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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.8 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.8 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Dose descriptor:
NOAEC
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:
16.7 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
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:
medium hazard (no threshold derived)

Additional information - workers

4-Hydroxyacetophenone did not show significant systemic toxicity in rats after repeated exposure in a 90-day study (OECD 408). In this 90-day gavage study, the top dose (45 mg/kg bw and day; Biodynamics, 1986) showed no effects and was considered as NOAEL; however, due to a missing effective dose, the validity of this study is somewhat limited. In addition, a screening study was performed in rats according to OECD 422 under GLP by oral gavage (BASF, 2013). No relevant systemic toxicity could be found and no indication was given for reproductive toxicity. The NOAEL was set at 600 mg/kg bw. This NOAEL was not used for the calculation of the DNEL due to the fact that the starting point would need to be modified from oral to inhalative exposure without available information on possible respiratory irritation at this concentration.

For the calculation of the DNELs, an available 28-day inhalation study was used. Here, 42 mg/m3 (the top dose) were without effects and considered as NOAEC. This dose descriptor is taken as a point of departure for the DNEL calculation. A correction for activity driven differences of respiratory volumes in workers compared to workers in rest has to be admitted so that the starting point has to be corrected to 28.14 mg/m3. The allometric assessment factor was set on 1 due to the inhalation route of the study. The time extrapolation factor is set on 2 since the inhalative NOAEC did not reach the oral NOAELs determined in the 28 day and the 90 day studies. This was calculated by the amount of substance uptake during a working day (10m3/working day) and the NOEC of 42 mg/m3 leading to 420 mg/person and approximated 6 mg/kg bw. 6 mg/kg bw lay clearly below the oral NOAELs of 600 mg/kg (28-day study) and 45 mg/kg (90-day study) which finally is the reason for the extrapolation from subchronic to chronic. The intraspecies variation in the work force is considered to be 5. The quality of the data base was set on 1. An overall assessment factor of 10 leads to a DNEL of 2.8 mg/m3. It has to be considered that the calculated DNEL is very conservative due to no available effects in the study. Since this DNEL is 15fold below the NOAEC of the 28-day inhalation study which also included the investigation of local irritative effects, the systemic DNEL is considered to be also protective from local effects.

Overview table:

Description Value Remark
Step 1) Relevant dose-descriptor NOAEC: 42 mg/ m3
Step 2) Modification of starting point × 6.7 m3/10 m3 Correction for activity driven differences of respiratory volumes in workers compared to workers in rest.
Modified dose-descriptor

42 * 0,67 = 28,14 mg/m3

Step 3) Assessment factors  
Interspecies 1 No allometric scaling has to be applied in case of inhalation to inhalation route to route extrapolation.
Intraspecies 5 Default assessment factor for workers
Exposure duration 2 Default assessment factor, extrapolation from sub-chronic to chronic (based on the oral NOAEL; see calculation in the discussion text)  
Dose response 1  Starting point=NO(A)EC, therefore no correction
Quality of database 1

 Starting point=NO(A)EC, therefore no correction

DNEL

28,14 / (1 × 5 × 2 × 1 × 1) =2.8 mg/m3  

For the calculation of the dermal DNEL, the 28-day OECD guideline study is used with the oral NOAEL of 600 mg/kg. This dose descriptor is taken as a point of departure for the DNEL calculation. A correction of differences in the absorption (assuming oral: 100%, dermal: 50%) has to be admitted so that the starting point has to be corrected to 1200 mg/kg. The allometric assessment factor was set on 4 based on the guidance document. The time extrapolation factor is set on 6. The intraspecies variation in the work force is considered to be 3 since no polymorphisms regarding enzyme activity or dermal absorption are expected. The quality of the data base was set on 1. An overall assessment factor of 24 leads to a DNEL of 50 mg/kg.

