Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.84 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):
225
Dose descriptor starting point:
LOAEL
DNEL value:
100 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
DNEL value:
1 764 mg/m³
Explanation for the modification of the dose descriptor starting point:

Modification: 1000 / (0,380 *0,1 *(10 / 6,7)

AF for dose response relationship:
3
Justification:
In absence of a NOAEL, an extra factor is used as described by ECHA Guidance R.8.
AF for differences in duration of exposure:
6
Justification:
ECHA default factor from subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Is already applied in route-to-route extrapolation from oral to inhalation
AF for other interspecies differences:
2.5
Justification:
ECHA default factor
AF for intraspecies differences:
5
Justification:
ECHA default factor
AF for the quality of the whole database:
1
Justification:
No indication that a factor for quality is needed
AF for remaining uncertainties:
1
Justification:
No indication that a factor is needed
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.11 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):
900
Dose descriptor starting point:
LOAEL
DNEL value:
100 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Correction: 1000 / 0,1 (10% absorption)

AF for dose response relationship:
3
Justification:
In absence of a NOAEL, an extra factor is used as described by ECHA Guidance R.8.
AF for differences in duration of exposure:
6
Justification:
ECHA default factor from subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default factor
AF for other interspecies differences:
2.5
Justification:
ECHA default factor
AF for intraspecies differences:
5
Justification:
ECHA default factor
AF for the quality of the whole database:
1
Justification:
No indication that a factor for quality is needed
AF for remaining uncertainties:
1
Justification:
No indication that a factor is needed
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

LD50 > 2000 mg/kg bw.

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
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

In the oral OECD 422 study in rats, test item related effects on body weight development, food consumption in male and female high-dose group, on haematology, coagulation and clinical biochemistry in male and female 300 and 1000 mg/kg dose groups and organ weights effect in all groups (100, 300, 1000 mg/kg) of males and females were observed. Histopathologically, in liver, hepatocellular vacuolation was observed in both surviving and decedent animals. Hepatocyte vacuolation (fatty changes) was observed in all dose groups and in both males and females. The observed hepatic change indicates hepatocyte functional alteration / disturbances related to the administration of 2,6-Di-tert-butyl-4-nonylphenol and the observed hepatic changes were considered to be adverse. In conclusion, the oral LOAEL = 100 mg/kg bw.

Based on toxicokinetics evaluation, 100% absorption was considered after oral exposure, and 10% absorption was considered after inhalation and dermal exposure.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
1.93 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):
450
Dose descriptor starting point:
LOAEL
DNEL value:
100 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
DNEL value:
870 mg/m³
Explanation for the modification of the dose descriptor starting point:

Correction: 1000 /0,1 * (1,150)

AF for dose response relationship:
3
Justification:
In absence of a NOAEL, an extra factor is used as described by ECHA Guidance R.8.
AF for differences in duration of exposure:
6
Justification:
ECHA default factor from subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Is already applied in route-to-route extrapolation from oral to inhalation
AF for other interspecies differences:
2.5
Justification:
ECHA default factor
AF for intraspecies differences:
10
Justification:
ECHA default factor
AF for the quality of the whole database:
1
Justification:
No indication that a factor for quality is needed
AF for remaining uncertainties:
1
Justification:
No indication that a factor is needed
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.56 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):
1 800
Dose descriptor starting point:
LOAEL
DNEL value:
100 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Correction: 1000 / 0,1 (10% absorption) = 1000 mg/kg bw

 (compensation for route)

AF for dose response relationship:
3
Justification:
In absence of a NOAEL, an extra factor is used as described by ECHA Guidance R.8.
AF for differences in duration of exposure:
6
Justification:
ECHA default factor from subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default factor
AF for other interspecies differences:
2.5
Justification:
ECHA default factor
AF for intraspecies differences:
10
Justification:
ECHA default factor
AF for the quality of the whole database:
1
Justification:
No indication that a factor for quality is needed
AF for remaining uncertainties:
1
Justification:
No indication that a factory is needed
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
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:
0.056 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):
1 800
Dose descriptor starting point:
LOAEL
DNEL value:
100 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
DNEL value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No corrrection.

AF for dose response relationship:
3
Justification:
In absence of a NOAEL, an extra factor is used as described by ECHA Guidance R.8.
AF for differences in duration of exposure:
6
Justification:
ECHA default factor from subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default factor
AF for other interspecies differences:
2.5
Justification:
ECHA default factor
AF for intraspecies differences:
10
Justification:
ECHA default factor
AF for the quality of the whole database:
1
Justification:
No indication that a factor for quality is needed
AF for remaining uncertainties:
1
Justification:
No indication that a factor is needed
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

In the oral OECD 422 study in rats, test item related effects on body weight development, food consumption in male and female high-dose group, on haematology, coagulation and clinical biochemistry in male and female 300 and 1000 mg/kg dose groups and organ weights effect in all groups (100, 300, 1000 mg/kg) of males and females were observed. Histopathologically, in liver, hepatocellular vacuolation was observed in both surviving and decedent animals. Hepatocyte vacuolation (fatty changes) was observed in all dose groups and in both males and females. The observed hepatic change indicates hepatocyte functional alteration / disturbances related to the administration of 2,6-Di-tert-butyl-4-nonylphenol and the observed hepatic changes were considered to be adverse. In conclusion, the oral LOAEL = 100 mg/kg bw.

Based on toxicokinetics evaluation, 100% absorption was considered after oral exposure, and 10% absorption was considered after inhalation and dermal exposure.