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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
12.23 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
152.93 mg/m³
Explanation for the modification of the dose descriptor starting point:

From prenatal development toxicity study, a NOAEL of 75mg/kg/day for maternal and development toxicity has been chosen for derivation of DNELs. The NOAEL of 75 mg/kg/day was converted to an inhalation dose using the conversion factor of 0.23 m3/kg BW/8 hours. Further adjustments are made for light work (0.67) and for 100% vs. 50% bioavailability and 1.4 for a 7 day experimental exposure to a 5 -day workweek. This results in the modified dose descriptor of 152.93 mg/m3


Corrected NOAEC = 75 mg/kg bw/day x (1/0.23 m3/ mg/kg bw/day) x 0.67 x 0.5 x 1.4 = 152.93 mg/m3

AF for dose response relationship:
1
Justification:
No uncertainties in the dose descriptor = NOAEL/NOAEC
AF for differences in duration of exposure:
1
Justification:
As the DART study duration is finite, therefore no assessment factor required
AF for interspecies differences (allometric scaling):
1
Justification:
Default for inhalation, no additional assessment factors for allometric scaling necessary. Since the interspecies differences have already been taken into account (delineation of corrected NOAEC)
AF for other interspecies differences:
2.5
Justification:
Default (a standard procedure to correct differences in metabolic rate, toxicokinetics and toxicodynamics
AF for intraspecies differences:
5
Justification:
Default assessment factor for workers
AF for the quality of the whole database:
1
Justification:
Default - No remaining uncertainties in the derived DNEL
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties to account for
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:
10.5 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):
30
Dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
315 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

From prenatal development toxicity study, a NOAEL of 75mg/kg/day for maternal and development toxicity has been chosen for derivation of DNELs. For modifying the dose descriptor, the dermal absorption of factor 100% is applied. Furthermore the NOAEL is corrected for duration of exposure (24h in rabbits Vs 8h in workers) and 7 days in rabbits vs 5 days in workers.


Corrected NOAEL = 75 mg/kg bw/day x (24h/8h) x 7d/5d = 315 mg/kg bw/day

AF for dose response relationship:
1
Justification:
No uncertainties in the dose descriptors = NAOEL/ NOAEC
AF for differences in duration of exposure:
1
Justification:
DART study duration is finite, therefore no assessment factor required
AF for interspecies differences (allometric scaling):
2.4
Justification:
Default allometric scaling factor for systemic effects oral to dermal for rabbits
AF for other interspecies differences:
2.5
Justification:
Default (a standard procedure to correct differences in metabolic rate, toxicokinetics and toxicodynamics
AF for intraspecies differences:
5
Justification:
Default assessment factor for workers
AF for the quality of the whole database:
1
Justification:
Default - No remaining uncertainties in the derived DNEL
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties to account for
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

No oral DNEL for workers.


Worker DNEL long-term systemic for inhalation route


Start point:       NOAEL 75 mg/kg bw/day (based on oral Prenatal developmental study in rabbits)


Respiratory volume rat (sRV) (worker (8 h): 1/0.23):                                                         326.09 mg/m3


Correction for respiratory bioavailability (100%/50%):                                                      163.04 mg/m3


Corrected for 7 days of animal dosing to a 5-day work week (1.4x value):                         228.26 mg/m3


Differences in respiratory volume (default factor "light activity worker"):                         152.93 mg/m3


Corrected NOAEC:                                                                                                       152.93 mg/m3


Remaining interspecies differences:                                                                                  2.5


Intraspecies differences:                                                                                                  5


Differences in duration of exposure (Development toxicity study):                                       1


Dose response and endpoint specific/severity issues:                                                          1


Quality of database:                                                                                                         1


Overall factor (product of individual factors):                                                                     12.5


=>Worker DNEL long-term for inhalation route-systemic:                                                   12.23 mg/m3


Worker DNEL long-term systemic for dermal route


Start point:      NOAEL 75 mg/kg bw/day (based on oral Prenatal developmental study in rabbits)


Differences in absorption:           Abs (oral-rat) / Abs (dermal-human):                                 1


Correction for 7 day/week dosing in the study to a 5 day work week:                                    1.4


NOAEL is corrected for duration of exposure (24h in rabbits Vs 8h  in workers)                       3


=>Corrected NOAEL:                                                                                                  315 mg/kg bw/day


Interspecies differences:  Allometric scaling:                                                                        2.4


Remaining interspecies differences:                                                                                     2.5


Intraspecies differences:                                                                                                     5


Differences in duration of exposure (Developmental toxicity):                                                 1


Dose response and endpoint specific/severity issues:                                                             1


Quality of database:                                                                                                            1


Overall factor (product of individual factors):                                                                         30


=>Worker DNEL long-term for dermal route-systemic:                                                 10.5 mg/kg bw/day

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.17 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
54.35 mg/m³
Explanation for the modification of the dose descriptor starting point:

From prenatal development toxicity study, a NOAEL of 75mg/kg/day for maternal and development toxicity has been chosen for derivation of DNELs. The NOAEL of 75 mg/kg/day was converted to an inhalation dose using the conversion factor of 0.69 m3/kg BW/24 hours for rabbit. Further adjustments are made for 100% vs. 50% bioavailability. This results in the modified dose descriptor of 152.93 mg/m3


Corrected NOAEC = 75 mg/kg bw/day x (1/0.69 m3/ mg/kg bw/day) x 0.5 = 54.35 mg/m3