Description Value Remark
Step 1) Relevant dose-descriptor NOAEL: 600 mg/kg  
Step 2) Modification of starting point 100/50 An oral absorption of 100 %, and a dermal absorption of 50 % is assumed. 
Modified dose-descriptor 1200 mg/kg  
Step 3) Assessment factors    
Interspecies 4 Allometric scaling has to be applied for the rat.
Intraspecies 3 Default assessment factor for workers
Exposure duration 6 Default assessment factor, extrapolation from subacute to chronic
Dose response 1 Starting point=NOAEL, for that reason no correction
Quality of database 1 OECD-guideline study
DNEL Value  
DNEL of hydroxyacetophenone 1200 / (4 × 3 × 6 × 1 × 1) =16.7 mg/kg  

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.21 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
Value:
42 mg/m³
AF for dose response relationship:
1
Justification:
Not required for a NOAEC point of departure
AF for differences in duration of exposure:
2
Justification:
See Discussion
AF for interspecies differences (allometric scaling):
1
Justification:
Not required for concentrations
AF for other interspecies differences:
2.5
Justification:
Default for remaining differences
AF for intraspecies differences:
10
Justification:
Default for general popultaion
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.21 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor:
NOAEC
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:
DNEL (Derived No Effect Level)
Value:
2 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:
600 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
In the absence of any relevant studies by the dermal route of exposure, the relevant dose descriptor was considered to be a NOAEL for repeat dose oral exposure to rats, 600 mg/kg/day. This starting point was modified based on the relative absorption rates of 100% via oral exposure, taken as the worst case in the absence of any other data, and 50% by dermal exposure as the deafult absorption rate by this route. Therefore the modified point of departure NOAEL = 600 * 100/50 = 1200 mg/kg/day.
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Conversion from sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default for conversion from rat to human
AF for other interspecies differences:
2.5
Justification:
Default for remaining differences
AF for intraspecies differences:
10
Justification:
Default actor for General population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
1 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:
600 mg/kg bw/day
AF for dose response relationship:
1
Justification:
No AF required when starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default conversion rat to human
AF for other interspecies differences:
2.5
Justification:
Default for remaining differences
AF for intraspecies differences:
10
Justification:
Default for General population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

Although the material is not specifically designed for exposure of the customer or the general population, it is anticipated that accidental exposure by inhalation, dermal and oral routes of exposure are possibilities. Consequently, DNELs have been calculated to cover these exposures.

For the calculation of inhalation DNELs, an available 28-day inhalation study was used in which 42 mg/m3 was without effect and considered as a NOAEC. This dose descriptor is taken as the point of departure for the inhalatory DNEL calculations. A correction for the differences in exposure time between the rat study (6h/day) and the general population (24h/day) is made (42 * ¼ mg/m3) so that the starting point is corrected to 10.5 mg/m3. An overall assessment factor of 50 lead to a DNEL of 0.21 mg/m3. It has to be considered that the calculated DNEL is very conservative due to no available effects in the study. Since this DNEL is 200-fold below the NOEC of the 28-day inhalation study which also included the investigation of local irritative effects, the systemic DNEL is considered to be also protective for long term local effects.

For the calculation of the dermal DNEL, the 28-day OECD rat guideline study was used with the oral NOAEL of 600 mg/kg. This dose descriptor is taken as a point of departure for the DNEL calculation. A correction of differences in the absorption (assuming oral: 100%, dermal: 50%) was applied so that the starting point was corrected to 1200 mg/kg. An overall assessment factor of 600 lead to a DNEL of 2 mg/kg/day.

No specific local dermal hazard could be identified since the acute dermal LD50 was above the limit dose of 2000 mg/kg.

Since it is considered that accidental oral exposure could be a hazard associated with this material, hence an oral DNEL for the general population was calculated based on the No Observed Adverse Effect Level (NOAEL) taken from the findings in a repeated dose toxicity in rats (600 mg/kg/day) with dosing over a 28-day period. Using an overall assessment factor of 600, the general population oral systemic long-term exposure DNEL is 1 mg/kg/day.