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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
13.2 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
NOAEL
Value:
800 mg/kg bw/day
Modified dose descriptor starting point:
other: NAEC
Value:
987 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL (No Observed Adverse Effect Level) for general toxicity and for fertility/reproduction parameters by oral route obtained in the Reproduction/Developmental Toxicity Screening Test (OECD 421, oral route) was selected as the most representative starting dose based on: expusure route, study duration, presence of adverse effects, parameters observed.

Starting from an oral NOAEL, a corrected value is obtained considering: 8h- breathing volume of rat (0.38 m3/kg bw), 8h- breathing volume of human general population (6.7 m3), 8 h- workers (10 m3) and correction for differences between human and experimental exposure conditions (7 d /5 d). As no experimental data on absorption by inhalation is available, worst case assumption for absorption is applied: 50 % orally and 100 % by inhalation.

NAEC inh for worker = 800 mg/kg bw/d / (0.38 m3/kg bw) × (6.7 m3/10 m3 (8h)) × (7 d /5 d) × 0.5

AF for dose response relationship:
1
Justification:
NOAEL used for NAEC derivation
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling has been already considered in starting point derivation
AF for other interspecies differences:
2.5
Justification:
toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part)
AF for intraspecies differences:
5
Justification:
workers
AF for the quality of the whole database:
1
Justification:
good quality of available data
AF for remaining uncertainties:
1
Justification:
no significant uncertainties remaining
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

According to “ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health”, a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential for high peak exposures. Since the substance is not classified for acute toxicity, no DNEL derivation is necessary.

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:
2.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
750 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

DNEL is derived from the NOAEL obtained in the repeated dose toxicity study (28 d) by dermal route.

Starting from an oral NOAEL, a corrected value is obtained considering the correction for differences between human and experimental exposure conditions (0.75).

NOAELdermal for worker = 1000 mg/kg bw/day (NOAELdermal) x 0.75

AF for dose response relationship:
1
Justification:
NOAEL (28 d, dermal exposure) is available
AF for differences in duration of exposure:
6
Justification:
subacute (28 d) to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
study performed on rat
AF for other interspecies differences:
2.5
Justification:
toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part)
AF for intraspecies differences:
5
Justification:
workers
AF for the quality of the whole database:
1
Justification:
good quality of available data
AF for remaining uncertainties:
1
Justification:
no significant uncertainties remaining
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

Based on the available acute dermal toxicity study, the substance is not classified for acute toxicity (LD50 > 2000 mg/kg bw).

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

HAZARD VIA INHALATION ROUTE

Systemic effects long term exposure

The NOAEL (No Observed Adverse Effect Level) for general toxicity and for fertility/reproduction parameters by oral route obtained in the Reproduction/Developmental Toxicity Screening Test (OECD 421, oral route) was selected as the most representative starting dose based on: expusure route, study duration, presence of adverse effects, parameters observed.

Starting from an oral NOAEL, a corrected value is obtained considering: 8h- breathing volume of rat (0.38 m3/kg bw), 8h- breathing volume of human general population (6.7 m3), 8 h- workers (10 m3) and correction for differences between human and experimental exposure conditions (7 d /5 d).

As no experimental data on absorption by inhalation is available, worst case assumption for absorption is applied: 50 % orally and 100 % by inhalation.

NAEC inh for worker = 800 mg/kg bw/d / (0.38 m3/kg bw) × (6.7 m3/10 m3(8h)) × (7 d /5 d) × 0.5 = 987 mg/m³

An overall assessment factor of 75 to be applied is calculated considering AF for dose response relationship 1 (NOAEL used for NAEC derivation), AF for difference in duration of exposure 6 (subacute to chronic), AF for interspecies differences 1 (allometric scaling has been already considered in starting point derivation), AF for other interspecies differences 2.5 (toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part)), AF for intraspecies differences 5 (workers), AF for quality of the whole database 1 (good quality of available data) and AF for remaining uncertainties 1 (no significant uncertainties remaining).

Therefore, DNEL is calculated: 987 mg/m³ / 75 = 13.2 mg/m3.

Systemic effects short term exposure

According to “ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health”, a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential for high peak exposures. Since the substance is not classified for acute toxicity, no DNEL derivation is necessary and no hazard is identified.

Local effects long and short term exposures

Since no inhalation test was performed, no local effect could be observed. However, since the substance is non irritant to eye, an effect on mucous is not expected and no hazard is idenfied.

