Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
106 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
25
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:
30 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
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:
no hazard identified

Additional information - workers

In general, the calculation of DNELs is based on the observed effect level which has to be modified as described in “Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health” (ECHA, May 2008).

For calculation of the DNEL for long-term dermal systemic effects the No-(Adverse) -Effect-Level for oral repeated-dose toxicity was used, which was obtained in a subchronic feeding study in rats with the test substance Vinasses, residue of fermentation (Appel, 2003). Based on significant changes in clinical chemistry parameters a NOAEL of 3000 mg/kg bw/d for males and 3600 mg/kg bw/d for females was determined. For calculation of DNELs, the more sensitive NOAEL of 3000 mg/kg bw/d is used.

Since the NOAEL was obtained in an oral toxicity study, the dose descriptor has to be converted into a corrected starting point by route-to-route extrapolation. As a worst-case, the dermal absorption is assumed to be identical to that of the oral route. Thus, the starting point is 3000 mg/kg bw/d for dermal exposure.

The DNEL for dermal exposure is calculated using the starting point of 3000 mg/kg bw/day / overall assessment factor (100) = 30 mg/kg bw/day.

 

Since there is no inhalation repeated dose toxicity study available, the calculation of the DNEL for long-term inhalative systemic effects is performed using route-to-route extrapolation again based on the oral subchronic repeated dose (feeding) study (Appel, 2003).

For calculation of the DNEL for long-term inhalative systemic effects, the available dose descriptor needs to be converted into a corrected starting point by route-to-route extrapolation. This conversion of the rat oral NOAEL of 3000 mg/kg bw/day to a corrected inhalatory human NAEC takes into account the differences in standard respiratory volumes between rats and humans as well as differences in exposure conditions. Furthermore, as a worst-case the inhalative absorption is assumed to be higher than that of the oral route. Thus, the corrected NAEC (corrected starting point) is NOAEL 3000 mg / kg bw/day x 1/0.38 m³/kg bw/day x 6.7 m³ (8h) /10 m³ (8h) x 1/2 = 2645 mg/m³.

The DNEL for inhalative exposure is calculated using the corrected starting point of 2645 mg/kg bw/day / overall assessment factor (25) = 106 mg/m³.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
26 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
50
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:
15 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
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:
15 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
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 general, the calculation of DNELs is based on the observed effect level which has to be modified as described in “Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health” (ECHA, May 2008).

For calculation of the DNELs for long-term dermal and oral systemic effects the No-(Adverse) -Effect-Level for oral repeated-dose toxicity was used, which was obtained in a subchronic feeding study in rats with the test substance Vinasses, residue of fermentation (Appel, 2003). Based on significant changes in clinical chemistry parameters a NOAEL of 3000 mg/kg bw/d for males and 3600 mg/kg bw/d for females was determined. For calculation of DNELs, the more sensitive NOAEL of 3000 mg/kg bw/d is used.

Since the NOAEL was obtained in an oral toxicity study, the dose descriptor has to be converted into a corrected starting point by route-to-route extrapolation. As a worst-case, the dermal absorption is assumed to be identical to that of the oral route. Thus, the starting point is 3000 mg/kg bw/d for dermal as well as oral exposure.

The DNEL for dermal/oral exposure is calculated using the starting point of 3000 mg/kg bw/day / overall assessment factor (200) = 15 mg/kg bw/day.

 

Since there is no inhalation repeated dose toxicity study available, the calculation of the DNEL for long-term inhalative systemic effects is performed using route-to-route extrapolation again based on the oral subchronic repeated dose (feeding) study (Appel, 2003).

For calculation of the DNEL for long-term inhalative systemic effects, the available dose descriptor needs to be converted into a corrected starting point by route-to-route extrapolation. This conversion of the rat oral NOAEL of 3000 mg/kg bw/day to a corrected inhalatory human NAEC takes into account the differences in standard respiratory volumes between rats and humans as well as differences in exposure conditions. Furthermore, as a worst-case the inhalative absorption is assumed to be higher than that of the oral route. Thus, the corrected NAEC (corrected starting point) is NOAEL 3000 mg / kg bw/day x 1/1.15 m³/kg bw/day x 1/2 = 1304 mg/m³.

The DNEL for inhalative exposure is calculated using the corrected starting point of 1304 mg/kg bw/day / overall assessment factor (50) = 26 mg/m³.