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EC number: 309-913-1 | CAS number: 101357-16-8
- 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
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- 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

Toxicity to reproduction
Administrative data
- Endpoint:
- screening for reproductive / developmental toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Test method according to OECD Guideline 422. GLP study.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 011
- Report date:
- 2011
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Benzenamine, reaction products with aniline hydrochloride and nitrobenzene, hydrochlorides
- EC Number:
- 309-913-1
- EC Name:
- Benzenamine, reaction products with aniline hydrochloride and nitrobenzene, hydrochlorides
- Cas Number:
- 101357-16-8
- Molecular formula:
- Not applicable. Multiconstituent substance.
- IUPAC Name:
- (2Z,7Z)-5-phenyl-2,7-bis(phenylimino)-2,7-dihydro-5λ⁵-phenazin-5-ylium (7Z)-N2,N3,5-triphenyl-7-(phenylimino)-5,7-dihydrophenazine-2,3-diamine N2,N3,5,7-tetraphenyl-5,7,12,14-tetrahydro-5,7,12,14-tetraazapentacene-2,3-diamine chloride
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- - Name of test material (as cited in study report): C.I. Solvent Black 5 (analogue CAS 11099-03-9).
- Lot/batch No.: 10137087
- Physical state: Blackish brown powder
- Storage condition of test material: Room temperature.
- Stability and uniformity were property has been confirmed.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Age at study initiation: 10 weeks old
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: Methylcellulose aqueous solution
- Details on exposure:
- VEHICLE
- Amount of vehicle (if gavage): 5 mL/kg
- 0.5%w/v Methylcellulose aqueous solution (suspended) - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Males: 42 days (from 14 days before mating, and through the mating period until a day before necropsy).
Females: 41-48 days (from 14 days before mating, and through the mating period until day 4 of lactation). - Frequency of treatment:
- Daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0 (control), 40, 200 and 1000 mg/kg bw/day
Basis:
nominal conc.
- No. of animals per sex per dose:
- Males: 7 (control), 12 (40 mg/kg bw/day), 12 (200 mg/Kg bw/day), 7 (1000 mg/kg bw/day), 5 (control with recovery), 5 (1000 mg/kg bw/day with recovery).
Females: 12 (control), 11 (40 mg/kg bw/day), 11 (200 mg/Kg bw/day), 12 (1000 mg/kg bw/day), 5 (control with recovery), 5 (1000 mg/kg bw/day with recovery). - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: In the 14-day range finding study with 5 males and 5 females at dose levels of 0, 100, 300, 1000 mg/kg/day, there were no changes attributed to the treatment at any groups. (Inspection items: clinical signs, body weight, food consumption, necropsy, organ weight, hematology and blood chemistry).
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION: Yes
HAEMATOLOGY: Yes
- Time schedule for collection of blood: End of the dosing and recovery period.
- How many animals: All animals
- Parameters checked: RBC, WBC, Hb, Plat., MCV, MCH, MCHC, Ret., Eosino., Baso., Mono., Lymph., Neutro., LUC, PT, APTT, Fibrin.,
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: End of the dosing and recovery period.
- How many animals: All animals
- Parameters checked: ASAT, ALTA, ALP, CPK, T. Bil., T. Prot., Albumin, T. Chol., TGL, PL, Glucosa, BUN, Creat., IP, Ca, Na, K, Cl, α1-glob., α2-glob., β-glob., γ-glob., A/G.
URINALYSIS: Yes (in males)
NEUROBEHAVIOURAL EXAMINATION: Yes
- Battery of functions tested: sensory activity / grip strength / motor activity - Oestrous cyclicity (parental animals):
- The following parameters were observed: Frequency of estrous, estrous interval, irregular estrous cycle.
- Sperm parameters (parental animals):
- Parameters examined in male parental generations: testis weight, epididymis weight.
- Litter observations:
- PARAMETERS EXAMINED
Clinical signs, external examinations and body weight. - Postmortem examinations (parental animals):
- GROSS PATHOLOGY: Yes, all animals at the end of the dosing and recovery periods.
Absolute and relative organ weight:
Males: Adrenals, testis, thymus, spleen, brain, heart, lung, liver, kidney, epididymus, sem. vesic., prostate.
