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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:
14.7 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):
30
Modified dose descriptor starting point:
NOAEC
DNEL value:
440.8 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:
1
Justification:
No default additional interspecies factor is used, since additional interspecies variability is accounted for in the default assessment factor for intraspecies variability (ECETOC Technical Report 86, 2003).
AF for intraspecies differences:
5
Justification:
Default value for workers
AF for the quality of the whole database:
1
Justification:
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).
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:
2.6 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):
96
Modified dose descriptor starting point:
NOAEL
DNEL value:
250 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:
1
Justification:
No default additional interspecies factor is used, since additional interspecies variability is accounted for in the default assessment factor for intraspecies variability (ECETOC Technical Report 86, 2003).
AF for intraspecies differences:
5
Justification:
Default value for workers
AF for the quality of the whole database:
1
Justification:
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).
AF for remaining uncertainties:
0.8
Justification:
ca. 80% dermal absorption in human based on a QSAR calculation.
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:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

There are no data available on long-term systemic toxicity of Sodium Methylparaben (sodium 4-(methoxycarbonyl)phenolate). However, there are reliable data for Methylparaben which is considered to be suitable for read-across using the analogue approach. For details refer to analogue justification.

 

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

There are no quantitative dose-response data available for local short- and long-term effects on skin and respiratory tract of Sodium Methylparaben. The most sensitive local effects observed are skin irritation and eye corrosion.

 

The long-term worker DNEL for dermal systemic effects is based on a subacute repeated dose oral toxicity study in rats performed according to OECD 407 and GLP (Beerens-Heijnen, 2009). In this study, no spontaneous mortality occurred during and no effects on body weight, body weight gain and food consumption were observed. However, one male and one female at 1000 mg/kg bw/d were killed in extremis, showing several clinical signs (lethargy, hunched posture, laboured respiration and rales, swelling of the abdomen, piloerection, diarrhoea, salivation, ptosis, hypothermia, dehydration and lean appearance). The histopathologic examination of both animals sacrificed revealed minimal/slight erosions in the forestomach, correlating to the irregular surface recorded at necropsy, slight red pulp atrophy of the spleen and slight/moderate lymphoid atrophy of the thymus, correlating to the reduced thymus size recorded at necropsy.

Based on the results of this study, the NOAEL for Methylparaben was considered to be 250 mg/kg bw/d.

There is no dermal repeated dose toxicity study available. The subacute repeated dose oral toxicity study was chosen as the starting point for deriving the DNEL since the study represents the most sensitive NOAEL among the valid studies. 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, Version 2.1, November 2012).

Data on dermal absorption of Methylparaben show that the dermal absorption of Methylparaben lies at 84.7% in human skin (Fasano, 2004). A QSAR calculation regarding the dermal absorption of Sodium Methylparaben resulted in ca. 80% dermal absorption.

 

The long-term worker DNEL for inhalation systemic effects is again based on the subacute repeated dose oral toxicity study in rats performed according to OECD 407 and GLP (Beerens-Heijnen, 2009). This study was chosen as the starting point for deriving the DNEL since there is no inhalation repeated dose toxicity study and due to the fact that this study represented the most sensitive NOAEL among the valid studies. According to the “Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health” (ECHA, Version 2.1, November 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 440.8 mg/m³. The absorption via the inhalative route is considered to be in the same order as via the oral route.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.62 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):
60
Modified dose descriptor starting point:
NOAEC
DNEL value:
217.4 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:
1
Justification:
No default additional interspecies factor is used, since additional interspecies variability is accounted for in the default assessment factor for intraspecies variability (ECETOC Technical Report 86, 2003).
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).
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:
1.3 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):
192
Modified dose descriptor starting point:
NOAEL
DNEL value:
250 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:
1
Justification:
No default additional interspecies factor is used, since additional interspecies variability is accounted for in the default assessment factor for intraspecies variability (ECETOC Technical Report 86, 2003).
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).
AF for remaining uncertainties:
0.8
Justification:
ca. 80% dermal absorption in human based on a QSAR calculation of Sodium Methylparaben
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:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.04 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):
240
Modified dose descriptor starting point:
NOAEL
DNEL value:
250 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:
1
Justification:
No default additional interspecies factor is used, since additional interspecies variability is accounted for in the default assessment factor for intraspecies variability (ECETOC Technical Report 86, 2003).
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).
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:
medium hazard (no threshold derived)

Additional information - General Population

There are no data available on long-term systemic toxicity of Sodium Methylparaben (sodium 4-(methoxycarbonyl)phenolate). However, there are reliable data for Methylparaben which is considered to be suitable for read-across using the analogue approach. For details refer to analogue justification.

 

The general population is not exposed to neat Sodium Methylparaben, 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 the short-term dermal, inhalation and oral exposure of Sodium Methylparaben 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.

There are no quantitative dose-response data available for local short- and long-term effects on skin and respiratory tract of Sodium Methylparaben. The most sensitive local effects observed are skin irritation and eye corrosion.

 

The long-term DNEL for the general population for dermal systemic effects is based on a subacute repeated dose oral toxicity study in rats performed according to OECD 407 and GLP (Beerens-Heijnen, 2009). In this study, no spontaneous mortality occurred during the study period and no effects on body weight, body weight gain and food consumption were observed. However, one male and one female at 1000 mg/kg bw/d were killed in extremis, showing several clinical signs (lethargy, hunched posture, laboured respiration and rales, swelling of the abdomen, piloerection, diarrhoea, salivation, ptosis, hypothermia, dehydration and lean appearance).

The histopathologic examination of both animals sacrificed revealed minimal/slight erosions in the forestomach, correlating to the irregular surface recorded at necropsy, slight red pulp atrophy of the spleen and slight/moderate lymphoid atrophy of the thymus, correlating to the reduced thymus size recorded at necropsy.

Based on the results of this study, the NOAEL for Methylparaben was considered to be 250 mg/kg bw/d.

There is no dermal repeated dose toxicity study available. The subacute repeated dose oral toxicity study was chosen as the starting point for deriving the DNEL since the study represents the most sensitive NOAEL among the valid studies. 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, Version 2.1, November 2012).

Data on dermal absorption of Methylparaben show that the dermal absorption of Methylparaben lies at 84.7% in human skin (Fasano, 2004).

A QSAR calculation regarding the dermal absorption of Sodium Methylparaben resulted in ca. 80% dermal absorption.

 

The long-term DNEL for the general population for inhalation systemic effects is again based on the subacute repeated dose oral toxicity study in rats performed according to OECD 407 and GLP (Beerens-Heijnen, 2009). This study was chosen as the starting point for deriving the DNEL since there is no inhalation repeated dose toxicity study and due to the fact that this study represented the most sensitive NOAEL among the valid studies. According to the “Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health” (ECHA, Version 2.1, November 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 217.4 mg/m³. The absorption via the inhalative route is considered to be in the same order as via the oral route.

 

The long-term DNEL for the general population for oral systemic effects is directly derived from the subacute repeated dose oral toxicity study in rats performed according to OECD 407 and GLP (Beerens-Heijnen, 2009). Since this study represented the most sensitive NOAEL among the valid studies, it was chosen as the starting point for deriving the DNEL.