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EC number: 221-375-9 | CAS number: 3081-14-9
- 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:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP and guideline study (OECD TG 414)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 986
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- N,N'-bis(1,4-dimethylpentyl)-p-phenylenediamine
- EC Number:
- 221-375-9
- EC Name:
- N,N'-bis(1,4-dimethylpentyl)-p-phenylenediamine
- Cas Number:
- 3081-14-9
- Molecular formula:
- C20H36N2
- IUPAC Name:
- N1,N4-bis(5-methylhexan-2-yl)benzene-1,4-diamine
- Details on test material:
- Santoflex 77, purity: 100%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Charles River CD rats
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Analytical verification of doses or concentrations:
- yes
- Details on mating procedure:
- M/F ratio per cage: 1:1
- Duration of treatment / exposure:
- days 6 to 15 of gestation
- Frequency of treatment:
- daily
- Duration of test:
- study termination on gestation day 20
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 25, 75, 150 mg/kg bw/day
Basis:
- No. of animals per sex per dose:
- 25 per group
- Control animals:
- yes, concurrent vehicle
Results and discussion
Results: maternal animals
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 150 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 25 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- LOAEL
- Effect level:
- 75 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
MATERAL TOXICITY
Mortality
control: 0/25
25 mg/kg/day: 0/25
75 mg/kg bw/day: 1/25
150 mg/kg/day: 4/25
Four 150 mg/kg/day females died between gestation days 16 and 17 and one 75 mg/kg/day female died on gestation day 17. All control and 25 mg/kg/day females survived to scheduled sacrifice.
Clinical signs
The 150 mg/kg/day females that died prior to sacrifice generally exhibited red matter (presumably blood) around and/or expelled from the vaginal opening; red matter under the cage; stained, wet and/or matted haircoat; and ptyalism. Of the aforementioned clinical signs, ptyalism was the only observation also noted in the 75 mg/kg/day female that died. The necropsy observations of the animals that died were not meaningfully different from those of the control animals. Of the animals that survived to scheduled sacrifice, stained, wet
and/or matted haircoat (primarily located in the anogenical region) was noted at increased incidence at the 150 mg/kg/day dosage level and ptyalism was apparent at all tested dosage levels although the incidencewas very low.
Gross lesions
Treatment-related gross internal lesions were not noted at necropsy.
Body Weights
Body weight loss was observed during the initial subinterval of treatment (gestation days 6—9) at the 150 mg/kg/day dose level.
Moreover, body weight gains during both the overall treatment and gestation intervals (gestation days 6-15 and 0-20, respectively) were reduced, relative to the control, at the 75 and 150 mg/kg/day dosage levels.Treatment-induced differences in body weight gain were not evident at the 25 mg/kg/day dose level.
(GD 0 to 20):
Group mean Body weight change
Group mean maternal body weight change (grams) | ||||
Day of gestation | Control | 25 mg/kg/d | 75 mg/kg/d | 150 mg/kg/d |
0 to 6 | 29 ± 7.4 | 26 ± 6.0 | 25 ± 5.4 | 24 ± 10.7 |
6 to 9 | 3 ± 5.7 | 6 ± 5.0 | 3 ± 6.2 | -4 ± 6.5 |
9 to 12 | 11 ± 4.8 | 11 ± 5.9 | 9 ± 8.1 | 14 ± 7.4 |
12 to 16 | 18 ± 6.7 | 21 ± 6.2 | 14 ± 8.1 | 5 ± 17.3 |
16 to 20 | 58 ± 7.2 | 58 ± 8.6 | 56 ± 16.6 | 58 ± 11.9 |
6 to 15 | 32 ± 10.1 | 38 ± 7.2 | 26 ± 13.5 | 16 ± 18.3 |
0 to 20 | 119 ± 16.2 | 122 ± 14.9 | 108 ± 15.6 | 105 ± 20.4 |
Group mean body weight
Group mean maternal body weights (grams) | ||||
Day of gestation | Control | 25 mg/kg/d | 75 mg/kg/d | 150 mg/kg/d |
0 | 275 ± 21.7 | 272 ± 22.2 | 265 ± 23.5 | 263 ± 26.9 |
6 | 305 ± 26.1 | 299 ± 24.5 | 290 ± 26.2 | 287 ± 29.5 |
9 | 307 ± 28.9 | 304 ± 25.4 | 293 ± 27.1 | 283 ± 28.5 |
12 | 318 ± 29.9 | 316 ± 24.2 | 302 ± 25.9 | 297 ± 29.6 |
16 | 337 ± 32.0 | 336 ± 28.2 | 316 ± 28.0 | 304 ± 31.1 |
20 | 394 ± 33.9 | 394 ± 31.5 | 373 ± 36.0 | 366 ± 40.2 |
Cesarean Section Observations
No differences attributable to treatment were observed in the dams or fetuses at Cesarean section.
The mean fetal body weight value at 25 mg/kg/day was significantly higher than the control and was attributed to inherent biological
variation for lack of similar findings at the 75 and 150 mg/kg/day dose levels.
