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EC number: 210-431-8 | CAS number: 615-50-9
- 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
Acute Toxicity: inhalation
Administrative data
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- calculation (if not (Q)SAR)
- Adequacy of study:
- weight of evidence
- Study period:
- 2012
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable calculated/extrapolated data
Data source
Reference
- Reference Type:
- other: Expert opinion
- Title:
- Unnamed
- Year:
- 2 012
- Report date:
- 2012
Materials and methods
Test guideline
- Qualifier:
- no guideline required
- Principles of method if other than guideline:
- To assess the acute inhalational toxicity of toluene-2,5-diamine (free base and sulphate salt), a kinetic based calculation was done. The kinetic data were derived from various kinetic studies, and the details of the test methods and the results are provided in this summary (refer to executive summary for details). The derived data were consistent with the determined acute toxicity values (derived by in-vivo studies) from p-phenylenediamine, the most appropriate analogue for toluene-2,5-diamine.
- Test type:
- other: Estimated data by calculation
- Limit test:
- no
Test material
- Reference substance name:
- 2-methyl-p-phenylenediamine sulfate
- EC Number:
- 210-431-8
- EC Name:
- 2-methyl-p-phenylenediamine sulfate
- Cas Number:
- 615-50-9
- Molecular formula:
- C7H10N2.H2O4S
- IUPAC Name:
- 2-methylbenzene-1,4-diamine; sulfuric acid
- Reference substance name:
- toluene-2,5-diamine sulfate
- IUPAC Name:
- toluene-2,5-diamine sulfate
- Reference substance name:
- 2-methyl-p-phenylenediamine
- EC Number:
- 202-442-1
- EC Name:
- 2-methyl-p-phenylenediamine
- Cas Number:
- 95-70-5
- Molecular formula:
- C7H10N2
- IUPAC Name:
- 2-methylbenzene-1,4-diamine
- Reference substance name:
- toluene-2,5-diamine
- IUPAC Name:
- toluene-2,5-diamine
- Details on test material:
- - Name of test material: TOLUENE-2,5-DIAMINE (free base and sulphate salt) is 1,4-phenylene diamine with a single methyl substituent on the benzene ring. Therefore, it is a member of the p-phenylenediamine family.
Constituent 1
Constituent 2
Constituent 3
Constituent 4
Results and discussion
Effect levelsopen allclose all
- Sex:
- not specified
- Dose descriptor:
- LC50
- Effect level:
- 0.99 mg/L air
- Based on:
- other: kinetic based calculation
- Exp. duration:
- 4 h
- Remarks on result:
- other: The calculated inhalational LC50 of 0.99 mg/L for toluene-2,5-diamine is comparable to the determined value for p-phenylenediamine (0.92 mg/L)
- Sex:
- not specified
- Dose descriptor:
- LC50
- Effect level:
- 1.77 mg/L air
- Based on:
- other: kinetic based calculation
- Exp. duration:
- 4 h
- Remarks on result:
- other: The calculated inhalational LC50 of 1.77 mg/L for toluene-2,5-diamine sulphate salt is comparable to the determined value for p-phenylenediamine (0.92 mg/L)
Applicant's summary and conclusion
- Interpretation of results:
- Category 4 based on GHS criteria
- Remarks:
- Criteria used for interpretation of results: EU
- Conclusions:
- Based on the available acute oral toxicity and kinetic data for toluene-2,5-diamine, the extrapolated acute inhalation toxicity (4 h, LC50) of toluene-2,5-diamine was 0.99 mg/L for the free base and 1.77 mg/l for the sulphate salt. This value is comparable to the determined value for p-phenylenediamine (0.92 mg/L).
- Executive summary:
To assess the acute inhalational toxicity of toluene-2,5-diamine (free base and sulphate salt) , a kinetic based calculation was done. The kinetic data were derived from various kinetic studies, and the details of the test methods and the results are provided in the SCCS Opinion 1479/12, 26 – 27June 2012.In addition, the calculated data for toluene-2,5-diamine (free base and the sulphate salt) were compared with those of the most appropriate analogue, the p-phenylenediamine (refer to below table).
COLIPA Number
Chemical Name
CAS Number
Acute Toxicity
Oral
LD50
Dermal
LD50
Inhalation LC50
Colipa No. A005
Toluene-2,5-Diamine
95-70-5 (free base)
102 mg/kg bw
(rat)
> 2000 mg/ kg bw
(rat, extrapolated)
0.99 mg/l,
(4h, rat, extrapolated)
Colipa No. A005
Toluene-2,5-diaminesulphate
615-50-9
183 mg/kg bw
(rat, extrapolated)
> 2000 mg/kg bw
(rat, extrapolated)
1.77 mg/L,
(4h, rat, extrapolated)
Colipa No. A007
p-Phenylenediamine
106-50-3 (free base)
80-100 mg/kg bw
(rat)
> 7940 mg/kg bw
(male/female rabbit)
0.92 mg/l air
(4 h ,rat)
Studies used for the determination of acute toxicity of TOLUENE-2,5-DIAMINE:
Conversion Factor between the free base and the sulphate salt:
The toxic potential of both forms of 2 Toluene-2,5-diamine is attributable to the free base component. Therefore, study results derived with one of the two forms of Toluene-2,5-diamine, namely the free base or the sulphate salt, can be converted to the other form by applying a conversion factor that is related to the molecular weight and content of the free base in each form.
