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:
other: NOAECcorr
DNEL value:
881.6 mg/m³
Explanation for the modification of the dose descriptor starting point:
There are no relevant experimental data on repeated exposure by the dermal route.
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
The default value for extrapolation from subacute to chronic exposure is used in order to cover the min. exposure duration for male animals (at least 28 days).
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not applied, because the ventilation rate directly depends on the basal metabolic rate.
AF for other interspecies differences:
2.5
Justification:
The default value for interspecies differences is used.
AF for intraspecies differences:
5
Justification:
The default value for the relatively homogenous group "worker" is used.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
3.3 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
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
There are no relevant experimental data on repeated exposure by the dermal route.
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
The default value for extrapolation from subacute to chronic exposure is used in order to cover the min. exposure duration for male animals (at least 28 days).
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
2.5
Justification:
The default value for interspecies differences is used.
AF for intraspecies differences:
5
Justification:
The default value for the relatively homogenous group "Workers" is used.
AF for the quality of the whole database:
1
Justification:
The quality of the whole database is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factor is required.
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

Long-term exposure - systemic effects

Inhalation exposure

In the absence of a suitable inhalation toxicity study with repeated exposure, the worker-DNEL long-term for inhalation route - systemic was derived from the NOAEL obtained in the combined repeated dose toxicity study with the reproduction/developmental toxicity screening test in Wistar rats (IIBAT, 2010). A corrected inhalatory NOAEC (NOAECcorr) was calculated using the default respiratory volume for the rat and a correction for the difference between human respiratory rates under standard conditions and under conditions of light activity (under the assumption of no difference in absorption between rat and human). As specified in the toxicokinetic section oral absorption rate was similar to inhalation absorption rate.

 

Calculation of the NOAECcorr

- Standard dose descriptor (NOAEL): 500 mg/kg bw/d

- Standard respiratory volume of the rat (sRVrat) for 8 hours: 0.38 m³/kg bw/d

- Oral absorption of the rat/inhalation absorption of humans (ABSoral-rat)/ABSinhal-human): 1/1

- Standard respiratory volume of humans (sRVhuman) for 8 hours: 6.7 m³

- Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m³

Corrected inhalatory NOAEC for workers:

= NOAEL * (1/sRVrat) * (ABSoral-rat/ABSinhal-human) *(sRVhuman/wRV)

= 500 mg/kg bw/d * (1/0.38 m³/kg bw/d)* (1/1) * (6.7 m³/10 m³)

= 881.6 mg/m³

References

ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version: 2.1, ECHA-2012 -G-19 -EN.

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