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EC number: 204-493-5 | CAS number: 121-69-7
- 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
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Link to relevant study records
- Endpoint:
- one-generation reproductive toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Qualifier:
- according to guideline
- Guideline:
- other: Maternal and developmental effect of N,N-dimethylaniline in CD-1 albino mice were assessed in a 1-generation study.
- GLP compliance:
- not specified
- Species:
- mouse
- Strain:
- CD-1
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc.
- Age: No data available
- Weight at study initiation: 21.0 to 30.0 g
Fasting period before study: N/A
- Housing: The mice were housed individually in suspended •polycarbonate cages with San-i-cel bedding in a controlled environment.
- Diet (e.g. ad libitum): Purina Certified
Rodent Chow® #5002, ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimatization period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3°C
- Humidity (%): No data available
- Air changes (per hr): 10-15 times per hour
- Photoperiod (hrs dark / hrs light): 12-hr dark/12-hr light - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
DIET PREPARATION
- Rate of preparation of diet (frequency): N/A
- Mixing appropriate amounts with (Type of food): N/A
- Storage temperature of food: N/A
VEHICLE
- Justification for use and choice of vehicle (if other than water): Corn oil
- Concentration in vehicle: 365 mg/kg/day
- Amount of vehicle (if gavage): 5.0 mg/kg of body weight
- Lot/batch no. (if required): No data available
- Purity: No data available - Details on mating procedure:
- - M/F ratio per cage: N/A (timed-pregnant female from supplier)
- Length of cohabitation: No data available
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy No data available
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility. No data available
- Further matings after two unsuccessful attempts: [no / yes (explain)] No data available
- After successful mating each pregnant female was caged (how): No data available
- Any other deviations from standard protocol: No data available - Duration of treatment / exposure:
- 8 days
- Frequency of treatment:
- Once daily on gestation day 7 through gestation day 14.
- Details on study schedule:
- - F1 parental animals not mated until [...] weeks after selected from the F1 litters.: No data available
- Selection of parents from F1 generation when pups were [...] days of age.: No data available
- Age at mating of the mated animals in the study: [...] weeks: No data available - Remarks:
- Doses / Concentrations:
365 mg/kg-bw/day
Basis:
actual ingested - No. of animals per sex per dose:
- Control: 50 females
365 mg/kg/day: 50 females - Control animals:
- yes, concurrent vehicle
- Details on study design:
- Constant dosing volume of 5.0 ml/kg of body weight based on the weights measured on Day 7 of gestation of mice.
- Parental animals: Observations and examinations:
- All animal s were observed -twice daily during the study (morning and afternoon) for clinical signs of toxicity and mortality. Body weights for the dams were also recorded on gestation day 2, 7 and 18 plus on day 4 of postpartum.
- Oestrous cyclicity (parental animals):
- No data available
- Sperm parameters (parental animals):
- Parameters examined in [all/P/F1/F2] male parental generations:No data available
- Litter observations:
- Pup counts and litter weights were recorded within 12 hours of birth and on Day 3 postpartum. Litter weight and mean pup weight changes (Day 3-Birth) were also calculated, and the viability of offspring from birth to Day 3 was assessed.
- Postmortem examinations (parental animals):
- Necropsy examinations were performed only on females which did not deliver. The nongravid uteri were treated with a. 10% sodium sulfide solution to determine the prior existence of a pregnant state.
- Postmortem examinations (offspring):
- No data available
- Statistics:
- Means and standard deviations were calculated for the following parameters: maternal body weights for each interval collected, litter weights, mean pup weights, and pup counts (live and dead) for each interval collected, weight changes for dams (Day 18-Day 7 of gestation) and litters (Day 3-Birth), and offspring viability ratios from birth to Day 3 postpartum. Treatment group means were compared to the common control group by Student's t-test.
- Reproductive indices:
- Number of live/dead litters was observed.
- Offspring viability indices:
- Number of live/dead litters was observed.
- Clinical signs:
- effects observed, treatment-related
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No differences in mean maternal body weight or mean weight change were observed.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- No differences in mean maternal body weight or mean weight change were observed.
- 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:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
- Dose descriptor:
- LOAEL
- Effect level:
- 365 mg/kg bw/day
- Based on:
- test mat.
