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EC number: 204-376-9 | CAS number: 120-20-7
- 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
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- Nanomaterial surface chemistry
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- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Data is from J-check
Data source
Reference
- Reference Type:
- review article or handbook
- Title:
- Preliminary Reproduction Toxicity Screening Test of 1,3-Bis (aminomethyl) benzene by Oral Administration in Rats
- Author:
- J-check
- Year:
- 2 010
- Bibliographic source:
- J-check, Ministry of Health, Labour and Welfare", "Ministry of the Environment" and "National Institute of Technology and Evaluation, 2010
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Principles of method if other than guideline:
- Preliminary Reproduction Toxicity Screening Test of 1,3-Bis (aminomethyl) benzene in Rats
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 1,3-Bis (aminomethyl) benzene
- Cas Number:
- 1477-55-0
- Molecular formula:
- C8H12N2
- IUPAC Name:
- 1,3-Bis (aminomethyl) benzene
- Details on test material:
- - Name of test material (as cited in study report): 1,3-Bis (aminomethyl) benzene
- Molecular formula (if other than submission substance): C8H12N2
- Molecular weight (if other than submission substance): 136.19 g/mole
- Substance type: Organic
- Physical state: colorless liquid
- Impurities (identity and concentrations): purity 99.8 wt%
Constituent 1
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): 1,3-Bis (aminomethyl) benzene
- Molecular formula (if other than submission substance): C8H12N2
- Molecular weight (if other than submission substance): 136.19 g/mole
- Substance type: Organic
- Physical state: colorless liquid
- Impurities (identity and concentrations): purity 99.8 wt%
Test animals
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Source: Japan Charles River Co., Ltd. (Kanagawa)
- Age at study initiation: (P) x wks; (F1) x wks: 10 weeks
- Weight at study initiation: (P) Males: x-x g; Females: x-x g; (F1) Males: x-x g; Females: x-x g: Body weight during grouping ranged from 354 to 399 g for males and from 216 to 247 g for females.
- Fasting period before study:
- Housing: One animal was housed and housed in an aluminum front and floor stainless steel mesh breeding cage in a breeding room. Maternal animals after gestation day 18 were kept in aluminum front and floor stainless steel mesh breeding cages with nursery trays and nest making materials until nursing 4th.
- Diet (e.g. ad libitum): NMF solid feed (radiation sterilized feed) and was taken free during the breeding period.
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 ± 2 ° C
- Humidity (%): 55 ± 10%
- Air changes (per hr): 15 times / hour, illuminance of 150 to 300 lux
- Photoperiod (hrs dark / hrs light): 12 hours (7 am lights, 7 pm off)
Administration / exposure
- Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- water
- Remarks:
- Purified
- Details on exposure:
- VEHICLE
- Justification for use and choice of vehicle (if other than water): Purified Water
- Concentration in vehicle: 0 (vehicle), 50, 150, 450 mg/kg/day
- Amount of vehicle (if gavage): 1 mL / 100 g body weight
- Lot/batch no. (if required): - Details on mating procedure:
- - M/F ratio per cage: 1:1
- Length of cohabitation: 5 days
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy Sperm in vaginal plaque, and that day was taken as the 0th day of pregnancy.
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility. Not specified
- Further matings after two unsuccessful attempts: [no / yes (explain)] Not specified
- After successful mating each pregnant female was caged (how): Individually - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- For the analysis of the concentration and homogeneity of the administration solution, samples were randomly extracted from batches of each group prepared at the start of preparation. As a result, the error with respect to the display density was in the range of -0.8 to + 6.9% and within the reference range (within ± 10%). Therefore, it was confirmed that a predetermined amount of 1,3-bis (aminomethyl) benzene was contained in the administration liquid used.
- Duration of treatment / exposure:
- Male : 48 days
Female : 41 to 45 days - Frequency of treatment:
- Daily
- Details on study schedule:
- not specified
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day
- Dose / conc.:
- 50 mg/kg bw/day
- Dose / conc.:
- 150 mg/kg bw/day
- Dose / conc.:
- 450 mg/kg bw/day
- No. of animals per sex per dose:
- Total: 96
0 (vehicle) mg/kg/day: 12 male, 12 female
50 mg/kg/day: 12 male, 12 female
150 mg/kg/day: 12 male, 12 female
450 mg/kg/day: 12 male, 12 female - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Dose was selected based on previous toxicity study, at 600 mg / kg group, salivation, decrease in locomotor activity, piloerection, abdominal distension Postmenopausal symptoms were observed in males and females, reduction in food intake and suppression of increase in body weight were observed in males, 1 in 12 males and 4 in females died. In the same group, epithelial hyperplasia accompanied by ulcer and hyperkeratosis in the mucous membrane of the forestomach of the stomach, an increase in granulocytic hematopoietic cells in the bone marrow, hypertrophy / vacuolation of the cortical cells in the adrenal glands and cecal enlargement in both sexes. Based on these results, preliminary study "1,3-bis (aminomethyl) benzene rats conducted at the same dose for 28-day repeated dose toxicity test, at 0, 10, 40, 150 and 600 mg / kg Oral administration simple oral reproductive toxicity test in 2 weeks preliminary test ", 2 out of 6 males in 600 mg / kg group and 1 in female died, salivation and the like were observed in males and females as symptoms after administration, the body weight gain was suppressed in males of the same group, and high levels of adrenal glands were observed in males and females.
