Registration Dossier
Registration Dossier
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 202-429-0 | CAS number: 95-53-4
- 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

Endpoint summary
Administrative data
Description of key information
acute oral toxicity: LD 50= 750 mg/ kg bw;
acute inhalative toxicity: LD50= 862 ppm;
acute dermal toxicity: LD50=3250 mg/kg bw
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study with acceptable restrictions (no necropsy and no histopathological examinations were performed)
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- yes
- Remarks:
- Analytical purity not reported. Females were not tested. Fasting of animals not reported. No necropsy and no histopathological examinations. Body weights not recoreded. Few informations on environmental conditions.
- GLP compliance:
- no
- Remarks:
- GLP was not mandatory at the time of the study
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Wistar-II
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Winkelmann, Germany
- Age: 6 - 7 weeks
- Weight at study initiation: 160 -180 g
-Housing conditions. animals were housed in groups of 5 per cage
- Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- single oral application of different doses of undiluted substance to groups of male rats
- Doses:
- 0.600 - 0.650 - 0.700 - 0.800 - 0.900 mL/kg bw, undiluted (corresponding to 600, 650, 700, 800, 900 mg/kg bw (density: 0.998 g/cm³)
- No. of animals per sex per dose:
- 10
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs - Statistics:
- Calculation of the median lethal dose (LD50) according to Fink and Hund (Arzneim. Forsch. 15, 1965, 624)
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 750 mg/kg bw
- 95% CL:
- 710 - 790
- Mortality:
- Dose [ml/kg bw]: 600 mg/kg: 0/10 650 mg/kg: 1/10 4d post application 700 mg/kg: 4/10 within 3-4 days post application 800 mg/kg: 6/10 within 2-4 days post application 900 mg/kg: 10/10 within 2-5 days post application
- Clinical signs:
- other: 600 mg/kg: reduced general condition at day 2; 650 mg/kg: reduced general condition, anesthesia day 1 up to day 14; 700 mg/kg: reduced general condition, anaesthesia, increased diurese - day 1 up to day 14; 800 mg/kg: reduced general
- Executive summary:
Löser E (1978)
In male Wistar rats (n = 10) dosed with 0.6, 0.65, 0.7, 0.8 or 0.9 ml/kg bw (app. 600, 650, 700, 800 or 900 mg/kg bw) undiluted o-toluidine, deaths occurred at dose levels of = 0.65 ml/kg bw within 2 - 5 days after application. In moribund animals anesthesia, increased diurese, cyanosis, bloody eyes were observed. No necropsy and no histopathological examinations were performed. From this study a LD50 value of 0.75 ml/kg bw (corresponding to 750 mg/kg bw) was derived. This study was conducted with a method similar to OECD guideline 401 with acceptable deviations (Analytical purity not reported. Females were not tested. Fasting of animals not reported. No necropsy and no histopathological examinations. Body weights not recoreded. Few informations on environmental conditions of the animals.)
Reference
MORTALITY:
Dose [ml/kg bw]:
600 mg/kg: 0/10
650 mg/kg: 1/10 4d post application
700 mg/kg: 4/10 within 3-4 days post application
800 mg/kg: 6/10 within 2-4 days post application
900 mg/kg: 10/10 within 2-5 days post application
CLINICAL SIGNS:
600 mg/kg: reduced general condition at day 2
650 mg/kg: reduced general condition, anesthesia
day 1 up to day 14
700 mg/kg: reduced general condition, anaesthesia,
increased diurese - day 1 up to day 14
800 mg/kg: reduced general condition, anaesthesia,
cyanosis, bloody eyes - day 1 up to day 14
900 mg/kg: reduced general condition, anaesthesia,
cyanosis, bloody eyes - day 1 up to time of
death
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 750 mg/kg bw
- Quality of whole database:
- There is a reliable study which is performed equal to the current guidelines and therefore evaluated with Klimisch score 2
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Although only adopted from OECD SIDS Report published by UNEP basic data are given and significant symptoms are reported to evaluate this toxicological endpoint
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- Principles of method if other than guideline:
- LC50 was calculated with the Probit Analysis, Finney DJ, 3rd ed. Cambridge University Press.
- GLP compliance:
- not specified
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 8 weeks
- Weight at study initiation: 230-260 g
- Route of administration:
- inhalation
- Type of inhalation exposure:
- head only
- Vehicle:
- other: air
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE
The atmosphere was generated by passing nitrogen over o-toluidine liquid contained in a 3-neck round-bottom flask heated from 115 to 120°C. The vapor/aerosol was diluted with humified and O2-enriched houseline air and passed into the exposure chamber. Test atmosphere was regularly controlled. - Duration of exposure:
- 4 h
- Concentrations:
- 492, 606, 722, 799, 848, 931, 1000 ppm (approx. 2184, 2691, 3206, 3548, 3765, 4134, 4440 mg/m³)
- No. of animals per sex per dose:
- 10
- Control animals:
- other: not applicable
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weights and clinical signs were observed daily - Statistics:
- LC50 calculated with the Probit Analysis, Finney DJ, 3rd ed. Cambridge University Press.