- Remarks:
- Body weight
- Sex:
- female
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- 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
- 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:
- not specified
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- not specified
- Dose descriptor:
- other: not specified
- Based on:
- not specified
- Sex:
- not specified
- Basis for effect level:
- other: not specified
- Remarks on result:
- other: not specified
- Clinical signs:
- not specified
- Mortality / viability:
- not specified
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Statistical evaluation of mean litter and per-pup average weights revealed no noteworthy variations.
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Histopathological findings:
- not specified
- Dose descriptor:
- LOAEL
- Generation:
- F1
- Effect level:
- 365 mg/kg bw/day
- Based on:
- test mat.
- Remarks:
- Body weight
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: not specified
- Reproductive effects observed:
- not specified
- Conclusions:
- LOAEL for the parental generation and the F1 generation were considered to be 365 mg/kg/day when N,N-dimethylaniline was administered orally.
- Executive summary:
In a 1-generation study, N,N-dimethylaniline was assessed for its potential to cause adverse reproductive effects in timed-pregnant female CD-1 albino mice. The test material was administered orally by gavage on a daily basis on gestation day 7 through gestation day 14 with corn oil as vehicle. For test material, means and standard deviations were calculated by using two factors related mortality and body weight. No differences in mean maternal body weight or mean weight change observed in parents. Since N,N-dimethylaniline had no adverse effects on reproductive potential, survival or weight gain of the dams, or the fact that evaluation of mean litter and per-pup average weights revealed no noteworthy variations but with an indication of lowered offspring viability ratio, LOEAL was considered to be 365 mg/kg/day.
Reference
Deaths occurred in two mice from the test material and an additional N,N-dimethylaniline-treated animal was sacrificed in extremis on Day 18 of gestation (Study Day 12); this animal was noted to be lethargic, prostrate, cold to the touch and had mucoid secretion from the vagina prior to sacrifice. Prostration, tremors, ataxia, lethargy, piloerection, vaginal secretion, and/or anal bleeding were observed in an occasional test material -treated animal prior to death.
Reproductive performance:
No apparent adverse effects on reproductive outcome and time to delivery. Litters were born on days 18 through 23 of gestation.
Vehicle Control N,N-Dimethylaniline
(365 mg/kg/day)
Number Treated 50 50
Number of Deaths 0 3
Number of Survivors:
No pregnant 9 7
Pregnant 41 37
Fertilized without Subsequent
Implantation 0 3
Number of Litters:
Live litters 41 36
Dead Litters 0 1
Resorbed Litters 0 0
Deli very Index:
Ratio 41/41 36/37
Percent 100 97
Other observation: The percentage of litters cannibalized in test material was 4% (5/36).
Offspring viability ratio was significantly lower than the control group; however, this difference was slight and is considered to be incidental.
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LOAEL
- 365 mg/kg bw/day
- Study duration:
- subacute
- Species:
- mouse
- Quality of whole database:
- K2 level data is referred from reliable source of journal
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
WoE Summary of 121-69-7 for toxicity to reproduction
Based on the various studies available with Klimish rating 2 for the target as well as read across substances for CAS: 121-69-7 based on the USEPA’s HPV category approach ofsubstances that are part of a group of compounds known as Monocyclic Aromatic Amines Category. Also category is based on organic functional group along with similar mechanistic approach and having structural similarities defined by QSAR toolbox. The results for target as well as analogues are summarized as follows
Sr. No |
End point |
Value |
Species |
Effects |
Remarks |
1 |
LOAEL
|
274.66 mg/Kg bw /d |
Rat |
Effects observed on kidney enlargement (histopath: basophilic cortical tubular changes). Liver enlargement (histopath equivocal) |
Predicted data |
2 |
LOAEL |
365 mg/Kg bw /d |
Mouse |
Effects observed in clinical signs, and reproductive performance |
Data from Publication for CAS: 121-69-7 |
3 |
NOAEL (F1)
LOAEL (P) |
10 mg/kg bw/d
10 mg/kg bw/d |
Rat |
No adverse effects on presence of methemoglobinemia, increased relative spleen weight, decreased red blood cell (RBC) count, and haematological changes indicative of increased Hematopoietic activity.