AF for dose response relationship:
1
Justification:
No uncertainties in the dose descriptor = NOAEL/NOAEC
AF for differences in duration of exposure:
1
Justification:
As the DART study duration is finite, therefore no assessment factor required.
AF for interspecies differences (allometric scaling):
1
Justification:
Default for inhalation, no additional assessment factors for allometric scaling necessary. Since the interspecies differences have already been taken into account (delineation of corrected NOAEC)
AF for other interspecies differences:
2.5
Justification:
Default (a standard procedure to correct differences in metabolic rate, toxicokinetics and toxicodynamics
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population
AF for the quality of the whole database:
1
Justification:
Default - No remaining uncertainties in the derived DNEL
AF for remaining uncertainties:
1
Justification:
There are no additional 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:
DNEL (Derived No Effect Level)
Value:
1.25 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):
60
Dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

From prenatal development toxicity study, a NOAEL of 75mg/kg/day for maternal and development toxicity has been chosen for derivation of DNELs. For modifying the dose descriptor, the dermal absorption of factor 100% is applied and route to route extrapolation is 100%


Corrected NOAEL = 75 mg/kg bw/day x (100%/100%) = 75 mg/kg bw/day

AF for dose response relationship:
1
Justification:
No uncertainties in the dose descriptor = NOAEL/NAOEC
AF for differences in duration of exposure:
1
Justification:
As the DART study duration is finite, therefore no assessment factor required
AF for interspecies differences (allometric scaling):
2.4
Justification:
Default allometric scaling factor for systemic effects oral to dermal for rabbits
AF for other interspecies differences:
2.5
Justification:
Default (a standard procedure to correct differences in metabolic rate, toxicokinetics and toxico-dynamics
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population
AF for the quality of the whole database:
1
Justification:
No remaining uncertainties for this derived DNEL
AF for remaining uncertainties:
1
Justification:
There are no additional 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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.25 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):
60
Dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

From prenatal development toxicity study, a NOAEL of 75mg/kg/day for maternal and development toxicity has been chosen for derivation of DNELs. For modifying the dose descriptor, the factor 100% bioavailability (oral to oral) has been selected and default value for route-to-route extrapolation is 100%


Corrected NOAEL = 75 mg/kg bw/day x (100%/100%) = 75 mg/kg bw/day

AF for dose response relationship:
1
Justification:
No uncertainties in the dose descriptor = NOAEL/NAOEC
AF for differences in duration of exposure:
1
Justification:
As the DART study duration is finite, therefore no assessment factor required
AF for interspecies differences (allometric scaling):
2.4
Justification:
Default allometric scaling factor for systemic effects oral / dermal for rabbits
AF for other interspecies differences:
2.5
Justification:
Default (a standard procedure to correct differences in metabolic rate, toxicokinetics and toxico-dynamics
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population
AF for the quality of the whole database:
1
Justification:
No remaining uncertainties for this derived DNEL
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties for this derived DNEL
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

General Population DNEL long-term systemic for oral route


Start point:        NOAEL:               75 mg/kg bw/day (based on oral Prenatal developmental toxicity study in rabbits).


Differences in absorption Abs (oral-rabbit) / Abs (oral-human):                                               1


=> Corrected NOAEL:    75 mg/kg bw/day


Interspecies differences: Allometric scaling:                                                                           2.4


Remaining interspecies differences:                                                                                       2.5


Intraspecies differences:                                                                                                       10


Differences in duration of exposure (DART study):                                                                   1


Dose response and endpoint specific/severity issues:                                                                1


Quality of database:                                                                                                               1


Overall factor (product of individual factors):                                                                            60


=>General Population DNEL long-term for oral route-systemic:                              1.25 mg/kg bw/day


 


General Population DNEL long-term systemic for dermal route


Start point:        NOAEL:               75 mg/kg bw/day (based on oral Prenatal developmental toxicity study in rabbits).


Differences in absorption Abs (oral-rabbit) / Abs (dermal-human):                                                   1


=> Corrected NOAEL:    75 mg/kg bw/day


Interspecies differences: Allometric scaling:                                                                                    2.4


Remaining interspecies differences:                                                                                                2.5


Intraspecies differences:                                                                                                                10


Differences in duration of exposure (DART study):                                                                            1


Dose response and endpoint specific/severity issues:                                                                        1


Quality of database:                                                                                                                       1


Overall factor (product of individual factors):                                                                                    60


=>General Population DNEL long-term for dermal route-systemic:                              1.25 mg/kg bw/day


 


General Population DNEL long-term systemic for inhalation route


Start point:                                        NOAEL 75 mg/kg bw/day (based on oral Prenatal developmental toxicity study in rabbits).


Respiratory volume of rabbit (sRV) (Rabbit - human 24h general population: 1/0.69):            108.70 mg/m3


Correction for respiratory bioavailability (100%/50%):                                                         54.35 mg/m3


Corrected NOAEC:                                                                                                             54.35 mg/m3


 


Remaining interspecies differences:                                                                                      2.5


Intraspecies differences:                                                                                                      10


Differences in duration of exposure (for DART studies):                                                           1


Dose response and endpoint specific/severity issues:                                                              1


Quality of database:                                                                                                             1


Overall factor (product of individual factors):                                                                         25


=>General Population DNEL long-term for inhalation route-systemic:                       2.17 mg/m3