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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14.69 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC 2010
Overall assessment factor (AF):
18
Modified dose descriptor starting point:
NOAEC
Value:
264.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
Route to route extraploation required for oral to inhalation route as no long term inhalation study available.
AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation is a NOAEL, therefore an assessment factor of 1 is applicable.
AF for differences in duration of exposure:
6
Justification:
Default AF for subacute to chronic studies (an OECD 422 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:
1
Justification:
An extra AF for additional toxicodynamic differences was not applied, as inhalation absorption to oral absorption was assessed in the modification of starting point.
AF for intraspecies differences:
3
Justification:
AF of 3 by ECETOC (2010) for workers is sufficiently conservative.
AF for the quality of the whole database:
1
Justification:
All 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:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.17 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC 2010
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Route to route extraploation required for oral to dermal route as no long term dermal study available.
AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation is a NOAEL, therefore an assessment factor of 1 is applicable.
AF for differences in duration of exposure:
6
Justification:
Default AF for subacute to chronic studies (an OECD 422 study)
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for allometric scaling for rats
AF for other interspecies differences:
1
Justification:
An extra AF for additional toxicodynamic differences was not applied, as dermal absorption is expected to be lower in humans as in rats..
AF for intraspecies differences:
3
Justification:
AF of 3 by ECETOC (2010) for workers is sufficiently conservative.
AF for the quality of the whole database:
1
Justification:
All 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
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The substance is classified for human health as a skin irritant (R38) according to Directive 67/548/EEC (DSD) criteria. However, the substance is not classified as a skin irritant according to CLP ((Regulation (EC) No 1272/2008).

Inhalation:

Inhalation is not considered to be a significant route of exposure based on the substances physico-chemical properties and use patterns. However, a long-term DNEL for systemic effects has been derived, based on the results obtained OECD 422 Oral (Gavage) Combined Repeat Dose Toxicity Study With Reproduction / Developmental Toxicity Screening Test in the Rat conducted on the substance.

Long-term systemic effects:

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

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 in ECHA Guidance: Characterisation of dose [concentration] - response for human health (Chapter R.8) (see below) for workers (in the case of 8 hour exposure/day).

Default parameters for rats and humans (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.

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= 300 mg/kg bw/day x (1 / 0.38 m3/kg/d) x (0.5) x (6.7 m3(8h) / 10 m3(8h)) = 264.5 mg/m3

Where:

ABS: Absorption

sRV: standard Respiratory Volume

wRV: worker Respiratory Volume (light activity)

Default parameters:

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 18

Long-term systemic DNEL (inhalation)= 14.69 mg/m3

This long-term inhalation systemic effect DNEL is used in the quantitative assessment of risk for systemic toxicity to workers via the inhalation route. The long-term DNEL shall also cover short-term exposure.

Any potential local effects from inhalation exposure are assessed qualitatively.

Dermal:

A DNEL has been derived for long-term systemic effects by the dermal route, based on the results obtained from a OECD 422 Oral (Gavage) Combined Repeat Dose Toxicity Study With Reproduction / Developmental Toxicity Screening Test in the Rat conducted on the substance.

Long-term systemic DNEL (dermal) = 4.17 mg/kg bw/day

This long-term inhalation systemic effect DNEL is used in the quantitative assessment of risk for systemic toxicity to workers via the dermal route.

Although the substance is a moderate skin irritant (low hazard), DNELs for local effects have not been derived as the dermal irritation study did not give adequate data for a DNEL to be determined. It is considered that a qualitative assessment of risk for local effects to workers is sufficient.

 

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

DNELs have not been derived for the general public (apart from via the oral route for systemic effects) as there will be no exposure to the general public/consumers as the substance only has industrial applications.

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