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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:
3.526 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):
50
Modified dose descriptor starting point:
NOAEC
Value:
176.3 mg/m³
Explanation for the modification of the dose descriptor starting point:
Good quality oral study available. While no inhalation exposure anticipated, it is possible to derive systemic NOAEC for this route using default assumptions and the oral data to extrapolate, as per ECHA guidance ("Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.)
AF for dose response relationship:
1
Justification:
Adequate dosing and study information. No justification for deviating from the standard AF outlined in Ch R:8 based on the database.
AF for differences in duration of exposure:
4
Justification:
4 : in between sub-acute and sub-chronic (54 days) to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling for inhalation route
AF for other interspecies differences:
2.5
Justification:
According to Chapter R.8-Dose [Concentration]-Response Regarding Human Health, an additional assessment factor of 2.5 should be applied for remaining differences between test species and human. In cases where differences are not related to basal metabolic rate, the assessment factor should be modified. In terms of dynamics, one might assume that animals and humans will respond in the same way (p. 33). Based on the physicochemical properties, absorption is believed to be limited to such a degree that metabolic differences are not relevant for remaining differences. for more details see systemic dermal DNELs.
AF for intraspecies differences:
5
Justification:
Standard default value for workers as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for the quality of the whole database:
1
Justification:
Reliable study, good quality database
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
66.8 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Modified dose descriptor starting point:
NOAEC
Value:
835 mg/m³
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling for inhalation route
AF for other interspecies differences:
2.5
Justification:
Standard default value as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for intraspecies differences:
5
Justification:
Standard default value for workers as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
3.12 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Value:
125 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no route-to-route extrapolation needed
AF for dose response relationship:
1
Justification:
No justification for deviating from the standard AF outlined in Ch R:8 based on the database.
AF for differences in duration of exposure:
2
Justification:
It was considered relevant to include information from a 90d dietary feeding study (Haas 2010) on a related category material which demonstrated low systemic toxicity; it is considered that the properties of the registration material will mean that dermal absorption is very low and that bioavailability via the gut will be higher, thus tthis is a conservative application of oral data to enhance the database being used for this derivation. In short, the oral data can be used in a weight of evidence which provides for a more robust and longer term dataset - hence the AF for the duration of exposure can be reduced using this sub-chronic data.
AF for interspecies differences (allometric scaling):
4
Justification:
Standard default value as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for other interspecies differences:
1
Justification:
Justification for use of 1 for Remaining Differences: According to Chapter R.8-Dose [Concentration]-Response Regarding Human Health, an additional assessment factor of 2.5 should be applied for remaining differences between test species and human. In cases where differences are not related to basal metabolic rate, the assessment factor should be modified. In terms of dynamics, one might assume that animals and humans will respond in the same way. Based on the physicochemical properties, absorption is believed to be limited to such a degree that metabolic differences are not relevant for remaining differences. Physicochemical properties have a decisive influence on the penetration of molecules through the skin. EC# 272-234-3 has Log Kow 9.5, these parameters are not favourable for absorption when in contact with skin. This assumption was confirmed by a QSAR assay, which calculated dermal penetration coefficient (Kp) or Pd (the permeability of the skin) by using empirical formulas. This is supported by animal testing in which no effects were observed following acute dermal exposure and minimal effects were observed in subacute testing. These observations suggest poor percutaneous penetration and/or the substance has low inherent systemic toxicity. This adjustment is believed to apply for long term systemic effects via the dermal route for workers and general population, and also for the general population for acute toxicity (workers will wear PPE which will mean that only in consumers would the skin penetration element be a factor).
AF for intraspecies differences:
5
Justification:
Standard default value for workers as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for the quality of the whole database:
1
Justification:
Reliable study used
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
80 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEL
Value:
4 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation needed
AF for interspecies differences (allometric scaling):
4
Justification:
Standard default value as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for other interspecies differences:
2.5
Justification:
Standard default value as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health. Workers will wear PPE which will mean that dermal penetration potential is not a signficant factor in the toxicity, hence normal defaults apply.
AF for intraspecies differences:
5
Justification:
Standard default value for workers as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
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

DNELS: Category approach and mammalian toxicity

The substance being Registered in this particular dossier is one of a series of chemically similar materials each of which is composed of a closely related series of alkylated phenol species. For further details on the Category, see section 13. The data for other members of the category can be used to complete the hazard characterisation for the Registration material where substance-specific data are lacking. For the derivation of DNEL values, the presence/absence of the highly refined base oil is taken into account here; the Registration material does not comprise as a constituent the base oil, but all toxicology testing has been carried out with oil present, hence the end results and DNELs are adjusted to take account of this and to end up with DNELs relevant to the active ingredient of this Registration material.

