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EC number: 201-603-3 | CAS number: 85-41-6
- 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
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- Flash point
- Auto flammability
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- 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
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- 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
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- Nanomaterial surface chemistry
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- Endpoint summary
- Stability
- Biodegradation
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- 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
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- Terrestrial toxicity
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- 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

Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- November 30th, 2009 - December 3rd, 2009
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 009
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Principles of method if other than guideline:
- A modification of the Local Lymph Node assay by measuring the cell counts instead of radioactive labeling was performed.
- GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- Phthalimide
- EC Number:
- 201-603-3
- EC Name:
- Phthalimide
- Cas Number:
- 85-41-6
- Molecular formula:
- C8H5NO2
- IUPAC Name:
- 1H-isoindole-1,3(2H)-dione
- Reference substance name:
- 3-iminoisoindolinone
- EC Number:
- 238-314-7
- EC Name:
- 3-iminoisoindolinone
- Cas Number:
- 14352-51-3
- Molecular formula:
- C8H6N2O
- IUPAC Name:
- 3-amino-1H-isoindol-1-one
- Reference substance name:
- Phthalide
- EC Number:
- 201-744-0
- EC Name:
- Phthalide
- Cas Number:
- 87-41-2
- Molecular formula:
- C8H6O2
- IUPAC Name:
- 2-benzofuran-1(3H)-one
- Reference substance name:
- Phthalic anhydride
- EC Number:
- 201-607-5
- EC Name:
- Phthalic anhydride
- Cas Number:
- 85-44-9
- Molecular formula:
- C8H4O3
- IUPAC Name:
- 2-benzofuran-1,3-dione
- Reference substance name:
- Benzoic acid
- EC Number:
- 200-618-2
- EC Name:
- Benzoic acid
- Cas Number:
- 65-85-0
- Molecular formula:
- C7H6O2
- IUPAC Name:
- benzoic acid
- Details on test material:
- - Name of test material (as cited in study report): Phthalimide
- Physical state: white solid
- Approval: until October 13, 2011
- Analytical purity: 99.8%
- Storage condition of test material: room temperature
Constituent 1
impurity 1
impurity 2
impurity 3
impurity 4
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- other: Hsd Win:NMRI
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Harlan Nederland, Horst, Netherland
- Age at study initiation: 8 weeks
- Weight at study initiation: 26 - 37 grams
- Housing: During the adaptation period up to 8 mice were housed together in conventional Makrolon type III cages. While during the study period the animals were single-housed in type II cages.
- Diet (e.g. ad libitum): The feed, PROVIMI KLIBA SA 3883 maintenance diet for rats and mice (from Provimi Kliba SA, CH-4303 Kaiseraugs, Germany)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 6 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2° C
- Humidity (%): 40%-70%
- Air changes (per hr): About 10 changes per hour
- Photoperiod (hrs dark / hrs light): 12 h/12 h
The animals were identified by cage labels giving the test item, the animal number, dose, sex, and the study number and marking of the tail immediately before autopsy.
Study design: in vivo (LLNA)
- Vehicle:
- dimethylformamide
- Concentration:
- 0 (vehicle control), 2%, 10% and 50%.
- No. of animals per dose:
- 6
- Details on study design:
- The test substance or the vehicle were applied epicutaneously onto the dorsal part of both ears of the animals.
This treatment was repeated on three consecutive days (d1, d2 and d3).
TREATMENT PREPARATION AND ADMINISTRATION:
The test item was formulated once at day 1 of the study.
The stability and the homogeneity of the test item in the vehicle was analytically verified for up to 4 days.
The test item or the vehicle were applied epicutaneously onto the dorsal part of both ears of the animals. This treatment was repeated on three consecutive days (d1, d2 and d3). The volume administered was 25µL/ear. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- When it was statistically reasonable, the values from treated groups were compared with those from the control group(s; vehicle) by a one-way analysis of variance (ANOVA) when the variances are considered homogeneous according to a homogeneity testing like Cochran`s test. Alternatively, if the variances are considered to be heterogenous (p = 0.05), a non-parametric Kruskal-Wallis test has been used (Kruskal-Wallis ANOVA) at significance levels of 5%. Two-sided multiple test procedures were done according to Dunnett or Bonferroni-Holm, respectively. Outlying values in the LN weights were eliminated at a probability level of 99% by Nalimov's method. In addition, for the LLNA/IMDS the smallest significant differences in the means were calculated by Scheffe's method, which according to Sachs can be used for both equal and unequal sample sizes.
