Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.75 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:
NOAEC
Value:
881.05 mg/m³
Explanation for the modification of the dose descriptor starting point:
Route to route extrapolation required for oral to dermal route as no long term inhalation study available.
AF for dose response relationship:
1
Justification:
An assessment factor of 1 is applicable when the starting point is a NOAEL/NOEL
AF for differences in duration of exposure:
6
Justification:
Default AF for subacute to chronic studies. This is considered appropriate based on the exposure duration in an OECD 421 study (46 days in males) and in the 28-day repeat dose toxicity study.
AF for interspecies differences (allometric scaling):
1
Justification:
AF for allometric scaling not required as the differences in allometry (respiration rate and rat to human body sizes) were considered in the conversion from oral to inhalation starting point.
AF for other interspecies differences:
2.5
Justification:
Default AF for remaining differences
AF for intraspecies differences:
5
Justification:
Default AF for worker population
AF for the quality of the whole database:
1
Justification:
Relevant studies conducted to GLP and of reliability 1.
AF for remaining uncertainties:
1
Justification:
None identified.
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:
3.33 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:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Route to route extrapolation required for oral to dermal route as no long term dermal study available.
AF for dose response relationship:
1
Justification:
An assessment factor of 1 is applicable when the starting point is a NOAEL/NOEL
AF for differences in duration of exposure:
6
Justification:
Default AF for subacute to chronic studies. This is considered appropriate based on the exposure duration in an OECD 421 study (46 days in males) and in the 28-day repeat dose toxicity study.
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for allometric scaling for rats
AF for other interspecies differences:
2.5
Justification:
Default AF for remaining differences
AF for intraspecies differences:
5
Justification:
Default AF for worker population
AF for the quality of the whole database:
1
Justification:
Relevant studies conducted to GLP and of reliability 1.
AF for remaining uncertainties:
1
Justification:
None identified
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

The substance is not classified for human health.

Inhalation is not considered to be a significant route of exposure. An acute dermal toxicity study showed no toxicity and local effects are not considered to be a hazard as the substance is not a skin irritant or sensitiser.

Full exposure scenarios and risk characterisation are not required and therefore DNELs are not required for risk characterisation purposes. However, long-term systemic DNELs have been derived for inhalation and dermal routes for additional information.

The DNELs have been based on the OECD 421 Reproduction/Developmental Toxicity Screening test, which gives data on both general systemic toxicity and reproduction/developmental toxicity, rather than the 90 -day repeat dose study or 1 -generation reproduction study.

Inhalation long-term systemic DNEL:

A DNEL has been derived for long-term systemic effects by the inhalation route. The DNEL is derived by route-to-route extrapolation from an oral NO(A)EL of 1000 mg/kg bw/day for general toxicity and reproduction/developmental toxicity obtained in an OECD 421 Reproduction/Developmental Toxicity Screening Test.

A modification of the dose descriptor starting point (oral to inhalation) was conducted. It is assumed that the oral absorption rate is 50% of that of the inhalation absorption.

The corrected 8 hr inhalation NOAEC was 881.05 mg/m3.

The corrected dose descriptor (NOAEC) for inhalation was calculated in accordance with the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health.

The conversion of an oral rat NOAEL into a corrected inhalatory NOAEC to assess human inhalatory exposure was performed using the modification of starting point equation as given in Figure R. 8-3 (see below) for workers (in the case of 8 hour exposure/day).

Default parameters for rats and human (for 8 hour exposure) were used for the modification of starting point under the allometric scaling principle as given in Table R. 8-2 of the above ECHA guidance.

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

Conversion of an oral rate N(L)OAEL into a correct inhalatory N(L)OAEC to assess human inhalatory exposure:

For workers (in case of 8h exposure/day):

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

 

 

Corrected inhalatory N(L)OAEC= 1000 mg/kg bw/day x (1 / 0.38 m3/kg/d) x (1 / 2) x (6.7 m3(8h) / 10 m3(8h))

                                                         = 881.05 mg/m3

 

Where:

ABS: Absorption

sRV: standard Respiratory Volume

wRV: worker Respiratory Volume (light activity)

 

Default parametrs:

sRVrat (8 h) : 0.38m3/kg bw

sRVhuman (8 h) : 6.7 m3/ person

wRV (8 h): 10 m3/ person

The appropriate assessment factors were then applied to give an overall assessment factor of 75.

DNEL (inhalation)= Inhalatory NOAEC / Overall assessment factor = 881.05 mg/m3/ 75 = 11.75 mg/m3

Dermal long-term systemic DNEL:

A long-term systemic DNEL has been derived by route-to-route extrapolation from an oral NO(A)EL of 1000 mg/kg bw/day for general toxicity and reproduction/developmental toxicity obtained in an OECD 421 Reproduction/Developmental Toxicity Screening Test.

Appropriate assessment factors were applied to give an overall assessment factor of 300.

The derived DNEL is 3.33 mg/kg bw/day.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
no hazard identified
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:
no hazard identified
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

The substance is used solely in industry in the manufacture of polyolefin compounds. The substance has no general population/consumer uses so exposure to the general population from use is not anticipated. Once the substance is bound into polyolefin compounds there should be no release, so exposure to the general population from release of the substance from final products is not anticipated.