Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.47 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):
6
Modified dose descriptor starting point:
NOAEC
Value:
8.82 mg/m³
Explanation for the modification of the dose descriptor starting point:
as no long-term study via inhalation route of exposure is available, route-to-route extrapolation has been performed
AF for dose response relationship:
1
Justification:
starting from NOAEC
AF for differences in duration of exposure:
2
Justification:
difference in duration subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
differences in allometry are assumed to be compensated by differences in respiration rate
AF for other interspecies differences:
1
Justification:
ECETOC assessment factor, included in total allometry
AF for intraspecies differences:
3
Justification:
ECETOC assessment factor for worker population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
0.42 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):
24
Modified dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
as no long term study via dermal exposure was available, route-to-route extrapolation has been performed
AF for dose response relationship:
1
Justification:
starting from NOAEL
AF for differences in duration of exposure:
2
Justification:
difference in duration subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
differences allometry rat to human
AF for other interspecies differences:
1
Justification:
ECETOC assessment factor, included in total allometry
AF for intraspecies differences:
3
Justification:
ECETOC assessment factor for worker population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
medium hazard (no threshold derived)

Additional information - workers

Acute / short-term exposure (systemic and local effects):

- Jeffamine RFD 270 is classified as acute toxic category 4 for dermal exposure (LD50 of > 1000 mg/kg bw but < 2000 mg/kg). No acute DNEL for short-term exposure, systemic effects was derived (dermal exposure route) as no peak exposure is expected.

- No data were available on acute toxicity via the inhalation route of exposure. Therefore, a short-term exposure DNEL for inhalation is not quantifiable.

- Based on the available data and according to the criteria laid down in the CLP Regulation (EC) 1272/2008, Jeffamine RFD270 is classified as Eye damage category 1 (moderate hazard) and Skin corrosion category 1C (moderate hazard). No dose response curve can be derived based on the available data and so only an indication of the moderate hazard category can be given. The hazard categories are indicated in the Guidance on Information Requirements and Chemical Safety Assessment - Part E Risk Characterisation.

 

Long-term exposure (systemic effects):

- Dermal: No long-term dermal toxicity studies are available for Jeffamine RFD 270. However, data from an oral ninety day repeated dose toxicity could be used after extrapolation to the dermal route. The test substance was administered daily, by gavage, on a 7-day per week basis. Parental wistar rats (10 per sex and per dose) were treated; starting at 11 -12 weeks old and ending when the animals were euthanized, at dose levels of 10, 30 and 75 mg/kg/day. A control group of 10 males and 10 females was dosed with vehicle only (distilled water). The NOEL was determined at 10 mg/kg/day. For route-to-route extrapolation (oral to dermal), no default factor (i.e. factor 1) should be applied as part of the overall assessment factor, as it is assumed that dermal absorption will not be higher than oral absorption. The long-term dermal, systemic DNEL is derived with an overall assessment factor of 24: 4 (interspecies differences) x 2 (difference in duration subchronic to chronic) x 3 (intraspecies differences). A long-term, systemic DNEL of 10 mg/kg/day/24 = 0.42 mg/kg/day is derived. The registrant used the ECETOC assessment factors as reported in the Technical Report No. 110 of October 2010. These assessment factors were considered sufficiently protective taking into account the available hazard information on the substance.

- Inhalation: The NOAEL observed in the ninety day repeated dose toxicity was used to derive a DNEL long-term, systemic effects via the inhalation route. For the route-to-route extrapolation from oral to inhalation, the dose descriptor starting point = 10 mg/kg bw/day x 1/(0.38 m³/kg/day) x 6.7m³/10m³ x 0.5 = 8.82 mg/m³. The oral dose for rats was converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m³/kg for 8 hours exposure of workers). For workers the resulting air concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity. This correction factor is derived from the inhaled volumes in 8 hours under the respective conditions (6.7 m³ for base level, 10 m³ for light activity). In addition, the NOAEL need to be divided by 2 as the bioavailability via the inhalation route is considered as 100%, while for oral exposure this is only 50%. With an overall assessment factor of 6: 2 (difference in duration subchronic to chronic) x 3 (intraspecies differences) x 1 (interspecies differences - allometric scaling) x 1 (interspecies - remaining differences), the long-term DNEL, inhalation for systemic effects of 8.82 mg/m³/6 = 1.47 mg/m³ is derived. The registrant used the ECETOC assessment factors as reported in the Technical Report No. 110 of October 2010. These assessment factors were considered sufficiently protective taking into account the available hazard information on the substance.

