Registration Dossier
Registration Dossier
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EC number: 619-447-3 | CAS number: 99607-70-2
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.303 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 12.5
- Modified dose descriptor starting point:
- NOAEC
Acute/short term exposure
- Hazard assessment conclusion:
- no-threshold effect and/or no dose-response information available
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no-threshold effect and/or no dose-response information available
Acute/short term exposure
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 3.33 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 75
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
- Hazard assessment conclusion:
- no-threshold effect and/or no dose-response information available
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no-threshold effect and/or no dose-response information available
- Most sensitive endpoint:
- sensitisation (skin)
Workers - Hazard for the eyes
Additional information - workers
Long-term – inhalation, systemic
Repeat-dose Toxicity - rat
Dose-descriptor selection
Potential dose-descriptors are available resulting from a chronic study (rat, oral dietary, 24 month).
Assessment of mode of action
The identified endpoint, and the observed effects, have a threshold mode of action.
Dose-descriptor modification
The dose descriptor was modified by the following defaults as laid out in Guidance on Information Requirements and Chemical Safety Assessment, December 2010, R.8.4.2 and Appendix R.8-2: extrapolation from the oral-to-inhalation route, light-work respiratory volume in the worker, 50% oral absorption, 100% inhalation absorption, assumed no first-pass effect.
NOAELcorr (worker) = NOAEL*(1/rat respiratory volume)*(human/worker respiratory volume)*(Oral absorption/Inhalation absorption)
NOAELcorr (worker) = 4.33 mg/kg*(1/0.38 m3/kg)*(6.7 m3/10 m3)*(1/2) = 3.8 mg/m3
Assessment factors
The default assessment factors were applied as laid out in Guidance on Information Requirements and Chemical Safety Assessment, December 2010, R.8.4.3.3. Allometric scaling has been accounted for (implicitly) in the dose-descriptor modification.
Assessment factor = (Interspecies) * (Intraspecies) * (Exposure Duration) * (Dose-response) * (Quality of whole database)
Assessment factor (worker) = 2.5 * 5 * 1* 1 * 1 = 12.5
DNEL derivation
DNEL = NOAELcorr / Assessment factor
DNEL = 3.8 mg/m3/ 12.5 = 0.303 mg/m3
Repeat-dose Toxicity - rat
Dose-descriptor selection
Potential dose-descriptors are also available resulting from a subchronic study (rat, oral dietary, 13 week).
Assessment of mode of action
The identified endpoint, and the observed effects, have a threshold mode of action.
Dose-descriptor modification
The dose descriptor was modified by the following defaults as laid out in Guidance on Information Requirements and Chemical Safety Assessment, December 2010, R.8.4.2 and Appendix R.8-2: extrapolation from the oral-to-inhalation route, light-work respiratory volume in the worker, 50% oral absorption, 100% inhalation absorption, assumed no first-pass effect.
NOAELcorr (worker) = NOAEL*(1/rat respiratory volume)*(human/worker respiratory volume)*(Oral absorption/Inhalation absorption)
NOAELcorr (worker) = 9.66 mg/kg*(1/0.38m3/kg)*(6.7m3/10m3)*(1/2) = 8.5 mg/m3
Assessment factors
The default assessment factors were applied as laid out in Guidance on Information Requirements and Chemical Safety Assessment, December 2010, R.8.4.3.3. Allometric scaling has been accounted for (implicitly) in the dose-descriptor modification.
Assessment factor = (Interspecies) * (Intraspecies) * (Exposure Duration) * (Dose-response) * (Quality of whole database)
Assessment factor (worker) = 2.5 * 5 * 2* 1 * 1 = 25
DNEL derivation
DNEL = NOAELcorr / Assessment factor
DNEL = 8.5 mg/m3/ 25 = 0.339 mg/m3
The lower value i.e. 0.303 mg/m3is selected as long term (systemic) inhalation DNEL for workers.
Long-term – dermal, systemic
Repeat-dose Toxicity - rat
Dose-descriptor selection
Potential dose-descriptors are also available resulting from a subacute study (rat, dermal, 28 day).
Assessment of mode of action
The identified endpoint, and the observed effects, have a threshold mode of action.