Effect observed on Maternal toxicity and Absolute weight gain, spleen liver weight, increased methemoglobinemia and decreased red blood cell count. |
Data from Publication for CAS: 142-04-1 |
Based on the studies summarized in the above table it can be observed that NOAEL values for F1 genertion is from 10 mg/Kg bw/d as well as LOAEL value varies from 10-365 mg/kg bw/d based on the data from prediction as well as publication for target & read across substance. The effect observed on the above doses are
· Effects observed on kidney enlargement (histopath: basophilic cortical tubular changes). Liver enlargement (histopath equivocal)
· Effects observed in clinical signs, and reproductive performance
· Effect observed on Maternal toxicity and Absolute weight gain, spleen liver weight, increased methemoglobinemia and decreased red blood cell count.
Thus based on above discussion it can be concluded that substance CAS: 121-69-7 is expected to show the similar toxicological effect based on the effects observed on the other category members. Since the no effective dose value (NOAEL) is higher than 10 mg/Kg bw/d and LOAEL value is more than 10 mg/kg bw/d for one of read across as well as 365 mg/kg bw/d for target substance. Thus based on this value it can be concluded that substance CAS: 121-69-7 is considered to be not toxic to reproduction at the above mentioned dose. Also there are no known evidence of adverse effect on reproduction to Human of CAS: 121-69-7 as well as estrogen receptor binding affinity does not indicates any mechanistic trigger based on absence of noncyclic structure that would raise concern of CAS: 121-69-7 on toxicity to human reproduction.
Justification for selection of Effect on fertility via oral route:
LOAEL for the parental generation and the F1 generation were considered to be 365 mg/kg/day when N,N-dimethylaniline was administered orally.
Effects on developmental toxicity
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Principles of method if other than guideline:
- This study, conducted for the Monsanto Company. was designed to evaluate the embryotoxic. fetotoxic and/or teratogenic potential of diethyl alanine in the rat.
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- CD-1
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source:Charles River Breeding Laboratories. Inc. Shaver Road Portage. Michigan 49081
- Age at study initiation: Six weeks
- Weight at study initiation: 207 gms
- Fasting period before study:
- Housing: Individually, except during the first week of the acclimation period (two females/cage) and mating, in stainless steel suspended cages with wire mesh floors.
- Diet (e.g. ad libitum): Purina. Certified Rodent Chow No. 5002 (mash) fed ad libitum.
- Water (e.g. ad libitum): Tap water
- Acclimation period: 21 days
ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-74 deg F
- Humidity (%): Pretest - 33-66%
Study - 26-68%.
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle (7 AM to 7 PM) via automatic timer. - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on mating procedure:
- - M/F ratio per cage: 1:1
- Length of cohabitation: overnight
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy : Vaginal smears were taken early in the morning following intervals of cohabitation and females were considered to have mated if sperm and/or a vaginal plug was observed(Day 0 of gestation).
- After successful mating each pregnant female was caged (how):Individually, except during the first week of the acclimatization period (two females per cage) and mating, in stainless steel suspended cages with wire mesh floors. - Frequency of treatment:
- daily
- Duration of test:
- Days 6-15 of gestation
- Remarks:
- Doses / Concentrations:
0, 50, 250 and 500 mg/kg/day
Basis:
nominal in diet - No. of animals per sex per dose:
- Control: 24 pregnant females
50 mg/kg/day: 24 pregnant females
250 mg/kg/day: 24 pregnant females
500 mg/kg/day: 29 pregnant females - Control animals:
- yes, concurrent vehicle
- Maternal examinations:
- Body weights Recorded on Days 0, 6, 10, 12, 15 and 20 of gestation.
- Ovaries and uterine content:
- The ovaries were dissected free from the uterus and evaluated for the presence and number of corpora lutea. When no uterine implants were grossly apparent, the uterus was stained with ammonium sulphides and the number of foci was counted.
- Fetal examinations:
- All fetuses were given a gross examination for malformations/variations of the external form. Subsequently, each fetus was weighed and sexed (ano-genital distance) which was confirmed by internal inspection of the gonads at subsequent evaluation.
- Statistics:
- Due to the small group sizes involved, data were not evaluated statistically.
- Indices:
- No data
- Historical control data:
- No data
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
Symptoms in dams included decreased body weight gain and food consumption, as well as excessive salivation and staining of the fur in the ano-genital region. Gross necropsy revealed discolored lungs in some dams at all dose levels. - Dose descriptor:
- LOAEL
- Effect level:
- 50 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects. Remark: Treatment with the highest dose level of diethylaniline was observed to be fetotoxic (reduced fetal weight gain), however, it was not considered to be embryotoxic or teratogenic.