 

Long-term exposure (local effects):

- No reliable repeated dose toxicity study was available for this substance via the dermal and inhalation route of exposure. Therefore, a DNEL long-term exposure, local effects cannot be derived for the dermal and inhalation route.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.44 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):
10
Modified dose descriptor starting point:
NOAEC
Value:
4.35 mg/m³
Explanation for the modification of the dose descriptor starting point:
as no long-term study on inhalation is available, route-to-route extrapolation has been performed
AF for dose response relationship:
1
Justification:
starting point is NOAEL
AF for differences in duration of exposure:
2
Justification:
differences in exposure duration subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
covered by calculation for route-to-route extrapolation
AF for other interspecies differences:
1
Justification:
ECETOC assessment factor, included in total allometry
AF for intraspecies differences:
5
Justification:
ECETOC assessment factor for general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
0.25 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):
40
Modified dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no long-term study via dermal exposure is available, route-to-route extrapolation has been performed
AF for dose response relationship:
1
Justification:
starting from NOAEL
AF for differences in duration of exposure:
2
Justification:
difference in exposure duration subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
difference in allometry rat to human
AF for other interspecies differences:
1
Justification:
ECETOC assessment factor, included in total allometry
AF for intraspecies differences:
5
Justification:
ECETOC assessment factor for general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
0.25 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):
40
Modified dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
difference in exposure duration subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
difference in allometry rat to human
AF for other interspecies differences:
1
Justification:
ECETOC assessment factor, included in total allometry
AF for intraspecies differences:
5
Justification:
ECETOC assessment factor for general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

Acute/short-term exposure (systemic and local effects)

- Jeffamine RFD 270 is classified as acute toxic category 4 for oral (LD50 of 550 mg/kg body weight) and dermal (LD50 between 1000 mg/kg body weight) exposure routes. No acute DNEL for short-term exposure, systemic effects was derived (oral and dermal exposure route) as no peak exposure is expected.

- No data were available on acute toxicity via inhalation route. Therefore, a short-term DNEL for inhalation is not quantifiable.

- Based on the available data and according to the criteria laid down in the CLP Regulation (EC) 1272/2008, Jeffamine RFD 270 is classified as eye damage category 1 (moderate hazard) and skin corrosion category 1C (moderate hazard). No dose-response curve can be derived based on the available data and so only an indication of the moderate hazard category can be given. The hazard categories are indicated in the Guidance on Information Requirements and Chemical Safety Assessment - Part E Risk characterisation.

 

Long-term exposure (systemic effects):

- Oral:

An oral ninety day repeated dose toxicity has been performed. The test substance was administered daily, by gavage, on a 7-day per week basis. Parental wistar rats (10 per sex and per dose) were treated; starting at 11 -12 weeks old and ending when the animals were euthanized, at dose levels of 10, 30 and 75 mg/kg/day. A control group of 10 males and 10 females was dosed with vehicle only (distilled water). The NOEL was determined at 10 mg/kg/day. The long-term oral, systemic DNEL is derived with an overall assessment factor of 40 = 4 (interspecies differences) x 2 (difference in exposure duration subchronic to chronic) x 5 (intraspecies differences). A long-term, systemic DNEL of 10 mg/kg/day/40 = 0.25 mg/kg/day is derived. The registrant used the ECETOC assessment factors as reported in the Technical Report No. 110 of October 2010. These assessment factors were considered sufficiently protective taking into account the available hazard information on the substance.

 

-Dermal:

No long-term dermal toxicity studies are available for Jeffamine RFD 270. However, data from an oral combined repeated dose toxicity study with reproduction/developmental toxicity screening could be used after extrapolation to the dermal route. For route-to-route extrapolation (oral to dermal), no default factor (i.e. factor 1) should be applied as part of the overall assessment, as it is assumed that dermal absorption will not be higher than oral absorption. The long-term dermal, systemic DNEL is derived with an overall assessment factor of 40 = 4 (interspecies differences) x 2 (difference in exposure duration subacute to chronic) x 5 (intraspecies difference). A long-term systemic DNEL of 10 mg/kg/day/40 = 0.25 mg/kg/day.

The registrant used the ECETOC assessment factors as reported in the Technical Report No. 110 of October 2010. These assessment factors were considered sufficiently protective taking into account the available hazard information on the substance.

 

-Inhalation:

The NOEL observed in the oral ninety day repeated dose toxicity was used to derive a DNEL long-term, systemic effects via the inhalation route. For the route-to-route extrapolation from oral to inhalation, the dose descriptor starting point = 10 mg/kg bw/day x 1/(1.15 m³/kg/day) x 0.5 = 4.35 mg/m³. The oral dose for rats was converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m³/kg for 24 hours exposure). In addition, the NOEL needed to be divided by 2 as the bioavailability via the inhalation route is considered 100%, while for oral exposure this is only 50%.

With an overall assessment factor of 10 = 2 (differences in exposure duration subacute to chronic) x 5 (intraspecies differences) x 1 (interspecies differences), the long-term DNEL inhalation for systemic effects of 4.35 mg/m³/10 = 0.44 mg/m³ is derived.

The registrant used the ECETOC assessment factors as reported in the Technical Report No. 110 of October 2010. These assessment factors were considered sufficiently protective taking into account the available hazard information on the substance.

 

Long-term exposure (local effects):

-No reliable repeated dose toxicity study was available for the substance via the dermal and inhalation route of exposure. Therefore, a DNEL long-term exposure, local effects cannot be derived for the dermal and inhalation route.