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EC number: 200-875-0 | CAS number: 75-50-3
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline study; no data regarding GLP; No data on detailed clinical observation, sensory reactivity to stimuli, assessment of grip strength, and motor activity.
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Combined repeat dose and reproductive/developmental toxicity screening test of trimethylamine by oral administration in rats.
- Author:
- Takashima, H., Kuwagata, M., Miyahara, T., Katou, H., Seki, T., Shindou, T., Marumo, H., Horiuchi, S., Inada, H., Saegusa, K., Anjou, T., and Ichihara, S.
- Year:
- 2 003
- Bibliographic source:
- Hatano Research Institute, Food and Drug Safety Center, Japan.
- Reference Type:
- publication
- Title:
- Trimethylamine (CAS No. 75-30-3), Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test
- Author:
- Takashima, H. et al.
- Year:
- 2 001
- Bibliographic source:
- in: Tox. Testing Reports of Env. Chemicals, v. 8 (1), p 44-59, Chem. Investigation Promoting Council, Office of Chem. Safety, Evaluation, & Licensing Div., Pharmaceutical & Medical Safety Bureau, Ministry of Health, Labour & Welfare, Japan
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: OECD 422/OPPTS 870.3650 - Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test
- Deviations:
- yes
- Remarks:
- No data on detailed clinical observation, sensory reactivity to stimuli, assessment of grip strength, and motor activity.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Trimethylamine
- EC Number:
- 200-875-0
- EC Name:
- Trimethylamine
- Cas Number:
- 75-50-3
- Molecular formula:
- C3H9N
- IUPAC Name:
- N,N-dimethylmethanamine
- Details on test material:
- CAS 75-50-3 (trimethylamine), 30.8% trimethylamine solution, SOURCE: Mitsubishi Gas Chemical Company, Inc. (Niigata; lot # M381012).
The solution contained < 10 ppm of dimethylamine as impurities. Stable for at least 8 days under refrigerated and shielded conditions with a concentration of between 0.08 and 10w/v%.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- - Age: 9 week old
- no further details given
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- no details given
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- no details given
- Details on mating procedure:
- Male/female per cage maximum for 2 weeks beginning evening of dosing day 15. Mating confirmed by existence of sperm in the vaginal plug and vaginal smear every morning.
- Duration of treatment / exposure:
- 42 days; Females: 2 weeks prior to breeding, continuing through breeding (2 weeks), gestation (3 weeks), lactation (4 days), and until the day of necropsy (test day 40 or 54).
- Frequency of treatment:
- Once daily
- Duration of test:
- day 40 or 54
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- (in water)
- Dose / conc.:
- 8 mg/kg bw/day (nominal)
- Remarks:
- (in water)
- Dose / conc.:
- 40 mg/kg bw/day (nominal)
- Remarks:
- (in water)
- Dose / conc.:
- 200 mg/kg bw/day (nominal)
- Remarks:
- (in water)
- No. of animals per sex per dose:
- 13/sex/dose group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Sex: male/female
Duration of test: test item administration for 40 or 54 days
Examinations
- Maternal examinations:
- - Clinical Observations and Frequency: General condition was observed at least once a day during mating and at least twice a day before and after dosing over the administration period. The state of delivery was recorded. The state of nursing was observed daily after delivery.
- Body weights: Parent: Body weights for males were determined on days 1, 7, 14, 21, 28, 35, 42 and on the day of necropsy. Body weights were determined for all females on days 1, 7, 14. Females who took time before mating were weighed on days 35 and 42. Females who copulated were weighed on pregnancy days 0, 7, 14 and 20. Females who delivered were weighed on nursing days 0, 4, and on the day of necropsy. Females who copulated but did not deliver were weighed on the equivalent of pregnancy day 25 (day of necropsy).
- Observation of delivery: With all cases where delivery was confirmed, the pregnancy period (number of days from pregnancy day 0 to delivery day) was calculated and the birth rate ((number of females who delivered live pups/number of animals conceived) x 100) for each group was found.
