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EC number: 203-583-1 | CAS number: 108-44-1
- 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
![](https://poisoncentres.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Endpoint summary
Administrative data
Description of key information
In a study according to OECD TG 422 and GLP conditions male and female
SD (Crj:CD) rats received 0, 30, 100, or 300 mg/kg bw/day m-toluidine by
gavage (MHLW 1995). Hematological and biochemical analysis was conducted
only for males. Compound related clinical signs were low locomotor
activity and pale skin at 300 mg/kg bw. At the lowest dose of 30 mg/kg
bw marginal deposit pigmentation and extramedullary hematopoiesis in the
spleen were observed suggesting that a slight hemolysis occurred..
Therefore, the dose of 30 mg/kg bw/day should be considered to be
adverse effect level because of suggestive evidence of hemolytic anemia.
LOAEL for repeat dose toxicity was 30 mg/kg bw/day (UNEP 2003).
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Remarks:
- Combined repeated dose and reproduction / developmental screening test
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Reason / purpose for cross-reference:
- reference to same study
- 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
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- initial bw (females): 200-247 g
initial bw (males): 267-361g
acclimisation: 5 days
temperature of the animal room: 24 °C
relative humidity: 55 %
lighting 12 hours light 12 hours dark
food ad libitum,
water ad libitum
pregnant females should be caged individually - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- Dosing of both sexes should begin 2 weeks prior to mating, continued through mating period(14d).
Males: dosing continued up to the day when females are killed.
Females. dosing continued throughout pregnancy and up to day 4 of lactation. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- data not given
- Duration of treatment / exposure:
- Males 42 days;
Females: from day 14 prior to mating to day 3 of lactation ( ca.42 days) - Frequency of treatment:
- Daily
- Remarks:
- Doses / Concentrations:
0, 30, 100, 300 mg/kg bw/day
Basis:
actual ingested - No. of animals per sex per dose:
- 13
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- As required by OECD TG 422
- Positive control:
- no
- Observations and examinations performed and frequency:
- At least once per day:
--behavioual changes , signs of difficult or prolonged parturition, mortality and all signs of toxicity
--cage side observations: changes in skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system function
--food cinsumption, males and females should be weighed
--duration of gestation, examination of the litter as soon as possible: number and sex of pups, stillbirth, live birth, pup weight, and the presence of gross anomalies
clinical examinations: hematology, clinical chemistry, urinalysis
Pathology: gross necropsy, histopathology - Sacrifice and pathology:
- --sacrifice:
male: day 43;
females: day 4 of lactation
--organ weights of all parental animals:
reported: liver, kidney,thymus, testes, epididymides , not reported: adrenals, brain, heart, spleen, ovaries and
--Gross necropsy
examination for macroscopic changes
--histological examination
preserved organs : male and female
brain, liver, thymus, spleen, heart, kidney, adrenal,urinary bladder, testis, epididymis, ovar
- Other examinations:
- As required by OECD TG 422
- Statistics:
- yes
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- effects observed, treatment-related
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
no deaths occurred during the study,
clinical signs included: brownish urine, increased salivation in males and females receiving 100 mg/kg bw/day and more , pale extremies at 300 mg/kg bw in males and females
BODY WEIGHT AND WEIGHT GAIN
mean body weight gain during week 1 of the 300 mg/kg bw/day males and of the 100 and 300 mg/kg bw/day females was significantly lower than those of the controls
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
mean food consumption of the 300 mg/kg bw/day males and females was significantly reduced at week 1
HAEMATOLOGY (significant changes only)
No female data were mentioned
Males
in the 100 and 300 mg/kg bw/day males values for erythrocyte count, hemoglobin concentration and hematocrit were decreased and mean corpuscular volume was increased.
At 300 mg/kg bw/day males mean corpuscular hemoglobin was significantly increased, mean corpuscular hemoglobin concentration was decreased.At 300 mgU/kg bw/day: in the differential blood picture segmented neutrophils and monocytes were significantly reduced as well as lymphocytes and platelet count
CLINICAL CHEMISTRY
no female data were mentioned
males
in the 100 and 300 mg/kg bw/day males the A/G ratio, , serum bilirubin, potassium and chloride levels significantly increased with the dose
in the 300 mg/kg bw/day males significant increases in serum glucose and total cholesterol levels
in the 300 mg/kg bw/day males significant decreases in albumin, phospherous and GOT levels
NEUROBEHAVIOUR
low motor activity and pale extremities in males and females given 300 mg/kg bw/day
ORGAN WEIGHTS
relative kidney weights of the 300 mg/kg bw/day males and females were significantly greater than those of the controls
PATHOLOGY
HISTOPATHOLOGY: NON-NEOPLASTIC
--from30 mg/kg bw/day onwards a slight increase in severity of pigmentation or extramedullary hematopoiesis in the spleen in males and females were noted
--Pigment deposites and extramedullary hematopoiesis in the liver and spleen and congestion in the spleen in males and females that received 100 mg/kg bw/day and more.
