Registration Dossier
Registration Dossier
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EC number: 603-101-3 | CAS number: 125962-78-9
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.548 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):
- 225
- Dose descriptor starting point:
- LOAEL
- Value:
- 100 mg/kg bw/day
- Modified dose descriptor starting point:
- LOAEC
- Value:
- 123 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Default (DNEL calculator)
- AF for dose response relationship:
- 3
- Justification:
- Default (DNEL calculator)
- AF for differences in duration of exposure:
- 6
- Justification:
- Default (DNEL calculator)
- 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:
- Standard information requirements according to REACH requirements Annex VIII are fulfilled. The study was conducted according to ECD Guideline 422 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:
- 0.156 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):
- 900
- Dose descriptor starting point:
- LOAEL
- Value:
- 100 mg/kg bw/day
- Modified dose descriptor starting point:
- LOAEL
- Value:
- 140 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Default (DNEL calculator)
- AF for dose response relationship:
- 3
- Justification:
- Default (DNEL calculator)
- AF for differences in duration of exposure:
- 6
- Justification:
- Default (DNEL calculator)
- 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:
- Standard information requirements according to REACH requirements Annex VIII are fulfilled. The study was conducted according to ECD Guideline 422 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:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
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 available study results after oral exposure. No acute systemic toxicity after dermal exposure is to be expected as no systemic effects were observed in rabbits in the in vivo skin irritation study (OECD 404). Since no peak exposure is to be expected, the DNEL for acute sytemic (inhalation) is covered by the long term DNEL (systemic, inhalation). Thus, no hazard is identified for acute systemic exposure after inhalation and no DNEL has to be derived.
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 classified for skin sensitization category 1B and labelled with H317 (May cause an allergic skin reaction) according to Regulation (EC) No 1272/2008. According to the ECHA Guidance Document, Part E: Risk Characterisation (Ver. 3.0, May 2016) the test item is allocated to the moderate hazard band.
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 sub-acute oral toxicity study in rats according to OECD 422 Guideline is available. The LOAEL was determined to be 100 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 following parameters:
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 LOAEC (inhal) for workers = 100 mg/kg bw/d * (1/0.38 m3/kg bw/d) * (6.7 m3/10 m3) * 0.5 * (7 d/5 d) = 123 mg/m3.
c) Assessment factors: 225
Dose response relationship: 3 (default)
Duration of exposure: 6 (default)
Interspecies differences (allometric): 1 (default)
Other interspecies differences: 2.5 (default)
Intraspecies differences: 5 (default)
By applying an assessment factor of 225, the inhalatory DNEL for workers is considered to be 0.548 mg/m3.
Long term systemic DNEL - dermal
a) Relevant dose descriptor - starting point
A sub-acute oral toxicity study in rats according to OECD 422 Guideline is available. The LOAEL was determined to be 100 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 following parameters:
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 LOAEL (dermal) for workers = 100 mg/kg bw/d * 1 * (7 d/5 d) = 140 mg/kg bw/d
c) Assessment factors: 900
Dose response relationship: 3 (default)
Duration of exposure: 6 (default)
Interspecies differences (allometric): 4 (default)
Other interspecies differences: 2.5 (default)
Intraspecies differences: 5 (default)
By applying an assessment factor of 900, the DNEL (dermal) for workers is considered to be 0.156 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:
- 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
DNEL related information
- Justification:
- Default (DNEL calculator)
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
No consumer uses are intended. Thus, no hazard information are required as exposure to general population can be excluded.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
