by correcting respiration from 6.7 m3/day to 10 m3/day. The correction values used are:

               Intraspecies:                                    5 for worker, 10 for general population

               Remaining interspecies:               2.5

               Subchronic to chronic study:      2

               Allometric scaling:                           4

               

               Calculations:

                               Worker:  NOAEL 479 mg/kg

                               Correct for 90% bioavailability = 479 mg/kg-day *0.9 = 431.1 mg/kg-day

                               Correct for light work = 431.1 mg/kg-day * 0.67 = 288.83 mg/kg-day

                               Apply total correction factors of 100 = 760.08 m3/kg-day /100 =2.88 mg/kg-day

 

                               General Population: NOAEL 479 mg/kg

                               Correct for 90% bioavailability = 479 mg/kg-day *0.9 = 431.1 mg/kg-day

                               Apply total correction factors of 200 = 760.08 m3/kg-day /200 =1.44 mg/kg-day