Therefore, in this study, considering that dead animals were found in males and females at 600 mg / kg / day, in addition to considering that the administration period was extended to three times or more than the preliminary test, high doses of 450 mg / kg / day and was divided by the common ratio 3 below to 150 and 50 mg / kg / day. - Positive control:
- not specified
Examinations
- Parental animals: Observations and examinations:
- Survival, Clinical sign, Body weight and weight gain, food consumption were examined.
- Oestrous cyclicity (parental animals):
- Any irregularity in estrous cyclicity was examined.
- Sperm parameters (parental animals):
- Not specified
- Litter observations:
- Numbers of offspring or live offspring, the sex ratio and Body weights sex were examined.
- Postmortem examinations (parental animals):
- Organ weight, gross pathology and histopathology was examined.
- Postmortem examinations (offspring):
- External, visceral and skeletal malformations were examined.
- Statistics:
- Weight, food consumption, number of corpus luteums, number of implantation traces, number of births, number of stillbirths, sex ratio, average sex, pregnancy period, implantation rate, delivery rate, birth rate, abnormal incidence of abnormal outer table, newborn 4th Multiple comparison test was performed on the survival rate, organ weight and relative weight of the mice .
For the birth rate, mating rate and conception rate, x 2 tests were used. The abnormal periodic incidence rate and the incidence of findings of pathological examination were tested using Fisher's exact test method 6). In addition, as for the results on newborns during the nursing period, the average per mother was taken as one sample. The significance level was carried out with 5 and 1% two-sided test. - Reproductive indices:
- Copulation index, fertility index, gestation length, number of corpora lutea or implantations, implantation index, gestation index, delivery index and, parturition or maternal behavior were examined.
- Offspring viability indices:
- Viability index on day 0 and day 4 were examined.
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- When treated wtih 450 mg/kg bw, Salivation, nasal, rattle, irregular respiration, abdominal distension and nasal discharge were observed.
When treated wtih 150 mg/kg bw, Salivation were observed in male rats as compared to control. - Dermal irritation (if dermal study):
- not specified
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- When treated wtih 450 mg/kg bw, three males and one female died.
When treated wtih 150 mg/kg bw, one male died as compared to control. - Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- When treated wtih 450 mg/kg bw, Decreased in body weight was observed in treated male and female rats as compared to control.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- When treated wtih 450 mg/kg bw, Decreased in food consumption was observed in treated male and female rats as compared to control.
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Ulceration and squamous hyperplasia of the forestomach were observed in male and female at 450 mg/kg bw
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Description (incidence and severity):
- No effect on estrous cycle of treated rats were observed as compared to control.
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- No effect on copulation index, fertility index, gestation length, number of corpora lutea or implantations, implantation index, gestation index, delivery index and, parturition or maternal behavior was observed in treated rats as compared to control.
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Effect level:
- 450 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- organ weights and organ / body weight ratios
- reproductive function (oestrous cycle)
- reproductive performance
- Remarks on result:
- other: No effect observed
Target system / organ toxicity (P0)
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- no mortality observed
- Description (incidence and severity):
- No effect on viability of pups on day 0 and 4 were observed as compared to control.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No effect on body weight of pups on day 0 and 4 were observed as compared to control.
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No external abnormality were observed in pups as compared to control.
- Histopathological findings:
- not specified
- Other effects:
- not specified
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not specified
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not specified
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 450 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- viability
- mortality
- body weight and weight gain
- gross pathology
- Remarks on result:
- other: No effect observed
Target system / organ toxicity (F1)
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
- Treatment related:
- not specified
- Relation to other toxic effects:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Applicant's summary and conclusion
- Conclusions:
- NOAEL was considered to be 450 mg/kg bw for P and F1 generation when Crj:CD(SD) male and female rats were treated with 1,3-Bis (aminomethyl) benzene orally by gavage for 45 -48 days.
- Executive summary:
In a Preliminary Reproduction Toxicity Screening Test, Crj:CD(SD) male and female rats were treated with D-Camphor in the concentration of 0 (vehicle), 50, 150, 450 mg/kg/day orally by gavage for 45 -48 days. Three males and one female died at 450 mg/kg bw and one male died at 150 mg/kg bw as compared to control. Salivation, nasal, rattle, irregular respiration, abdominal distension and nasal discharge were observed at 450 mg/kg bw. Salivation were observed in male rats at 150 mg/kg bw as compared to control. Decreased in body weight and food consumption was observed in treated male and female rats as compared to control. Similarly, No effect on estrous cycle, copulation index, fertility index, gestation length, number of corpora lutea or implantations, implantation index, gestation index, delivery index and, parturition or maternal behavior was observed in treated rats as compared to control. Significant increase in absolute and relative thymus weight and decrease in adrenal gland were observed at 450 mg/kg bw and Significant increase in relative weight of the testes were observed in male rats, but not statistically significant as compared to control. No effect on reproductive organ weight was observed as compared to control. Ulceration of the stomach and squamous hyperplasia of the forestomach were observed in male and female at 450 mg/kg bw as compared to control. In addition, No effect on viability and body weight of pups on day 0 and 4 were observed as compared to control. No external abnormalities were observed in pups as compared to control. Therefore, NOAEL was considered to be 450 mg/kg bw for P and F1 generation when Crj:CD(SD) male and female rats were treated with 1,3-Bis (aminomethyl) benzene orally by gavage for 45 -48 days.
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