Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.86 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
Value:
120 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
146.56 mg/m³
Explanation for the modification of the dose descriptor starting point:

There are no data available regarding repeated dose toxicity studies of the target substance sodium 4-chloro-3-methylphenolate (CAS 15733-22-9). The calculation of the DNEL is based on an oral NOAEL observed in a 90 day repeated dose toxicity study in rats (EPA OPP 82-1) conducted with the source substance 4-chloro-3-methylphenol (CAS 59-50-7).

To correct the interspecies difference between rat and human the NOAEL has to be corrected as follows:

 Corrected inhal NOAEC = NOAEL(oral) × (1 ÷ sRVrat) × (ABSoral-rat ÷ ABSinh-human) × (sRVhuman ÷ wRV)

= 120 mg/kg bw/day × (1 ÷ 0.384 m³/kg bw) × (1 ÷ 2) × (6.7 m³ ÷ 10 m³) × (7 days ÷ 5 days) = 146.56 mg/m³

sRV = standard respiratory volume; wRV = respiratory volume light activity for worker (8 h); ABS = absorption

As worst case as recommended in the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of the dose [concentration]-response for human health (2012), it is assumed that oral absorption rate is 50% of that of inhalation absorption. Exposure was 7 day/week in the subchronic oral repeated dose toxicity study in rats while workers are exposed 5 days/week.

Thus, the corrected starting point for workers is 146.56 mg/m³ for inhalation.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
2
Justification:
The DNEL is based on a subchronic study.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
5
Justification:
Default value for workers according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No route-to-route extrapolation necessary.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
2
Justification:
The DNEL is based on a subchronic study.
AF for interspecies differences (allometric scaling):
4
Justification:
Default value according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
5
Justification:
Default value for workers according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

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

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.04 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
Dose descriptor starting point:
NOAEL
Value:
120 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
52.17 mg/m³
Explanation for the modification of the dose descriptor starting point:

There are no data available regarding repeated dose toxicity of the target substance sodium 4-chloro-3-methylphenolate (CAS 15733-22-9). The calculation of the DNEL is based on an oral NOAEL observed in a 90-day repeated dose toxicity study in rats (EPA OPP 82-1) conducted with the source substance 4-chloro-3-methylphenol (CAS 59-50-7).

To correct the interspecies difference between rat and human the NOAEL has to be corrected as follows:

 Corrected inhal NOAEC = NOAEL(oral) × (1 ÷ sRVrat) × (ABSoral-rat ÷ ABSinh-human) = 120 mg/kg bw/day × (1 ÷ 1.15 m³/kg bw) × (1 ÷ 2) = 52.17 mg/m³

sRV = standard respiratory volume; ABS = absorption

As worst case as recommended in the ECHA Guidance IR&CSA, Chapter R.8: Characterisation of the dose [concentration]-response for human health (2012), it is assumed that oral absorption rate is 50% of that of inhalation absorption.

Thus, the corrected starting point for the general public is 52.17 mg/m³ for inhalation.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
2
Justification:
The DNEL is based on a subchronic study.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default value according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

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

General Population - Hazard via dermal route

Systemic effects

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

No route-to-route extrapolation necessary.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
2
Justification:
The DNEL is based on a subchronic study.
AF for interspecies differences (allometric scaling):
4
Justification:
Default value according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default value according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.6 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
Dose descriptor starting point:
NOAEL
Value:
120 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No route-to-route extrapolation necessary.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
2
Justification:
The DNEL is based on a subchronic study.
AF for interspecies differences (allometric scaling):
4
Justification:
Default value according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default value according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population