Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
23.3 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
Modified dose descriptor starting point:
NOAEC
Value:
1 750 mg/m³
Explanation for the modification of the dose descriptor starting point:
for route-to-route extrapolation the following factors were applied to come to a human NOAEC: interspecies 4, bw 70 kg, 10 m3 inhalation volume/working day
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
default factor for extrapolation sub-acute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
included in the derivation of the NOAEC to account for differences in metabolic rate
AF for other interspecies differences:
2.5
Justification:
default factor
AF for intraspecies differences:
5
Justification:
default factor worker variability
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.33 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
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
based on similar very low absorption via the oral and the dermal route
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
default factor for extrapolation from sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default factor for differences in metabolic rate rat versus human
AF for other interspecies differences:
2.5
Justification:
default factor
AF for intraspecies differences:
5
Justification:
default factor for worker variability
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14.7 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
90
Dose descriptor:
other: EC3 = 5.3%
AF for dose response relationship:
3
Justification:
LOAEL to NOAEL
AF for other interspecies differences:
10
Justification:
standard factor according to the guidance
AF for remaining uncertainties:
3
Justification:
matrix effects
Acute/short term exposure
Hazard assessment conclusion:
medium 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

No adverse effects up to the highest dose tested have been found in any available study on repeated-dose toxicity or toxicity on reproduction/developmental toxicity used for assessment to Reaction products of C16 saturated and C18 unsaturated fatty acids and fatty acid glycerides with by-products from 2-aminoethanol and ammonia reaction. As the NOAEL is >1000 mg/kg bw/day, the statement “no hazard identified” is applicable. Due to the substance's low volatility and its use pattern the inhalation route is considered irrelevant as exposure route except for the use in oil and gas industry where the substance may be applied to high temperature surfaces. Therefore next to a DNEL for dermal exposure, a DNEL for inhalation exposure will be derived. In risk assessment the inhalation DNEL will only be taken into account for the drilling fluid use phase.

In addition, Reaction products of C16 saturated and C18 unsaturated fatty acids and fatty acid glycerides with by-products from 2-aminoethanol and ammonia reactionwas found to be sensitizing to skin as it showed positive results in a local lymph node assay perfumed according to OECD 429.

Therefore the DNEL for dermal long-term local effects is derived in addition to the DNEL for dermal systemic effects to cover the overall toxicological effects of sensitizing, because exposure via the dermal route cannot be excluded.

Acute toxicity

ECHA Guidance R.8 (Chapter R.8.1.2.5) indicates that DNELs for acute toxicity are not required if no acute toxicity hazard leading to classification has been identified. The substanceReaction products of C16 saturated and C18 unsaturated fatty acids and fatty acid glycerides with by-products from 2-aminoethanol and ammonia reactionwas not found to be acutely harmful while a low vapour pressure precludes inhalation exposure indicating a low of concern for this route of exposure. No DNELs for acute toxicity are therefore necessary.

Repeated dose toxicity

No adverse effects up to the highest dose tested have been found in the available study on repeated-dose toxicity or toxicity on reproduction/developmental toxicity used for assessment to Reaction products of C16 saturated and C18 unsaturated fatty acids and fatty acid glycerides with by-products from 2-aminoethanol and ammonia reaction. As the NOAEL is >1000 mg/kg bw/day, the statement “no hazard identified” is applicable.

However, Reaction products of C16 saturated and C18 unsaturated fatty acids and fatty acid glycerides with by-products from 2-aminoethanol and ammonia reaction was found to be sensitizing to skin as it showed positive results in a local lymph node assay perfumed according to OECD 429.

