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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
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):
150
Modified dose descriptor starting point:
NOAEC
Value:
1 763.2 mg/m³
Explanation for the modification of the dose descriptor starting point:
No study on long-term inhalation toxicity available
AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Default value for workers
AF for the quality of the whole database:
2
Justification:
Remaining uncertainties due to data waiving for toxicity to reproduction
AF for remaining uncertainties:
1
Justification:
No further remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.67 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No study on long-term dermal toxicity available
AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
The experimental animal was the rat.
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Default value
AF for the quality of the whole database:
2
Justification:
Remaining uncertainties due to data waiving for toxicity to reproduction
AF for remaining uncertainties:
1
Justification:
No further remaining unceratainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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

No DNELs have been derived for systemic effects after short-term exposure of 2-(4-tert-butylphenyl)-6-cyano-5-[bis(ethoxycarbonylmethyl)carbamoyloxy]-1 H-pyrrolo[1 ,2-b][1 ,2,4]triazole-7-carboxylic acid-2,6-di-tert-butyl-4-methyl-cyclohexyl ester (UC-141) for workers, as it is assumed that the assessment of hazard is sufficiently covered by deriving the respective DNELs for long-term exposure. In addition, no DNEL has been derived for short-term dermal exposure, since no hazard was identified. Moreover, UC-141 was not skin or eye irritating neither skin sensitising (Hooiveld, 2003b,c,d).

The long-term worker DNEL for dermal systemic effects is based on the 28-day repeated dose toxicity study (Hooiveld, 2004b), which was performed according to OECD Guideline 407 in rats. No animals died and no effects with toxicological relevance were observed on body weights, organ weights, haematology and clinical chemistry parameters in the study. The necropsy and histopathological examinations did not show treatment-related effects. As no effects were observed up to and including the highest dose level, the NOAEL is ≥ 1000 mg/kg bw/day. This study was chosen as the starting point for deriving the DNEL as there is no dermal repeated dose study available. To convert the oral NOAEL [mg/kg bw/day] into a dermal NOAEL [mg/kg bw/day], the differences in absorption between routes as well as differences in dermal absorption between rats and humans have to be accounted for (Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health, European Chemicals Agency, November 2012). For UC-141 the dermal bioavailability is expected to be in the same order of magnitude as oral absorption (refer to Toxicokinetics, metabolism and distribution).

The long-term worker DNEL for inhalation systemic effects is based on the 28-day repeated dose toxicity study (Hooiveld, 2004b). No toxicologically relevant effects were observed up to and including the highest dose level, therefore the NOAEL is considered to be ≥ 1000 mg/kg bw/day. This NOAEL was chosen as the starting point for deriving the DNEL as there is no inhalation repeated dose study available. According to the “Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health” (European Chemicals Agency, November 2012), the oral NOAEL should be converted into an inhalatory NAEC: the oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m³/kg for 8 h exposure). Additionally, it should be taken into account that during 8 hours light activity at work the respiratory rate becomes higher (10 m³/person) than standard (6.7 m³/person). Considering these differences, the correct starting point is a NAEC of 1763.2 mg/m³.

Based on the water insolubility and the high log Pow, absorption of UC-141 via the oral and inhalation is limited (refer to Toxicokinetics, metabolism and distribution). Therefore, it is assumed, that the inhalation absorption rate is in the same order of magnitude as the oral absorption.

In general, AFs recommended by ECHA (Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose[concentration]-response for human health. European Chemicals Agency, November 2012) were used when applicable to derive the DNELs.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.9 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):
300
Modified dose descriptor starting point:
NOAEC
Value:
869.6 mg/m³
Explanation for the modification of the dose descriptor starting point:
No repeated dose inhalation study was available
AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
10
Justification:
Default value
AF for the quality of the whole database:
2
Justification:
Remaining uncertainties due to data waiving for toxicity to reproduction
AF for remaining uncertainties:
1
Justification:
No further remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.83 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):
1 200
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No repeated dose dermal study was available
AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
The experimental animal was the rat.
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
10
Justification:
Default value
AF for the quality of the whole database:
2
Justification:
Remaining uncertainties due to data waiving for toxicity to reproduction
AF for remaining uncertainties:
1
Justification:
No further remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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:
0.83 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):
1 200
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation required.
AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
The experimental animal was the rat.
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
10
Justification:
Default value
AF for the quality of the whole database:
2
Justification:
Remaining uncertainties due to data waiving for toxicity to reproduction
AF for remaining uncertainties:
1
Justification:
No further remaining uncertainties.
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 general population is not exposed to 2-(4-tert-butylphenyl)-6-cyano-5-[bis(ethoxycarbonylmethyl)carbamoyloxy]-1 H-pyrrolo[1 ,2-b][1 ,2,4]triazole-7-carboxylic acid-2,6-di-tert-butyl-4-methyl-cyclohexyl ester (UC-141), based on its identified uses. However, the long-term consumer DNELs for oral, dermal and inhalation systemic effects have been derived. No DNELs have been derived for systemic effects after short-term dermal, inhalation and oral exposure of UC-141 for the general population, as it is assumed that the assessment of hazard is sufficiently covered by deriving the respective DNELs for long-term exposure or since no hazard was identified based on experimental data, respectively. Moreover, AF-654 was not skin or eye irritating neither skin sensitising (Hooiveld, 2003b,c,d).

The long-term DNEL for the general population, dermal systemic effects is based on the 28-day repeated dose toxicity study (Hooiveld, 2004b), which was performed according to OECD Guideline 407 in rats. No animals died and no effects with toxicological relevance were observed on body weights, organ weights, haematology and clinical chemistry parameters in the study. The necropsy and histopathological examinations did not show treatment-related effects. As no effects were observed up to and including the highest dose level, the NOAEL is ≥ 1000 mg/kg bw/day. This study was chosen as the starting point for deriving the DNEL as there is no dermal repeated dose study available. To convert the oral NOAEL [mg/kg bw/day] into a dermal NOAEL [mg/kg bw/day], the differences in absorption between routes as well as differences in dermal absorption between rats and humans have to be accounted for (Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. European Chemicals Agency, November 2012). For UC-141 the dermal bioavailability is expected to be in the same order of magnitude as oral absorption (refer to Toxicokinetics, metabolism and distribution). The NOAEL for the oral and dermal exposure route is therefore identical.

The long-term DNEL for the general population in regard to systemic effects after inhalation exposure is based on the 28-day repeated dose toxicity study (Hooiveld, 2004b). No toxicologically relevant effects were observed up to and including the highest dose level, therefore the NOAEL is considered to be ≥ 1000 mg/kg bw/day. The NOAEL determined in this study was chosen as the starting point for deriving the DNEL as there is no inhalation repeated dose study available. According to the Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose[concentration]-response for human health (European Chemicals Agency, November 2012), the oral NOAEL should be converted into an inhalatory NAEC: the oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m³/kg for 24 h exposure). Therefore, the corrected starting point is a NAEC of 869.6 mg/ m³. For UC-141, it is assumed, that the inhalation absorption rate is in the same order of magnitude as the oral absorption.

The long-term DNEL for the general population in regard to oral systemic effects is also based on the 28-day repeated dose toxicity study (Hooiveld, 2004b), performed according to OECD Guideline 407 in rats. No toxicologically relevant effects were observed up to and including the highest dose level, therefore the NOAEL is considered to be ≥ 1000 mg/kg bw/day. The study was performed via the oral route and the value can be used directly to derive the oral DNEL.

In general, AFs recommended by ECHA (Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose[concentration]-response for human health. European Chemicals Agency, November 2012) were used when applicable to derive the DNELs.