- Food consumption was measured on days 1, 7, 13, 29, 35 and 41 for males, and on days 1, 7, and 13 for all females. Females with unconfirmed copulation were measured for food consumption on days 29, 35 and 41.
- Urinalysis was conducted on 5 rats/sex/dose level at week 6.
- Haematology and clinical chemistry: Males prior to necropsy and on the following day after day 42 administration; Females prior to necropsy: females who delivered-following nursing day 4, females who mated but did not deliver-equivalent of pregnancy day 25, and females who did not mate- following day 54 of administration
ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC):
- Macroscopic: organ weights: brain, heart, thymus, liver, kidneys, spleen, adrenals, testes and epididymides; pups were autopsied on day 4 and external and internal organs observed; with females, ovaries and uteri were extracted, the pregnancy corpora lutea number of the ovary was counted under the stereoscopic microscope, the implantation number of the uterus was counted, and the implantation rate ((implantation number/pregnancy corpora lutea number) x 100) was calculated.
- Microscopic: 5 animals/sex/control and high dose group- brain, pituitary gland, spinal cord, digestive tract, liver, kidneys, adrenal, spleen, heart, thymus, thyroid gland, trachea, lung, bladder, mesenteric lymph nodes, lower jaw lymph nodes, sciatic nerves, thigh bone marrow, sperm and prostrate ventral lobes of all males and vagina, ovaries and uteri of all females; also testes, epididymides, ovaries and stomachs found to be abnormal during pathologic examinations were all examined histopathologically - Ovaries and uterine content:
- Ovaries and uteri were extracted, the pregnancy corpora lutea number of the ovary was counted under the stereoscopic microscope, the implantation number of the uterus was counted, and the implantation rate ((implantation number/pregnancy corpora lutea number) x 100) was calculated.
- Fetal examinations:
- Fetus: Pup weight was recorded on day 0 and 4 of lactation.
With the delivered pups, external malformation and the sex were checked and the sex ratio ((number of male live pups/number of female live pups) x 100) was calculated.
- Number of dead pups: The number of dead pups was checked daily, and the birth rate ((number of delivered live pups/number of delivered pups) x 100) and the viable rate of new-born pups on day 4 ((number of live pups on nursing day 4/number of live pups on nursing day 0) x 100) were calculated. Dead pups were autopsied and abnormality and internal organs were observed
- Number of delivered pups: The number of delivered pups (live pups + stillborns) was counted on nursing day 0, and the delivery rate ((number of delivered pups/number of implantation traces) x 100) and the live birth rate ((number of delivered live pups/number of implantation traces) x 100) were calculated. With the delivered pups, external malformation and the sex were checked and the sex ratio ((number of male live pups/number of female live pups) x 100) was calculated.
- Macroscopic: pups were autopsied on day 4 and external and internal organs observed. - Statistics:
- Fisher's Exact Test- mating and conception rate
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- - Clinical signs prior to death (200 mg/kg/day):
Day 25 male, showed salivation, emaciation, abnormal breathing noise and dyspnoea from administration day 19, and vulval periphery fur soil and loose passage were observed from the day before the death.
Day 42 male, showed salivation, emaciation, abnormal breathing noise, dyspnoea, a drop in body temperature, faded auricle, tottering and brown soil around the nose were observed from administration day 10, although discontinuously.
The female was observed with salivation and abnormal breathing noise sporadically from administration day 11.
- Clinical signs in surviving animals: 200 mg/kg/day: Males- salivation 10/13, abnormal breathing noise 3/13, and decreased contact response 1/13; Females-salivation 10/13, abnormal breathing noise 3/13, and emaciation 1/13. 40 mg/kg/day: no abnormalities - Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Mortality and time to death: 1 male given 200 mg/kg/day died on day 25, 1 male given 200 mg/kg/day died on day 42 and 1 female died on pregnancy day 22 (administration day 38)
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Males - No significant differences in body weights at 200 mg/kg/day; however, body weight gains were decreased when compared to controls. There were no significant differences in body weight or body weight gains in males administered 40 mg/kg/day.
