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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.364 mg/m³
Most sensitive endpoint:
genetic toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
other: BMD10
Value:
62 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
54.65 mg/m³
Explanation for the modification of the dose descriptor starting point:

The DNEL for inhalation exposure for workers is was derived using lowest available NOAEL derived from the Comet assay based on the values derived for the effects seen in the liver. The EPA Benchmark dose software was used to derive the BMD10 value based on the liver values in the comet assay which resulted in a point of departure of 62mg/kg/day. This value further used in the deriving the modified starting point for the inhalation DNEL.

NOAEC (The DNEL for inhalation exposure for workers is given by the formula: corrected inhalation NOAEC= LOAEL(oral-rat) * 1/sRVrat * (Absorption (oral-rat) / Absorption(inhal-human)) * (sRVhuman/wRV) Where SRV is the standard Respiratory Volume and wRV is the worker Respiratory Volume. The default values assumed for these factors are as follows: Absorption(oral-rat) =50%; Absorption(inhal-human) =100%; sRVrat=0.38 m3/kg/d; sRVhuman= 6.7m3 (8hr); wRV=10m3(8hr). NOAEC(corrected) = 62 mg/kg bw/day* (1/0.38 m3/kg/d) *(50%/100%) * 6.7m3 (8hr) / 10m3(8hr) NOAEC(corrected) = 54.65 mg/m3)

AF for dose response relationship:
3
Justification:
ECHA, 2010 Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health states when the starting point for the DNEL calculation is a LOAEL, it is suggested to use an assessment factor between 3 (as minimum/majority of cases) and 10 (as maximum/exceptional cases).
However, the benchmark dose (BMD) approach is, when possible, preferred over the LOAEL/NAEL extrapolation. A BMD calculated as the lower confidence limit of the dose that produces a response of 5% (BMD5) has, on average, been proposed to be comparable to a NOAEL (WHO, 2000). If other BMD indicators are used, e.g. a BMD10, it should be considered on a case-by-case basis whether an additional dose-response assessment factor is needed. The Benchmark-dose representing a 10% response was used in this instance. When the starting point for the DNEL calculation is a NOAEL, the default assessment factor, as a standard procedure, is 1 but that a larger assessment factor may be applied. In this instance the value of 3 has been selected to take into account any concerns related to the use of the BMD10 value
AF for differences in duration of exposure:
10
Justification:
ECHA guidance document Chapter R8, in Table R.8-5, indicates that a higher factor may for instance be used if there are indications for potential severe chronic effects, which cannot possibly be detected in a short term study. In this case a conservative value of 10 has been selected
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is already included in the route to route extrapolation from the Comet assay BMD10 value to the equivalent human inhalation NOAEC.
AF for other interspecies differences:
1
Justification:
ECETOC reported in 2010 after an extensive review (see discussion) that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 has been applied.
AF for intraspecies differences:
5
Justification:
ECHA, 2010 Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2 December 2010. Value of 5 used to represtnt workers as per the guidance
AF for the quality of the whole database:
1
Justification:
The BMD10 was derived from a Guideline study conducted to GLP and is judged to be of high quality and reliable results
AF for remaining uncertainties:
1
Justification:
All uncertainties are already included so a factor of 1 is applied
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.103 mg/kg bw/day
Most sensitive endpoint:
genetic toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
other: BMD10
Value:
62 mg/kg bw/day
Modified dose descriptor starting point:
BMD05
Value:
62 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

ECHA guidance assumes that absorption for dermal exposure is the same as for oral exposure, which is a worst case assumption.

AF for dose response relationship:
3
Justification:
ECHA, 2010 Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human healt states when the starting point for the DNEL calculation is a LOAEL, it is suggested to use an assessment factor between 3 (as minimum/majority of cases) and 10 (as maximum/exceptional cases).
However, the benchmark dose (BMD) approach is, when possible, preferred over the LOAEL/NAEL extrapolation. A BMD calculated as the lower confidence limitof the dose that produces a response of 5% (BMD5) has, on average, been proposed to be comparable to a NOAEL (WHO, 2000). If other BMD indicators are used, e.g. a BMD10, it should be considered on a case-by-case basis whether an additional dose-response assessment factor is needed. The Benchmark-dose representing a 10% response was used in this instance. When the starting point for the DNEL calculation is a NOAEL, the default assessment factor, as a standardprocedure, is 1 but that a larger assessment factor may be applied. In this instance the value of 3 has been selected to take into account any concerns related to the use of the BMD 10 value
AF for differences in duration of exposure:
10
Justification:
ECHA guidance document Chapter R8, in Table R.8-5, indicates that a higher factor may for instance be used if there are indications for potential severe chronic effects, which cannot possibly be detected in a short term study. In this case a conservative value of 10 has been selected
AF for interspecies differences (allometric scaling):
4
Justification:
In the absence of dermal absorption data, equivalence is assumed. A default allometric scaling factor of 4 between rats and humans is applied.
AF for other interspecies differences:
1
Justification:
ECETOC reported in 2010 after an extensive review (see discussion) that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 has been applied
AF for intraspecies differences:
5
Justification:
ECHA, 2010 Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2 December 2010. Value of 5 used to represtnt workers as per the guidance
AF for the quality of the whole database:
1
Justification:
The BMD10 was derived from a Guideline study conducted to GLP and is judged to be of high quality
AF for remaining uncertainties:
1
Justification:
uncertainties are already included so a factor of 1 is applied
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:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

Selection of Assessment factors for Intra – Inter species variation for workersvariation for workers

ECHA (2010) has produced guidance on the assessment factors to use to derive a DNEL for human exposure based the application of assessment factors (safety factors) to an NOAEL or LOAEL in animal studies. The ECHA guidance proposes an assessment factor of 4 for the allometric scaling from rats to humans when calculating oral and dermal DNELs. However it then proposes an additional factor of 2.5 to cover remaining differences (uncertainties). There is no clear scientific justification for this additional factor. ECETOC in itsGuidance on Assessment Factors to Derive a DNEL(2010) reviewed the scientific evidence and concluded that the factor of 4 for rats was sufficient to cover the allometric scaling from rats to humans and any remaining differences are of intra-species rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter-species variability will not be used.

References:

ECHA, 2010 Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2 December 2010

ECETOC, 2010Guidance on Assessment Factors to Derive a DNEL,Technical Report No.110,ISSN-0773-8072-110 (print),ISSN-2079-1562-110 (online), October 2010

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
DNEL related information
Explanation for the modification of the dose descriptor starting point:

BMS 217947 is an intermediate, manufactured under strict engineering control conditions; there is no potential for exposure of the General Population.

Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

BMS 217947 is an intermediate, manufactured under strict engineering control conditions; there is no potential for exposure of the General Population.

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