Table: Summary of maternal and fetal observation at Cesaren Section
Control | 25 mg/kg/d | 75 mg/kg/d | 150 mg/kg/d | |
Animal on study | 25 | 25 | 25 | 25 |
Animals that were gravid | 23 | 23 | 20 | 22 |
Animals that died | 0 | 0 | 1 | 4 |
Animals that diet nongravid | 0 | 0 | 0 | 0 |
Animals that diet gravid | 0 | 0 | 1 | 4 |
Animals examined at Cesarean section: | 25 | 25 | 24 | 21 |
Nongravid: | 2 | 2 | 5 | 3 |
Gravid | 23 | 23 | 19 | 18 |
Dams with viable fetuses | 23 | 23 | 19 | 18 |
Viable fetuses/dam | 13.7 ± 2.36 | 13.7 ± 1.5 | 13.4 ± 3.13 | 13.1 ± 2.63 |
Postimplantation loss/dam: | 1.2 ± 1.19 | 1.2 ± 1.03 | 1.5 ± 1.74 | 1.3 ± 1.67 |
Total Implantations/dam | 14.9 ± 2.09 | 14.8 ± 1.56 | 14.9 ± 3.31 | 14.4± 2.20 |
Corpora lutea/dam | 16.4 ± 2.17 | 16.0 ± 1.99 | 15.8 ± 2.49 | 15.9 ± 2.19 |
Group mean preimplantation loss (%) | 9.0 | 7.6 | 5.3 | 9.4 |
Group mean postimplantation loss (%) | 7.9 | 7.9 | 10.2 | 8.9 |
Mean fetal body weight (g) | 3.3 ± 0.29 | 3.5*± 0.44 | 3.3 ± 0.26 | 3.3 ± 0.21 |
Fetal sex distribution - male (%) | 152 (48.1) | 160 (51.0) | 126 (49.4) | 117 (49.6) |
Fetal sex distribution- female (%) | 164 (51.9) | 154 (49.0) | 129 (50.6) | 119 (50.4) |
* significant different from control (p<0.05)
FETAL MORPHOLOGICAL OBSERVATIONS
Malformations
Malformations that were observed in the treated groups occurred in low incidence and were not considered treatment related. One high-dose fetus had anophthalmia, one mid-dose and two control fetuses had microphthalmia and another mid-dose fetus had ectopia cordis and scernoschisis.
Table summary of the Incidence of fetal malformation
dosage levels | control | 25 mg/kg/d | 75 mg/kg/d | 150 mg/kg/d |
No. of litters examined | 23 | 23 | 19 | 18 |
No. of fetuses examined externally | 315 | 314 | 255 | 236 |
No. of fetuses examined viscerally | 157 | 157 | 128 | 118 |
No. of fetuses examined skeletally | 159 | 157 | 127 | 118 |
Malformations observed | No. of fetuses (no. of litters) | |||
Anophthalmia | 1 (1) | |||
Microphthalmia | 2 (2) | 1 (1) | ||
Ectopia cordis | 1 (1) | |||
Sternoschisis | 1 (1) | |||
total fetuses (litters) with malformations | 2 (2) | 0 (0) | 2 (2) | 1 (1) |
Developmental Variations
No meaningful differences were noted between the incidence of developmental variations seen in the treated groups and those in the
control.
Table: summary of the incidence of fetal devlopmental variations
Dosage levels | control | 25 mg/kg/d | 75 mg/kg/d | 150 mg/kg/d |
No. of litters examined | 23 | 23 | 19 | 18 |
No. of fetuses examined externally | 315 | 314 | 255 | 236 |
No. of fetuses examined viscerally | 157 | 157 | 128 | 118 |
No. of fetuses examined skeletally | 159 | 157 | 127 | 118 |
Developmental Variations observed | No. of fetuses (No. of litters) | |||
retroesophageal right subclavian | 1 (1) | |||
Renal papilla not developed and/or distended ureters | 1 (1) | 4 (3) | ||
Skull reduced in ossification | 4 (1) | 2 (2) | 4 (3) | |
hyoid unossified | 2 (2) | 4 (4) | 10 (6) | 1 (1) |
27 presacral vertebrae | 1 (1) | 1 (1) | ||
25 presacral vertebrae | 1 (1) | 5 (3) | 1 (1) | |
Vertebrae reduced in ossification | 1 (1) | |||
7th cervical rib(s) | 3 (3) | 3 (3) | 1 (1) | 8 (4) |
Greater than 13 full pairs of ribs | 1 (1) | |||
14th rudimentary rib(s) | 4 (4) | 3 (3) | 1 (1) | |
Fewer than 13 full pairs of ribs | 10 (5) | 7 (3) | 17 (4) | 13 (6) |
entire sternum unossified | 1 (1) | |||
Sternebrae #5 and/or #6 unossified | 65 (20) | 46 (17) | 50 (16) | 51 (16) |
other sternebra unossified | 1 (1) | 3 (3) | ||
misalligned sternebra | 1 (1) | 2 (2) | ||
Ischium(a)reduced in ossification | 1 (1) | 1 (1) | ||
total fetuses (litters) with variations | 77 (22) | 57 (20) | 68 (17) | 64 (17) |
TEST ARTICLE ANALYSES
Stability
Means of 6 hour stability assay values were within + 10% of target concentrations. These results indicated that the test
material/vehicle preparations were stable and suitable for study initiation.
Concentration
Test suspensions contained average concentrations ranging from 92% to 95% (October 7, 1985) and 102% to 108% (October 18, 1985) of target levels.
Applicant's summary and conclusion
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.
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