HAZARD VIA DERMAL ROUTE

Systemic effects long term exposure

DNEL is derived from the NOAEL obtained in the repeated dose toxicity study (28 d) by dermal route.

Starting from an oral NOAEL, a corrected value is obtained considering the correction for differences between human and experimental exposure conditions (0.75).

NOAELdermal for worker = 1000 mg/kg bw/day (NOAELdermal) x 0.75 = 750 mg/kg bw/day

An overall assessment factor of 300 to be applied is calculated considering AF for dose response relationship 1 (NOAEL dermal, 28 d), AF for difference in duration of exposure 6 (subacute (28 d) to chronic), AF for interspecies differences 4 (study performed on rat), AF for other interspecies differences 2.5 (toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part)), AF for intraspecies differences 5 (workers), AF for quality of the whole database 1 (good quality of available data) and AF for remaining uncertainties 1 (no significant uncertainties remaining).

Therefore, DNEL is calculated: 750 mg/kg bw/day / 300 = 2.5 mg/kg bw/day.

Systemic effects short term exposure

Based on the available acute dermal toxicity study, the substance is not classified for acute toxicity (LD50> 2000 mg/kg bw).

Local effects long term exposure

During the subacute dermal toxicity study (28 d), no evidence of local effects were reported.

Local effects short term exposure

No local effects of irritation were observed in studies (i.e. acute dermal toxicity, skin irritation/corrosion and subacute dermal toxicity).

HAZARD TO THE EYE

As the available test showed that the substance is not irritant to eye, no hazard is identified.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.32 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
NOAEL
Value:
800 mg/kg bw/day
Modified dose descriptor starting point:
other: NAEC
Value:
348 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL (No Observed Adverse Effect Level) for general toxicity and for fertility/reproduction parameters by oral route obtained in the Reproduction/Developmental Toxicity Screening Test (OECD 421, oral route) was selected as the most representative starting dose based on: expusure route, study duration, presence of adverse effects, parameters observed.

Starting from an oral NOAEL, a corrected value is obtained considering: 24 h- breathing volume of rat (1.15 m3/kg bw) and 24 h- breathing volume of human general population (20 m3). As no experimental data on absorption by inhalation is available, worst case assumption for absorption is applied: 50 % orally and 100 % by inhalation.

NAEC inh for general public = 800 mg/kg bw/d / (1.15 m3/kg bw) × 0.5

AF for dose response relationship:
1
Justification:
NOAEL used for NAEC derivation
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling has been already considered in starting point derivation
AF for other interspecies differences:
2.5
Justification:
toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part)
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
good quality of available data
AF for remaining uncertainties:
1
Justification:
no significant uncertainties remaining
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

According to “ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health”, a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential for high peak exposures. Since the substance is not classified for acute toxicity, no DNEL derivation is necessary.

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:
0.298 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
179 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

DNEL is derived from the NOAEL obtained in the repeated dose toxicity study (28 d) by dermal route.

Starting from an oral NOAEL, a corrected value is obtained considering the correction for differences between human and experimental exposure conditions (0.178571).

NOAELdermal for general population = 1000 mg/kg bw/day (NOAELdermal) x 0.178571

AF for dose response relationship:
1
Justification:
NOAEL (28 d, dermal exposure) is available
AF for differences in duration of exposure:
6
Justification:
subacute (28 d) to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
study performed on rat
AF for other interspecies differences:
2.5
Justification:
toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part)
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
good quality of available data
AF for remaining uncertainties:
1
Justification:
no significant uncertainties remaining
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

Based on the available acute dermal toxicity study, the substance is not classified for acute toxicity (LD50> 2000 mg/kg bw).

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:
1.33 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
800 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
800 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL (No Observed Adverse Effect Level) for general toxicity and for fertility/reproduction parameters by oral route obtained in the Reproduction/Developmental Toxicity Screening Test (OECD 421, oral route) was selected as the most representative starting dose based on: expusure route, study duration, presence of adverse effects, parameters observed.

AF for dose response relationship:
1
Justification:
NOAEL for general toxicity and for fertility/reproduction parameters (OECD 421, oral route) is available
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rats were used in the available test
AF for other interspecies differences:
2.5
Justification:
toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part)
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
good quality of available data
AF for remaining uncertainties:
1
Justification:
no other uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

Based on the available acute oral toxicity study, the substance is not classified for acute toxicity (LD50 > 2000 mg/kg bw).

