Registration Dossier
Registration Dossier
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 221-242-5 | CAS number: 3039-83-6
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 11.75 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):
- 75
- Modified dose descriptor starting point:
- other: NOAECcorr
- Value:
- 881.6 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- There are no relevant experimental data on repeated exposure by the dermal route.
- 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:
- 6
- Justification:
- The default value for extrapolation from subacute to chronic exposure is used in order to cover the min. exposure duration for male animals (at least 28 days).
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Allometric scaling is not applied, because the ventilation rate directly depends on the basal metabolic rate.
- AF for other interspecies differences:
- 2.5
- Justification:
- The default value for interspecies differences is used.
- 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 quality of the whole data base is considered to be sufficient and uncritical.
- 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:
- 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:
- 3.3 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):
- 300
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 000 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- There are no relevant experimental data on repeated exposure by the dermal route.
- 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:
- 6
- Justification:
- The default value for extrapolation from subacute to chronic exposure is used in order to cover the min. exposure duration for male animals (at least 28 days).
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The default allometric scaling factor for the differences between rats and humans is used.
- AF for other interspecies differences:
- 2.5
- Justification:
- The default value for interspecies differences is used.
- AF for intraspecies differences:
- 5
- Justification:
- The default value for the relatively homogenous group "Workers" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The quality of the whole database is considered to be sufficient and uncritical.
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factor is required.
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
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
Long-term exposure - systemic effects
Inhalation exposure
In the absence of a suitable inhalation toxicity study with repeated exposure, the worker-DNEL long-term for inhalation route - systemic was derived from the NOAEL obtained in the combined repeated dose toxicity study with the reproduction/developmental toxicity screening test in Wistar rats (IIBAT, 2010). A corrected inhalatory NOAEC (NOAECcorr) was calculated using the default respiratory volume for the rat and a correction for the difference between human respiratory rates under standard conditions and under conditions of light activity (under the assumption of no difference in absorption between rat and human). As specified in the toxicokinetic section oral absorption rate was similar to inhalation absorption rate.
Calculation of the NOAECcorr
- Standard dose descriptor (NOAEL): 500 mg/kg bw/d
- Standard respiratory volume of the rat (sRVrat) for 8 hours: 0.38 m³/kg bw/d
- Oral absorption of the rat/inhalation absorption of humans (ABSoral-rat)/ABSinhal-human): 1/1
- Standard respiratory volume of humans (sRVhuman) for 8 hours: 6.7 m³
- Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m³
Corrected inhalatory NOAEC for workers:
= NOAEL * (1/sRVrat) * (ABSoral-rat/ABSinhal-human) *(sRVhuman/wRV)
= 500 mg/kg bw/d * (1/0.38 m³/kg bw/d)* (1/1) * (6.7 m³/10 m³)
= 881.6 mg/m³
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, ECHA-2012 -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
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
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.