- Sex:
- male
- Dose descriptor:
- LC50
- Effect level:
- 862 ppm
- 95% CL:
- 816 - 913
- Exp. duration:
- 4 h
- Remarks on result:
- other: ca. 3827 mg/m³: clinical signs included cyanosis, labored breathing, lethargy
- Mortality:
- 492 ppm: 0/10
606 ppm: 0/10
722 ppm: 1/10
799 ppm: 2/10
848 ppm: 6/10
931 ppm: 5/10
1000 ppm: 10/10 - Clinical signs:
- other: Compound related signs of intoxication, observed during and immediately following exposure, consisted of tremor, slight to moderate cyanosis, muscle spasm, labored breathing, slight to moderate corneal opacity, prostation and semi- prostation, and redd
- Body weight:
- Body weight losses of 6 to 22 % were observed 1 to 3 days post exposure, with normal weight gains occurring thereafter (individual animal data not given).
- Executive summary:
DuPont Chem, 1981, cited in OECS SIDS for o-toluidine in 2005, reported of groups of ten male rats that were exposed head-only to o-toluidine-vapor/aerosol for 4 hours in concentrations ranging from 492 up to 1000 ppm (corresponding to 2184 - 4440 mg/m3). Death occurred at 722 ppm (3206 mg/m3) in 1/10 rats on day 3 post exposure and the concentration of 1000 ppm (4440 mg/m3) was lethal to all animals within 24 hours post exposure. Major treatment related clinical signs included cyanosis, labored breathing, lethargy, prostration, reddish-brown nasal discharge and stained wet perinea, symptoms which show clear evidence for methemoglobinemia. In this study no histopathological investigations were performed. The calculated LC50 value is 862 ppm (3827 mg/m³).
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LC50
- Value:
- 3 827 mg/m³ air
- Quality of whole database:
- A peer reviewed publication describes this inhalation study providing information that leads to evaluation with Klimisch Score 2
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Basic data given (No data on mortality, no data on clinical signs, no necropsy and no histopathological examinations were performed/reported)
- Principles of method if other than guideline:
- according to Draize et al., J.Pharmacol.Exper.Therap. 82, 377 (1944)
- GLP compliance:
- no
- Remarks:
- GLP was not mandatory at the time of the study
- Test type:
- standard acute method
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male
- Type of coverage:
- occlusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- -Type of wrap: plastic film
- Duration of exposure:
- 24 h
- Doses:
- No data on the doses employed were given in the publication. However, the publication stated that doses above 20 mL/kg could not be retained in contact with the skin of the animals
- No. of animals per sex per dose:
- 4
- Control animals:
- no
- Details on study design:
- Penetration of rabbit skin was estimated by a technique closely alike to the one-day cuff method of Draize and associates. Before application, the fur was clipped from the entire trunk of the animals and the substance applied under a plastic film for 24h within which time the animals were immobilized (type of wrap: occlusive). The film was removed at the end of the application period and the animals were subsequently caged and observed for another 14d. LD 50 and its fiducial range were estimated by the method of Thompson (Use of Moving averages and interpolation to Estimate Median Effective Dose. Bacteriol. Rev. 1 115 (June 1947)) using the tables of Weils (Tables for Convenient Calculation of Median-Effective Dose (LD50 or: ED 50) and Instructions in Their Use. Biometrics 8: 249 (Sept. 1952))
- Statistics:
- LD 50 and its fiducial range were estimated by the method of Thompson (Use of Moving averages and interpolation to Estimate Median Effective Dose. Bacteriol. Rev. 1 115 (June 1947)) using the tables of Weils (Tables for Convenient Calculation of Median-Effective Dose (LD50 or: ED 50) and Instructions in Their Use. Biometrics 8: 249 (Sept. 1952))
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 3 250 mg/kg bw
- 95% CL:
- 2 010 - 5 250
- Mortality:
- No data on mortality
- Clinical signs:
- other: No data on clinical symptoms
- Gross pathology:
- No data on necropsy
- Executive summary:
Penetration of rabbit skin was estimated by a technique closely alike to the one-day cuff method of Draize and associates using groups of 4 male rabbits. Before application, the fur was clipped from the entire trunk of the animals and the substance (2010 -5250 ml/kg bw) applied under a plastic film for 24h within which time the animals were immobilized (type of wrap: occlusive). The film was removed at the end of the application period and the animals were subsequently caged and observed for another 14d. LD50 value of 3250 mg/kg bw was calculated
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 3 250 mg/kg bw
- Quality of whole database:
- This is a reliable study performed by a method equal to the respective guideline and therefore evaluated with Klimisch score 2
Additional information
OECD SIDS
Studies in Animals
Inhalation
Groups of ten male rats were exposed head-only to o-toluidine-vapor/aerosol for 4 hours in concentrations ranging from 492 up to 1000 ppm (corresponding to 2184 - 4440 mg/m3). Death occurred at 722 ppm (3206 mg/m3) in 1/10 rats on day 3 post exposure and the concentration of 1000 ppm (4440 mg/m3) was lethal to all animals within 24 hours post exposure. Major treatment related clinical signs included cyanosis, labored breathing, lethargy, prostration, reddish-brown nasal discharge and stained wet perinea. In this study no histopathological investigations were performed. The calculated LC50value is 862 ppm (3827 mg/m3, DuPont Chem, 1981).
