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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
0.53 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Modified dose descriptor starting point:
NOAEC
Value:
39.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

The dose descriptor was modified by the following defaults as laid out in Guidance on Information Requirements and Chemical Safety Assessment, May 2008, R.8.4.2: extrapolation from the oral-to-inhalation route, assuming no first-pass effect. NOAELInhal-rat= NOAELOral-rat*1/RVrat, NOAELInhal-rat= 15 mg/kg bw*1/0.38 m3/kg bw/8h = 39.5 mg/m3/8h

AF for dose response relationship:
1
Justification:
The default dose-response factors were used from the Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, R.8.4.3.1 Assessment factors relating to the extrapolation procedure, Dose-response relationship (p29).
AF for differences in duration of exposure:
2
Justification:
The default subchronic-chronic factors were used from the Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, Table R. 8-5 Assessment factors for duration extrapolation.
AF for interspecies differences (allometric scaling):
3
Justification:
The allometric scaling factor was calculated by the following method as laid out in Guidance on Information Requirements and Chemical Safety Assessment, May 2008, R.8.4.2: extrapolation from the oral-to-inhalation route, using the following assumptions: light-work respiratory volume in the worker, 50% oral absorption, and 100% inhalation absorption. AFInterspecies = 1/(RVhuman/RVworker*OA rat/IAhuman), AFInterspecies = 1/(6.7m3/8h/10m3/8h * 50%/100%) = 1/(0.335) = 3; Where RV is respiratory volume, OA is oral absorption, IA is inhalation absorption.
AF for other interspecies differences:
2.5
Justification:
The default remaining interspecies factors were used from the Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, R.8.4.3.1 Assessment factors relating to the extrapolation procedure, Interspecies differences (p24).
AF for intraspecies differences:
5
Justification:
The default intraspecies factors were used from the Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, R.8.4.3.1 Assessment factors relating to the extrapolation procedure, Intraspecies differences (p28).
AF for the quality of the whole database:
1
Justification:
The default quality of whole database factors were used from the Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, R.8.4.3.1 Assessment factors relating to the extrapolation procedure, Quality of whole database (p31).
AF for remaining uncertainties:
1
Justification:
No further assessment factors were applied.
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:
0.15 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
Modified dose descriptor starting point:
NOAEL
Value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The dose descriptor was modified by the following defaults as laid out in Guidance on Information Requirements and Chemical Safety Assessment, May 2008, R.8.4.2: extrapolation from the oral-to-dermal route, assumed no first-pass effect, and in the absence of substance specific absorption values, dermal absorption is assumed to be no higher than oral absorption. NOAELCorr(worker) =NOAELOral-rat*OArat/DAhuman NOAELCorr(worker) = 15 mg/kg bw*100%/100% NOAELCorr(worker) = 15 mg/kg bw, where OA is oral absorption, DA is dermal absorption.

AF for dose response relationship:
1
Justification:
The default dose-response factors were used from the Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, R.8.4.3.1 Assessment factors relating to the extrapolation procedure, Dose-response relationship (p29).
AF for differences in duration of exposure:
2
Justification:
The default subchronic-chronic factors were used from the Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, Table R. 8-5 Assessment factors for duration extrapolation.
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor from rats to humans was applied as given in Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Table R. 8-3 Allometric scaling factors for different species as compared to humans.
AF for other interspecies differences:
2.5
Justification:
The default remaining interspecies factors were used from the Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, R.8.4.3.1 Assessment factors relating to the extrapolation procedure, Interspecies differences (p24).
AF for intraspecies differences:
5
Justification:
The default intraspecies factors were used from the Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, R.8.4.3.1 Assessment factors relating to the extrapolation procedure, Intraspecies differences (p28).
AF for the quality of the whole database:
1
Justification:
The default quality of whole database factors were used from the Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, R.8.4.3.1 Assessment factors relating to the extrapolation procedure, Quality of whole database (p31).
AF for remaining uncertainties:
1
Justification:
No further assessment factors were applied.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Worker inhalation, systemic effects:

Information relevant to long-term inhalation, systemic effects, is available from two endpoints – repeat-dose toxicity and reproductive toxicity, using route-to-route extrapolation. The critical DNEL for both endpoints is the same and reflects the leading health effect, fertility impairment.

Worker dermal, systemic effects:

Information relevant to long-term dermal, systemic effects, is available from two endpoints – repeat-dose toxicity and reproductive toxicity, using route-to-route extrapolation. The critical DNEL for both endpoints is the same and reflects the leading health effect, fertility impairment.

Semi-quantitative dermal hazard assessment, local effects:

On the basis of ECETOC Technical Report No. 87, Contact Sensitisation: Classification According to Potency, 2.2.1, Table 3, the test substance could be categorised as a “weak sensitiser”, using the 75w/v% concentration used in topical administration during induction, and the subsequent 45% elicitation incidence in the 50w/v% challenge.

The report recommendation is that the emphasis be placed on the induction concentration, since it is this stage of sensitisation that is most susceptible to dose-response effects. Furthermore, the concentration of the chemical used for topical administration during induction, rather than the concentration of chemical used for intradermal injection employed during induction, should be used for categorisation. The basis for this recommendation is that the concentration of test chemical used for intradermal injection is frequently determined, and limited, by the addition of Freundʹs Complete Adjuvant.

