Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
36
Dose descriptor starting point:
NOAEL
Value:
92.5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
163 mg/m³
Explanation for the modification of the dose descriptor starting point:
The oral rat NOAEL of 92.5 mg/kg bw/day is first converted into a corrected inhalatory NOAEC (in accordance with “Guidance on information requirements and chemical safety assessment, Chapter R.8”): Corrected inhalatory NOAEC = oral NOAEL*(1/0.38 m3/kg/d)*(Absorption oral (rat)/Absorption inhalation (human))*(6.7 m3/10 m3) = 92.5*2.63*0.67 = 163 mg/m3. The ECETOC safety factors have been applied on this NOAEC. Factors applied: interspecies extrapolation: Not applicable, intraspecies extrapolation 3, exposure duration 6, dose-response 1 and quality of the whole database 2 = 36. No correction for the route-to-route extrapolation.
AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure worker
AF for interspecies differences (allometric scaling):
1
Justification:
No correction for caloric demand for inhalation; is included in dose descriptor starting point
AF for other interspecies differences:
1
Justification:
No remaining differences
AF for intraspecies differences:
3
Justification:
Difference in sensitivity among workers
AF for the quality of the whole database:
2
Justification:
Conclusion derived via read across
AF for remaining uncertainties:
1
Justification:
No remaining differences
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:
6.42 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
144
Dose descriptor starting point:
NOAEL
Value:
92.5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
925 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No evidence is available that route-to-route extrapolation is not possible. The ratio between the oral absorption (100%) and dermal absorption (10%) is 10.
AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure worker
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand from rat to human
AF for other interspecies differences:
1
Justification:
No remaining differences
AF for intraspecies differences:
3
Justification:
Difference in sensitivity among workers
AF for the quality of the whole database:
2
Justification:
Value derived based on read across
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.34 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
60
Dose descriptor starting point:
NOAEL
Value:
92.5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
80.4 mg/m³
Explanation for the modification of the dose descriptor starting point:
No evidence is available that route-to-route extrapolation is not possible. The DNEL here derived is the DNEL that is considered relevant to use for the exposure route via the (local) environment; a DNEL applicable for 24 hours exposure per day. In the CSR an additional listing has been added for the DNEL that is considered relevant to use for the exposure route via the use of consumer products; a DNEL applicable for 1 hour exposure per day. The oral rat NOAEL of 92.5 mg/kg bw/day is first converted into a corrected inhalatory NOAEC (in accordance with “Guidance on information requirements and chemical safety assessment, Chapter R.8”): Corrected inhalatory NOAEC = oral NOAEL*(1/1.15 m3/kg/d)*(Absorption oral (rat)/Absorption inhalation (human)) = 80.4 mg/m3 [for 24h exposure/day].
AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
6
Justification:
Extrapolation from sub-acute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
No correction for caloric demand for inhalation; is included in dose descriptor starting point
AF for other interspecies differences:
1
Justification:
No remaining differences
AF for intraspecies differences:
5
Justification:
Difference in sensitivity within general population
AF for the quality of the whole database:
2
Justification:
Vaue derived based on read across
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
DNEL (Derived No Effect Level)
Value:
3.85 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
240
Dose descriptor starting point:
NOAEL
Value:
92.5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
925 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No evidence is available that route-to-route extrapolation is not possible. The ratio between the oral absorption (100%) and dermal absorption (10%) is 10.
AF for dose response relationship:
1
Justification:
Value is NOAEL.
AF for differences in duration of exposure:
6
Justification:
Extrapolation from sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand from rat to human
AF for other interspecies differences:
1
Justification:
No remaining differences
AF for intraspecies differences:
5
Justification:
Difference in sensitivity within general population
AF for the quality of the whole database:
2
Justification:
Value derived via read across
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
DNEL (Derived No Effect Level)
Value:
0.39 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
240
Dose descriptor starting point:
NOAEL
Value:
92.5 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
6
Justification:
Extrapolation from sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand from rat to human
AF for other interspecies differences:
1
Justification:
No remaining differences
AF for intraspecies differences:
5
Justification:
Difference in sensitivity within general population
AF for the quality of the whole database:
2
Justification:
Value derived via read across
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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

Source chemical

EC number

931-291-0

CAS number

Not available

IUPAC name

Reaction products of 1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-(C7-C17 odd-numbered, C17-unsatd. alkyl) derivs. and sodium hydroxide and chloroacetic acid

 Common name  Amphoacetates C8-18

Based on their structural similarity, similar composition, physico-chemical and toxicological properties, the substance and the source chemical are considered part of the same chemical category. In the report “Category Approach for REACH Registration of ALKYLAMPHOACETATES” the category is documented (see IUCLID Chapter 13).

Relevant starting points, considering the available data

Considering the available data, the following starting points on the source chemical are considered relevant.

 

Endpoint

Result

Sub-acute oral repeated dose toxicity study (rat)

NOAEL: 92.5 mg/kg bw/day

 

Basis: a dose-dependent effect on liver weight. At the LOAEL, the liver weights were > 10% higher compared to the control. The presence of such an increased liver weight needs to be considered as a potential serious effect after prolonged exposure and should not be considered as a physiological adaptive response without further thought.

Reproductive toxicity

No reproduction/ developmental study conducted, but histological examinations were performed on the reproductive organs of the 10 male and 10 female rats in the highest dose group in the 28-day study, showing no effects on these organs.

Route-to-route extrapolation

For the derivation of the DNELs:

Long-term – dermal, systemic effects

Long-term – inhalation, systemic effects

Route-to-route extrapolation has been performed. In absence of relevant data, only differences between the different routes as determined by the assumed percentages of absorption into the systemic circulation could be accounted for. A certified toxicologist assessed the toxicokinetic behaviour of the substance (in accordance with Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance):

Absorption oral (rat) = Absorption oral (human) = 100%

Absorption dermal (human) = 10%

Absorption inhalation (human) = 100%

Assessment factors

The assessment factors (AFs) that are applied to obtain the endpoint-specific DNELs for the relevant exposure pattern are based on the ECETOC report “Guidance on assessment factors to derive DNELs”. In the following overview the relevant AFs are shown: 

Aspect

Assessment Factor (AF)

Interspecies extrapolation; rat to human, for the dermal and oral route (inhalation route: not applicable)

4

(to correct for metabolic rate)

 

Intraspecies extrapolation; worker

3

Intraspecies extrapolation; general population

5

Exposure duration; sub-acute to chronic

6

(to correct for difference in study duration and actual exposure situation)

Dose-response

1

(default, as the starting point is a NOAEL)

Quality of whole database

2

(to compensate for the lack of a reproduction/developmental study)

As the substance considered is the main constituent of the source chemical, no additional factor is deemed necessary.

Leading to the following Assessment Factors: 

 

Assessment Factor

DNEL

Worker

General population

Long-term – dermal, systemic effects

144

240

Long-term – inhalation, systemic effects

36

60

Long-term – oral,

systemic effects

Not relevant

240