Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
24.5 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 Technical Report No. 110
Overall assessment factor (AF):
18
Modified dose descriptor starting point:
NOAEC
Value:
440.8 mg/m³
Explanation for the modification of the dose descriptor starting point:
There is no adequate experimental data on the inhalation route available.
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not applied, because the ventilation rate directly depends on the basal metabolic rate.
AF for other interspecies differences:
1
Justification:
There is no additional evidence for species differences including toxicodynamics. Therefore, no additional factor is used.
AF for intraspecies differences:
3
Justification:
The (ECETOC) default value for the relatively homogenous group "worker" is used.
AF for the quality of the whole database:
1
Justification:
The qualitiy of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach of the DNEL derivation is conservative. No further assessment factors are required.
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:
6.94 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC Technical Report No. 110
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
There is no adequate experimental data on the dermal route available.
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
1
Justification:
Interspecies differences are fully covered by the allometric scaling. There is no additional evidence for species differences including toxicodynamics. Therefore, no additional factor is used.
AF for intraspecies differences:
3
Justification:
The (ECETOC) default value for the relatively homogenous group "worker" is used.
AF for the quality of the whole database:
1
Justification:
The qualitiy of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach of the DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
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:
no hazard identified

Additional information - workers

Acute/short term exposure – systemic effects

According to ECHA Guidance on information requirements and CSR, chapter R8, a DNEL for acute systemic toxicity should be derived only if an acute systemic toxicity hazard leading to C & L has been identified. 4 -acetylmorpholine is not subject to classification and labelling with respect to acute toxicity and consequently the establishment of DNELs for acute/short-term exposure - systemic effects is not required.

Acute/short term and long term exposure – local effects

4 -Acetylmorpholine is not a skin or eye irritant, but it was considered to be sensitising to skin in a Local Lymph Node Assay (LLNA) and therefore subjected to classification as R43 (May cause sensitization by skin contact) according to Directive 67/548/EEC and Cat 1b / H 317 (May cause an allergic skin reaction) according to Regulation 1272/2008/EC. No experimental data are available addressing local effects in the respiratory tract. However, local effects in the respiratory tract are not expected since the substance is not irritating to skin and eye, did not cause any clinical signs in the acute inhalation toxicity study when rats were exposed to a vapor saturated atmosphere and its chemical structure does not indicate an alert for respiratroy sensitisation.

Due to the R43 classification and the EC3 value of 70.3 %, 4 -acetylmorpholine is allocated to the moderate hazard category according to ECHA Guidance on IR/CSR Part E (Nov, 2012). The operation conditions and risk management measures indicated in the respective IUCLID 5 and CSR chapters are appropriate and sufficient for controlling the risks.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

4-acetylmorpholine is not used in consumer products. Thus the derivation of DNELs is not required.