Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.3 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:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
176 mg/m³
Explanation for the modification of the dose descriptor starting point:

Modification of the starting point (R.8 Figure R.8 -3):

Corrected inhalatory N(L)OAEC = oral N(L)OAEL*(1/sRVrat)*ABSoral-rat/ABSinh-human)*(sRVhuman/wRV)

= oral N(L)OAL*(1/0.38 m3/kg/d)*(1/1)*6.7m3(8h)/10 m3 (8h))

ABS: Absoprtion

sRV: standard Respiratory Volume

wRV: worker Respiratory Volume

ABSoral-rat: 1 [-]: worst case default

ABSinh-human: 1 [-]: worst case default

AF for dose response relationship:
1
Justification:
No issues in relevance or reliability of dose response: REACH guidance R.8 (default)
AF for differences in duration of exposure:
6
Justification:
Subacute to Chronic: REACH guidance R.8 (default)
Justification:
Not relevant for corrected inhalation DNEL: REACH guidance R.8 (default)
AF for other interspecies differences:
2.5
Justification:
Interspecies remaining differences: REACH guidance R.8 (default)
AF for intraspecies differences:
5
Justification:
Worker: REACH guidance R.8 (default)
AF for the quality of the whole database:
1
Justification:
No significant reduction in relevance or reliability across the database: REACH guidance R.8 (default)
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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:
0.8 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):
120
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No absorption data is available, therefore a worst case modification factor of 1 is used: REACH guidance R.8 (default)

AF for dose response relationship:
1
Justification:
No issues in relevance or reliability of dose response: REACH guidance R.8 (default)
AF for differences in duration of exposure:
6
Justification:
Subacute to Chronic: REACH guidance R.8 (default)
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to Human: REACH guidance R.8 (default)
AF for other interspecies differences:
1
Justification:
Interspecies remaining differences: REACH guidance R.8 (default)
AF for intraspecies differences:
5
Justification:
Worker: REACH guidance R.8 (default)
AF for the quality of the whole database:
1
Justification:
No significant reduction in relevance or reliability across the database: REACH guidance R.8 (default)
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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

Summary of results

The substance is of low acute oral (LD50> 5000 mg/kg bw) and low acute dermal toxicity (LD50> 2000 mg/kg bw). Additionally, the substance is not irritating to the skin and the eye when applied to rabbits. After application in a modified guinea pig maximisation test, no skin sensitising potential was observed. The product induced neither chromosome aberrations in-vitro in a mammalian cell line, nor in the micronucleus test in Chinese hamster. It was not mutagenic to different Salmonella typhimurium strains in the Ames test. Additionally, in a cell mutation assay at the thymidine kinase locus (tk+/-) in mouse lymphoma l5178y cells also no mutagenicity was seen. A study on chromosome aberration on Chinese hamster ovary cell line CCL 61 revealed no increase in chromosome aberrations. In accordance, upon in-vivo-treatment of Chinese hamster no increase of micronuclei in bone marrow cells was observed. Therefore, the substance has no genotoxic potential and a threshold can be expected.

A NOAEL of 100 mg/kg bw was determined for subacute oral exposure of rats for the endpoints of both developmental toxicity and general systemic toxicity.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.6 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):
150
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
87 mg/m³
Explanation for the modification of the dose descriptor starting point:

Modification of the starting point (R.8 Figure R.8 -3):

Corrected inhalatory N(L)OAEC = oral N(L)OAEL*(1/sRVrat)*ABSoral-rat/ABSinh-human)

= oral N(L)OAL*(1/1.15 m3/kg/d)*(1/1)

ABS: Absoprtion

sRV: standard Respiratory Volume

ABSoral-rat: 1 [-]: worst case default

ABSinh-human: 1 [-]: worst case default

AF for dose response relationship:
1
Justification:
No issues in relevance or reliability of dose response: REACH guidance R.8 (default)
AF for differences in duration of exposure:
6
Justification:
Subacute to Chronic: REACH guidance R.8 (default)
Justification:
Not relevant for corrected inhalation DNEL: REACH guidance R.8 (default)
AF for other interspecies differences:
2.5
Justification:
Interspecies remaining differences: REACH guidance R.8 (default)
AF for intraspecies differences:
10
Justification:
General population: REACH guidance R.8 (default)
AF for the quality of the whole database:
1
Justification:
No significant reduction in relevance or reliability across the database: REACH guidance R.8 (default)
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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:
0.42 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):
240
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No absorption data is available, therefore a worst case modification factor of 1 is used: REACH guidance R.8 (default)

AF for dose response relationship:
1
Justification:
No issues in relevance or reliability of dose response: REACH guidance R.8 (default)
AF for differences in duration of exposure:
6
Justification:
Subacute to Chronic: REACH guidance R.8 (default)
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to Human: REACH guidance R.8 (default)
AF for other interspecies differences:
1
Justification:
Interspecies remaining differences: REACH guidance R.8 (default)
AF for intraspecies differences:
10
Justification:
Generaql population: REACH guidance R.8 (default)
AF for the quality of the whole database:
1
Justification:
No significant reduction in relevance or reliability across the database: REACH guidance R.8 (default)
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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:
0.42 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):
240
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No data on absorption in the rat and in humans is available, therefore the dose descriptor starting point could not be corrected.

AF for dose response relationship:
1
Justification:
No issues in relevance or reliability of dose response: REACH guidance R.8 (default)
AF for differences in duration of exposure:
6
Justification:
Subacute to Chronic: REACH guidance R.8 (default)
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to Human: REACH guidance R.8 (default)
AF for other interspecies differences:
1
Justification:
Interspecies remaining differences: REACH guidance R.8 (default)
AF for intraspecies differences:
10
Justification:
Generaql population: REACH guidance R.8 (default)
AF for the quality of the whole database:
1
Justification:
No significant reduction in relevance or reliability across the database: REACH guidance R.8 (default)
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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

Please refer to the discussion on DNELs for workers mentioned above.