However, the recommendations in the ECHA Guidance, Chapter R.8, May 2008, Appendix R.8-10, Table R.8-24, based on the EU Working Group on Skin Sensitisation, suggest that the concentration of the intra-dermal injection be used. Based on 3w/v% used in the intra-dermal injection, and 45% elicitation in the challenge, the substance would be categorised as a “moderate sensitiser”.

The LLNA study tested the substance at 1, 3, 10 and 30w/v% in dimethylformamide, all at which resulted in less than a 3-fold isotope incorporation. The positive control confirmed the validity of the test system. It has been suggested that the EC3 value can be used as a starting point for quantitative risk assessment purposes, and DNEL derivation (Appendix R.8-10). In this case because the highest concentration tested (30w/v%) is not a LOAEL, and effectively only represents an upper limit for the potency, it would potentially result in an excessively conservative DNEL. As a result, a qualitative risk assessment approach based on the “moderate sensitiser” potency categorisation is undertaken.

The potency categorisation of the test substance based on the GPMT, in combination with the Hazard Categories given in the Guidance, Part E: Risk Characterisation, May 2008, Table E.3-1, results in a “moderate hazard” categorisation for the purposes of risk assessment. This categorisation is carried forward to Risk Characterisation.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.13 mg/m³
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
Modified dose descriptor starting point:
NOAEC
Value:
6.57 mg/m³
Explanation for the modification of the dose descriptor starting point:

The dose descriptor was modified by the following defaults as laid out in Guidance on Information Requirements and Chemical Safety Assessment, May 2008, R.8.4.2: extrapolation from the oral-to-inhalation route, assuming no first-pass effect and 50% absorption via oral route in the rat and 100% absorption via inhalation route in humans. NOAELInhal-corrected= NOAELOral-rat*1/sRVrat*ABSoral-rat/ABSinh-human= 15 mg/kg bw*1/1.15 m3/kg bw/d*50%/100% = 6.57 mg/m3/d

AF for dose response relationship:
1
Justification:
The default dose-response factors were used from the Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, R.8.4.3.1 Assessment factors relating to the extrapolation procedure, Dose-response relationship (p29).
AF for differences in duration of exposure:
2
Justification:
The default subchronic-chronic factors were used from the Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, Table R. 8-5 Assessment factors for duration extrapolation.
AF for interspecies differences (allometric scaling):
1
Justification:
No further assessment factor applied since corrected starting point is a concentration (compare to ECHA guidance R.8, section 8.4.3, page 25)
AF for other interspecies differences:
2.5
Justification:
The default remaining interspecies factors were used from the Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, R.8.4.3.1 Assessment factors relating to the extrapolation procedure, Interspecies differences (p24).
AF for intraspecies differences:
10
Justification:
The default intraspecies factors were used from the Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, R.8.4.3.1 Assessment factors relating to the extrapolation procedure, Intraspecies differences (p28).
AF for the quality of the whole database:
1
Justification:
The default quality of whole database factors were used from the Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, R.8.4.3.1 Assessment factors relating to the extrapolation procedure, Quality of whole database (p31).
AF for remaining uncertainties:
1
Justification:
No further assessment factors were applied.
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:
DNEL (Derived No Effect Level)
Value:
0.075 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A reliable, sub-chronic oral repeated dose toxicity study is available and the oral NOAEL from this study is used as the starting point for DNEL derivation.

AF for dose response relationship:
1
Justification:
No assessment factor is required, since the starting point is a reliable NOAEL.
AF for differences in duration of exposure:
2
Justification:
The default subchronic-chronic factors were used from the Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, Table R. 8-5 Assessment factors for duration extrapolation.
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor from rats to humans was applied as given in Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Table R. 8-3 Allometric scaling factors for different species as compared to humans.
AF for other interspecies differences:
2.5
Justification:
The default remaining interspecies factors were used from the Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, R.8.4.3.1 Assessment factors relating to the extrapolation procedure, Interspecies differences (p24).
AF for intraspecies differences:
10
Justification:
The default intraspecies factors were used from the Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, R.8.4.3.1 Assessment factors relating to the extrapolation procedure, Intraspecies differences (p28).
AF for the quality of the whole database:
1
Justification:
The default quality of whole database factors were used from the Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, R.8.4.3.1 Assessment factors relating to the extrapolation procedure, Quality of whole database (p31).
AF for remaining uncertainties:
1
Justification:
No further assessment factors were applied.
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

The substance is used exclusively as an intermediate in chemical synthesis, in an industrial setting, and is not made available to professional workers or consumers. As outlined in Guidance on information requirements and chemical safety assessment, Part R.16, assessment of indirect exposure of humans via the environment is usually required, if the annual tonnage is greater than 100 tonnes per year and the substance is classified as toxic after repeated, prolonged exposure, carcinogenic, mutagenic or toxic to reproduction. With regard to the classification of NMST as toxic to reproduction, Category 1B, and the annual tonnage exceeding 100 tonnes per year, an assessment of indirect exposure of humans via the environment is warranted. Hence, DNELs were derived for the general public, although the substance is not contained in retail products and direct exposure of consumers to the substance is highly unlikely.