Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.7 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
Modified dose descriptor starting point:
NOAEC
DNEL value:
352.6 mg/m³
Explanation for the modification of the dose descriptor starting point:
The oral NOAEL of 200 mg/kg bw/d, derived form the subacute OECD407-study, is converted to a NOAEC by dividing by 0.38 and multiplying by 0.67 according to ECHA Guidance taking into account differences in respiratory volume (rat/humans) and light-work activity by workers: NOAEC 200 * 0.67/ 0.38 = 352.6 mg/m3. As inhalatory and oral absorption are both considered 100%, no adjustment for absorption is applied.
AF for dose response relationship:
1
Justification:
NOAEC is used as a starting point
AF for differences in duration of exposure:
6
Justification:
AF based on a sub-acute study according to OECD407
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route according to ECHA guidance
AF for other interspecies differences:
2.5
Justification:
Default factor for other interspecies differences
AF for intraspecies differences:
5
Justification:
For workers the default factor of 5 is applied, according to ECHA guidance
AF for the quality of the whole database:
1
Justification:
Underlying OECD407 study is rated Klimisch 1 performed under GLP without deviations
AF for remaining uncertainties:
1
Justification:
No further uncertainties have to be taken into account
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information

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)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.66 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):
300
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The oral NOAEL of 200 mg/kg bw/d, derived form the subacute OECD407-study, is converted to a dermal NOAL by applying a factor of 10 according to ECHA Guidance taking into account differences in absorption rate of the substance (10% dermal versus 100% oral): NOAEL(dermal) = 200 * 100/10 = 2000 mg/m3.
AF for dose response relationship:
1
Justification:
NOAEL is used as a starting point.
AF for differences in duration of exposure:
6
Justification:
AF based on a sub-acute study according to OECD407
AF for interspecies differences (allometric scaling):
4
Justification:
AF according to ECHA guidance as rats were used in the OECD407 study.
AF for other interspecies differences:
2.5
Justification:
Default factor for other interspecies differences
AF for intraspecies differences:
5
Justification:
For workers the default factor of 5 is applied, according to ECHA guidance
AF for the quality of the whole database:
1
Justification:
Underlying OECD407 study is rated Klimisch 1 performed under GLP without deviations
AF for remaining uncertainties:
1
Justification:
No further uncertainties have to be taken into account
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
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

WORKER

Acute DNELs:

Production of epoxy resins is in excess of 10 t/y. According to the REACh "Guidance on information requirements and chemical safety assessment, Part B: Hazard Assessment", above 10 t/y, the establishment of acute toxicity DNEL is unnecessary in most cases, as the DNEL based on long-term exposure is normally sufficient to ensure that adverse effects do not occur. Thus, acute DNELs should default to the long term systemic DNELs.

 

For local effects, a DNEL was not quantifiable; however, as epoxy resins are classified as skin sensitizers, local effects must be assessed qualitatively and risk management measures applied as necessary. The potential for respiratory sensitization is unknown; however, given its skin sensitization potential, this endpoint also is assessed qualitatively.

Long-term DNELs:

DNELs are based on the oral 28-day study in rats (key study selected) entitled "A 28-Day Oral Gavage Toxicity Study of Butanediol Diglycidylether in Sprague Dawley Rats (WIL-749003)” with the most sensitive endpoint selected as repeated dose toxicity.

 

Starting Dose for DNEL calculation:

NOAEL: 200 mg/kg/day

 

Absorption Information:

Oral absorption was considered to be 100% based on experimental data.

Inhalation absorption was considered to be 100% based on consideration of the molecular weight and log Kow values.

Dermal absorption was considered to be 10% based on the physicochemical properties of epoxy resins and the lack of observed systemic effects following dermal exposure.

 

Modified dose for DNEL Calculation:

Worker – Inhalation = 200 mg/kg/day x 1/0.38 x 6.7/10 (no adjustment for absorption) = 352.6 mg/m3

Worker – Dermal = 200 mg/kg/day x 100%/10% (adjustment for absorption) = 2,000 mg/kg/day

 

Assessment Factors (AF) were selected as described in line with ECHA guidance documents.