Dose-descriptor modification
The dose descriptor was modified by the following defaults as laid out in Guidance on Information Requirements and Chemical Safety Assessment, December 2010, R.8.4.2 and Appendix R.8-2: dermal absorption rat = dermal absorption human, allometric scaling (AS) = 4 (rat).
NOAELcorr = NOAEL*(1/AS)*(Dermal absorption rat/Dermal absorption human)
NOAELcorr (worker) = 1000 mg/kg/day*(1/4)*(1) = 250 mg/kg/day
Assessment factors
The default assessment factors were applied as laid out in Guidance on Information Requirements and Chemical Safety Assessment, December 2010, R.8.4.3.3. Allometric scaling has been accounted for (explicitly) in the dose-descriptor modification.
Assessment factor = (Interspecies) * (Intraspecies) * (Exposure Duration) * (Dose-response) * (Quality of whole database)
Assessment factor (worker) = 2.5 * 5 * 6* 1 * 1 = 75
(remark: the assessment factor including allometric scaling is 300)
DNEL derivation
DNEL = NOAELcorr / Assessment factor
DNEL = 250 mg/kg/day / 75 = 3.33 mg/kg/day
Long-term – dermal, local
Identification of relevant endpoints
Relevant long-term dermal-route data for local effects are available.
Available dose-descriptors per endpoint as a result of hazard assessment |
||||
Endpoint |
Qualitative dose-descriptor |
Associated Effect |
Remarks on Study |
|
Local Effect |
||||
Skin sensitisation |
Dermal |
Sensitising |
Sensitisation observed |
GPMT. All 20 treated guinea pigs showed positive skin reactions to the test material after epicutaneous challenge. |
Skin Sensitisation
1. Dose-descriptor selection
A single study is available which gives information on skin sensitisation potential. The test substance was found to be sensitising on the basis of an OECD 406 guideline study. The substance was classified based on the clearly positive result.
2. Assessment of mode of action
The identified endpoint, and the observed effects, have a threshold mode of action. However, no quantitative dose-response information for this endpoint is available and as such no DNEL can be derived. As a result, a qualitative risk assessment is required.
3. Semi-quantitative risk assessment
The intradermal concentration of the test material during induction phase was 0.1% in 20% propylene glycol and 80% physiological saline. Epicutaneous challenge was with 1% substance in Vaseline.
On the basis of ECETOC Technical Report No. 87, Contact Sensitisation: Classification According to Potency, April 2003, 2.2.1, Table 3, the test substance could be categorised as a “moderate sensitiser”, using the 1% concentration used in topical administration during induction, and the subsequent 100% elicitation incidence in the challenge.
However, the recommendations in the ECHA Guidance, Chapter R.8,December 2010, Appendix R.8-10, Table R.8-24, based on the EU Working Group on Skin Sensitisation, suggest that with an induction concentration of 0.1%, and >=60% observed sensitisation, the potency is “extreme”.
A qualitative risk assessment approach based on the “extreme sensitiser” potency categorisation is undertaken.The potency categorisation of the test substance, in combination with the Hazard Categories given in the Guidance, Part E: Risk Characterisation, May 2008, Table E.3-1, results in a “high hazard” categorisation for the purposes of risk assessment. This categorisation is carried forward to Risk Charaterisation.
Selection of leading health effect and DNEL
Information relevant to long-term dermal, local effects, is available from one endpoint – skin sensitization. The result of the qualitative assessment of potency “high hazard” is taken forward to Risk Characterisation.
General Population - Hazard via inhalation route
Systemic effects
Acute/short term exposure
DNEL related information
Local effects
Acute/short term exposure
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Acute/short term exposure
DNEL related information
General Population - Hazard via oral route
Systemic effects
Acute/short term exposure
DNEL related information
General Population - Hazard for the eyes
Additional information - General Population
According to Guidance on Information Requirements and Chemical Safety Assessment, December 2010, R.8.1.2.3: "DNELs may have to be derived for workers and the general population. The general population includes consumers, and humans exposed via the environment, with the DNEL usually being identical for consumers and human via the environment."
The substance is, during its whole life-cycle, used only by workers/professionals, thus never by consumers. The assessment of indirect exposure of humans via the environment is not considered to be required for this substance (based on tonnage band and classification, see Guidance on Information Requirements and Chemical Safety Assessment, May 2010, R.16.6.8.3).
As a consequence the derivation of DNELs for the general population is not required.
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