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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:
0.74 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):
25
Dose descriptor starting point:
NOAEL
Value:
15 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
18.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

For route to route extrapolation (oral to inhalative) a factor of 2 is applied for the potential higher bioavailability via inhalation according to Guidance on information requirements and chemical safety assessment, chapter R.8.

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
NOAEL 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 (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 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
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.21 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):
100
Dose descriptor starting point:
NOAEL
Value:
15 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
21 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For oral-to-dermal extapolation a default factor of 1 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).

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
NOAEL 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
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

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

A combined repeated dose toxicity study with the reproduction/developmental toxicity screening test according to OECD 422 Guideline is available. Rats were exposed to the test item via oral route 7days per week for 42 days (males) or up to 7 weeks (females). The NOAEL was determined to be 15 mg/kg bw/d.

b) Modification of starting point

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

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

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

Standard respiratory volume of workers (wRV) with light physical activity for 8 hours: 10 m3

Exposure conditions (rat): 7 days per week

Exposure conditions (worker): 5 days per week

Furthermore, a factor of 2 is applied for the potential higher bioavailability via inhalation compared to oral route (ABSoral-rat/ABSinhal-human = 50%/100% = 0.5) according to Guidance on information requirements and chemical safety assessment, chapter R.8.

Corrected NOAEC (inhal) for workers = 15 mg/kg bw/d * (1/0.38 m3/kg bw/d) * (6.7 m3/10 m3) * 0.5 * (7 d/5 d) = 18.5 mg/m3.

c) Assessment factors: 25

Duration of exposure: 2 (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 25, the inhalatory DNEL for workers is considered to be 0.74 mg/kg bw/d.

Long term systemic DNEL - dermal

a) Relevant dose descriptor - starting point

A combined repeated dose toxicity study with the reproduction/developmental toxicity screening test according to OECD 422 Guideline is available. Rats were exposed to the test item via oral route 7days per week for 42 days (males) or up to 7 weeks (females). The NOAEL was determined to be 15 mg/kg bw/d.

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): 5 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 = 15 mg/kg bw/d * 1 * (7 d/5 d) = 21 mg/kg bw/d

c) Assessment factors: 100

Duration of exposure: 2 (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 100, the DNEL (dermal) for workers is considered to be 0.21 mg/kg bw/d.

References

1) Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7a: Endpoint specific guidance, 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.