Females: Adrenals, ovaries, thymus, spleen, brain, heart, lung, liver, kidneys.
HISTOPATHOLOGY: Yes, animals within control and highest dose tested (1000 mg/kg bw/day), at the end of dosing and recovery period.
Male: Femoral bone marrow, heart, kidney, liver, lung, prostate, stomach, thyroid, trachea.
Females: Adrenal, femoral bone marrow, heart, kidney, liver, lung, spleen, stomach, thymus, thyroid, trachea, uterus, adipose tissue. - Postmortem examinations (offspring):
- SACRIFICE
- Offspring were sacrified at day 4 after birth.
GROSS NECROPSY: Yes - Reproductive indices:
- Copulation rate, fertily rate.
- Offspring viability indices:
- Gestation index, implantation index, delivery index, live birth index (Day 0), sex ratio (Days 0 and 4), viability index (Days 0 and 4).
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Other effects:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
Details on results (P0)
No animal died in any test article group.
No test article-related changes were observed in clinical signs.
Only test article-colored feces were observed in all groups.
BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
No effects were observed.
TEST SUBSTANCE INTAKE (PARENTAL ANIMALS)
No effects were observed.
REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS)
No effects were observed.
REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS)
No data reported.
REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
No effects were observed.
ORGAN WEIGHTS (PARENTAL ANIMALS)
No effects were observed.
GROSS PATHOLOGY (PARENTAL ANIMALS)
No effects were observed.
HISTOPATHOLOGY (PARENTAL ANIMALS)
No effects were observed.
OTHER FINDINGS (PARENTAL ANIMALS)
HAEMATOLOGY
No effects were observed.
CLINICAL CHEMISTRY
No effects were observed.
URINALYSIS
No effects were observed in males.
NEUROBEHAVIOUR
No effects were observed.
Effect levels (P0)
- Dose descriptor:
- NOEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed at highest dose
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not specified
Details on results (F1)
No effects were observed.
CLINICAL SIGNS (OFFSPRING)
No effects were observed.
BODY WEIGHT (OFFSPRING)
No effects were observed.
GROSS PATHOLOGY (OFFSPRING)
No effects were observed.
Effect levels (F1)
- Dose descriptor:
- NOEL
- Generation:
- F1
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No effect observed at highest dose
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
Fertility and pregnancy data in female rats:
Dose (mg/kg bw/day) |
0 |
40 |
200 |
1000 |
Number of females |
12 |
12 |
12 |
12 |
Frequency of estrous |
3.7 ± 0.5 |
3.8 ± 0.4 |
3.5 ± 0.7 |
3.8 ± 0.6 |
Estrous interval |
4.08 ± 0.19 |
4.08 ± 0.19 |
4.63 ± 2.01 |
4.07 ± 0.16 |
Irregular estrous cycle |
0/12 |
1/12 |
2/12 |
1/12 |
Number of pairs used for mating |
12 |
12 |
12 |
12 |
Number of pairs with suffessful copulation |
12 |
12 |
12 |
12 |
Copulation rate (%) |
100.0 |
100.0 |
100.0 |
100.0 |
Mean copulatory interval (days) |
2.3 ± 1.4 |
2.8 ± 1.9 |
1.8 ± 0.8 |
3.0 ± 0.9 |
Number of fertile pairs |
12 |
11 |
11 |
12 |
Fertility rate (%) |
100.0 |
91.7 |
91.7 |
100.0 |
Not significantly different from control.
