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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
Default value for NOAEL as starting point for DNEL calculation
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not necessary for the inhalation route
AF for other interspecies differences:
2.5
Justification:
Default value for additional interspecies differences
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 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:
Default value for NOAEL as starting point for DNEL calculation
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat to human
AF for other interspecies differences:
2.5
Justification:
Default value for additional interspecies differences
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 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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

No DNELs have been derived for the short-term dermal and inhalation exposure of UY-330 for workers, as the assessment of hazard is considered to be sufficiently covered by deriving the respective DNELs for long-term exposure.

 

In a repeated dose oral toxicity study according to OECD 407, 5 Wistar rats per sex and dose were treated for 28 d with UY-330 (van Otterdijk, 2004). The test substance was applied in doses of 50, 150 and 1000 mg/kg bw/d as suspension in propylene glycol via oral gavage. 

All animals survived the treatment period and no effects on body weight, body weight gain and food consumption were observed. No test substance related findings were noted on clinical signs, haematology, clinical chemistry, neurobehavioural examinations, gross pathology, organ weights and histopathology. Based on the results of this study, the NOAEL is ≥ 1000 mg/kg bw/d for males and females.

 

This study was chosen as the starting point for deriving the long-term worker DNELs for inhalation and dermal systemic effects since there are no inhalation and dermal repeated dose toxicity studies available.

For deriving the long-term worker DNEL for inhalation systemic effects according to the “Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health” (ECHA, 2012), the oral NOAEL has to 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). Based on the water insolubility and the high log Pow, absorption of UY-330 is not likely to occur (refer to Toxicokinetics, metabolism and distribution). Therefore, absorption via the inhalation route is considered to be comparable to absorption via the oral route. Taken toghether, the corrected starting point is a NOAEC of 1763.2 mg/m³.

To convert the oral NOAEL [mg/kg bw/d] into a dermal NOAEL [mg/kg bw/d], the differences in absorption between routes, the differences in duration of exposure 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, ECHA, 2012).

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 study on long-term inhalation toxicity available
AF for dose response relationship:
1
Justification:
Default value for NOAEL as starting point for DNEL calculation
AF for differences in duration of exposure:
6
Justification:
subacute to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not necessary for the inhalation route
AF for other interspecies differences:
2.5
Justification:
Default value for additional interspecies differences
AF for intraspecies differences:
10
Justification:
Default value for general population
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 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 study on long-term dermal toxicity available
AF for dose response relationship:
1
Justification:
Default value for NOAEL as starting point for DNEL calculation
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat to human
AF for other interspecies differences:
2.5
Justification:
Default value for additional interspecies differences
AF for intraspecies differences:
10
Justification:
Default value for general population
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 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
AF for dose response relationship:
1
Justification:
Default value for NOAEL as starting point for DNEL calculation
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat to human
AF for other interspecies differences:
2.5
Justification:
Default value for additional interspecies differences
AF for intraspecies differences:
10
Justification:
Default value for general population
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 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

No DNELs have been derived for the short-term oral, dermal and inhalation exposure of UY-330 for consumers, as it is considered that the assessment of hazard is sufficiently covered by deriving the respective DNELs for long-term exposure.

 

In a repeated dose oral toxicity study according to OECD 407, 5 Wistar rats per sex and dose were treated for 28 d with UY-330 (van Otterdijk, 2004). The test substance was applied in doses of 50, 150 and 1000 mg/kg bw/d as suspension in propylene glycol via oral gavage.

All animals survived the treatment period and no effects on body weight, body weight gain and food consumption were observed. No test substance related findings were noted on clinical signs, haematology, clinical chemistry, neurobehavioural examinations, gross pathology, organ weights and histopathology. Based on the results of this study, the NOAEL is ≥ 1000 mg/kg bw/d for males and females.

 

This study was chosen as the starting point for deriving the long-term DNELs for the general population for inhalation and dermal systemic effects since there are no inhalation and dermal repeated dose toxicity studies available. The long-term DNEL for the general population oral systemic effects was derived directly from the oral repeated dose toxicity study.

For deriving the long-term consumer DNEL for inhalation systemic effects according to the “Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health” (ECHA, 2012), the oral NOAEL has to be converted into an inhalatory NOAEC: 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).

Based on the water insolubility and the high log Pow, absorption of UY-330 is not likely to occur (refer to Toxicokinetics, metabolism and distribution). Therefore, absorption via the inhalation route is considered to be comparable to absorption via the oral route. Taken toghether, the corrected starting point is a NOAEC of 869.6 mg/m³.

To convert the oral NOAEL [mg/kg bw/d] into a dermal NOAEL [mg/kg bw/d], the differences in absorption between routes, the differences in duration of exposure 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, ECHA, 2012).