Summary of Toxicity (Registration material and category members)

The substance is not acutely toxic following oral and dermal routes of exposure. Inhalation exposure is unlikely to occur because the substance only exists in liquid form and it will not be aerosolised in its normal use pattern. The substance is not irritating either to the skin and eye and is not a sensitiser. It is not positive in any genotoxicity testing, and shows no potential for repeat dose toxicity or carcinogenicity based on existing data and expert judgement. There are some effects seen on fertility which are believed to be due to one component/impurity (the material is a UVCB) and hence classification for that one endpoint is performed using the % of that CMR material in the Registration substance (see Section 1 for composition details, Section 2 for Classification details).

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.87 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):
100
Modified dose descriptor starting point:
NOAEC
Value:
86.96 mg/m³
Explanation for the modification of the dose descriptor starting point:
Good quality oral study available. While no inhalation exposure anticipated, it is possible to derive systemic NOAEC for this route using default assumptions and the oral data to extrapolate, as per ECHA guidance ("Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.)
AF for differences in duration of exposure:
4
Justification:
In between subacute and subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling applied via inhalation route
AF for other interspecies differences:
2.5
Justification:
Standard default value after route to route extrapolation as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health."
AF for intraspecies differences:
10
Justification:
Standard default value for the general population as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
66.8 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Modified dose descriptor starting point:
NOAEC
Value:
835 mg/m³
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling via inhalation
AF for other interspecies differences:
2.5
Justification:
Standard default value as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health."
AF for intraspecies differences:
10
Justification:
Standard default value for general population as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health."

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
1.56 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
80
Modified dose descriptor starting point:
NOAEL
Value:
125 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no extrapolation needed
AF for differences in duration of exposure:
2
Justification:
It was considered relevant to include information from a 90d dietary feeding study on a related category material which demonstrated low systemic toxicity; it is considered that the properties of the registration material will mean that dermal absorption is very low and that bioavailability via the gut will be higher, thus tthis is a conservative application of oral data to enhance the database being used for this derivation. In short, the oral data can be used in a weight of evidence which provides for a more robust and longer term dataset - hence the AF for the duration of exposure can be reduced using this sub-chronic data.
AF for interspecies differences (allometric scaling):
4
Justification:
Standard default value as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for other interspecies differences:
1
Justification:
According to Chapter R.8-Dose [Concentration]-Response Regarding Human Health, an additional assessment factor of 2.5 should be applied for remaining differences between test species and human. In cases where differences are not related to basal metabolic rate, the assessment factor should be modified. In terms of dynamics, one might assume that animals and humans will respond in the same way (p. 33). Based on the physicochemical properties, absorption is believed to be limited to such a degree that metabolic differences are not relevant for remaining differences. Physicochemical properties have a decisive influence on the penetration of molecules through the skin. EC# 272-234-3 has Log Kow 9.5, these parameters are not favourable for absorption when in contact with skin. This assumption was confirmed by a QSAR assay, which calculated dermal penetration coefficient (Kp) or Pd (the permeability of the skin) by using empirical formulas. This is supported by animal testing in which no effects were observed following acute dermal exposure and minimal effects were observed in subacute testing. These observations suggest poor percutaneous penetration and/or the substance has low inherent systemic toxicity. This adjustment is believed to apply for long term systemic effects via the dermal route for workers and general population, and also for the general population for acute dermal toxicity (where no PPE are worn).
AF for intraspecies differences:
10
Justification:
Standard default value for the general population as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for the quality of the whole database:
1
Justification:
adequate database and study
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
40 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
4 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No extrapolation required
AF for interspecies differences (allometric scaling):
4
Justification:
Standard default value as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for other interspecies differences:
2.5
Justification:
Standard default value for the general population as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for intraspecies differences:
10
Justification:
Standard default value for the general population as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
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:
0.25 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):
400
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
AF for differences in duration of exposure:
4
Justification:
from inbetween subacute and subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Standard default value as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for other interspecies differences:
2.5
Justification:
Standard default value as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for intraspecies differences:
10
Justification:
Standard default value for the general population as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for the quality of the whole database:
1
Justification:
Reliable study
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
2 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no extrapolation required
AF for interspecies differences (allometric scaling):
4
Justification:
Standard default value as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for other interspecies differences:
2.5
Justification:
Standard default value as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for intraspecies differences:
10
Justification:
Standard default value for general population as indicated by the ECHA guidance document “Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for the quality of the whole database:
1
Justification:
Good quality study and supporting information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

see above Discussion section (workers) for toxicity summary and category rationale.

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