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EC number: 408-090-7 | CAS number: 100418-33-5 METHYLGELB
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 992
- Report date:
- 1992
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- yes
Test material
- Reference substance name:
- 2-((4-methyl-2-nitrophenyl)amino)ethanol
- EC Number:
- 408-090-7
- EC Name:
- 2-((4-methyl-2-nitrophenyl)amino)ethanol
- Cas Number:
- 100418-33-5
- Molecular formula:
- C9H12N2O3
- IUPAC Name:
- 2-[(4-methyl-2-nitrophenyl)amino]ethan-1-ol
- Test material form:
- solid: crystalline
- Details on test material:
- red powder
Batch # : M266/4279
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Remarks:
- 0.5 %
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Test substance concentrations were performed colorimetrically. Deviations of +- 10 % of the target concentration were tolerated. Homogeneity and concentrations of the tested solutions of Hydroxyethyl-2-nitro-p-toluidine were analytically confirmed. The determined concentrations revealed mean values of 94 – 103 % of nominal. Thus, the nominal concentrations were used in the report. Investigation on homogeneity showed deviations of less than 5 %. Based on these results, a sufficient homogeneity in the chosen vehicle was demonstrated.
- Duration of treatment / exposure:
- 4 consecutive weeks
- Frequency of treatment:
- once daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Remarks:
- Control group
- Dose / conc.:
- 80 mg/kg bw/day (nominal)
- Dose / conc.:
- 240 mg/kg bw/day (nominal)
- Dose / conc.:
- 720 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control:
- no
Examinations
- Observations and examinations performed and frequency:
- Mortality, clinical signs and behavioural changes were recorded once daily and individual body weights and food consumption were recorded weekly. A detailed ophthalmologic investigation was performed before treatment and at day 28. Clinical laboratory investigations (haematology, blood/clinical biochemistry) were performed with 5 animals per sex and dose group at day 0 and day 28 and additionally on day 42 for selected parameters. Urine was collected in metabolism cages over night between the days –1/0, 27/28 and additionally between days 41/42 (satellite groups).
- Sacrifice and pathology:
- All animals were subjected to a detailed necropsy. Adrenals, kidneys, liver and testes were weighed and various tissues and organs were fixed and stored for further examination if required. The following organs/tissues of the control and high dose animals were examined histopathologically: adrenal glands, kidney, liver, heart and spleen. In addition, all gross lesions noted in any organ were also examined microscopically.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The observed staining of fur, tail and bedding material noted for all dose groups is attributed to the dying properties of the test substance and is therefore not regarded as a toxic change.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- The body weight development was not affected by the treatment with Hydroxyethyl-2-nitro-p-toluidine. The food consumption, although significantly decreased if compared to the controls in high dose females, did not affect the body weight development. For the high dose males a significant increase in food consumption was noted during the recovery period only. However, this had no influence on the body weight development.
- Ophthalmological findings:
- no effects observed
- Description (incidence and severity):
- The ophthalmologic examination revealed no abnormalities
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- In the high dose group some haematological parameters were affected. In particular, mean corpuscular haemoglobin concentration (MCHC) and lymphocytes were decreased in males, whereas the number of neutrophils was elevated. In females the Hb (hemoglobin concentration) and the RBC- (erythrocyte count) values showed a decrease if compared to the control. No clear dose-dependent effect was noted with regard to the haematocrit value. A statistically significant decrease was seen in the mid dose females, but not in the high dose females, where only a slight decrease was observed. In the animals observed until the end of the recovery period, only the MCHC values in males were significantly different to the control.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Statistically significant effects on clinical parameters were seen in the male high dose group only. Elevated levels for calcium, alkaline phosphatase, GOT, GPT and total bilirubin as well as decreased levels for glucose and cholesterol were noted. In females only, alkaline phosphatase was elevated, but without showing a statistically significant difference to the concurrent control. After the 2 week recovery period, the only noted statistically significant differences observed were elevated GOT and GPT levels in males.
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Urinalysis revealed a lower pH value for the high dose males (statistically significant) and for females (not statistically significant). The determination of other urinary parameters was compromised in some animals of all dose groups due to the intensive staining (dark yellow to dark red) of the urine. This discoloration of the urine was due to the renal excretion of the tested dye and was thus not considered as a toxic effect. However, it clearly demonstrates the bioavailability of Hydroxyethyl-2-nitro-p-toluidine after oral exposure. All other urine parameter besides colour and pH-value revealed no differences to the concurrent controls. The intensive colouring of the urine as well as the lower pH value was still noted in the animals of high dose group at the end of the recovery period.
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The weights of some organs varied in a statistically significant manner. However, the effect noted for kidney weights reveal no dose-response and no consistent alteration for the contra-lateral organ. Therefore those variations are considered as incidental. The effects noted in females of the mid dose group (lower relative adrenal weight) is most likely due to the high body weight of this group at this observation time point as all relative organ weights were lower in this group, but without reaching statistical significance. This variation is therefore also not considered as treatment related. In summary, the increase in the relative liver weights of high dose males is judged as substance related effect, as effects on marker enzymes for a potential liver damage were also noted in this group.
- Description (incidence and severity):
- The gross necropsy revealed some tissue staining especially for the high dose groups. In the mid and high dose males one animal revealed a red thymus; no other lesions were noted. For the recovery groups besides some external staining (fur and or tail) no lesions were observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- The histopathological examination revealed no treatment related findings.