In this method of statistical processing of measurements a large number of comparisons is made, and as a result of the multiple tests the overall probability of error is considerably greater than the p values suggest (increased number of false-positive results). On the other hand, the known methods of adjusting p values lead to an excessive increase in the number of false negatives. In view of these problems the biological and toxico¬logical relevance is also taken into consideration in the evaluation of statistical significance.
For this reason, in the case of indices only the standard deviations between groups and difference analysis of the mean values were used in the evaluation of the biological relevance.
Results and discussion
- Positive control results:
- The last reliability test using Alpha Hexyl Cinnamic Aldehyde formulated in acetone/olive oil (4:1) at concentrations of 3%, 10% and 30% clearly showed the sensitizing potential of the test item.
In vivo (LLNA)
Resultsopen allclose all
- Key result
- Parameter:
- SI
- Value:
- 0.97
- Test group / Remarks:
- NMRI mice, female, 6 animals/group
Dose 2% Test item dissolved in DMF
- Parameter:
- SI
- Value:
- 0.9
- Test group / Remarks:
- NMRI mice, female, 6 animals/group
Dose 10% Test item dissolved in DMF
- Parameter:
- SI
- Value:
- 1.07
- Test group / Remarks:
- NMRI mice, female, 6 animals/group
Dose 50% Test item dissolved in DMF
Any other information on results incl. tables
The "positive level" of ear swelling, which is 2x10-2 mm increase, i.e. about 10% of the control values, has not been reached or exceeded in any dose group.
It has to be clarified that the "positive levels" mentioned above are exclusively defined for the NMRI outbreed mice used for this study. Such positive limits have to be calculated for each strain of mice individually.
The body weights of the animals were not affected by any treatment.
1. Direct LLNA (NMRI mice, female, 6 animals/group)
Based on results obtained in validation studies and general experiences with this test system groups of mice were treated with vehicle, 2%, 10% or 50% Phthalimide in DMF. The NMRI mice did not show an increase in the stimulation indices for cell counts or for weights of the draining lymph nodes after application of the test item Phthalimide. The "positive level", which is 1.4 for the cell count index, was never reached or exceeded in any dose group.
Dose (%) Weight index Cell count index
(index of mean +/- SD in %)
0* 1.00 +/- 19.79 1.00 +/- 26.55
2 1.04 +/- 8.99 0.97 +/- 14.76
10 1.03 +/- 25.13 0.90 +/- 34.13
50 1.08 +/- 21.21 1.07 +/- 23.29
Applicant's summary and conclusion
- Interpretation of results:
- not sensitising
- Executive summary:
Lanxess (2009):
The modified Local Lymph Node Assay (IMDS) was performed in 24 female NMRI mice of the strain Hsd Win:NMRI (6 animals/test item group and 6 control animals) to determine if there is any specific (sensitizing) or non-specific (irritant) stimulating potential of the test item Phthalimide. The study was conducted according to OECD Guidelines No. 429 with the following test item concentrations: 0 (vehicle control), 2%, 10% and 50%. The test item was formulated in dimethylformamide (DMF) to yield a solution in the low and the mid concentration and a suspension in the high concentration. Compared to vehicle-treated animals, none of the parameters measured in the substance-treated groups, i.e. cell counts and weights of the draining lymph nodes, ear weights and ear swelling, reached or exceeded the "positive levels" defined for this assay .These results show that there is no indication for a skin sensitizing effect after administration of a concentration of up to and including 50% Phthalimide in this test system. In conclusion, these results show that the test item Phthalimide has no sensitizing potential in mice after dermal application of up to and including a 50% concentration. In addition, no indication for a non-specific (irritant) activation was detected. Therefore, the concentration of 50% turned out to be the NOEL for the parameters investigated in this study with respect to skin sensitization.
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