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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
52.89 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
Modified dose descriptor starting point:
NOAEC
Value:
1 322 mg/m³
Explanation for the modification of the dose descriptor starting point:
The oral NOAEL of 750 mg/kg bw/d is converted to a NOAEC by dividing by 0.38 and multiplying by 0.67 according to ECHA Guidance
AF for dose response relationship:
1
Justification:
NOAEC is used as a starting point
AF for differences in duration of exposure:
2
Justification:
based on an oral 200 days feeding study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
no substance specific data are available.
AF for intraspecies differences:
5
Justification:
for workers the default factor of 5 is used
AF for the quality of the whole database:
1
Justification:
Available data from substance fulfilling scientific principle is used .
AF for remaining uncertainties:
1
Justification:
No further uncertainties to be taken into account
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
52.89 mg/m³
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:
7.5 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
Modified dose descriptor starting point:
NOAEL
Value:
750 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
oral to dermal extrapolation as no dermal study is available
AF for dose response relationship:
1
Justification:
NOAEL is used as a starting point.
AF for differences in duration of exposure:
2
Justification:
based on an oral 200-day study
AF for interspecies differences (allometric scaling):
4
Justification:
rats are used in the animal test.
AF for other interspecies differences:
2.5
Justification:
no substance-specific data are available.
AF for intraspecies differences:
5
Justification:
for worker, a default AF of 5 is to be used.
AF for the quality of the whole database:
1
Justification:
Available data from substance fulfilling scientific principle is used .
AF for remaining uncertainties:
1
Justification:
no other uncertainties needed to be considered.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.5 mg/kg bw/day
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:
no hazard identified

Additional information - workers

According to the results of toxicokinetic assessment, as there is no quantitative data available for dermal adsorption of test material, a worst case scenario is assumed in which the absorption rate from dermal route is considered to be same as oral route, and for both routes assumed to be 100%. The inhalation route is not considered further as exposure scenarios for test article do not indicate inhalative exposure to be the likely route of exposure to human in regular use.

As basis for DNEL derivation the result from a sub-chronic feeding study with rats was used, published by R.A. Wilson et al. In this study hesperidin was dosed up to 1% in food over 200 days and no evidence of cumulative injury, blood sugar levels, weights of important viscera or macroscopic and microscopic tissues has been observed. Hence this study is chosen as basis for DNEL derivation, applying the highest applied dose as NOAEL value (750 mg/kg bw/d) in this study in line with a worst case approach. By Lina et al. a sub-chronic 90-day oral toxicity test was conducted in the rats with neohesperidin dihydrochalcone as structural surrogates for test article. It was indicated that no object adverse effect level (NOAEL) was of 750 mg/kg. bw/day supporting this approach. Based on the above description, the basis for the DNEL therefore is this oral NOAEL (750 mg/kg bw/day), and NOAELcorr for the dermal route is still 750 mg/kg.bw/day. According to ECHA guidance document the oral NOAEL is converted to an inhalative NOAECWorker by dividing through 0.38 m3/kg and multiplied by 0.67 resulting in a NOAEC of 1322 mg/m3.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
13.04 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
Modified dose descriptor starting point:
NOAEC
Value:
652 mg/m³
Explanation for the modification of the dose descriptor starting point:
The oral NOAEL of 750 mg/kg bw/d is converted to a NOAEC by dividing by 1.15 according to ECHA Guidance
AF for dose response relationship:
1
Justification:
NOAEC is used as a starting point
AF for differences in duration of exposure:
2
Justification:
based on an oral 200 days feeding study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
no substance specific data are available.
AF for intraspecies differences:
10
Justification:
for general population the default factor of 10 is used
AF for the quality of the whole database:
1
Justification:
Available data from substance fulfilling scientific principle is used .
AF for remaining uncertainties:
1
Justification:
No further uncertainties to be taken into account
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
13.04 mg/m³
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:
3.75 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
Modified dose descriptor starting point:
NOAEL
Value:
750 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
oral to dermal extrapolation as no dermal study is available
AF for dose response relationship:
1
Justification:
NOAEL is used as starting point
AF for differences in duration of exposure:
2
Justification:
based on oral 200 days study
AF for interspecies differences (allometric scaling):
4
Justification:
rats had been used as test animals
AF for other interspecies differences:
2.5
Justification:
no substance-specific data are available.
AF for intraspecies differences:
10
Justification:
default value for general population
AF for the quality of the whole database:
1
Justification:
Available data fromsubstance fulfilling scientific principle is used .
AF for remaining uncertainties:
1
Justification:
no other uncertainties needed to be considered.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
3.75 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
Modified dose descriptor starting point:
NOAEL
Value:
750 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no route-to-route extrapolation
AF for dose response relationship:
1
Justification:
NOAEL is used as a starting point.
AF for differences in duration of exposure:
2
Justification:
DNEL is based on an oral 200-day study.
AF for interspecies differences (allometric scaling):
4
Justification:
Rats were used in the animal study.
AF for other interspecies differences:
2.5
Justification:
No substance-specific data is available.
AF for intraspecies differences:
10
Justification:
For general population, a default AF of 10 is to be used.
AF for the quality of the whole database:
1
Justification:
Available data from substance fulfilling scientific principle.
AF for remaining uncertainties:
1
Justification:
No other uncertainties needed to be considered.
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

According to the results of the toxicokinetic assessment, as there is no quantitative data available for dermal adsorption of test material, a worst case scenario is assumed in which the absorption rate from dermal route is considered to be same as oral route, and for both routes assumed to be 100%. The inhalation route is not considered further as exposure scenarios for test article do not indicate inhalative exposure to be the likely route of exposure to human in regular use.

As basis for DNEL derivation the result from a sub-chronic feeding study with rats was used, published by R.A. Wilson et al. In this study hesperidin was dosed up to 1% in food over 200 days and no evidence of cumulative injury, blood sugar levels, weights of important viscera or macroscopic and microscopic tissues has been observed. Hence this study is chosen as basis for DNEL derivation, applying the highest applied dose as NOAEL value (750 mg/kg bw/d) in this study in line with a worst case approach. By Lina et al. a sub-chronic 90-day oral toxicity test was conducted in the rats with neohesperidin dihydrochalcone as structural surrogates for test article. It was indicated that no object adverse effect level (NOAEL) was of 750 mg/kg. bw/day supporting this approach. Based on the above description, the basis for the DNEL therefore is this oral NOAEL (750 mg/kg bw/day), and NOAELcorr for the dermal route is still 750 mg/kg.bw/day. According to ECHA guidance document the oral NOAEL is converted to an inhalative NOAECWorkerby dividing through 1.15 m3/kg resulting in a NOAEC of 652 mg/m3.