N,N',N'',N'''-tetrakis(4,6-bis(butyl-(N-methyl-2,2,6,6-tetramethylpiperidin-4-yl)amino)triazin-2-yl)-4,7-diazadecane-1,10-diamine

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.14 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Guidelines

Overall assessment factor (AF):

15

Modified dose descriptor starting point:

NOAEC

Value:

17.1 mg/m³

Explanation for the modification of the dose descriptor starting point:

Only oral repeated toxicity studies are available for HALS 11.

AF for dose response relationship:

1

Justification:

The starting point for the DNEL calculation was a NOAEL, therefore the default assessment factor, as a standard procedure, is 1.

AF for differences in duration of exposure:

2

Justification:

An assessment factor of 2 has been applied in order to consider the differences in the duration of the exposure between the oral 90-day repeated toxicity study and a chronic exposure.

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling does not apply in case of oral-inhalation route to route extrapolation.

AF for other interspecies differences:

2.5

Justification:

No substance-specific data are available, so a default assessment factor of 2.5 has been applied for other interspecies differences.

AF for intraspecies differences:

3

Justification:

An assessment factor of 3 has been chosen to cover workers, as this population does not cover the very young, the very old, and the very ill.

AF for the quality of the whole database:

1

Justification:

Data regarding HALS 11 are complete and of good quality, indeed, where no specific studies regarding the substance are available, data regarding the similar substance Uvasorb HA88 cover all the data gaps.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties are foreseen. Assessment factors have been set according to ECHA and ECETOC guidelines (ECHA, 2010. Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterization of dose (concentration)-response for human health; ECETOC, 2010. Guidance on Assessment Factors to Derive a DNEL. Technical Report No. 110).

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

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.16 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidelines and ECETOC Guidelines

Overall assessment factor (AF):

60

Modified dose descriptor starting point:

NOAEL

Value:

9.7 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Only oral repeated toxicity studies are available for HALS 11.

AF for dose response relationship:

1

Justification:

The starting point for the DNEL calculation was a NOAEL, therefore the default assessment factor, as a standard procedure, is 1.

AF for differences in duration of exposure:

2

Justification:

An assessment factor of 2 has been applied in order to consider the differences in the duration of the exposure between the oral 90-day repeated toxicity study and a chronic exposure.

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling is not appropriate, because HALS 11 is not renally excreted (n rats only 0.28 – 0.6% of the administered dose).

AF for other interspecies differences:

10

Justification:

The 96-99% of the substance is excreted via feces, mainly because, considering its bio-physico-chemical characteristics (molecular weight, solubility, biodegradation), it will be poorly absorbed by skin (European Commission, Health and Consumer Protection Directorate, 2004. Guidance Document on Dermal Absorption. Sanco/222/2000 rev.7) and by the gastrointestinal tract (Milman and Weisburger, 1994. Handbook of Carcinogen Testing. William Andrew. 856 pages). The absorbed amount, moreover, will probably be excreted via bile, on the basis of the observations in liver in the 90-day study (mottled liver and increase of organ weight). Differences in biliary excretion between species (i.e. rats and humans) depend also by liver weight and transport proteins on hepatocytes. Studies demonstrated that this way of excretion is much more efficient in rats than in humans, hence humans should be considered, in the absence of specific data, more sensitive than laboratory animals (Yurong Lai, 2009. Identification of interspecies difference in hepatobiliary transporters to improve extrapolation of human biliary secretion. Expert Opin.Drug Metab. Toxicol., 5(10), 1175-1187). Considering available data and the worst case assumption, an A.F. of 10 has been considered conservative enough to protect human population.

AF for intraspecies differences:

3

Justification:

An assessment factor of 3 has been chosen to cover workers, as this population does not cover the very young, the very old, and the very ill.

AF for the quality of the whole database:

1

Justification:

Data regarding HALS 11 are complete and of good quality, indeed, where no specific studies regarding the substance are available, data regarding the similar substance Uvasorb HA88 cover all the data gaps.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties are foreseen. Assessment factors have been set according to ECHA and ECETOC guidelines (ECHA, 2010. Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterization of dose (concentration)-response for human health; ECETOC, 2010. Guidance on Assessment Factors to Derive a DNEL. Technical Report No. 110).

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

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

Two DNEL values were derived for systemic effects after long-term exposure in workers: a dermal DNEL and an inhalation DNEL. Both values were obtained from the NOAEL of the 90-day repeated toxicity study: 9.7 mg/kg bw/day. As this NOAEL was observed in an oral study, a route-to-route extrapolation was needed in order to obtain the correct starting points for the derivation of the DNELs. The correct starting points were than divided by an overall assessment factor, which was a result of various consideration on uncertainties in inter-and intra-species variations, and on differences in the duration of exposure between test animals and humans. Moreover also the whole quality of the database was considered.

For acute local effects no DNEL has be derived, as the substance is considered of no concern for this endpoint and because the long-term DNEL are considered protective enough to prevent also acute exposure effects.

A qualitative approach has been chosen for the sensitization endpoint, as the substance is classified as a strong skin sensitizer.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.34 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidelines and ECETOC Guidelines

Overall assessment factor (AF):

25

Modified dose descriptor starting point:

NOAEC

Value:

8.43 mg/m³

Explanation for the modification of the dose descriptor starting point:

Only an oral 90-day repeated toxicity study is available for HALS 11.

AF for dose response relationship:

1

Justification:

The starting point for the DNEL calculation was a NOAEL, therefore the default assessment factor, as a standard procedure, is 1.

AF for differences in duration of exposure:

2

Justification:

An assessment factor of 2 has been applied in order to consider the differences in the duration of the exposure between the oral 90-day repeated toxicity study and a chronic exposure.

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling does not apply in case of oral-inhalation route to route extrapolation.

AF for other interspecies differences:

2.5

Justification:

No substance-specific data are available, so a default assessment factor of 2.5 has been applied for other interspecies differences.

AF for intraspecies differences:

5

Justification:

An assessment factor of 5 has been chosen to cover general population, as this population includes also the very young, the very old, and the very ill.

AF for the quality of the whole database:

1

Justification:

Data regarding HALS 11 are complete and of good quality, indeed, where no specific studies regarding the substance are available, data regarding the similar substance Uvasorb HA88 cover all the data gaps.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties are foreseen. Assessment factors have been set according to ECHA and ECETOC guidelines (ECHA, 2010. Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterization of dose (concentration)-response for human health; ECETOC, 2010. Guidance on Assessment Factors to Derive a DNEL. Technical Report No. 110).

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

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

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:

no hazard identified

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

An inhalation DNEL value was derived for systemic effects after long-term exposure in general population. The value was obtained from the NOAEL of the 90-day repeated toxicity study: 9.7 mg/kg bw/day. As this NOAEL was observed in an oral study, a route-to-route extrapolation was needed in order to obtain the correct starting point for the derivation of the DNEL. The correct starting point was than divided by an overall assessment factor, which was a result of various consideration on uncertainties in inter-and intra-species variations, and on differences in the duration of exposure between test animals and humans. Moreover also the whole quality of the database was considered.No assessment for the other end-points like acute exposure effects or sensitizing effects was deemed necessary for general population, as the exposure to substance is not likely to occur. Further details on exposure patterns are available in the relative section of the report.