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EC number: 201-853-3 | CAS number: 88-72-2
- 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
- Type of information:
- experimental study
- Adequacy of study:
- supporting 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 o-nitrotoluene for 13 weeks.
- GLP compliance:
- yes
Test material
- Reference substance name:
- 2-nitrotoluene
- EC Number:
- 201-853-3
- EC Name:
- 2-nitrotoluene
- Cas Number:
- 88-72-2
- Molecular formula:
- C7H7NO2
- IUPAC Name:
- 1-methyl-2-nitrobenzene
- Details on test material:
- - Source: Aldrich Chemical Co. (Milwaukee, WI),
- Analytical purity: >96%
- Impurities: < 1% (mostly m- and p-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: 132 - 145g (male), 110 - 116g (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 (45, 89, 179, 353, 694 mg/kg bw in male rats and 44, 87, 178, 340, 675 mg/kg bw in females; estimated from consumed diet)
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)
open allclose all
- Dose descriptor:
- LOAEL
- Effect level:
- 179 mg/kg bw/day (nominal)
- Sex:
- male
- Basis for effect level:
- other: see 'Remark'
- Dose descriptor:
- NOAEL
- Effect level:
- 340 mg/kg bw/day (nominal)
- Sex:
- female
- Basis for effect level:
- other: see 'Remark'
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
GROSS PATHOLOGY AND TESTES WEIGHTS AND HISTOPATHOLOGY
In all males from the 10000 ppm exposure group, the testes was smaller than in controls; alterations in the color (pale, mottled focus) of testis were also observed. Absolute testis weights at 5000 and 10000 ppm dose groups experienced a statistically significant reduction by 71.7% and 36.6%, respectively compared to controls. Relative testis weight in the 10000 ppm dose group was reduced by 34.5% compared to controls (p <= 0.01).
Absolute epididymal weights were markedly lower than controls in animals in the 2500, 5000, and 10000 ppm groups by 20, 44 and 76%, respectively.
REPRODUCTIVE ORGANS
MALES
In animals of the 5000 and 10000 ppm dose group, a decrease in epididymal sperm motility (6.5% and 73.1%, respectively versus 78% in control) and epididymal sperm concentration (179 million and 14 million, respectively versus 417 million/g caudal epididymal tissue) and in testicular spermatid count/ 1E +05 ml (70.1 and 11.9, respectively versus 91.5) was seen in rats from the 5000 and 10000 ppm groups. Testicular degeneration was seen in rats from the 5000 (10/10 animals, moderate) and 10000 ppm groups (10/10 animals, marked).
FEMALES
There were no histopathologic, treatment-related effects in the uterus or ovaries in any group. Only effect seen was an increase in estrous cycle length in the females of the highest dose group (10000 ppm, ca 6.63 days versus 4.90 in controls), with only 4/10 animals having a measurable estrous cycle (see table 2 below)
Table1:Summary of Reproductive Tissue Evaluations in Male Rats in the 13-Week Feed Study of o-Nitrotoluene (n=10 animals/dose)
Study Parameter |
| 0 ppm | 2500 ppm | 5000 ppm | 10000 ppm |
Weights (g) | Necropsy weight | 353 ± 5 | 309 ± 6** | 254 ± 4** | 198 ± 3** |
Left testicle | 1.48 ± 0.028 | 1.39 ± 0.025* | 1.07 ± 0.045** | 0.54 ± 0.024 ** | |
Left epididymis | 0.50 ± 0.011 | 0.40 ± 0.014 ** | 0.28 ± 0.012 | 0.12 ± 0.008 ** | |
Left epididymal tail | 0.20 ± 0.010 | 0.16 ± 0.008 * | 0.12 ± 0.007 ** | 0.05 ± 0.003 ** | |
Spermatid measurements | Spermatid heads 107/ g testis | 12.4 ± 0.44 | 12.58 ± 0.48 | 13.17 ± 0.85 | 4.41 ± 1.19 ** |
Spermatid heads 107/ testis | 18.3 ± 0.65 | 17.39 ± 0.62 | 14.02 ± 0.97 ** | 2.35 ± 0.63 ** | |
Spermatid count (mean/104/ml suspension) | 91.48 ± 3.23 | 86.93 ± 3.11 | 70.08 ± 4.83 ** | 11.88 ± 3.10 ** | |
Spermatozoal Measurements | Motility (%) | 78 ± 1 | 76 ± 2 | 73 ± 1* | 6.5 ± 5.5 ** |
Concentration (106/g cet)1 | 417 ± 28 | 433 ± 38 | 179 ± 22** | 14 ± 5 ** |
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 o-Nitrotoluene (n= 10 animals/dose except where indicated)
|
| 0 ppm | 2500 ppm | 5000 ppm | 10000 ppm |
Necropsy body weight | - | 205 ± 3 | 179 ± 3 ** | 170 ± 2 ** | 158 ± 3 ** |
Estrous cycle length | - | 4.9 ± 0.1 | 4.7 ± 0.17 | 5.3 ± 0.21 | 6.63± 0.8 **2 |
Estrous stages as % of cycle | Diestrus | 36.7 | 39.2 | 40.8 | 62.5 |
Proestrus | 7.5 | 15.8 | 15.0 | 10.8 | |
Estrus | 32.5 | 25.0 | 25.0 | 15.8 | |
Metestrus | 23.3 | 20.0 | 19.2 | 10.8 |
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) Repeated Dose Toxicity (oral).10 animals/sex/dose (F344/N rats) were fed diets containing o-nitrotoluene at nominal concentrations of 0, 625, 1250, 2500, 5000, or 10000 ppm. Compound intake via feed over the entire study period of 13 weeks was estimated at 45, 89, 179, 353, 694 mg/kg bw in male rats and 44, 87, 178, 340, 675 mg/kg bw in females. Only animals in the 3 highest dose groups were subjected to reproductive system evaluations. Gross and histopathological examinations of the reproductive systems indicated that o-nitrotoluene might be a reproduction toxicant. Testicular degeneration (5000 and 10000 ppm) with concomitant decrease in testicular spermatid heads counts (5000 and 10000 ppm), decrease in sperm motility (5000 and 10000 ppm) and decrease in sperm concentrations (5000 and 10000 ppm) in the caudal epididymal tissue, were seen in male rats. Small testes (10000 ppm), reduced absolute (5000 and 10000 ppm) and relative testes weights (10000 ppm) and reduced absolute epididymis weights (2500, 5000 and 10000 ppm) were also seen. In female rats, o-nitrotoluene increased the length of the oestrus cycle at the nominal concentration of 10000 ppm in diet. LOAEL (male) is <=179 mg/kg bw/d. NOAEL (female) is 340 mg/kg bw/d.
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