Molar Masssulfate: 218.23 g/mol
Molar Massfree base: 122.71 g/mol
Conversion factor free base → sulphate = 1.79
Conversion factor sulphate →free base = 0.56
Acute Oral Toxicity study result
LD50oral: 102 mg/kg bw in the rat (CFY strain); “The acute median lethal oral dose was calculated to be 102 mg/kg bw (95% confidence limits of 69-152 mg/kg bw)”.The study was carried out with the free base.
LD50oral=102 mg/kg bw (Toluene-2,5-Diamine)
Conversion factor free base→sulphate = 1.78628
LD50oral=182 mg/kg bw (Toluene-2,5-Diamine Sulphate)
Toxicokinetic study results in Sprague Dawley rats:
Dose levels:
IV: 2.5 mg/kg bw
Oral: 2.5, 25 mg/kg bw
Dermal:0.5 mg/cm² equal to 33.3 mg/kg bw
Bioavailability, assuming 100% bioavailability IV
Oral dosing: 69%
Dermal dosing: 2%
The studies are summarized as follows in SCCS 1479/12:
“In toxicokinetic studies with Sprague-Dawley rats the comparison of AUCs showed differences between oral (25 mg/kg bw: 112 mgeqx h/l) and dermal application (33 mg/kg bw in formulation: 2.27 mgeqx h/l). Following 2.5 mg/kg bw the AUC was 8.53 mgeqx h/l. The bioavailability (derived from comparison to iv administration) after oral dosing of 10 mg/kg bw was 69% while 2% bioavailability was found after dermal administration in a formulation.”The Studies were carried out with the sulphate salt.
This summary provides calculation ofextrapolation of the acute inhalation toxicity of toluene-2,5-diamine. The summary of calculation of extrapolation of the acute dermal toxicity is provided under section 7.2.3 of IUCLID.
Extrapolation of the acute inhalational toxicity of TOLUENE-2,5-DIAMINE:
Required maximum exposure concentration to test material (OECD 403): 5 mg/L
Assumed body weight of the rat for the calculation: 250 g
Respiratory volume of the rat: 0.074 L/min
Required duration (OECD 403): 4 h
Ventilation in 4 hours 0.074 L/min x 60 min x 4 hour = 17.76L
Toluene-2,5-diamine LD50oral = 102 mg/kg bw in the ratwith the free base
Calculation:
Maximum achievable exposure regarding required 5 mg/L for 4 hours (OECD 403):
Exposure during 4 hours:17.76 L x 5 mg/L = 88.8 mg/rat
88.8 mg/0.250 kg bw = 355 mg/kg bw maximum achievable exposure
Oral Bioavailability = 69% (at 25 mg/kg bw, using the data from the toxicokinetic study in Sprague Dawley rats)
Inhalation Bioavailability: Assumed to be 100%
Determination of the correction factor oral vs. inhalation route:
69% oral vs. 100% inhalation = 0.69
LC50 calcinhal. free base: 102 mg/kg bw x 0.250 kg bw x 0.69/17.76 L = 0.99 mg/L
LC50 calcinhal. free base: 0.99 mg/L x 1.79 (conversion free base to sulphate) = 1.77 mg/L
LC50inhal. forp-phenylenediamine = 0.92 mg/L
LC50 calcinhal. for toluene-2,5-diamine = 0.99 mg/L free base
LC50 calcinhal.Toluene-2,5-diamine = 1.77 mg/l sulphate salt
The calculated LC50for toluene-2,5-diamine, namely 0.99 mg/L for the free base and 1.77 mg/L for the sulphate saltcomparable to the determined value forp-phenylenediamine (0.92 mg/L)
The calculated inhalation toxicity value for toluene-2,5-diamine is in the same order of magnitude (0.99 mg/lfor the free base and 1.77 mg/L for the sulphate salt) as the official classification of Acute Tox Cat 4; H332 in Annex VI of the CLP regulation which is being applied in case of 1 mg/L<LC50≤5 mg/L (for dusts/mists).
ASSESSMENT OF VALIDITY:
Since the Weight of Evidence Approach (WoE) used was considered as sufficiently robust to determine the acute inhalation toxic potential of toluene-2,5-diamine, the performance of an animal test for hazard identification purposes was considered to be not justified.
In addition the completion of acute toxicity studies on toluene-2,5-diamine as an ingredient used in cosmetic products would not be considered to comply with the EU regulations regarding animal testing. Furthermore, applying WoE complies with the REACH regulation to avoid animal testing. The validity of the WoE/extrapolation approach used in order to estimate the acute toxicity potential of toluene-2,5-diamine by inhalation route was finally confirmed by the comparison of the extrapolated values on toluene-2,5-diamine with experimental values obtained on the primary member of the p-phenylenediamine family, p-phenylenediamine.
In conclusion, the extrapolated acute inhalation toxicity (4 h, LC50) of toluene-2,5-diamine was 0.99 mg/Lfor the free base and 1.77 mg/L for the sulphate salt. This value is comparable to the determined value for p-phenylenediamine (0.92 mg/L)
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