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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.023 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEC
Value:
1.16 mg/m³
Value:
0.58 mg/m³
Explanation for the modification of the dose descriptor starting point:

A subchronic inhalation toxicity study in rats is available. NOAEC was determined to be 1.16 mg/m^3 and was corrected according to ECHA REACH Guidance:

Corrected inhalatory NOAEC = 1.16 mg/m^3 * (6 h/d /8 h/d) * (6.7 m^3 (8h) / 10 m^3 (8h)) = 0.5829 mg/m^3

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:
2
Justification:
The default extrapolation factor for exposure duration is used: starting point - subchronic to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scalling is applied for inhalation as the inhalative data is standardized with reference to the respiratory rates. Respiratory rates depend directly on caloric demand, therefore inhalative study results are already extrapolated to humans on the basis of metabolic rate scaling (=allometric scaling).
AF for other interspecies differences:
2.5
Justification:
Recommended AF for other interspecies differences.
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:
DNEL (Derived No Effect Level)
Value:
0.07 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:

The substance is classified as acute toxic via the oral route cat. 4 and via the inhalation route cat 3. Therefore, a DNEL is derived from long term DNEL by applying a conservative factor of 3 according to ECHA Guidance document R8.

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.16 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1
Dose descriptor:
NOAEC
Value:
1.16 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.16 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 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):
100
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A valid experimental subchronic toxicity study via the dermal route is available, in which a NOAEL was determined to be 200 mg/kg bw/d.

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:
2
Justification:
The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).
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:
Recommended AF for other interspecies differences.
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
Explanation for the modification of the dose descriptor starting point:

The test material is not classified and labelled for acute systemic toxicity via the dermal route, according to Regulation (EC) No 1272/2008 (CLP).

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

The primary route of industrial exposure to the test item is by skin contact and inhalation. In an industrial setting, ingestion is not an expected route of exposure.

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA.

 

Local, long-term and acute

 

Exposure by inhalation

Local larynx effects were observed in a subchronic inhalation study with rats. These local effects are considered to be independent from inter- and intra species differences. Therefore, no further assessment factors are applied. Furthermore, for local irritation the concentration is in most cases the relevant parameter, and prolongation of epxosure is expected to influence the severity of effect and morphology of change, but not the NOAEC (VCI, 2008).

Dermal exposure

Based on available data a skin sensitization potential was observed with the test item. The substance is therefore classified as skin sensitizer Cat 1 according to Regulation (EC) No 1272/2008 (CLP). The substance is not classified as skin irritant according to Regulation (EC) 1272/2008 (CLP). Since there are no data to establish a dose-response relationship a qualitative risk assessment is applied for dermal exposure and a high hazard is assumed. The substance is classified as eye irritant according to Regulation (EC) 1272/2008 (CLP). A qualitative risk assessment is applied for eye exposure and a moderate hazard is assumed.

Systemic, acute

The test substance is classified and labelled for acute systemic toxicity via oral and inhalation route, according to Regulation (EC) 1272/2008 (CLP). Therefore, a short term inhalation DNEL is derived on the basis of the long term DNEL applying a conservative factor of 3.

 

Systemic, long-term

Occupational exposure to the test item occurs mainly by dermal route, and may also occur by inhalation exposure. Therefore long-term dermal and inhalation DNELs are calculated for workers.

In view of the data used for evaluation, the "quality of whole database factor" is considered to a value of 1, and is thus not shown in the calculations presented below.

 

Exposure by inhalation

Step 1: Selection of the relevant dose descriptor (starting point):

The NOAEC of 1.16 mg/m^3 assessed in the key repeated dose inhalation toxicity study (OECD 413, 1981) is identified as the relevant dose descriptor and starting point.

 

Step 2: Modification into a correct starting point:

Using a conservative approach, a worker DNEL (long-term inhalation exposure) is derived.

Relevant dose descriptor (NOAEL): 1.16 mg/m^3

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

= 1.16 mg/m^3 × (6h/d / 8h/d) × (6.7 m³/10 m³)

= 0.5829 mg/m³

 

Step 3: Use of assessment factors: 25

Interspecies: No allometric scalling is applied for inhalation as the inhalative data is standardized with reference to the respiratory rates. Respiratory rates depend directly on caloric demand, therefore inhalative study results are already extrapolated to humans on the basis of metabolic rate scaling (=allometric scaling).

Intraspecies AF (worker): 5

Interspecies AF, remaining differences: 2.5

Dose response relationship AF: 1

Exposure duration AF (subchronic to chronic): 2

In conclusion, the long-term inhalation DNEL, worker = 0.023 mg/m3  

 

Dermal exposure

Step 1: Selection of the relevant dose descriptor (starting point):

The NOAEL of 200 mg/kg bw/day, assessed in the repeated dose dermal toxicity study (OECD 411, 1991) was identified as the relevant dose descriptor and starting point.  

Step 2: Modification into a correct starting point:

A worker DNEL (long-term dermal exposure) is derived based on a dermal NOAEL, therefore no further modification is needed.

Step 3: Use of assessment factors: 100

Interspecies AF, allometric scaling (rat to human): 4

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

Dose-response relationship AF: 1

Exposure duration AF (OECD 411, exposure period 90 days): 2

In conclusion, long term systemic dermal DNEL, workers = 2.0 mg/kg bw/day

References

(not included as endpoint study record)

- ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2. ECHA-2010 -G-19 –EN.  

- ECHA (2014). Guidance on information requirements and chemical safety assessment. Chapter R.7.C: Endpoint specific guidance: Guidance on Toxicokinetics. Nov 2014.  

- ECHA (2012) Practical Guide 15: How to undertake a qualitative human health assessment and document it in a chemical safety report, November 2012.

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

Any uses associated with the general population are covered by Cosmetic Directive and are therefore not within the scope of REACH. No exposure is intended for the general population, therefore no DNELs were derived.