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The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
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EC number: 203-702-7 | CAS number: 109-76-2
- 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:
- DNEL (Derived No Effect Level)
- Value:
- 3 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 60
- Value:
- 177.6 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- No route to route extrapolation is necessary since a repeated dose inhalative toxicity study (6 weeks) is 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: subchronic (starting point) to chronic (end point)
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Allometric scaling is not applicable for inhalation
- 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:
- 5
- Justification:
- Intraspecies differences of worker are considered to be fully covered by the selected factor.
- 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:
- 2
- Justification:
- An additional factor of 2 was used to cover every uncertainty of the read across approach. Therefore, the DNEL derivation is most conservative.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- By inhalation
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (respiratory tract)
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (respiratory tract)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.26 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Dermal
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 40
- Value:
- 10.2 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- No route to route extrapolation is necessary since a repeated dose dermal toxicity study is available (in mice; complete life span).
- 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:
- 1
- Justification:
- No default extrapolation factor for exposure duration is required as the DNEL derivation is based on a long-term dermal chronic study
- 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:
- There is no additional evidence for species differences including toxicodynamics. Therefore, no additional factor is used.
- AF for intraspecies differences:
- 5
- Justification:
- Intraspecies differences of worker are considered to be fully covered by the selected factor.
- 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:
- 2
- Justification:
- An additional factor of 2 was used to cover every uncertainty of the read across approach. Therefore, the DNEL derivation is most conservative.
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- high hazard (no threshold derived)
Additional information - workers
Trimethylenediamine is of high acute toxicity by the dermal route of exposure (LD50 = 178 mg/kg bw). After oral uptake or inhalation the toxicity is less pronounced: LD50 = 311 mg/kg bw and no mortality after inahalation of a saturated vapour. Trimethylenediamine has been reported to be corrosive to the skin and eyes and is considered to be a skin and respiratory sensitizer, since the structurally very similyr ethylenediamine is reported to be a respiratory sensitizer (difference: chain length / one CH2-group).
The available valid in vitro (Ames, HPRT, CA) genetic toxicity data with trimethylenediamine do not suggest a mutagenic potential. Moreover, the read across substance ethylenediamine was not carcinogenic when given as the corresponding hydrochloride to rats in their diets for two years up to doses of 350 mg/kg bw/day (corresponding to 195 mg/kg bw trimethylenediamine).
In a two-generation reproductive toxicity study, rats were dosed via feed to 0, 50, 150, and 500 mg/kg/day ethylenediamine hydrochloride. The NOAEL for reproductive effects was 500 mg/kg/day.
No developmental toxicity was observed when pregnant rats or rabbits were dosed with ethylenediamine hydrochloride up to 1000 mg/kg/day (for more detailed toxicodynamic overviews see also chapter toxicokinetics, metabolism, and distribution).
For worker exposure, respiratory sensitization has been identified as the key toxicological concern for trimethylenediamine. Human evidence has implicated trimethylenediamine as a dermal and respiratory sensitizer capable of causing early and late asthma. Based on the available data without reliable quantitative dose-response information, it is not possible to derive long or short term DNELs for the most sensitive endpoint respiratory sensitization with respect to a threshold for induction or elicitation. Therefore, a qualitative assessment for local respiratory sensitization has been carried out specifically for the production and uses of trimethylenediamine. In general, exposure should be minimized as low as reasonably achievable. Nevertheless, worker DNELs for other systemic effects were also derived.
Long-term exposure – systemic effects
Inhalation exposure:
In order to derive the worker DNEL (long-term inhalation exposure), the NOAEC assessed in a read across approach from a subchronic repeated dose inhalation toxicity study (Yang, 1983), recalculated for trimethylenediamine (resulting in a NOAEC of 177.6 mg/m³) was identified as the relevant dose descriptor. Considering the appropriate modification and assessment factors, the worker DNEL (long-term dermal exposure) is calculated as follows:
- Calculation of the worker DNEL
Inhalatory NOAEC for workers: 177.6 mg/m³
Assessment factor for exposure duration (subchronic to chronic): 6
Assessment factor for intraspecies differences (worker): 5
Assessment factor for remaining uncertainty: 2
Worker DNEL (long-term inhalation exposure)
= 177.6 mg/m³ / (6 x 5 x 2)
= 2.96 mg/m³
Dermal exposure:
In order to derive the worker DNEL (long-term dermal exposure), the NOAEL assessed in a read across approach from a chronic repeated dose dermal toxicity study (DePass, 1984) was identified as the relevant dose descriptor. Considering the appropriate modification and assessment factors, the worker DNEL (long-term dermal exposure) is calculated as follows:
Relevant dose descriptor (NOAEL): 10.2 mg/kg bw/day
Exposure duration factor (subchronic-to-chronic): 1
Allometric scaling factor (rat-to-human): 4
Assessment factor for intraspecies differences (worker): 5
Assessment factor for remaining uncertainty: 2
Worker DNEL (long-term dermal exposure)
= 10.2 mg/kg bw/day / (4 x 5 x 2)
= 0.26 mg/kg bw/day
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:
- 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 for the eyes
Local effects
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Additional information - General Population
Since no exposure of the general population is intended, no DNEL is derived.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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