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EC number: 203-815-1 | CAS number: 110-91-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
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Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation 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:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 36 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
- DNEL derivation method:
- other: German occupational exposure limit (MAK)
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 72 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
- DNEL derivation method:
- other: German occupational exposure limit (MAK) - short term
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.84 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):
- 100
- Dose descriptor starting point:
- NOAEL
- Value:
- 60 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 84 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Please refer to " Additional information".
- 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:
- 2
- Justification:
- The default extrapolation factor for exposure duration is used: subchronic (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:
- 2.5
- Justification:
- The default value for other interspecies differences is used.
- AF for intraspecies differences:
- 5
- Justification:
- The default value for the relatively homogenous group "worker" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The quality of the whole data base is considered to be sufficient and uncritical.
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - workers
General
DNEL derivation for the test item is performed under consideration of the recommendations of ECHA, Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose-response for human health (Version: 2.1, November 2012).
Long term, systemic DNEL – exposure via inhalation (workers)
In a two-year chronic inhalation study similar to OECD TG 452 (Huntsman, 1983), male and female rats that inhaled Morpholine at concentrations of 0, 10, 50, or 150 ppm (0, 36, 181 or 543 mg/m3), 6 hours/day, 5 days/week for 104 weeks showed normal growth, survival, hematology, and clinical chemistries. The incidence of neoplasia in morpholine-exposed rats was not altered significantly compared to the concurrent controls. Rats exposed at the 150 ppm concentration developed focal erosion and focal squamous metaplasia of the epithelium of the anterior nasal cavity. Obvious evidence of chronic nasal irritation and inflammation with neutrophilic infiltration was documented in these same tissues. Ocular injury, including retinal degeneration, corneal irritation, uveitis, and corneal damage, were demonstrated only in rats exposed at 150 ppm. The distribution of ocular changes recorded in the groups exposed at 10 or 50 ppm Morpholine was similar to that seen in the controls. Chronic exposure of rats to morpholine for 2 years at concentrations of 150 ppm or less revealed no carcinogenic potential or chronic systemic toxicity. Consistent with its known irritating properties, Morpholine produced only local irritation, which was limited almost exclusively to high-dose animals. Based on this study, a systemic NOEC of 543 mg/m3(150 ppm) and a local NOEC of 36 mg/m3 for repeated dose toxicity is derived. Local effects are considered to be more critical and the derived DNEL for local effects by inhalation exposure is considered to be sufficient to protect against possible systemic effects.
Acute, systemic DNEL- exposure via inhalation (workers)
The substance is harmonized classified for acute inhalation toxicity Cat.4 (H332) according to Annex VI of Regulation (EC) No 1272/2008. Local effects after long term exposure are considered more relevant and the MAK value ensures a sufficient level of protection for the systemic effects following acute/short term inhalative exposure. Nevertheless, a qualitative approach has to be implemented to deal with the corrosive potential of the substance. Therefore, a medium hazard was identified.
Long term, local DNEL- exposure via inhalation (workers)
The health-based German occupational exposure limit (MAK-value, implemented in TRGS 900 01/2006) of 36 mg/m3 is used as worker-DNEL (inhalation, long-term/local). An Occupational Exposure Limit (OEL) of 36 mg/m3(Long-term Exposure Value, eight-hours time weighted average) was also established from the Scientific Committee for Occupational Exposure Limits (SCOEL).
Short term, local DNEL- exposure via inhalation (workers)
The substance is irritating to the upper respiratory tract and is harmonized classified for acute inhalation toxicity Cat.4 (H332) according to Annex VI of Regulation (EC) No 1272/2008. The health-based short-term German occupational exposure limit of 72 mg/m3 (MAK-value, implemented in TRGS 900 01/2006) is used as worker-DNEL(inhalation, acute/short-term/local). The short-term value concentration results from the product of the occupational exposure limit value (36 mg/m3) and the excursion factor (2). This is in line with the ECHA guidance on information requirements and chemical safety assessment, Chapter R.8 (2012). An Occupational Exposure Limit (OEL) of 72 mg/m3(Short-term Exposure Value, 15 minutes) was also established from the Scientific Committee for Occupational Exposure Limits (SCOEL).
2. Dermal
Long term, systemic DNEL- dermal exposure (workers)
The worker-DNEL for systemic effects associated with dermal long-term exposure is derived by means of route-to-route extrapolation based on the NOAEL of 60 mg/kg bw/day from the extended-one generation reproduction toxicity study (BASF SE, 2020). In this study Morpholine hydrochloride was administered to groups of 25 male and 25 female healthy young Wistar rats for test as an aqueous preparation by stomach tube at different dosages (0, 60, 200 and 600 mg/kg body weight/day [mg/kg bw/d]). F0 animals were treated at least for 10 weeks prior to mating to produce a litter (F1 generation). Pups of the F1 litter were selected (F1 rearing animals) and assigned to 2 different cohorts (1A and 1B) which were subjected to specific post-weaning examinations. Under the conditions of the extended one-generation reproduction toxicity study the NOAEL for general, systemic toxicity is 200 mg/kg bw/day, based on clinical pathological findings indicating marginal anemia, changed protein and lipid metabolism as well as metabolic acidosis at the LOAEL of 600 mg/kg bw/day. The NOAEL for fertility and reproductive performance for the parental male rats is 60 mg/kg bw/day, based on increased incidence of males showing tubular degeneration in the testis and subsequent alteration of sperm at 200 mg/kg bw/day and above. The NOAEL for fertility and reproductive performance for the parental female rats is 600 mg/kg bw/day, the highest tested dose. Neither the ability of the affected males to reproduce nor the integrity of female sexual organs was influenced by the test compound at any dose. The NOAEL for developmental toxicity in the F1 progeny is 600 mg/kg bw/day, the highest tested dose.
