Registration Dossier
Registration Dossier
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EC number: 277-962-5 | CAS number: 74665-14-8
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.97 mg/m³
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 12.5
- Dose descriptor starting point:
- NOAEL
- Value:
- 20 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 24.68 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- sufficient data about curve of dose/response
- AF for differences in duration of exposure:
- 1
- Justification:
- Duration of pregnancy covered; as the experimental exposure of a study according to OECD 443 adequately covered the pregnancy of the species under investigation over 2 generations an AF for exposure duration is not necessary.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Already included in NOAEC calculation
- AF for other interspecies differences:
- 2.5
- Justification:
- remaining differences
- AF for intraspecies differences:
- 5
- Justification:
- NAEC human worker
- AF for the quality of the whole database:
- 1
- Justification:
- GLP compliant with OECD and EU guidelines.
- AF for remaining uncertainties:
- 1
- Justification:
- 100% absorption for the inhalative route for animals and humans is assumed.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- acute toxicity
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.68 mg/kg bw/day
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
- 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:
- 20 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 14.28 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
It is assumed, that the dermal absorption will not be higher than the oral absorption (ECHA's Guidance R.8, v2.1, Nov 2012). Therefore, the NOAEL obtained via the oral route is regarded as a worst-case staring point to determine the dermal DNEL. This NOAEL is corrected by a factor of 1.4 to account for differences in exposure conditions (5 days/week for workers and 7 days for week for animals in the test), and by a factor of 3 for differences in exposure conditions during the working day (8 hours/day vs 24 duration exposure).
DNEL = NOAEL(corrected)/overall AF = (20 mg/kg bw/d *1.4 * 3) / 50 = 1.68 mg/kg bw/d- AF for dose response relationship:
- 1
- Justification:
- good data about curve dose/response
- AF for differences in duration of exposure:
- 1
- Justification:
- Duration of pregnancy covered; as the experimental exposure of a study according to OECD 443 adequately covered the pregnancy of the species under investigation over 2 generations an AF for exposure duration is not necessary.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rat to human standard
- AF for other interspecies differences:
- 2.5
- Justification:
- remaining differences
- AF for intraspecies differences:
- 5
- Justification:
- human standard to human worker
- AF for the quality of the whole database:
- 1
- Justification:
- P compliant with international guideline
- AF for remaining uncertainties:
- 1
- Justification:
- assuming 100% of absorption
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- high hazard (no threshold derived)
Additional information - workers
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.35 mg/L
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
- 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:
- 20 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 8.7 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The lowest DNEL for the general population for inhalation exposure was derived based on the developmental toxicity NOAEL from the OECD 443 performed on the substance DHDPS and was used as a starting point for the DNEL derivation.
No experimental data on absorption via inhalation route was available. Worst case assumption for absorption was: 50 % orally and 100 % by inhalation = 0.5 correction for inhalation)
1.15 m³/kg bw: default respiratory volume for the rat corresponding to the daily duration (24h) of human exposure.
NAEC (human-24h) = NOAEL * (1/1.15 m³/kg bw) * 0.5 = 20*(1/1.15) *0.5 = 8.7 mg/m3
Thus, the corrected starting point for workers is 8.7 mg/m³ for inhalation.
The DNEL is calculated considering the Assessmment factor (AF): DNEL = NOAEC(corrected)/overall AF = 8.7 mg/m3 / 25 = 0.35 mg/m3
- AF for dose response relationship:
- 1
- Justification:
- sufficient data about curve of dose/response
- AF for differences in duration of exposure:
- 1
- Justification:
- Duration of pregnancy covered; as the experimental exposure of a study according to OECD 443 adequately covered the pregnancy of the species under investigation over 2 generations an AF for exposure duration is not necessary.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- default, NOAEL is used as starting point
- AF for other interspecies differences:
- 2.5
- Justification:
- remaining differences
- AF for intraspecies differences:
- 10
- Justification:
- human general population
- AF for the quality of the whole database:
- 1
- Justification:
- GLP compliance with international guidelines
- AF for remaining uncertainties:
- 1
- Justification:
- 100% absorption for the inhalative route for animals and humans is assumed.
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.2 mg/kg bw/day
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
- 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:
- 20 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 20 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
It is assumed, that the dermal absorption will not be higher than the oral absorption (ECHA's Guidance R.8, v2.1, Nov 2012). Therefore, the NOAEL obtained via the oral route is regarded as a worst-case staring point to determine the dermal DNEL.
- AF for dose response relationship:
- 1
- Justification:
- good data about curve dose/response
- AF for differences in duration of exposure:
- 1
- Justification:
- Duration of pregnancy covered; as the experimental exposure of a study according to OECD 443 adequately covered the pregnancy of the species under investigation over 2 generations an AF for exposure duration is not necessary.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rat to human standard
- AF for other interspecies differences:
- 2.5
- Justification:
- remaining differences
- AF for intraspecies differences:
- 10
- Justification:
- human standard to human general population
- AF for the quality of the whole database:
- 1
- Justification:
- GLP compliant with international guideline
- AF for remaining uncertainties:
- 1
- Justification:
- assuming 100 % absorption
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.2 mg/kg bw/day
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
- 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:
- 20 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 20 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The lowest DNEL for the general population for oral exposure was derived based on the developmental toxicity NOAEL from the OECD 443 performed on the substance DHDPS and was used as a starting point for the DNEL derivation.
- AF for dose response relationship:
- 1
- Justification:
- sufficient data about curve of dose/response
- AF for differences in duration of exposure:
- 1
- Justification:
- Duration of pregnancy covered; as the experimental exposure of a study according to OECD 443 adequately covered the pregnancy of the species under investigation over 2 generations an AF for exposure duration is not necessary.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rat to human
- AF for other interspecies differences:
- 2.5
- Justification:
- remaining differences
- AF for intraspecies differences:
- 10
- Justification:
- human standard to human general population
- AF for the quality of the whole database:
- 1
- Justification:
- GLP compliant with OECD and EU guidelines
- AF for remaining uncertainties:
- 1
- Justification:
- assuming 100 % absorption
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- high hazard (no threshold derived)
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.
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