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EC number: 202-808-0 | CAS number: 99-99-0
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- fertility, other
- Remarks:
- based on test type (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- NTP study (standard protocol comparable to OECD 408 with acceptable restrictions (no post exposure period, slight deviations from guideline recommended housing conditions, limited chemical chemistry, not all recommended organs were weighed). Study indicative of reproduction toxicity.
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 992
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: 408
- Deviations:
- yes
- Remarks:
- (no post exposure period, slight deviations from guideline recommended housing conditions, limited chemical chemistry, not all recommended organs were weighed)
- Principles of method if other than guideline:
- NTP standard protocol for determination of subchronic toxicity after 90 days repeated dose application. Groups of rats animals were fed diets containing p-nitrotoluene for 13 weeks.
- GLP compliance:
- yes
Test material
- Reference substance name:
- 4-nitrotoluene
- EC Number:
- 202-808-0
- EC Name:
- 4-nitrotoluene
- Cas Number:
- 99-99-0
- Molecular formula:
- C7H7NO2
- IUPAC Name:
- 1-methyl-4-nitrobenzene
- Details on test material:
- - Source: Aldrich Chemical Co. (Milwaukee, WI),
- Analytical purity: >96%
- Impurities: < 1% (mostly m- and o-nitrotoluene)
- Storage: RT
- Stability: reanalysis performed at approx. 4 months intervals indicated that the test
substance was stable under the storage conditions chosen
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Taconic Farms, Inc. (Germantown, NY)
- Age at study initiation: 6 weeks
- Mean weight range at study initiation: 133 - 145g (male), 106 - 110g (female)
- Housing: 5/cage
- Diet: ad libitum, NIH-07 feed (Zeigler Brothers, Gardners, PA)
- Water ad libitum
- Acclimation period: 10-15 days
- Other: 5 viral screens performed at the study start and termination indicated no positive antibody titer
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.9 - 26.1
- Humidity (%): 32-90%
- Air changes (per hr): 16-29
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- daily
- Details on study schedule:
- Groups of rats animals were fed diets containing o-nitrotoluene for 13 weeks. Reproductive system evaluation were then performed in male and female animals
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 625, 1250, 2500, 5000, or 10000 ppm
Basis:
nominal in diet
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, plain diet
Results and discussion
Results: P0 (first parental generation)
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Effect level:
- 5 000 ppm (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: see 'Remark'
Results: F1 generation
Effect levels (F1)
- Dose descriptor:
- other: not measured/tested
- Generation:
- other: not measured/tested
- Based on:
- other: not measured/tested
- Remarks on result:
- not measured/tested
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
GROSS PATHOLOGY AND TESTES WEIGHTS AND HISTOPATHOLOGY Relative testis weights were unchanged in dosed animals. Potential treatment-related gross lesions were limited to 2 males from the 10000 ppm exposure group which had small testes. Microscopically, treatment-related lesions were found in the kidney, spleen, and testis of rats
REPRODUCTIVE ORGANS MALES Degeneration of the testis (minimal to mild) was seen in high-dose male rats; this was characterized by the absence of spermatogenesis, decreased number of germinal epithelial cells, and the presence of syncytial giant cells (degenerate spermatids) in a few seminiferous tubules, usually at the periphery of the testis. Epididymal sperm concentration and testicular spermatid head count were reduced in high dose males.
