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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
35.3 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):
50
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 763 mg/m³
Explanation for the modification of the dose descriptor starting point:

Given a oral NOEL of 1000 mg/kg obtained in an OECD 407 and confirmed in an OECD 421 study, this oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m3 /kg for 8 hours exposure of workers, cf. ECHA guidance R8). An additionally correction for the difference between basal caloric demand and caloric demand under light activity (6.7 m3 for base level, 10 m3 for light activity) yields a NAEC as follows:

NAEC (worker, 8h) = 1000 mg/kg / 0.38 m3/kg *6.7/10 = 1763 mg/m3

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
4
Justification:
NOEL comprises most sensitive life stages (i.e. embryo-fetal development)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default for Worker
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
The study was conducted according to Guideline and under GLP conditions.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
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:
7 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:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Oral repeated dose toxicity studies and information from read across yields a NOEL (oral, rat) of 1000 mg/kg bw/d that provides the starting point for the calculation of the relevant dose descriptor.

Since no experimental data on the relevant route of exposure are available, route-to-route extrapolation (oral to dermal) has to be conducted taking into account the follwing paramters:

Exposure conditions (rat): 7 days per week

Exposure conditions (worker): 7 days per week

For oral-to-dermal extapolation a default factor of 1 (ABSoral-rat/ABSdermal-human) was used as in general dermal absorption will not be higher than oral absorption (Guidance on information requirements and chemical safety assessment, chapter R.8).

Corrected NOAEL (dermal) for workers = 1000 mg/kg bw/d * 1 * (7 d/5 d) = 1400 mg/kg bw/d

c) Assessment factors: 200

Duration of exposure: 4 (most sensitive life stage, i.e. embryonal-fetal development)

Interspecies differences (allometric): 4 (default)

Other interspecies differences: 2.5 (default)

Intraspecies differences: 5 (default)

By applying an assessment factor of 200, the DNEL (dermal) for workers is considered to be 7 mg/kg bw/d.

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
4
Justification:
NOEL comprises most sensitive life stages (i.e. embryo-fetal development)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
The study was conducted according to Guideline and under GLP conform conditions.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
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

Considering the Guidance on information requirements and chemical safety assessment, R.8 Characterisation of dose [concentration]-response for human health (May 2008) DNEL acute and DNEL long-term might be relevant for the chemical safety assessment.

Acute, systemic DNELs

The test item is not classified for acute systemic toxicity according to Regulation (EC) No 1272/2008 based on the availabale study results after oral and dermal exposure. Furthermore, acute systemic effects via inhalation can be excluded as no exposure via inhalation is assumed based on the physico-chemical profile of the test item.

Acute/long term DNELs for local effects

Skin irritation/corrosion: The test item is not classified for skin irritation/corrosion according to Regulation (EC) No 1272/2008. Therefore, no hazard was identified.

Eye irritation: The test item is not classified for eye irritation/corrosion according to Regulation (EC) No 1272/2008. Therefore, no hazard was identified.

Skin sensitization: The test item is not classified for skin sensitization according to Regulation (EC) No 1272/2008. Therefore, no hazard was identified.

Respiratory irritation: No experimental data on respiratory irritation are available. According to ECHA Guidance Doc R.7a, the term "respiratory tract irritation" is often used to indicate either or both of two different toxicological effects. These are

i) cytotoxic effects in the affected tissue, and

ii) sensory irritation.

Cytotoxic effects in the respiratory tract are comparable to dermal and eye irritation. "Sensory irritation" refers to the local and central reflex interaction of a substance with the autonomic nerve receptors, which are widely distributed in the mucosal tissues of the eyes and upper respiratory tract.

Since the test item is neither classified for skin irritation nor for eye irritation according to Regulation (EC) No 1272/2008, no respiratory irritation is to be expected.

Long term systemic DNEL - inhalation

a) Relevant dose descriptor - starting point

Oral repeated dose toxicity studies and information from read across yields a NOEL (oral, rat) of 1000 mg/kg bw/d that provides the starting point for the calculation of the relevant dose descriptor.

b) Modification of starting point

Given a oral NOEL of 1000 mg/kg bw/d obtained in an OECD 407 and confirmed in a read across OECD 421 study, this oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m3 /kg for 8 hours exposure of workers, cf. ECHA guidance R8). An additionally correction for the difference between basal caloric demand and caloric demand under light activity (6.7 m3 for base level, 10 m3 for light activity) yields a NAEC as follows:

NAEC (worker, inhal, 8h) = 1000 mg/kg / 0.38 m3/kg *6.7/10 = 1763 mg/m3

c) Assessment factors: 50

Duration of exposure: 4 (most sensitive life stage, i.e. embryonal-fetal development)

Interspecies differences (allometric): 1 (default)

Other interspecies differences: 2.5 (default)

Intraspecies differences: 5 (default)

By applying an assessment factor of 50, the inhalatory DNEL for workers is considered to be 35.3 mg/kg bw/d.

Long term systemic DNEL - dermal

a) Relevant dose descriptor - starting point

Oral repeated dose toxicity studies and information from read across yields a NOEL (oral, rat) of 1000 mg/kg bw/d that provides the starting point for the calculation of the relevant dose descriptor.

b) Modification of starting point

Since no experimental data on the relevant route of exposure are available, route-to-route extrapolation (oral to dermal) has to be conducted taking into account the follwing paramters:

Exposure conditions (rat): 7 days per week

Exposure conditions (worker): 7 days per week

For oral-to-dermal extapolation a default factor of 1 (ABSoral-rat/ABSdermal-human) was used as in general dermal absorption will not be higher than oral absorption (Guidance on information requirements and chemical safety assessment, chapter R.8).

Corrected NOAEL (dermal) for workers = 1000 mg/kg bw/d * 1 * (7 d/5 d) = 1400 mg/kg bw/d

c) Assessment factors: 200

Duration of exposure: 4 (most sensitive life stage, i.e. embryonal-fetal development)

Interspecies differences (allometric): 4 (default)

Other interspecies differences: 2.5 (default)

Intraspecies differences: 5 (default)

By applying an assessment factor of 200, the DNEL (dermal) for workers is considered to be 7 mg/kg bw/d.

References

1) Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7 Version 6.0, July 2017, ECHA-17 -G-18 -EN

2) Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, Nov 2012, ECHA-2010 -G-19 -EN

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

For general population no DNEL has to be derived as no consumer uses are intended and exposure to general population can be excluded.