Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
23.51 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
75
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.33 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

1. Identification of relevant dose descriptor

For the derivation of the DNELs, the 28-Day oral toxicity study in rats was qualified as the most relevant study. The dose descriptor chosen was the NOAEL of 1000 mg/kg/day.

2. Mode of action

No non-threshold mode of action is associated with the test substance. In particular, the test substance has no genotoxic potential.

3. Correction of dose descriptor

NOAEL (oral) is converted into a NOAEL(corrected) in accordance to guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose[concentration]-response for human health, ECHA, May 2008.

Workers: NOAEL (oral) = 1000 mg/kg bw =>NOAEL(corrected)= 1763 mg/m3

4. Application of assessment factors

The following assessment factors according to "ECHA guidance on information requirements and chemical safety assessment, Chapter R8" were chosen: A correction for differences in metabolic rate per body weight was made by an allometric scaling factor of 4 (except for inhalation). Intraspecies differences account for a factor of 5. Interspecies variations account for a factor of 2.5. For exposure duration a factor of 6 is employed. Overall, assessment factors of 300 and 75 were employed for oral/dermal and inhalation route, respectively.

 

5. Selection of the critical DNEL(s)/DMELs and/or qualitative/semi-quantitative descriptor for critical health effects

DNELs - acute, systemic; inhalation & dermal routes:

According to the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose[concentration]-response for human health", a DNEL for acute systemic toxicity should only be derived if an acute systemic toxicity hazard leading to classification is identified. Referring to the available data on acute toxicity, the test item displays low acute toxicity as evidenced by LD50 values of > 5000 mg/kg bw and > 2000 mg/kg bw determined in rats for the oral and the dermal route, respectively. Therefore, the test item is not subject to classification for acute toxicity according to Directive 67/548/EEC and Regulation 1272/2008/EC, and consequently the derivation of worker DNELs for acute/short-term exposure - systemic effects is not required.

DNELs - acute & long-term, local; inhalation & dermal routes:

Based on the available key toxicological information, the test item is not subject to classification for skin and eye irritation and skin sensitization. Accordingly, no worker DNELs for local effects following acute/short-term or long-term exposure are derived. This is in line with the ECHA guidance document (Chapter R.8).

DNEL - long-term, systemic, dermal:

The dermal route is typically covered by oral route information in the absence of data for this administration route.

NOAEL (oral) / Sum of assessment factors applicable

1000 mg/kg body weight / 300 = 3.33 mg/kg body weight

DNEL - long-term, systemic, inhalation:

NOAEL (corrected) / Sum of assessment factors applicable

1763 mg/m3 /75= 23.51 mg/m3

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.8 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
150
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.67 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.67 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

1. Identification of relevant dose descriptor

For the derivation of the DNELs, the 28-Day oral toxicity study in rats was qualified as the most relevant study. The dose descriptor chosen was the NOAEL of 1000 mg/kg/day.

 

2. Mode of action

No non-threshold mode of action is associated with the test substance. In particular, the test substance has no genotoxic potential.

 

3. Correction of dose descriptor

NOAEL (oral) is converted into a NOAEL(corrected) in accordance to guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose[concentration]-response for human health, ECHA, May 2008.

General population: NOAEL (oral) = 1000 mg/kg body weight =>NOAEL(corrected)= 869.6 mg/m3

 

4. Application of assessment factors

The following assessment factors according to "ECHA guidance on information requirements and chemical safety assessment, Chapter R8" were chosen: A correction for differences in metabolic rate per body weight was made by an allometric scaling factor of 4 (except for inhalation). Intraspecies differences account for a factor of 5. Interspecies variations account for a factor of 2.5. For exposure duration a factor of 6 is employed. Overall, assessment factors of 600 and 150 were employed for oral/dermal and inhalation route, respectively.

 

5. Selection of the critical DNEL(s)/DMELs and/or qualitative/semi-quantitative descriptor for critical health effects

DNELs - acute, systemic; oral, inhalation & dermal routes:

According to the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose[concentration]-response for human health", a DNEL for acute systemic toxicity should only be derived if an acute systemic toxicity hazard leading to classification is identified. Referring to the available data on acute toxicity, the test item displays low acute toxicity as evidenced by LD50 values of > 5000 mg/kg bw and > 2000 mg/kg bw determined in rats for the oral and the dermal route, respectively. Therefore, the test item is not subject to classification for acute toxicity according to Directive 67/548/EEC and Regulation 1272/2008/EC, and consequently the derivation of general population DNELs for acute/short-term exposure - systemic effects is not required.

DNELs - acute & long-term, local; inhalation & dermal routes:

Based on the available key toxicological information, the test item is not subject to classification for skin and eye irritation and skin sensitization. Accordingly, no general population DNELs for local effects following acute/short-term or long-term exposure are derived. This is in line with the ECHA guidance document (Chapter R.8).

DNEL - long-term, dermal, systemic:

The dermal route is typically covered by oral route information in the absence of data for this administration route.

NOAEL (oral) / Sum of assessment factors applicable

1000 mg/kg body weight / 600 = 1.67 mg/kg body weight

DNEL - long-term, inhalation, systemic:

NOAEL (corrected) / Sum of assessment factors applicable

869.6 mg/m3 /150= 5.8 mg/m3

DNEL - long-term, oral, systemic:

NOAEL (oral) / Sum of assessment factors applicable

1000 mg/kg body weight / 600 = 1.67 mg/kg body weight