Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.034 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
Value:
0.84 mg/m³
Explanation for the modification of the dose descriptor starting point:

In order to derive DNELs from a repeated-dose toxicity study by inhalation, a conversion must be made in order to take into account the differences between experimental and human exposure.

-       Workers: As the NOAEC was obtained on rats exposed 6 h/d to the substance, it must be corrected for an inhalation exposure of workers, taking into account that workers are considered to be working 8h/d, with inhalative volumes for 8h/d defined in the ECHA Guidance at 6.7m3 for base level activity and 10m3 for light activity.

Corrected NOAEC(inhalation) = NOAEC(inhalation) * (exp.cond.rat / exp.cond.human)

Corrected NOAEC(inhalation) = 1.67 mg/m3 * (6 h/d / 8 h/d) * (6.7 m3 / 10 m3)

Corrected NOAEC(inhalation) = 0.84 mg/m3

AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for differences in duration of exposure:
2
Justification:
Subchronic exposure to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.44 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor starting point:
other: LC50
Value:
18 mg/m³
Explanation for the modification of the dose descriptor starting point:

The European Union (2007) considered as acceptable to determine the Margin of Safety for an acute inhalation exposure to the registered substance based on a LC50 of 18 mg/m3. Therefore this value was used a starting point and was applied the relevant assessment factors.

Reference:

European Union (2007) Risk Assessment Report. Hexachlorocyclopentadiene. CAS No: 77-47-4. EINECS No: 201-029-3. Final Approved Version.

AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium 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:
0.028 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):
180
Dose descriptor starting point:
NOAEL
Value:
5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

It is assumed that the dermal absorption of the substance will be similar between human and rabbit, therefore the NOAEL(dermal) for systemic effects from the subacute repeated-dose toxicity by the dermal route does not need to be converted.

AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for differences in duration of exposure:
6
Justification:
Subacute exposure to chronic exposure
AF for interspecies differences (allometric scaling):
2.4
Justification:
Rabbits to Humans
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.167 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):
30
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
NOAEC
Value:
5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

It is assumed that the dermal absorption of the substance will be similar between human and rabbit, therefore the NOAEL(dermal) for systemic effects from the subacute repeated-dose toxicity by the dermal route does not need to be converted.

AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
2.4
Justification:
Rabbits to Humans
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance

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)

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:
0.008 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
Value:
0.42 mg/m³
Explanation for the modification of the dose descriptor starting point:

In order to derive DNELs from a repeated-dose toxicity study by inhalation, a conversion must be made in order to take into account the differences between experimental and human exposure.

-       General Population: As the NOAEC was obtained on rats, it must be corrected for an inhalation exposure of the general population, taking into account that the general population is considered as being exposed 24h/d.

Corrected NOAEC(inhalation) = NOAEC(inhalation) * (exp.cond.rat / exp.cond.human)

Corrected NOAEC(inhalation) = 1.67 mg/m3 * (6 h/d / 24 h/d)

Corrected NOAEC(inhalation) = 0.42 mg/m3

AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for differences in duration of exposure:
2
Justification:
Subchronic to Chronic
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.72 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
other: LC50
Value:
18 mg/m³
Explanation for the modification of the dose descriptor starting point:

The European Union (2007) considered as acceptable to determine the Margin of Safety for an acute inhalation exposure to the registered substance based on a LC50 of 18 mg/m3. Therefore this value was used a starting point and was applied the relevant assessment factors.

Reference:

European Union (2007) Risk Assessment Report. Hexachlorocyclopentadiene. CAS No: 77-47-4. EINECS No: 201-029-3. Final Approved Version.

AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.014 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):
360
Dose descriptor starting point:
NOAEL
Value:
5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

It is assumed that the dermal absorption of the substance will be similar between human and rabbit, therefore the NOAEL(dermal) for systemic effects from the subacute repeated-dose toxicity by the dermal route does not need to be converted.

AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for differences in duration of exposure:
6
Justification:
Subacute to Chronic
AF for interspecies differences (allometric scaling):
2.4
Justification:
Rabbits to Humans
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.83 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):
60
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
NOAEL
Value:
5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

It is assumed that the dermal absorption of the substance will be similar between human and rabbit, therefore the NOAEL(dermal) for systemic effects from the subacute repeated-dose toxicity by the dermal route does not need to be converted.

AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
2.4
Justification:
Rabbits to Humans
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.05 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:
10 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

It is assumed that the oral absorption of the substance will be similar between human and rat, therefore the NOAEL(oral) from the subchronic repeated-dose toxicity by the oral route does not need to be converted.

AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for differences in duration of exposure:
2
Justification:
Subchronic to Chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rats to Humans
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.1 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
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

It is assumed that the oral absorption of the substance will be similar between human and rat, therefore the NOAEL(oral) from the subchronic repeated-dose toxicity by the oral route does not need to be converted.

AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
4
Justification:
Rats to Humans
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population