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EC number: 202-442-1 | CAS number: 95-70-5
- 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
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Acute Toxicity: dermal
Administrative data
- Endpoint:
- acute toxicity: dermal
- Type of information:
- calculation (if not (Q)SAR)
- Remarks:
- Migrated phrase: estimated by calculation
- Adequacy of study:
- key study
- 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 available
- Principles of method if other than guideline:
- To assess the acute dermal toxicity of toluene-2,5-diamine, 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
- 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
- Test material form:
- not specified
- Details on test material:
- - Name of test material: Toluene-2,5-diamine 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
Results and discussion
Effect levels
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 3 520 mg/kg bw
- Based on:
- other: kinetic based calculation
- Remarks on result:
- other: The calculated dermal LD50 for toluene-2,5-diamine can be assumed to be > 2000 mg/kg bw, which is consistent with the LD50 dermal for the analogue, p-phenylenediamine
Applicant's summary and conclusion
- Interpretation of results:
- not classified
- Remarks:
- Migrated informationCriteria 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 dermal toxicity of toluene-2,5-diamine was 3520 mg/kg bw, while the determined LD50 dermal for p-phenylenediamine is > 7940 mg/kg bw. In conclusion, the LD50 dermal for toluene-2,5-diamine can be assumed to be > 2000 mg/kg bw, which is consistent with the LD50 dermal for the analogue, namely p-phenylenediamine
- Executive summary:
To assess the acute dermal and inhalational toxicity of toluene-2,5-diamine, 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 Opinion1479/12, 26 – 27June 2012.In addition, the calculated data for toluene-2,5-diamine 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. 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:
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)”
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.”
This summary provides calculation ofextrapolation of the acute dermal toxicity of toluene-2,5-diamine. The summary of calculation of extrapolation of the acute inhalation toxicity is provided under section 7.2.2 of IUCLID.
Extrapolation of the acute dermal toxicity of TOLUENE-2,5-DIAMINE:
TOLUENE-2,5-DIAMINE LD50oral = 102 mg/kg bw in the rat
Oral bioavailability = 69% (at 25.0 mg/kg bw, using the data from the toxicokinetic study in Sprague Dawley rats)
Dermal bioavailability =2% (at 33.3 mg/kg bw)
Calculation:
Determination of the correction factor oral vs. dermal route
69 % oral vs. 2 % dermal = 34.5 (69 : 2 = 34.5)
LD50 calcdermal: 102 mg/kg bw x 34.5 = 3520 mg/kg bw
Thus, the calculated LD50dermal for toluene-2,5-diamine is 3520 mg/kg bw, while the determined LD50dermal for p-phenylenediamine is > 7940 mg/kg bw.
The calculated dermal toxicity is >2000 mg/kg and does not support the official classification of toluene-2,5-diamine as Acute Tox Cat 4; H312. The calculated classification as not harmful in contact with skin is the same as that determined for the analoguep-phenylenediamine based on a rat study. This is also in contrast to the official classification ofp-phenylenediamine as Acute Tox 3;H311 in Annex VI of the CLP regulation. However, the official classification fortoluene-2,5-diamine as laid down in Annex VI of the CLP regulation is not based on animal data, as stated by the ECHA
ASSESSMENT OF VALIDITY:
Since theWeight of Evidence Approach (WoE)used was considered as sufficiently robust to determine the acute dermal toxic potential of toluene-2,5-diamine, the performance of an animal test for hazard identification purposes was considered to be not justified.
Based on the REACH regulation “REACH VO - Annex VIII, 8.5.3., (3).), testing of the dermal route is only required, if there is a potential for a significant rate of absorption through the skin. The ADME data demonstrated, that the oral bioavailability of toluene-2,5-diaminein rats is 34.5 times higher than the dermal bioavailability
In addition, the completion of acute toxicity studies ontoluene-2,5-diamineas 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-diamineby dermal routes was finally confirmed by the comparison of the extrapolated values on toluene-2,5-diaminewith experimental values obtained on the primary member of thep-phenylenediamine family,p-phenylenediamine.
In conclusion, the LD50dermal for toluene-2,5-diaminecan be assumed to be > 2000 mg/kg bw, which is consistent with the LD50 dermal for the analogue, namely p-phenylenediamine.
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