Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
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: 203-713-7 | CAS number: 109-86-4
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.31 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- other: See explanation for hazard conclusion below
- Overall assessment factor (AF):
- 12.5
- Dose descriptor starting point:
- NOAEC
- Value:
- 9.5 mg/m³
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 3.82 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Correction for exposure to workers
corrNOAEC =inhalNOAEC*6h/day/8h/day*6.7 m3(8h)/10 m3(8h)
corrNOAEC = 9.5 mg/m3*6h/day/8h/day*6.7 m3(8h)/10 m3(8h)
corrNOAEC = 4.8 mg/m3
Starting point is the Hanley rabbit developmental toxicity study.
The guidance states that ‘in case the inhalation route is involved one should also keep the principle of allometric scaling in mind when using inhalation volumes for animals and humans. This implies that standard respiratory volumes (in l/min/kg bw) for rats and humans differ by a factor of 4’ The factor of 4 comes from the difference of respiratory volume of 0.2l/min/kgbw for humans versus 0.8l/min/kgbw for rats, as shown in table 8-2 of the guidance. No figure is quoted for rabbits but a figure of 0.25L/min/kg is available elsewhere*. This leads to a factor of 1.25 for rabbits to humans.
The corrected NOAEL for starting the DNEL derivation is 4.8/1.25 = 3.82mg/m3
- AF for dose response relationship:
- 1
- Justification:
- Default. There is little change in outcome for 3x the exposure of the NOAEL
- AF for differences in duration of exposure:
- 1
- Justification:
- No correction required as the study is a developmental toxicity study.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- The guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health quite clearly states in table 8-4 that a correction is not required for the inhalation route. Any correction required is already accounted for in the correction for respiratory volumes.
- AF for other interspecies differences:
- 2.5
- Justification:
- Default
- AF for intraspecies differences:
- 5
- Justification:
- Default for workers
- AF for the quality of the whole database:
- 1
- Justification:
- Default. Large database of information available in mulitple specie
- AF for remaining uncertainties:
- 1
- Justification:
- Default
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:
- 0.22 mg/kg bw/day
- Most sensitive endpoint:
- effect on fertility
- 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:
- 11 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 11 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
For dermal effects, there is no adequate study, thefore route to route extrapolation is used from the oral data. The lowest figure is that from the fertility studies in rats. According to the guidance, it should be assumed as a worse case that oral uptake is 50% and dermal uptake 100%, which would mean dermal toxicity would be higher than oral toxicity. This is not the case. There is limited data available in the same species across multiple routes, but for the rabbit, the oral LD50 is actually lower than the dermal LD50. For rats, there is also data from repeat dose toxicity studies that show no evidence of the dermal route being more toxic. Therefore, no factor is required to extrapolate between the two routes. Absorption is assumed to be 100% in both cases.
- AF for dose response relationship:
- 1
- Justification:
- Default for NOAEL as starting point.
- AF for differences in duration of exposure:
- 1
- Justification:
- No correction for duration is required since this is a fertility study for an end point that is concentration rather than cumulative dose influenced.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Rat to human default extrapolation factor
- AF for other interspecies differences:
- 2.5
- Justification:
- Default factor
- AF for intraspecies differences:
- 5
- Justification:
- Default factor
- AF for the quality of the whole database:
- 1
- Justification:
- default
- AF for remaining uncertainties:
- 1
- Justification:
- default
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
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
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:
- high hazard (no threshold derived)
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:
- DNEL (Derived No Effect Level)
- Value:
- 0.11 mg/kg bw/day
- Most sensitive endpoint:
- effect on fertility
- 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:
- 11 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 11 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
No correction required.
- AF for dose response relationship:
- 1
- Justification:
- Default for NOAEL as starting point
- AF for differences in duration of exposure:
- 1
- Justification:
- No correction for duration is required since this is a fertility study for an end point that is concentration rather than cumulative dose influenced
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Rat to human extrapolation
- AF for other interspecies differences:
- 2.5
- Justification:
- Default
- AF for intraspecies differences:
- 10
- Justification:
- Proposed factor for general population. See detailed justification in document attached to this record.
- AF for the quality of the whole database:
- 1
- Justification:
- Defaullt
- AF for remaining uncertainties:
- 1
- Justification:
- Default
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
This substance is classified as a category 1B reprotoxic. As such it is not permitted in consumer products and no consumer uses are identified. The substance has very low bioaccumulation potential (low logKow, readily biodegradable) and has no wide dispersive uses, indirect exposure via the environment can be disregarded. Consumer DNELS are therefore not needed for risk characterisation. However, a figure is derived for systemic long term oral consumption to be used for risk characterisation for chronic exposure via the environment. For use in this way, a further factor of 3 should be applied to account for 24hr/day exposure rather than the 8hr exposure assumed in the DNEL.
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.