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

HAZARD VIA INHALATION ROUTE

Systemic effects long term exposure

The NOAEL (No Observed Adverse Effect Level) for general toxicity and for fertility/reproduction parameters by oral route obtained in the Reproduction/Developmental Toxicity Screening Test (OECD 421, oral route was selected as the most representative starting dose based on: expusure route, study duration, presence of adverse effects, parameters observed.

Starting from an oral NOAEL, a corrected value is obtained considering: 24 h- breathing volume of rat (1.15 m3/kg bw) and 24 h- breathing volume of human general population (20 m3). As no experimental data on absorption by inhalation is available, worst case assumption for absorption is applied: 50 % orally and 100 % by inhalation.

NAEC inh for general public = 800 mg/kg bw/d / (1.15 m3/kg bw) × 0.5 = 348 mg/m3

An overall assessment factor of 150 to be applied is calculated considering AF for dose response relationship 1 (NOAEL used for NAEC derivation), AF for difference in duration of exposure 6 (subacute to chronic), AF for interspecies differences 1 (allometric scaling has been already considered in starting point derivation), AF for other interspecies differences 2.5 (toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part)), AF for intraspecies differences 10 (general population), AF for quality of the whole database 1 (good quality of available data) and AF for remaining uncertainties 1 (no significant uncertainties remaining).

Therefore, DNEL is calculated: 348 mg/m³ / 150 = 2.32 mg/m³.

Systemic effects short term exposure

According to “ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health”, a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential for high peak exposures. Since the substance is not classified for acute toxicity, no DNEL derivation is necessary.

Local effects long and short term exposures

Since no inhalation test was performed, no local effect could be observed. However, since the substance is non irritant to eye, an effect on mucous is not expected.

HAZARD VIA DERMAL ROUTE

Systemic effects long term exposure

DNEL is derived from the NOAEL obtained in the repeated dose toxicity study (28 d) by dermal route.

Starting from an oral NOAEL, a corrected value is obtained considering the correction for differences between human and experimental exposure conditions (0.178571).

NOAELdermal for general population = 1000 mg/kg bw/day (NOAELdermal) x 0.178571 = 179 mg/kg bw/day.

An overall assessment factor of 600 to be applied is calculated considering AF for dose response relationship 1 (NOAEL 28 d, dermal), AF for difference in duration of exposure 6 (subacute (28 d) to chronic), AF for interspecies differences 4 (study performed on rat), AF for other interspecies differences 2.5 (toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part)), AF for intraspecies differences 10 (general population), AF for quality of the whole database 1 (good quality of available data) and AF for remaining uncertainties 1 (no significant uncertainties remaining).

Therefore, DNEL is calculated: 179 mg/kg bw/day / 600 = 0.298 mg/kg bw/day.

Systemic effects short term exposure

Based on the available acute oral toxicity study, the substance is not classified for acute toxicity (LD50 > 2000 mg/kg bw).

Local effects long term exposure

During the subacute dermal toxicity study (28 d), no evidence of local effects were reported.

Local effects short term exposure

No local effects of irritation were observed in studies (i.e. acute dermal toxicity, skin irritation/corrosion and subacute dermal toxicity).

HAZARD VIA ORAL ROUTE

Systemic effects long term exposure

The NOAEL (No Observed Adverse Effect Level) for general toxicity and for fertility/reproduction parameters by oral route obtained in the Reproduction/Developmental Toxicity Screening Test (OECD 421, oral route) was selected as the most representative starting dose based on: expusure route, study duration, presence of adverse effects, parameters observed.

An overall assessment factor of 600 to be applied is calculated considering AF for dose response relationship 1 (NOAEL used for NAEC derivation), AF for difference in duration of exposure 6 (subacuteto chronic), AF for interspecies differences 4 ( rats were used in the available test), AF for other interspecies differences 2.5 (toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part)), AF for intraspecies differences 10 (general population), AF for quality of the whole database 1 (good quality of available data) and AF for remaining uncertainties 1 (no significant uncertainties remaining).

Therefore, DNEL is calculated: 800 mg/kg bw / 600 = 1.33 mg/kg bw/day.

Systemic effects short term exposure

Based on the available acute oral toxicity study, the substance is not classified for acute toxicity (LD50 > 2000 mg/kg bw).

HAZARD TO THE EYE

As the available test showed that the substance is not irritant to eye, no hazard is identified.