FEMALES Among females, 9/10 in the 10000 ppm group did not have a discernible estrous cycle. There were no gross or histopathologic changes in the uterus or ovaries at the end of this 13-week study
Table1:Summary of Reproductive Tissue Evaluations in Male Rats in the 13-Week Feed Study of p-Nitrotoluene (n=10 animals/dose)
Study Parameter |
| 0 ppm | 2500 ppm | 5000 ppm | 10000 ppm |
Weights (g) | Necropsy weight | 353 ± 6 | 344 ± 11 | 320 ± 6** | 251 ± 6** |
Left testicle | 1.51 ± 0.025 | 1.47 ± 0.045 | 1.42 ± 0.028 | 1.09 ± 0.079 ** | |
Left epididymis | 0.46 ± 0.011 | 0.45 ± 0.020 | 0.44 ± 0.012 | 0.13 ± 0.027 ** | |
Left epididymal tail | 0.18 ± 0.007 | 0.18 ± 0.009 | 0.20 ± 0.0018 | 0.13 ± 0.016 * | |
Spermatid measurements | Spermatid heads 107/ g testis | 10.13 ±0.42 | 9.81 ±0.41 | 9.73 ± 0.49 | 8.71 ± 0.82 |
Spermatid heads 107/ testis | 15.29 ±0.71 | 14.31 ±0.55 | 13.78 ± 0.64 | 10.03± 1.34 ** | |
Spermatid count (mean/104/ml suspension) | 76.43 ± 3.55 | 71. 55 ±2.74 | 68.90 ± 3.22 | 50. 15 ±6.70 ** | |
Spermatozoal Measurements | Motility (%) | 79 ±2 | 77 ±3 | 81 ±2 | 59 ± 11 |
Concentration (106/g cet)1 | 501 ± 45 | 604 ± 1123 | 451 ± 40 | 325 ± 60*3 |
1g cet = grams of caudal epididymal tissue.
* Significantly different (P<= 0.05) from the control group by Dunn's or Shirley's test.
** Significantly different (P<= 0.01) from the control group by Dunn's or Shirley's test.
Table 2:Summary of Estrous Cycle Characterization in Female Rats in the 13-Week Feed Study of p-Nitrotoluene (n= 10 animals/dose except where indicated)
|
| 0 ppm | 2500 ppm | 5000 ppm | 10000 ppm |
Necropsy body weight | - | 202 ±3 | 196 ±3 | 185 ±3** | 174 ±3 ** |
Estrous cycle length | - | 5. 15 ±0.13 | 5. 15 ±0.08 | 6.05 ± 0.51 | 5.002 |
Estrous stages as % of cycle | Diestrus | 45.8 | 45.0 | 55.0 | 78.3 |
Proestrus | 15.0 | 14.2 | 12.5 | 4.2 | |
Estrus | 24.2 | 25.8 | 20.0 | 11.7 | |
Metestrus | 15.0 | 15.0 | 12.5 | 5.8 |
2n=4, estrous cycle length longer than 12 days or unclear in 6 of 10 animals
3Evidence by multivariate analysis of variance (MANOVA) suggests that females in all dose groups differ from controls in the relative frequency of time spent in the estrous stages; P=0.06 for the 2,500 ppm group, P=0.04 for the 5,000 ppm group, and P = 0.01 for the 10,000 ppm group
** Significantly different (P<=0.01) from the control group by Dunn's or Shirley's test
Applicant's summary and conclusion
- Executive summary:
NTP, 1992
The study was comparable to OECD guideline 408 with acceptable deviations (no post exposure period, slight deviations from guideline recommended housing conditions, limited chemical chemistry, not all recommended organs were weighed).10 animals/sex/dose (F344/N rats) were fed diets containing p-nitrotoluene at nominal concentrations of 0, 625, 1250, 2500, 5000, or 10000 ppm. Only animals in the 3 highest dose groups were subjected to reproductive system evaluations. Gross and histopathological examinations of the reproductive systems indicated that p-nitrotoluene might be a reproduction toxicant. Relative testis weights were unchanged in dosed animals. Potential treatment-related gross lesions were limited to 2 males from the 10000 ppm exposure group which had small testes. Microscopically, treatment-related lesions were found in the kidney, spleen, and testis of rats. Degeneration of the testis (minimal to mild) was seen in high-dose male rats; this was characterized by the absence of spermatogenesis, decreased number of germinal epithelial cells, and the presence of syncytial giant cells (degenerate spermatids) in a few seminiferous tubules, usually at the periphery of the testis. Epididymal sperm concentration and testicular spermatid head count were reduced in high dose males. Among females, 9/10 in the 10000 ppm group did not have a discernible estrous cycle. There were no gross or histopathologic changes in the uterus or ovaries at the end of this 13-week study
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