4,4'-thiodiethylene hydrogen -2-octadecenylsuccinate

Toxicological Summary

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):

75

Dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

264.47 mg/m³

Explanation for the modification of the dose descriptor starting point:

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.). Therefore the long-term inhalation DNEL for systemic effects has been extrapolated from the oral NOAEL of 300 mg/kg bw/day obtained in the OECD 407 study.

Based on the toxicokinetic assessment, and a conservative assumption that a low oral absorption is expected, 50% oral absorption has been assumed for the purposes of risk assessment. In the absence of any quantitative data, and as a worst-case assumption, for risk assessment purposes absorption by inhalation of the Substance is assumed to be 100%.

The modified dose descriptor has been calculated as follows:

NOAECcorr = NOAELoral*(1/0.38 m³/kg bw/day)*(ABSoral-rat/ABSinh-human)*(6.7 m³ (8h)/10 m³ (8h)).

NOAECcor = 300 x 1/0.38 x 0.5 [50% oral absorption rat / 100% inhalation absorption human] x 6.7/10

AF for dose response relationship:

1

Justification:

Adequate dosing and study information and based on a NOAEL. No justification for deviating from the standard AF outlined in Ch R:8 based on the database.

AF for differences in duration of exposure:

6

Justification:

Sub-acute to chronic exposure extrapolation.

AF for interspecies differences (allometric scaling):

1

Justification:

No additional allometric scaling as have already considered the differences in the modification of the dose descriptors.

AF for other interspecies differences:

2.5

Justification:

Default value in accordance with ECHA guidance- Chapter R.8

AF for intraspecies differences:

5

Justification:

Default value in accordance with ECHA guidance- Chapter R.8 for workers.

AF for the quality of the whole database:

1

Justification:

Reliable study, good quality database. Default value in accordance with ECHA guidance- Chapter R.8

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:

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):

300

Dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

600 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Based on the toxicokinetic assessment, low oral absorption is expected therefore, 50% oral absorption is assumed for the purposes of risk assessment. The registered Substance is likely to exhibit limited absorption profile following dermal exposure based on the physiochemical characteristics. Therefore, in line with latest EC guidance on dermal absorption (EFSA Guidance, 2012), 25% dermal absorption will be used for risk assessment purposes.

 

The long-term dermal DNEL for systemic effects has been extrapolated from the oral NOAEL of 300 mg/kg bw/day obtained in the OECD 407 study.

The modified dose descriptor is calculated as follows:

NOAECcorr = NOAELoral*(ABSoral-rat/ABSdermal-human)

 

NOAECcorr = 300 x 2 [oral absorption rat 50%/dermal absorption human 25%]

AF for dose response relationship:

1

Justification:

Adequate dosing and study information and based on a NOAEL. No justification for deviating from the standard AF outlined in Ch R:8 based on the database.

AF for differences in duration of exposure:

6

Justification:

Sub-acute to chronic exposure extrapolation.

AF for interspecies differences (allometric scaling):

4

Justification:

DNEL is based on study conducted in rats

AF for other interspecies differences:

2.5

Justification:

Default value in accordance with ECHA guidance- Chapter R.8

AF for intraspecies differences:

5

Justification:

Default value in accordance with ECHA guidance- Chapter R.8 for workers.

AF for the quality of the whole database:

1

Justification:

Reliable study, good quality database. Default value in accordance with ECHA guidance- Chapter R.8

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Explanation for the modification of the dose descriptor starting point:

ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8, Appendix R.8-8 on Acute Toxicity states that a DNEL for acute toxicity is only necessary if "an acute toxicity hazard (leading to C&L) has been identified and there is a potential for high peak exposures". No acute toxicity hazard has been identified for the substance and, thus, no acute hazard classification is proposed. Consequently, in accordance with the ECHA guidance, an acute DN(M)EL is not required.

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - workers

In accordance with ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8, Appendix R.8-8, DNELs for systemic acute effects have not been derived as no acute adverse effects had been observed in any of the available acute oral and dermal toxicity studies. The Substance is classified as a skin sensitiser, Category 1 and eye irritant, Category 2 therefore hazards related to local dermal and eye effects have also been considered. No inhalation data are available, inhalation DNELs for long term systemic exposure have been derived using extrapolation from the repeated dose oral study, however it should be noted that inhalation is not considered a relevant route of exposure given the physical-chemical properties of the material and its use pattern, both of which will mean exposure by the inhalation route will be negligible. A long-term dermal DNEL for systemic effects in workers of 1 mg/kg bw/day is proposed based on the repeated dose oral toxicity study in rats in which a NOAEL of 300 mg/kg bw/day was identified.

General Population - Hazard via inhalation 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

DNEL related information

General Population - Hazard via dermal route

Systemic 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

DNEL related information

Explanation for the modification of the dose descriptor starting point:

No dermal systemic toxicity hazards have been identified. The physico-chemical properties of the substances confirm that there is negligible potential for dermal exposure of the substance. Additionally, the registration Substance is only used in industrial and professional settings, there are no consumer uses and therefore no potential for exposure to the general population. Therefore no DNELs have been calculated and no risk characterization to the general population will be included as part of the chemical safety assessment.

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:

0.5 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):

600

Dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Based on the use of the Substance and the physico-chemical properties of the substances confirm that there is negligible potential for oral exposure of the substance. Additionally, the registration Substance is only used in industrial and professional settings, there are no consumer uses and therefore there is unlikely exposure to the general population via use of any product containing this Substance. Although there is unlikely exposure to man via the environment, a long term oral DNEL has been derived to demonstrate negligible risk.

There is no modification to the dose descriptor starting point there is no data that indicated that there is a difference in oral absorption between rats and humans. Therefore it is considered to be the same.

NOAECcorr = NOAEC (oral absorption in rats = oral absorption in humans)

AF for dose response relationship:

1

Justification:

Default value in accordance with ECHA guidance- Chapter R.8

AF for differences in duration of exposure:

6

Justification:

DNEL is based on 28 days oral study

AF for interspecies differences (allometric scaling):

4

Justification:

DNEL is based on study conducted in rats

AF for other interspecies differences:

2.5

Justification:

Default value in accordance with ECHA guidance- Chapter R.8

AF for intraspecies differences:

10

Justification:

DNEL is calculated forgenerl workers

AF for the quality of the whole database:

1

Justification:

Default value in accordance with ECHA guidance- Chapter R.8

Justification:

n/a

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

The registration Substance is only used in industrial and professional settings, there are no consumer uses. Additionally, based on the use of the Substance and the physico-chemical properties of the Substance there is unlikely exposure to the general population via use of any product containing this Substance. Therefore direct exposure to the general population via the lungs, skin, mouth and/or eyes are not expected therefore no hazard is expected. Although there is unlikely exposure to man via the environment, a long term oral DNEL has been derived to demonstrate negligible risk for completeness.