- Histopathological findings: neoplastic:
- no effects observed
- Description (incidence and severity):
- The histopathological examination revealed no treatment related findings.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 240 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- clinical biochemistry
- organ weights and organ / body weight ratios
- urinalysis
Target system / organ toxicity
- Critical effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- Treatment-related and toxicologically relevant effects (statistically significantly elevated liver weights and increased clinical chemistry values like GOT, GPT or alkaline phosphatase in males; decreased Hb- and RBC-values in females) were observed at the highest tested dose of 720 mg/kg bw/day. This was not the case for the next lower dose of 240 mg/kg bw/day. Therefore, a No Observed Adverse Effect Level (NOAEL) of 240 mg/kg bw/day was deduced from this 28-day oral toxicity study with Hydroxyethyl-2-nitro-p-toluidine.
- Executive summary:
Doses of 80, 240, 720 mg/kg bw/day Hydroxyethyl-2-nitro-p-toluidine (dissolved in bi-distilled water containing 0.5 % CMC) were administered daily to groups of 5 male and 5 female Wistar Crl: (Wi)/Br (SPF) rats by gavage in a total volume of 10 ml/kg bw over a period of 4 consecutive weeks. A control group of equal size received the same dose volume of the vehicle (10 ml/kg, 0.5 % CMC) daily throughout the dosing period. For recovery observations, satellite groups of additional 5 males and 5 females for the control and the high dose groups, respectively, were investigated after a 2-week treatment-free period. Mortality, clinical signs and behavioural changes were recorded once daily and individual body weights and food consumption were recorded weekly. A detailed ophthalmologic investigation was performed before treatment and at day 28. Clinical laboratory investigations (haematology, blood/clinical biochemistry) were performed with 5 animals per sex and dose group at day 0 and day 28 and additionally on day 42 for selected parameters. Urine was collected in metabolism cages over night between the days –1/0, 27/28 and additionally between days 41/42 (satellite groups). All animals were subjected to a detailed necropsy. Adrenals, kidneys, liver and testes were weighed and various tissues and organs were fixed and stored for further examination if required. The following organs/tissues of the control and high dose animals were examined histopatho-logically: adrenal glands, kidney, liver, heart and spleen. In addition, all gross lesions noted in any organ were also examined microscopically. Homogeneity and concentrations of the tested solutions of Hydroxyethyl-2-nitro-p-toluidine were analytically confirmed. The determined concentrations revealed mean values of 94 – 103 % of nominal. Thus, the nominal concentrations were used in the report. Investigation on homogeneity showed deviations of less than 5 %. Based on these results, a sufficient homogeneity in the chosen vehicle was demonstrated.
No deaths and no treatment-related clinical signs were noted in any animal (besides salivation in the high dose group). The observed staining of fur, tail and bedding material noted for all dose groups is attributed to the dying properties of the test substance and is therefore not regarded as a toxic change. The body weight development was not affected by the treatment with Hydroxyethyl-2-nitro-p-toluidine. The food consumption, although significantly decreased if compared to the controls in high dose females, did not affect the body weight development. For the high dose males a significant increase in food consumption was noted during the recovery period only. However, this had no influence on the body weight development. The ophthalmologic examination revealed no abnormalities. In the high dose group some haematological parameters were affected. In particular, mean corpuscular haemoglobin concentration (MCHC) and lymphocytes were decreased in males, whereas the number of neutrophils was elevated. In females the Hb (hemoglobin concentration) and the RBC- (erythrocyte count) values showed a decrease if compared to the control. No clear dose-dependent effect was noted with regard to the haematocrit value. A statistically significant decrease was seen in the mid dose females, but not in the high dose females, where only a slight decrease was observed. In the animals observed until the end of the recovery period, only the MCHC values in males were significantly different to the control. Statistically significant effects on clinical parameters were seen in the male high dose group only. Elevated levels for calcium, alkaline phosphatase, GOT, GPT and total bilirubin as well as decreased levels for glucose and cholesterol were noted. In females only, alkaline phosphatase was elevated, but without showing a statistically significant difference to the concurrent control. After the 2 week recovery period, the only noted statistically significant differences observed were elevated GOT and GPT levels in males. Urinalysis revealed a lower pH value for the high dose males (statistically significant) and for females (not statistically significant). The determination of other urinary parameters was compromised in some animals of all dose groups due to the intensive staining (dark yellow to dark red) of the urine. This discoloration of the urine was due to the renal excretion of the tested dye and was thus not considered as a toxic effect. However, it clearly demonstrates the bioavailability of Hydroxyethyl-2-nitro-p-toluidine after oral exposure. All other urine parameter besides colour and pH-value revealed no differences to the concurrent controls. The intensive colouring of the urine as well as the lower pH value was still noted in the animals of high dose group at the end of the recovery period. The gross necropsy revealed some tissue staining especially for the high dose groups. In the mid and high dose males one animal revealed a red thymus; no other lesions were noted. For the recovery groups besides some external staining (fur and or tail) no lesions were observed.
The weights of some organs varied in a statistically significant manner. However, the effect noted for kidney weights reveal no dose-response and no consistent alteration for the contra-lateral organ. Therefore those variations are considered as incidental. The effects noted in females of the mid dose group (lower relative adrenal weight) is most likely due to the high body weight of this group at this observation time point as all relative organ weights were lower in this group, but without reaching statistical significance. This variation is therefore also not considered as treatment related. In summary, the increase in the relative liver weights of high dose males is judged as substance related effect, as effects on marker enzymes for a potential liver damage were also noted in this group. The histopathological examination revealed no treatment related findings.
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