Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
500 mg/m³
DNEL related information
DNEL derivation method:
other: occupational exposure level (OEL or MAK)
Overall assessment factor (AF):
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 000 mg/m³
DNEL related information
DNEL derivation method:
other: occupational exposure level (OEL or MAK)

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:
1.4 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):
200
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
280 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Corrected NOAEL (dermal) for workers:

= 200 mg/kg bw/day x 1.4

= 280 mg/kg bw/day

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:
4
Justification:
The exposure duration of the OECD TG 422 study was up to 63 days for females and 29 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and developmental toxicity, which justifies the assessment factor of 4.
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for the differences between rats and humans is applied.
AF for other interspecies differences:
2.5
Justification:
The recommended AF for other interspecies differences is applied.
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 OECD TG 422 toxicity study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
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:
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

General

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA, Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose-response for human health (Version: 2.1, November 2012).

Inhalation

Long term, systemic DNEL – exposure via inhalation (workers)

No repeated dose inhalation toxicity study with the test item is available. The substance is an UVCB. Its constituents differ in their respective vapor pressure considerably. Thus, regarding exposure via the inhalation route, the most volatile constituent, i.e. 2 –propanol, is taken into account reflecting the worst case.
Hazard assessment of 2 -propanol has been performed by the German MAK commission (TRGS 900). A scientific occupational exposure level (OEL or MAK) of 500 mg/m^3 was determined for long-term exposure of workers. This long-term MAK value reflects a reasonable threshold applicable for Human Health Risk Assessment especially for workers and does not require further modification. Please also refer to disseminated dossier data of 2 -propanol available on ECHA´s website.

Acute, systemic DNEL- exposure via inhalation (workers)

There is no short-term toxicity study via inhalation route available for the test item. The substance is an UVCB. Its constituents differ in their respective vapor pressure considerably. Thus, regarding exposure via the inhalation route, the most volatile constituent, i.e. 2 –propanol, is taken into account reflecting the worst case.      
Hazard assessment of 2 -propanol has been performed by the German MAK commission. A scientific occupational exposure level OEL of 1000 mg/m^3 was determined for short-term exposure of workers. This short-term MAK value reflects a reasonable threshold applicable for Human Health Risk Assessment especially for workers and does not require further modification. Please also refer to disseminated dossier data of 2 -propanol available on ECHA´s website.

Long term & acute, local DNEL- exposure via inhalation (workers)

Hazard of local effects is considered sufficiently covered by threshold values for long-term and short term systemic effects via the inhalation route.

 

Dermal

Long term, systemic DNEL- exposure via dermal route (workers)

No dermal repeated dose toxicity study with the test item is available. Therefore, long-term dermal DNEL was derived by route-to-route extrapolation.

The NOAEL of 200 mg/kg bw/day derived from an OECD TG 422 study performed with the test item was used as the Point of Departure.

Step 1: PoD: NOAEL = 200 mg/kg bw/day

Step 2: Modification into a correct starting point:

Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker.
There are no relevant experimental data on repeated dermal exposure. A conservative approach is used assuming identical dermal and oral absorption values.

Corrected NOAEL (dermal) for workers:

= 200 mg/kg bw/day x 1.4

= 280 mg/kg bw/day

Step 3: Overall AF= 200

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

The default allometric scaling factor for the differences between rats and humans is applied.

 

Interspecies AF, remaining differences: 2.5

The recommended AF for other interspecies differences is applied.

 

Intraspecies AF (worker): 5

The default value for the relatively homogenous group "worker" is used

 

Dose-response relationship AF: 1

The dose response relationship is considered unremarkable, therefore no additional factor is used.

Exposureduration AF: 4
The exposure duration of the OECD TG 422 study was up to 63 days for females and 28 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and developmental toxicity, which justifies the assessment factor of 4.

Remaining uncertainties: 1
The approach used for DNEL derivation is conservative. No further assessment factors are required.

In conclusion,long term systemic dermal DNEL, workers = 1.4 mg/kg bw/day

Acute, systemic DNEL- dermal exposure (workers)

No acute dermal toxicity study is available for the test item. However, based on the results the test item is not classified for acute dermal toxicity according to Regulation (EC) No 1272/2008 (CLP). Thus, the acute systemic dermal DNEL was not derived. Further, long-term DNELs are considered sufficient to ensure that acute effects do not occur.

 

Long term & acute, local DNEL- dermal exposure (workers)

The test substance is classified as skin sensitizing cat 1 and appropriate qualitative risk managements measures should be implemented to avoid exposure. Thus, a qualitative risk assessment is applied and the substance is assigned to the high hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2016).

 

Hazard to the eye-local effects (worker)

The test item is classified as eye damaging Cat 1 according to Regulation (EC) No 1272/2008 (CLP). A qualitative risk assessment is applied and the substance is assigned to the moderate hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2016).

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, November 2012

ECHA (2016). Guidance on information requirements and chemical safety assessment. Part E: Risk Characterisation, Version 3.0, May 2016

BAuA (2006). TRGS 900, BArBl Heft 1/2006 S. 41-55, as amended by GMBl 2018 S. 9 [Nr. 1] (v. 29.1.2018)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

Since no exposure is intended for the general population no DNEL (long-term, systemic) was derived.