 

Final DNELs:

Worker – Inhalation = 4.7 mg/m3

Worker – Dermal = 6.66 mg/kg/day

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.16 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
Modified dose descriptor starting point:
NOAEC
DNEL value:
173.9 mg/m³
Explanation for the modification of the dose descriptor starting point:
The oral NOAEL of 200 mg/kg bw/d, derived form the subacute OECD407-study, is converted to a NOAEC by dividing by 1.15 according to ECHA Guidance taking into account differences in respiratory volume (rat/humans) by consumers: NOAEC 200 / 1.15 = 173.9 mg/m3. As inhalatory and oral absorption are both considered 100%, no adjustment for absorption is applied.
AF for dose response relationship:
1
Justification:
NOAEC is used as a starting point
AF for differences in duration of exposure:
6
Justification:
AF based on a sub-acute study according to OECD407
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route according to ECHA guidance
AF for other interspecies differences:
2.5
Justification:
Default factor for other interspecies differences
AF for intraspecies differences:
10
Justification:
For consumers the default factor of 10 is applied, according to ECHA guidance
AF for the quality of the whole database:
1
Justification:
Underlying OECD407 study is rated Klimisch 1 performed under GLP without deviations
AF for remaining uncertainties:
1
Justification:
No further uncertainties have to be taken into account
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:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (respiratory tract)
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:
3.33 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The oral NOAEL of 200 mg/kg bw/d, derived form the subacute OECD407-study, is converted to a dermal NOAL by applying a factor of 10 according to ECHA Guidance taking into account differences in absorption rate of the substance (10% dermal versus 100% oral): NOAEL(dermal) = 200 * 100/10 = 2000 mg/m3.
AF for dose response relationship:
1
Justification:
NOAEL is used as a starting point.
AF for differences in duration of exposure:
6
Justification:
AF based on a sub-acute study according to OECD407
AF for interspecies differences (allometric scaling):
4
Justification:
AF according to ECHA guidance as rats were used in the OECD407 study.
AF for other interspecies differences:
2.5
Justification:
Default factor for other interspecies differences
AF for intraspecies differences:
10
Justification:
For consumers the default factor of 10 is applied, according to ECHA guidance
AF for the quality of the whole database:
1
Justification:
Underlying OECD407 study is rated Klimisch 1 performed under GLP without deviations
AF for remaining uncertainties:
1
Justification:
No further uncertainties have to be taken into account
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
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:
0.33 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):
600
Modified dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no route to route extrapolation performed
AF for dose response relationship:
1
Justification:
NOAEL is used as a starting point.
AF for differences in duration of exposure:
6
Justification:
AF based on a sub-acute study according to OECD407
AF for interspecies differences (allometric scaling):
4
Justification:
AF according to ECHA guidance as rats were used in the OECD407 study.
AF for other interspecies differences:
2.5
Justification:
Default factor for other interspecies differences
AF for intraspecies differences:
10
Justification:
For consumers the default factor of 10 is applied, according to ECHA guidance
AF for the quality of the whole database:
1
Justification:
Underlying OECD407 study is rated Klimisch 1 performed under GLP without deviations
AF for remaining uncertainties:
1
Justification:
No further uncertainties have to be taken into account
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

GENERAL POPULATION

Acute DNELs:

General population: Production of epoxy resins is in excess of 10 t/y. According to the REACh "Guidance on information requirements and chemical safety assessment, Part B: Hazard Assessment", above 10 t/y, the establishment of acute toxicity DNEL is unnecessary in most cases, as the DNEL based on long-term exposure is normally sufficient to ensure that adverse effects do not occur. Thus, acute DNELs should default to the long term systemic DNELs.

 

For local effects, a DNEL was not quantifiable; however, as epoxy resins are classified as skin sensitizers, local effects must be assessed qualitatively. The potential for respiratory sensitization is unknown; however, given its skin sensitization potential, this endpoint also is assessed qualitatively.

 

Long-term DNELs:

DNELs are based on the oral 28-day study in rats (key study selected) entitled "A 28-Day Oral Gavage Toxicity Study of Butanediol

Diglycidylether in Sprague Dawley Rats (WIL-749003)” with the most sensitive endpoint selected as repeated dose toxicity.

 

Starting Dose for DNEL calculation:

NOAEL: 200 mg/kg/day

 

Absorption Information:

Oral absorption was considered to be 100% based on experimental data.

Inhalation absorption was considered to be 100% based on consideration of the molecular weight and log Kow values.

Dermal absorption was considered to be 10% based on the physicochemical properties of epoxy resins and the lack of observed systemic effects following dermal exposure.

 

Modified dose for DNEL Calculation:

General Population – Oral =  200 mg/kg/day (no adjustment for absorption) = 200 mg/kg/day

General Population – Inhalation = 200 mg/kg/day x 1/1.15 (no adjustment for absorption) = 173.9 mg/m3

General Population– Dermal = 200 mg/kg/day x 100%/10% (adjustment for absorption) = 2,000 mg/kg/day

 

Assessment Factors (AF) were selected as described in line with ECHA guidance documents.

 

Final DNELs:

General Population – Oral =  0.33 mg/kg/day

General Population – Inhalation = 1.18 mg/m3

General Population– Dermal = 3.33 mg/kg/day