--Swelling of hepatocytes in centrilobular zone in 100 mg/kg bw/day males and in the 300 mg/kg bw/day males and females;
--deposits of pigment in the renal tubular epithelium in 300 mg /kg bw/day males and females
--eosiophilic droplets in the renal tubular epithelium in males given 100 mg/kg bw/day and more;
--regenerated renal tubules in females given 100 mg/kg bw/day and more
--focal hyperplasia of epithelium in the urinary bladder in the 300 mg/kg bw/day males
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 30 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: based on suggestive evidence of hemolytic anemia such as marginal pigment deposit and extramedullary hematopoiesis in the spleen probabely caused by methemoglobin formation.
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 30 mg/kg bw/day (nominal)
- System:
- haematopoietic
- Organ:
- spleen
- Treatment related:
- yes
- Dose response relationship:
- yes
- Executive summary:
In a study according to OECD TG 422 and GLP male and female SD (Crj:CD) rats received 0, 30, 100, or 300 mg/kg bw/day m-toluidine by gavage (MHLW 1995). Hematological and biochemical analysis was conducted only for males.
Compound related clinical signs were low locomotor activity and pale skin at 300 mg/kg bw. Erythrocyte countes, blood hemoglobin concentration and hematocrit were decreased at 100 and 300 mg/kg bw of males. Histopathological lesions of both sexes were deposit of pigmentation and extramedullary hematopoiesis in the liver at 100 and 300 mg/kg bw and in the spleen at 30 mg/kg bw and more. Other histological findings were very slight hepatocyte swelling at 100 mg/kg bw males and 300 mg/kg bw males and females and change in renal tubular epithelium with pigment deposit at 100 and 300 mg/kg bw of both sexes.
At the lowest dose of 30 mg/kg bw marginal deposit pigmentation and extramedullary hematopoiesis in the spleen were observed suggesting that a slight hemolysis occurred. Additionally there are sufficient evidences that this chemicals induced methemoglobinemia but methemoglobin content was not determined in this study. Therefore, the dose of 30 mg/kg bw/day should be considered to be adverse effect level because of suggestive evidence of hemolytic anemia. LOAEL for repeat dose toxicity was 30 mg/kg bw/day (UNEP 2003)
Reference
no further data with respect of repeated dose toxicity
based on suggestive evidence of hemolytic anemia such as marginal pigment deposit and extramedullary hematopoiesis in the spleen probabely caused by methemoglobin formation.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LOAEL
- 30 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- This is the only reliable repeated dose toxicity study bercause it was performed according to the respective OECD Guideline under GLP condition and therefore evaluated with Klimisch score 1. Furthermore, the study meets the requirements of REACh for the tonnage band.
Additional information
In a study according to OECD TG 422 and GLP male and female SD (Crj:CD) rats received 0, 30, 100, or 300 mg/kg bw/day m-toluidine by gavage (MHLW 1995). Hematological and biochemical analysis was conducted only for males.
Compound related clinical signs were low locomotor activity and pale skin at 300 mg/kg bw. Erythrocyte countes , blood hemoglobin concentration and hematocrit were decreased at 100 and 300 mg/kg bw of males. Histopathological lesions of both sexes were deposit of pigmentation and extramedullary hematopoiesis in the liver at 100 and 300 mg/kg bw and in the spleen at 30 mg/kg bw and more. Other histological findings were very slight hepatocyte swelling at 100 mg/kg bw males and 300 mg/kg bw males and females and change in renal tubular epithelium with pigment deposit at 100 and 300 mg/kg bw of both sexes.
At the lowest dose of 30 mg/kg bw marginal deposit pigmentation and extramedullary hematopoiesis in the spleen were observed suggesting that a slight hemolysis occurred. Additionally there are sufficient evidences that this chemicals induced methemoglobinemia but menthemoglobin content was not determinded in this study. therefore, the dose of 30 mg/kg bw/day should be considered to be adverse effect level because of suggestive evidence of hemolytic anemia. LOAEL for repeat dose toxicity was 30 mg/kg bw/day (UNEP 2003)
Justification for classification or non-classification
In a study according to OECD TG 422 and GLP conditions male and female SD (Crj:CD) rats received 0, 30, 100, or 300 mg/kg bw/day m-toluidine by gavage (MHLW 1995). Hematological and biochemical analysis was conducted only for males. Compound related clinical signs were low locomotor activity and pale skin at 300 mg/kg bw. At the lowest dose of 30 mg/kg bw marginal deposit pigmentation and extramedullary hematopoiesis in the spleen were observed suggesting that a slight hemolysis occurred.. Therefore, the dose of 30 mg/kg bw/day should be considered to be adverse effect level because of suggestive evidence of hemolytic anemia. LOAEL for repeat dose toxicity was 30 mg/kg bw/day (UNEP 2003).
According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification as STOT Rep. Exp. 2 ( H373: May cause damage to organs) is justified.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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