Inhalation long-term

In view of the substance's low volatility and extreme viscosity, exposure via the inhalation route seems unlikely. However, for part of the life-cycle exposure to vapour cannot be excluded during use of the substance at higher temperatures. Therefore a DNEL for the inhalation route was derived based on route-to-route extrapolation from the oral NOAEL of 1000 mg/kg bw. Based on the toxicokinetic profile the inhalation absorption can be regarded as low (10%), while oral absorption was estimated to be very low (10% absorption as worst case). This leads to a human NOAECinhalation of 1750 mg/m3 (route-to-route extrapolation (1000/4) *(70/10)). Additional assessment factors (AF) are applied to derive the DNEL. The AFs were based on the procedures described ECHA Guidance R.8.

Dermal long-term

The NOAEL for oral repeated dose toxicity of was found to be 1000 mg/kg bw/d. and used for the purposes of DNEL derivation for the dermal route.

Based on the toxicokinetic profile the dermal absorption can be regarded as low (10%), while oral absorption was estimated to be very low (10% absorption as a worst case). This leads to a NOAELdermal of 1000 mg/kg bw (route-to-route extrapolation). Additional assessment factors (AF) are applied to derive the DNEL. The AFs were based on the procedures described ECHA Guidance R.8

Long-term DNEL Assessment Factors (Dermal)

Assessment Factor

Worker

Differences in metabolic rate per b. w. (allometric scaling)

2.5

Interspecies remaining differences (toxicodynamic and toxicokinetic)

4

Intraspecies differences

5

Duration extrapolation

(sub-acute/sub-chronic/chronic)

6 (subacute)

Issues related to dose-response

1

Quality of whole database

1

Overall AF

300

Sensitisation

The sensitisation potential of Reaction products of C16 saturated and C18 unsaturated fatty acids and fatty acid glycerides with by-products from 2-aminoethanol and ammonia reaction

was found to be sensitizing to skin as it showed positive results in a local lymph node assay perfumed according to OECD 429.

ECHA Guidance R.8, Appendix R.8-10, (ECHA, 2010) states that skin sensitisation is generally regarded as a threshold effect and thus it may be very difficult to derive a threshold and to set a DNEL. The general approach for sensitizers therefore involves a qualitative approach where a DNEL is used to judge any remaining/residual risks after the implementation of appropriate risk management measures (RMM) and occupational controls (OC).

The extent of the RMM and OC required is dependent on the intrinsic sensitising potency of the substance.

For results obtained using the LLNA, intrinsic sensitising potency is based on the EC3 and defined (ECHA (2010), Appendix R.8-10) as follows:

Category

EC3 (%)

Extreme

<0.2%

Strong

>0.2 - <2

Moderate

>2

Based on the derived EC3 value of 5.3% the substance Reaction products of C16 saturated and C18 unsaturated fatty acids and fatty acid glycerides with by-products from 2-aminoethanol and ammonia reaction is regarded to have moderate potential to cause skin sensitisation.

Derivation of a DNEL for sensitisation

ECHA Guidance R.8, Appendix R.8-10 (ECHA, 2010), indicates that the EC3 concentration from a LLNA test can be taken as a LOAEL for the induction of skin sensitisation (ECHA, 2010) after conversion into an equivalent dose per unit area of skin (ug/cm2). Assuming (i) a dose volume of 25 μl (according to the standard LLNA protocol); (ii) an estimated treatment area of 1 cm² for the mouse ear; and (iii) an assumed density of 1, the conversion is performed as follows: EC3[%]*250 [ug/cm²/% ] = EC3[ug/cm²] The equivalent EC3 [ug/cm²] is therefore: 5.3%*250 = 1325 ug/cm²

The EC3 of 1325 ug/cm² is used to assess the magnitude of any remaining/residual risks after the use of RMMs and OCs recommended in the Qualitative Risk Assessment.

Additional assessment factors (AF) are applied to derive the DNEL. The AFs were based on the procedures described ECHA Guidance R.8.

Sensitisation DNEL Assessment Factors

Assessment Factor

Value

Matrix effects

3

Interspecies differences

10

Issues related to dose-response

3

Overall AF

90

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

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:
low hazard (no threshold derived)

Additional information - General Population

No consumer exposure is expected