Delivery and litter data:
Dose (mg/kg bw/day) |
0 |
40 |
200 |
1000 |
Number of females examined |
12 |
11 |
11 |
12 |
Number of females with live pups |
12 |
11 |
11 |
12 |
Gestation index (%) |
100.0 |
100.0 |
100.0 |
100.0 |
Gestation period (days) |
21.96 ± 0.40 |
21.95 ± 0.42 |
22.18 ± 0.40 |
22.13 ± 0.43 |
Number of corpora lutea |
17.6 ± 1.7 |
16.9 ± 0.42 |
16.3 ± 2.1 |
16.1 ± 1.9 |
Number of implantation sites |
15.4 ± 1.9 |
15.5 ± 2.8 |
15.5 ± 1.8 |
14.8 ± 2.1 |
Implantation index (%) |
88.08 ± 11.30 |
91.63 ± 9.47 |
95.42 ± 7.66 |
91.68 ± 7.22 |
Delivery index (%) |
94.27 ± 5.71 |
90.07 ± 8.41 |
94.73 ± 3.79 |
96.18 ± 6.10 |
Number of pups delivered |
14.5 ± 1.8 |
14.0 ± 3.0 |
14.6 ± 1.7 |
14.2 ± 2.1 |
Number of live pups on Day 0 |
14.4 ± 1.7 |
13.5 ± 2.7 |
14.5 ± 1.8 |
14.0 ± 1.9 |
Live birth index (%) |
93.78 ± 5.97 |
87.46 ± 8.50 |
94.13 ± 4.49 |
95.18 ± 5.59 |
Sex ratio on Day 0 (male/total) |
0.50 ± 0.11 |
0.45 ± 0.08 |
0.49 ± 0.08 |
0.56 ± 0.14 |
Viability index on Day 0 (%) |
99.48 ± 1.79 |
97.23 ± 5.55 |
99.35 ± 2.14 |
99.02 ± 2.30 |
Number of live pups on Day 4 |
14.3 ± 1.6 |
13.3 ± 2.6 |
14.2 ± 2.0 |
13.8 ± 1.9 |
Sex ratio on Day 4 (male/total) |
0.51 ± 0.12 |
0.47 ± 0.08 |
0.49 ± 0.08 |
0.56 ± 0.14 |
Viability index on Day 4 (%) |
98.97 ± 2.41 |
98.14 ± 4.52 |
97.26 ± 3.85 |
98.85 ± 2.69 |
Body weight of pups Day 0 – Male |
6.68 ± 0.33 |
6.69 ± 0.45 |
6.68 ± 0.50 |
6.58 ± 0.37 |
Body weight of pups Day 0 – Female |
6.28 ± 0.44 |
6.42 ± 0.61 |
6.35 ± 0.48 |
6.14 ± 0.43 |
Body weight of pups Day 4 – Male |
10.38 ± 0.78 |
10.47 ± 1.16 |
10.60 ± 1.18 |
9.85 ± 1.14 |
Body weight of pups Day 4 – Female |
9.78 ± 0.86 |
10.06 ± 1.20 |
10.12 ± 1.15 |
9.33 ± 1.10 |
Not significantly different from control.
Applicant's summary and conclusion
- Conclusions:
- The NOEL/NOAEL for reproductive and developmental toxicity in rats were determined to be 1000 mg/kg bw/day since no effects were observed in the highest dose tested.
- Executive summary:
A combined repeated dose toxicity study with the reproduction/developmental screening test was performed with the test item according to OECD Guideline 422 (GLP study). Based on a preliminary 14 -days range-finding study, test item was administered orally to 12 male and female rats at 0 (control), 40, 200 and 1000 mg/kg bw/day for 42 days (from 14 days before mating, and through the mating period until a day before necropsy) and for 41-48 days (from 14 days before mating, and through the mating period until day 4 of lactation) respectively, to evaluate reproductive ability and viability and development of pups. Parental animals were subjected to necropsy at the end of the dosing. Pups were necropsied at Day 5 of lactation. No animals died in any test article group, and no test article related changes were observed in clinical signs, detailed observations, grip strength, locomotor activity, body weight, food consumption, hematology, blood chemistry, urinalysis (only perfomed in males), organ weight, necropsy, or histopathology. Related to the reproductive and devlopmental toxicity parameters, no test article-related changes were observed in any group in estrous cycle examination, copulation rate, fertility rate, gestation period, number of corporea lutea, number of implantations, implantation index, gestation index, delivery inidex, or nursing behaviour in dams. With respect to examination of pups, no test article related changes were observed in the number of pups delivered, number of live pups, live birth index, viability index or sex ration on Day 0 after birh, number of live pups, viability index or sex ration on Day 4 after birth, clinical signs, external examinations, body weight or necropsy. Accordingly, it was considered that the test article did not affect the developmental or growth of next generation. Based on these results, the NOEL/NOAEL for reproductive and developmental toxicity in rats was determined to be 1000 mg/kg bw/day since no effects were observed at the highest dose tested.
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