Step 1: PoD: NOAEL = 60 mg/kg bw/day
Step 2: Modification into a correct starting point:
Oral absorption of the rat/ dermal absorption of humans (ABS oral-rat / ABS derm-human): 100%/100%
Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker (=1.4)
Corrected NOAEL (dermal) for workers:
= 60 mg/kg bw/day x (100/100)x 1.4
= 84 mg/kg bw/day
Step 3: Overall AF= 100
Exposure duration AF: 2 for sub-chronic to chronic (default)
Interspecies AF, allometric scaling (rat to human): 4 (default)
Interspecies AF, remaining differences: 2.5 (default)
Intraspecies AF (worker): 5 (default)
Whole database AF: 1
The repeated dose oral toxicity study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
In conclusion, long term systemic dermal DNEL, workers = 0.84 mg/kg bw/day
Acute, systemic DNEL- dermal exposure (workers)
The substance is classified for acute dermal toxicity Cat.4 (H312) according to Regulation (EC) No 1272/2008 (CLP Regulation). Furthermore, morpholine is harmonized classified as corrosive to skin and eyes (Cat. 1B, H314) according to Annex VI of Regulation (EC) No 1272/2008. The available data do not allow a quantitative approach. According to the REACH guidance on information requirements and chemical safety assessment, Part E: Risk Characterisation, a qualitative risk characterisation should be performed for this endpoint. In order to guarantee ‘adequately control of risks’, it is necessary to stipulate risk management measures that prevent skin and eye corrosion.
Long term & acute, local DNEL- dermal exposure (workers)
According to the REACH guidance on information requirements and chemical safety assessment, Part E: Risk Characterization, a qualitative risk characterization should be performed for this endpoint. This qualitative approach has to be implemented to deal with the eye as well as skin corrosive properties of the substance. As a result, a high hazard is derived. In order to guarantee "adequately control of risks", it is necessary to stipulate risk management measures that prevent skin, eye and mucous membrane exposure.
Hazard to the eye-local effects (worker)
Morpholine is harmonized classified as corrosive to skin and eyes (Cat. 1B, H314) according to Annex VI of Regulation (EC) No 1272/2008. The available data do not allow a quantitative approach. According to the REACH guidance on information requirements and chemical safety assessment, Part E: Risk Characterisation, a qualitative risk characterisation should be performed for this endpoint. In order to guarantee ‘adequately control of risks’, it is necessary to stipulate risk management measures that prevent skin and eye corrosion.
References
ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8:
Characterisation of dose [concentration]-response for human health. Version 2.1, November 2012
ECHA (2016). Guidance on information requirements and chemical safety assessment.Part E: Risk Characterisation, Version 3.0, May 2016
MAK-Liste, Deutsche Forschungsgemeinschaft, Ständige Senatskommission zur Prüfung gesundheitlicher Arbeitsstoffe, Online-Ausgabe, 2018
SCOEL, Morpholine, Commission Directive 2006/15/EC of 7th February 2006 (second list of indicative occupational exposure limit values)
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:
- DNEL (Derived No Effect Level)
- Value:
- 0.3 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):
- 200
- Dose descriptor starting point:
- NOAEL
- Value:
- 60 mg/kg bw/day
- 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:
- 2
- Justification:
- The default extrapolation factor for exposure duration is used: subchronic (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:
- 2.5
- Justification:
- The default value for interspecies differences is used.
- AF for intraspecies differences:
- 10
- Justification:
- The default value for the more heterogenous group "general population" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The repeated dose oral toxicity study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
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 for the eyes
Local effects
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Additional information - General Population
Human via the environment
Although there are no consumer uses for morpholine (CAS 110-91-8), the oral systemic long-term DNEL for the general population is necessary for the assessment of indirect exposure of humans via the environment (ECHA GD R.16, 2016).
Long term, systemic DNEL- exposure by oral route (human via environment)
The NOAEL of 60 mg/kg bw/day from the extended-one generation reproduction toxicity study performed with rats was used as POD (BASF SE, 2020).
Step 1: PoD: NOAEL = 60 mg/kg bw/day
Step 2: Overall AF= 200
Exposure duration AF: 2 for sub-chronic to chronic (default)
Interspecies AF, allometric scaling (rat to human): 4 (default)
Interspecies AF, remaining differences: 2.5 (default)
Intraspecies AF (general population): 10 (default)
Dose-response relationship AF: 1
In conclusion, long term systemic oral DNEL, human via environment= 0.3 mg/kg bw/day
References
ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8:Characterisation of dose [concentration]-response for human health. Version 2.1, November 2012
ECHA (2016) Guidance on information requirements and Chemical Safety Assessment, Chapter R.16: Environmental exposure assessment, Version 3.0, Feb 2016
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