Females - No significant differences in body weight or body weight gains. There was no effect of trimethylamine administration on body weights and food consumption of the females and on organ weights, urine examination and haematological examination results in the males and females - Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- There was no effect of trimethylamine administration on food consumption of the females
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- There was no effect of trimethylamine administration on haematological examination results in the males and females.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Significant increase in urea nitrogen at 40 mg/kg/day
- Urinalysis findings:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Other effects:
- not specified
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- no effects observed
- Changes in number of pregnant:
- no effects observed
- Other effects:
- not specified
- Details on maternal toxic effects:
- Maternal toxic effects: yes
Details on maternal toxic effects:
- Mortality and time to death: 1 female died on pregnancy day 22 (administration day 38)
- Clinical signs prior to death (200 mg/kg/day): The female was observed with salivation and abnormal breathing noise sporadically from administration day 11.
- Clinical signs in surviving animals: 200 mg/kg/day: salivation 10/13, abnormal breathing noise 3/13, and emaciation 1/13. 40 mg/kg/day: no abnormalities
- Body weights: No significant differences in body weight or body weight gains.
- Food consumption: No significant differences in food consumption.
- Ophthalmoscopic examination: no data
- Urine tests: No treatment related changes
- Haematology: No treatment related changes
- Clinical chemistry: Significant increase in urea nitrogen at 40 mg/kg/day
Embryo-/fetotoxicity: not observed
No abnormality which can be considered the effects of trimethylamine administration was observed in the reproductive organs, and no effect on the observation results of oestrous cycle was found. Also no effect was found on the mating rate, conception rate, the birth rate, pregnancy period, and nursing state, the number of corpora lutea, the number and rate of implantation, the viability of the delivered pups, sex ratio, body weight and form.
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 40 mg/kg bw/day
- Basis for effect level:
- other: general toxicity
- Dose descriptor:
- NOEL
- Remarks:
- reproductive toxicity
- Effect level:
- 200 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: see "Remarks"
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- no effects observed
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
- Other effects:
- not specified
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
No abnormality which can be considered the effects of trimethylamine administration was observed in the reproductive organs, and no effect on the observation results of oestrous cycle was found. Also no effect was found on the mating rate, conception rate, the birth rate, pregnancy period, and nursing state, the number of corpora lutea, the number and rate of implantation, the viability of the delivered pups, sex ratio, body weight and form.
Effect levels (fetuses)
- Dose descriptor:
- NOEL
- Remarks:
- developmental toxicity
- Effect level:
- 200 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no teratogenicity
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
As a result of pathological examinations, no
abnormality which can be considered the effects of trimethylamine
administration was observed in the reproductive organs, and no effect on
the observation results of oestrous cycle was found. Also no effect was
found on the mating rate, conception rate, the birth rate, pregnancy
period, nursing state, the number of corpora lutea, the number and rate
of implantation, the viability of the delivered pups, sex ratio, body
weight and form. From the above, it was considered that
reproductive/developmental toxicity NOEL is 200 mg/kg/day for both males
and females and also for delivered pups.
Applicant's summary and conclusion
- Conclusions:
- The NOEL of 200 mg/kg bw, the highest dose level tested, was established for reproductive and developmental toxicity.
- Executive summary:
According to OECD guideline 422 rats (Sprague-Dawley) were investigated for developmental toxicity by oral adminstration (gavage) with trimethylamine. The test duration was 42 days, the dosis was given once per day. The concentrations were 0, 8, 40, 200 mg/kg/day (in water). As a result of pathological examinations, no abnormality which can be considered the effects of trimethylamine administration was observed in the reproductive organs, and no effect on the observation results of oestrous cycle was found. Also no effect was found on the mating rate, conception rate, the birth rate, pregnancy period, nursing state, the number of corpora lutea, the number and rate of implantation, the viability of the delivered pups, sex ratio, body weight and form. From the above, it was considered that reproductive/developmental toxicity NOEL is 200 mg/kg/day for both males and females and also for delivered pups.
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