Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
88.2 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):
20
Dose descriptor starting point:
NOAEL
Modified dose descriptor starting point:
NOAEC
DNEL value:
1 763.2 mg/m³
AF for dose response relationship:
1
Justification:
ECHA Guidance (no effect observed up to the limit dose of 1000 mg/kg bw)
AF for differences in duration of exposure:
2
Justification:
ECHA Guidance (subchronic to chronic exposure)
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA Guidance (allometric scaling is not necessary for the inhalation route)
AF for other interspecies differences:
1
Justification:
No additional interspecies default factor is necesarry (due to the substance characteristic no interspecies differences are to be expected. This is supported by a generally low toxicity profile. Additionally no species differences in the metabolism of the test substance were observed)
AF for intraspecies differences:
5
Justification:
ECHA Guidance (default factor for workers)
AF for the quality of the whole database:
1
Justification:
ECHA Guidance (default value for good quality of database, also taking into account completeness and consistency)
AF for remaining uncertainties:
2
Justification:
ECHA Guidance, route-to-route extrapolation (oral to inhalation)
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:
62.5 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):
40
Dose descriptor starting point:
NOAEL
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No study on long-term dermal toxicity available. Dermal absorption was taken with 40% acording to experimental data (Dal Pozzo and Pastori, 1996)
AF for dose response relationship:
1
Justification:
ECHA Guidance (no effect observed up to the limit dose of 1000 mg/kg bw)
AF for differences in duration of exposure:
2
Justification:
ECHA Guidance (subchronic to chronic exposure)
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA Guidance (allometric scaling rat to human)
AF for other interspecies differences:
1
Justification:
No additional interspecies default factor is necesarry (due to the substance characteristic no interspecies differences are to be expected. This is supported by a generally low toxicity profile. Additionally no species differences in the metabolism of the test substance were observed)
AF for intraspecies differences:
5
Justification:
ECHA Guidance (default value for workers)
AF for the quality of the whole database:
1
Justification:
ECHA Guidance (default value for good quality of database, also taking into account completeness and consistency)
AF for remaining uncertainties:
1
Justification:
ECHA Guidance, route-to-route extrapolation (oral to inhalation)
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
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 propylparaben for workers, as the assessment of hazard is considered to be sufficiently covered by deriving the respective DNELs for long-term exposure.

Since there are no inhalation and dermal repeated dose toxicity studies available as default, route-to-route extrapolation is performed using NOAEL of 1000 mg/kg body weight per day from a 90 day repeated dose oral toxicity study, which is identified as a key study for repeated dose toxicity. This study was performed according to OECD 408 (key study, 2018). 10 rats per sex and dose were treated with propylparaben at doses of 100, 300 and 1000 mg/kg bw via gavage for 90 days. During the study period, no mortality occurred and no significant effects on clinical signs, food consumption and body weight were observed. No adverse effects on haematology and clinical chemistry were noted throughout the study period. Based on the results of this study, the NOAEL for propylparaben was considered to be 1000 mg/kg bw/d for males and females. This NOAEL is used as starting pointfor the derivation of the worker DNEL "long-term inhalation exposure-systemic effecs".

 

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). Considering these differences, the corrected starting point is a NAEC of 1763.2 mg/m³.With regard to interspecies differences, allometric scalingconcerning concerning oral-to-inhalation extrapolation is not appropriate and no assessment factor is applied (ECHA guidance). Since the assessment is based on the outcome of a 90 day repeatd dose study, time extrapolation to chronic exposure conditions generally have to be be considered and the default factor of 2 (subchronic to chronis) is used. For itraspecies differences a an assessment factor of 5 as a default factor for workes is considered. Furthermore a conservative approach is taken and the default factor of 2 for remaining uncertainties using route-to-route extrapolation is applied. The resulting overall assessment factor is 20 (2x5x2) resulting in a DNEL "long-term inhalation exposure-systemic effects" of 88.2 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). The dermal absorption of propylparaben lies at about 40% in human skin (Dal Pozzo and Pastori, 1996). According to the “Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health” (ECHA, 2012), a corrected dermal NOAEL was derived by taking into account the dermal absorption. With respect to the dermal DNEL derivation, the same ratinal apply like for the ihnalation route.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
43.47 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):
20
Modified dose descriptor starting point:
NOAEC
DNEL value:
869.56 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:
2
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:
1
Justification:
No default additional interspecies factor is used, since no species differences in the metabolism of the test substance were observed.
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Default value for good quality of database, also taking into account completeness and consistency.
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:
31.25 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):
80
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 500 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:
2
Justification:
Subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat to human
AF for other interspecies differences:
1
Justification:
No default additional interspecies factor is used, since no species differences in the metabolism of the test substance were observed.
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Default value for good quality of database, also taking into account completeness and consistency.
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
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:
43.47 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):
20
Modified dose descriptor starting point:
NOAEL
DNEL value:
869.56 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:
2
Justification:
Subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling rat to human
AF for other interspecies differences:
1
Justification:
No default additional interspecies factor is used, since no species differences in the metabolism of the test substance were observed.
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Default value for good quality of database, also taking into account completeness and consistency.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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 propylparaben for consumers, as it is considered that the assessment of hazard is sufficiently covered by deriving the respective DNELs for long-term exposure.

 

A 90 day repeated dose oral toxicity study, which is identified as a key study for repeated dose toxicit was used for deriving the DNEL. This study was performedaccording to OECD 408 (key study, 2018). 10 rats per sex and dose were treated with propylparaben at doses of 100, 300 and 1000 mg/kg bw via gavage for 90 days. During the study period, no mortality occurred and no significant effects on clinical signs, food consumption and body weight were observed. No adverse effects on haematology and clinical chemistry were noted throughout the study period. Based on the results of this study, the NOAEL for propylparaben was considered to be 1000 mg/kg bw/d for males and females. This NOAEL is used as starting pointfor the derivation of the worker DNEL "long-term inhalation exposure-systemic effecs".

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 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). Considering these differences, the corrected starting point is a NAEC of 869.56 mg/m³. Based on the assessment of the toxicokinetic behavior of propylparaben, the absorption via the inhalative route is considered to be in the same range as via the oral route.

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). The dermal absorption of propylparaben lies at about 40% in human skin (Dal Pozzo and Pastori, 1996). According to the “Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health” (ECHA, 2012), a corrected dermal NOAEL was derived by taking into account the dermal absorption.