Dermal
Dermal application of 2010 - 5250 ml/kg bw over a period of 24 hours followed by a 14-day observation period yielded a LD50value of 3250 mg/kg bw using groups of 4 male rabbits and the one-day cuff method of Draize (Smyth et al., 1962). Signs of toxicity and individual animal data were not reported. In a further study with female Wistar rats single dermal application of 0.75, 1, or
1.25 % o-toluidine-solution (dosing volume not mentioned) resulted in dose-related increase in
methemoglobinemia up to 8 - 10 % (Senczuk and Rucinska 1984).
Oral
There are no studies according to the current OECD Test Guidelines, but there is one study, which is adequately documented and is considered of sufficient quality to allow an evaluation of this endpoint. In male Wistar rats (n = 10) dosed with 0.6, 0.65, 0.7, 0.8 or 0.9 ml/kg bw (app. 600, 650, 700, 800 or 900 mg/kg bw) undiluted o-toluidine deaths occurred at dose levels of = 0.65 ml/kg bw within 2 - 5 days after application. In moribund animals anesthesia, increased diurese, cyanosis, bloody eyes were observed. No necropsy and no histopathological examinations were performed.
From this study a LD50value of 0.75 ml/kg bw (corresponding to 750 mg/kg bw) was derived (Bayer AG, 1978).
Oral administration of 50 mg/kg bw o-toluidine to 2 cats per sex resulted in 59.6 to 71.7 % methemoglobin within 4 hours after administration, lateral position, tachypnea, cyanosis mydriasis, apathy, salivation and the death of one cat. During the 14 day-observation period, one cat was in poor condition and 2 cats recovered (BASF AG, 1979).
Studies in Humans
Cases of poisoning of workers with o-toluidine following acute exposure are described e.g.
Stark, 1892, cited in Greim (1997), who reported of a worker who inhaled vapor of toluidine (isomer not specified) during the transfer from one open vessel to another one. He lost consciousness, was cyanotic, exhaled levels of toluidine and suffered from strangury and blood was detected in the urine. Full recovery required 5 weeks. In another case, during repair of machines, a fitter was accidentally exposed against o-toluidine (exposure route probably: inhalation, concentration not given). Treatment with tolonium chloride reduced methemoglobinemia from 39.6 % to 2.6 % (BASF AG, 1989). Goldblatt (1955), reported in a survey article that concentrations of 40 ppm (176 mg/m3) toluidine (isomere not specified) in the atmosphere for more than 60 minutes caused severe toxic effects in workers, 10 ppm (44 mg/m3) lead to symptoms of illness and concentration in the atmosphere greater than 5 ppm (22 mg/m3) indicate unsatisfactory conditions (no further details included). In the recent open literature no further cases of acute poisoning are reported.
Conclusion
The LC50(rat) is 852 ppm/4 hrs (approx. 3827 mg/m3/4 hrs), and oral LD50(rat) is 750 mg/kg bw.
The dermal LD50(rabbit) is 3250 mg/kg bw in a limited study. The predominant symptoms after inhalation or oral application were cyanosis, labored breathing, lethargy or loss of consciousness.
o-Toluidine is a methemoglobin forming chemical; this was shown in rats and cats as well as in
humans.
Justification for selection of acute toxicity – oral endpoint
There is a reliable study which is performed equal to the current guidelines and therefore evaluated with Klimisch score 2
Justification for selection of acute toxicity – inhalation endpoint
A peer reviewed publication describes this inhalation study providing information that leads to evaluation with Klimisch Score 2
Justification for selection of acute toxicity – dermal endpoint
This is a reliable study performed by a method equal to the respective guideline and therefore evaluated with Klimisch score 2
Justification for classification or non-classification
The primary toxic effect of o-toluidine is methaemoglobin formation. Taking into account that humans are in general more sensitive to methaemoglobin producing substances than rats o-toluidine is classified as T, Toxic and labelled as R 23/25, toxic by inhalation and if swallowed. Due to the methemoglobin forming property Xn, R21= harmfull in contact with skin should be added. According to Regulation (EC) 1272/2008 the above mentioned statement leads ot tha allocation of o-toluidine to Category 3 (H331 and H301) with respect to acute inhalation and oral exposure and to Category 4 (H312) with respect to dermal exposure.
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.

EU Privacy Disclaimer
This website uses cookies to ensure you get the best experience on our websites.