- Dose descriptor:
- LOAEL
- Effect level:
- 500 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: teratogenicity
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- The lowest observed adverse effect level (LOAEL) for the parental generation is considered to be 50 mg/kg/day of diethylaniline given orally by gavag and the lowest observed adverse effect level (LOAEL) for the F1 generation is considered to be 500 mg/kg/day of diethylaniline.
- Executive summary:
In a 1-generation study, the embryotoxic, fetotoxic and/or teratogenic effect of diethylaniline was evaluated in female CD rats treated with 0, 50, 250 or 500 mg/kg/day of diethylaniline during Day 6-15 of gestation. No mortality occurred in the control, low- or mid-dose groups, but some maternal toxicity was evident at each dose level. Low-dosed females experienced depressed weight gain during the treatment period and their mean food consumption was statistically lower than control. Manifestations of maternal toxicity were also seen at the mid- and high-dose levels; however, these effects were more extreme. Physical examination of females in the mid- and high-dose groups revealed an increased incidence of females with excessive salivation, staining of the skin/fur in the ano-genital area and excessive lacrimation. No adverse effect of treatment was evident from uterine implantation data. Mean fetal weight and fetal sex distribution were unaffected by treatment at the low or mid-dose levels. Thus, LOAEL for the dams is considered to be 50 mg/kg/day and for the offspring 500 mg/kg/day when pregnant female CD rats are given diethylaniline orally.
Reference
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LOAEL
- 50 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- K2 level data obtained from relaible source
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
WoE Summary of 121-69-7 for developmental toxicity
Based on the various studies available with Klimish rating 2 for the target as well as read across substances for CAS: 121-69-7 based on the USEPA’s HPV category approach ofsubstances that are part of a group of compounds known as Monocyclic Aromatic Amines Category. Also category is based on organic functional group along with similar mechanistic approach and having structural similarities defined by QSAR toolbox. The results for target as well as analogues are summarized as follows
Sr. No |
End point |
Value |
Species |
Route |
Effects |
Remarks |
1 |
LOAEL (developmental)
LOAEL (maternal toxicity) |
365 mg/ kg bw/ d
365 mg/kg bw/d |
Mouse |
Oral |
Effects observed in clinical signs, and reproductive performance |
Data from Publication for 121-69-7 |
2 |
LOAEL (developmental)
LOAEL (maternal toxicity) |
50 mg/Kg bw /d
500 mg/kg bw/d |
Rat |
Oral |
Effects observed in weight gain, food consumption and uterine implantation.
Effects observed in Reduced fetal weight and retarded sternebral ossification. |
Data from Publication for CAS: 91-66-7 |
3 |
LOEL
|
149 mg/kg bw/d |
Rat |
Oral |
Fetal weight reduction |
Predicted data |
Based on the studies summarized in the above table with various routes it can be observed that LOAEL values varies from 50 - 500 mg/kg bw/d for oral route based on the data for target as well as read across substances. The no effects observed on the higher doses was listed as follows
o Effects observed in clinical signs, and reproductive performance
o Effects observed in weight gain, food consumption and uterine implantation.
o Effects observed in Reduced fetal weight and retarded sternebral ossification.
o Fetal weight reduction
Thus based on above discussion it can be concluded that substance CAS: 121-69-7 is expected to show the similar toxicological effect based on the effects observed on the other category members. Since the Low observed adverse effective dose value (LOAEL) is higher than 50 mg/Kg bw/d vial oral route. It can be concluded that substance CAS: 121-69-7 is considered to be not toxic to maternal toxicity as well as developmental effects via oral route for above mentioned doses. Also there are no known evidence of adverse effect on reproduction to Human of CAS: 121-69-7 as well as estrogen receptor binding affinity does not indicates any mechanistic trigger based on absence of noncyclic structure that would raise concern of CAS: 121-69-7 on developmental toxicity.
Justification for selection of Effect on developmental toxicity: via oral route:
The lowest observed adverse effect level (LOAEL) for the parental generation is considered to be 50 mg/kg/day of diethylaniline given orally by gavag and the lowest observed adverse effect level (LOAEL) for the F1 generation is considered to be 500 mg/kg/day of diethylaniline.
Justification for classification or non-classification
Based on above details it can be concluded that substance N,N-dimethylaniline is considered to be not toxic to reproduction as well as developmetal effects
Additional information
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.