Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.7 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):
37.5
Modified dose descriptor starting point:
LOAEC
Value:
26.4 mg/m³
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:
0.1 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):
150
Modified dose descriptor starting point:
LOAEL
Value:
15 mg/kg bw/day
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

DNEL Long-term – dermal, systemic effects

Relevant dose descriptor for the endpoint concerned: LOAEL of 15 mg/kg bw/d in male and female rats in a 2 year carcinogenicity study (NTP, 2006)

Assessment factors relating to the extrapolation procedure:

Interspecies: 4 (allometric scaling) and 2.5 (remaining differences)

Intraspecies: 5 (worker)

Time extrapolation: no correction necessary (chronic study)

Route to route extrapolation: 1 (oral to dermal)

Dose-response: 3 (LOAEL to NOAEL)

Quality of whole database: sufficient (no correction necessary)

Overall assessment factor: 4 * 2.5 * 5 * 1 * 3 = 150

DNEL long-term– dermal, systemic effects: 15 mg/kg bw/d ÷ 150 = 0.1 mg/kg bw/d

DNEL Long-term–inhalation, systemic effects

Relevant dose descriptor for the endpoint concerned: LOAEL of 15 mg/kg bw/d in male and female rats in a 2 year carcinogenicity study (NTP, 2006)

Correction of starting point:

Bioavailability: complete absorption is assumed (no correction necessary)

Route of exposure (oral vs. inhalation exposure): complete absorption assumed (no correction necessary)

Differences in respiratory volumes: respiratory volume of the rat in 8 h corresponds to 0.38 m3/kg bw, additional correction for the higher standard respiratory volumes of workers compared to resting persons: correction factor = (1 ÷ 0.38) * (6.7 ÷ 10) = 1.76

Overall correction factor: 1.76

Corrected starting point: 15 * 1.76 = 26.4 mg/m3

Assessment factors relating to the extrapolation procedure:

Interspecies: 2.5 (remaining differences)

Intraspecies: 5 (worker)

Time extrapolation: no correction necessary

Dose-response: 3 (LOAEL to NOAEL)

Quality of whole database: sufficient (no correction necessary)

Overall assessment factor: 2.5 * 5 * 3 = 37.5

DNEL Long-term–inhalation, systemic effects: 26.4 mg/m3 ÷ 37.5 = 0.7 mg/m3

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.17 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):
75
Modified dose descriptor starting point:
LOAEC
Value:
13 mg/m³
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:
0.05 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):
300
Modified dose descriptor starting point:
LOAEL
Value:
15 mg/kg bw/day
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:
0.05 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):
300
Modified dose descriptor starting point:
LOAEL
Value:
15 mg/kg bw/day
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

DNEL Long-term – dermal, systemic effects

Relevant dose descriptor for the endpoint concerned: LOAEL of 15 mg/kg bw/d in male and female rats in a 2 year carcinogenicity study (NTP, 2006)

Assessment factors relating to the extrapolation procedure:

Interspecies: 4 (allometric scaling) and 2.5 (remaining differences)

Intraspecies: 10 (general population)

Time extrapolation: no correction necessary (chronic study)

Route to route extrapolation: 1 (oral to dermal)

Dose-response: 3 (LOAEL to NOAEL)

Quality of whole database: sufficient (no correction necessary)

Overall assessment factor: 4 * 2.5 * 10 * 1 * 3 = 300

DNEL long-term– dermal, systemic effects: 15 mg/kg bw/d ÷ 300 = 0.05 mg/kg bw/d

DNEL Long-term–inhalation, systemic effects

Relevant dose descriptor for the endpoint concerned: LOAEL of 15 mg/kg bw/d in male and female rats in a 2 year carcinogenicity study (NTP, 2006)

Correction of starting point:

Bioavailability: complete absorption is assumed (no correction necessary)

Route of exposure (oral vs. inhalation exposure): complete absorption assumed (no correction necessary)

Differences in respiratory volumes: respiratory volume of the rat in 24 h corresponds to 1.15 m3/kg bw, correction factor 1 ÷ 1.15 = 0.87

Overall correction factor: 0.87

Corrected starting point: 15 * 0.87 = 13 mg/m3

Assessment factors relating to the extrapolation procedure:

Interspecies: 2.5 (remaining differences)

Intraspecies: 10 (general population)

Time extrapolation: no correction necessary

Dose-response: 3 (LOAEL to NOAEL)

Quality of whole database: sufficient (no correction necessary)

Overall assessment factor: 2.5 * 10 * 3 = 75

DNEL Long-term–inhalation, systemic effects: 13 mg/m3 ÷ 75 = 0.17 mg/m3

DNEL Long-term - oral, systemic effects

Relevant dose descriptor for the endpoint concerned: LOAEL of 15 mg/kg bw/d in male and female rats in a 2 year carcinogenicity study (NTP, 2006)

Correction of starting point:

Bioavailability: complete absorption is assumed (no correction necessary)

Route of exposure: similar to general population (no correction necessary)

Exposure conditions: oral uptake via food in humans compared to application via diet (no correction necessary)

Assessment factors relating to the extrapolation procedure:

Interspecies: 4 (allometric scaling) and 2.5 (remaining differences)

Intraspecies: 10 (general population)

Time extrapolation: no correction necessary

Dose-response: 3 (LOAEL to NOAEL)

Quality of whole database: sufficient (no correction necessary)

Overall assessment factor: 4 * 2.5 * 10 * 3 = 300

DNEL long-term– dermal, systemic effects: 15 mg/kg bw/d ÷ 300 = 0.05 mg/kg bw/d