Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
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: 242-555-3 | CAS number: 18755-43-6
- 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
- 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
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
- Report date:
- 2012
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- Guideline adopted 22 July 2010; Modified LLNA (IMDS; Integrated Model for the Differentiation of Skin Reactions). Modifications are authorised in the OECD TG 429 and in the Note for Guidance SWP/2145/00 of the CPMP (2001). Information on validation of IMDS and scientific justification is given in: Vohr HW et al., Arch. Toxicol., 73, 501-509 (2000); Ehling G et al., Toxicology 212, 60-68 and 69-79 (2005).
- Deviations:
- yes
- Remarks:
- IDMS LLNA: Measurement of cell counts instead of radioactive labelling. In addition, ear swelling and ear weights are determined to discriminate the irritating potential from the sensitizing potential of the test substance.
- Principles of method if other than guideline:
- This study is performed according to OECD TG 429. As stated in OECD TG 429 besides the classical radioactive method ‘other endpoints for assessment of the number of proliferating cells may be employed’ as so-called ‘me-too’ tests, if the required performance standards are fulfilled, they are ‘based on similar scientific principles and measure or predict the same biological or toxic effect’ and they are validated.
Here, an alternative method is used employing the lymph node weight and lymph node cell count to assess proliferation of lymphocytes (IMDS LLNA; Integrated Model for the Differentiation of Skin Reactions). In addition, the acute inflammatory skin reaction is measured by ear weight determination of circular biopsies of the ears and ear thickness measurements on test day 1 and test day 4 to identify skin irritation properties of the test item. It is important to determine if a positive test result is due to the skin irritation potential of the test item or due to its sensitising properties. Information on validation of the IMDS LLNA and scientific justification is given in: Vohr HW et al., Arch. Toxicol., 73, 501-509 (2000); Ehling G et al., Toxicology 212, 60-68 and 69-79 (2005).
In the IMDS LLNA stimulation indices were calculated for the lymph node cell count, lymph node weight, ear weight and ear thickness by dividing the average values per group of the test item treated animals by the respective vehicle treated ones.
Values above 1.4 (lymph node cell count to identify skin sensitisation) or 1.1 (ear weight to identify irritation) are considered positive (these values were fixed empirically during the interlaboratory validation of this method (Ehling et al. 2005a and 2005b)).
- Ehling, G., M. Hecht, A. Heusener, J. Huesler, A. O. Gamer, H. van Loveren, T. Maurer, K. Riecke, L. Ullmann, P. Ulrich, R. Vandebriel, H.-W. Vohr: An European inter-laboratory validation of alternative endpoints of the murine local lymph node assay: First round; Toxicology 212, 60-68 (2005a);
- Ehling, G., M. Hecht, A. Heusener, J. Huesler, A. O. Gamer, H. van Loveren, T. Maurer, K. Riecke, L. Ullmann, P. Ulrich, R. Vandebriel, H.-W. Vohr: An European inter-laboratory validation of alternative endpoints of the murine local lymph node assay: 2nd round; Toxicology 212, 69-79 (2005b).
- Vohr, H.-W., Blümel, J., Blotz, A., Homey, B. and Ahr, H.J. An intra-laboratory validation of IMDS: Discrimination between (Photo) Allergic and (Photo) Irritant Skin Reactions in Mice. Arch. Toxicol., 73, 501-509 (2000). - GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- Dimethyl propylphosphonate
- EC Number:
- 242-555-3
- EC Name:
- Dimethyl propylphosphonate
- Cas Number:
- 18755-43-6
- Molecular formula:
- C5H13O3P
- IUPAC Name:
- dimethyl propylphosphonate
- Test material form:
- other: liquid
- Details on test material:
- - Purity: 97.0%
Constituent 1
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 26-31 g
- Housing: singly during study
- Diet ad libitum
- Water ad libitum
- Acclimation period: at least 6 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 40 - 70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Study design: in vivo (LLNA)
- Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- Group 1 Vehicle (A/OO = acetone/olive oil)
Group 2 10% dimethyl propylphosphonate (in A/OO)
Group 3 30 % dimethyl propylphosphonate (in A/OO)
Group 4 100 % dimethyl propylphosphonate
Group 5 40 % Alpha Hexyl Cinnamic Aldehyde (in A/OO) - No. of animals per dose:
- 6 animals/test item group and 6 control animals
- Details on study design:
- The test item in the formulation, the positive control in the formulation or the vehicle were applied epicutaneousely onto the dorsal part of both ears of the animals. This treatment was repeated on three consecutive days. The volume administered was 25 µl/ear. The used concentrations were based on the experience with this test system and the properties of the test item.
The animals were anaesthetized by inhalation of carbon dioxide and sacrificed one day after the last application. The appropriate organs were then removed. Lymphatic organs (the auricular lymph nodes) were transferred into physiological saline
Investigations:
- weight of lymph nodes
- cell counts in lymph nodes
- stimulation index is calculated by dividing the absolute number of weight or cell count of the substance-treated lymph nodes by the vehicle treated ones
- ear swelling
- ear weight
- body weight - 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 by one-way Analysis of Vartiance (ANOVA) when the variances are considered homogenous according to a homogeneity testing like Cochran's test. Alternatively, if the variances are considered to be heterogeneous a non-parametric Kruskal-Wallis test has been used 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 Sheffe's method, which can be used for both equal and unequal sample sizes.
Results and discussion
In vivo (LLNA)
Resultsopen allclose all
- Parameter:
- SI
- Remarks on result:
- other: see Remark
- Remarks:
- A modified Local Lymph Node Assay (IMDS) was carried out in mice. The modifications refer to the measurement of cell proliferation by cell counting instead of radioactive labeling. In addition, the acute inflammatory skin reaction is determined to discriminate specific from non-specific activation of immune competent cells in the draining lymph nodes, as also recommend in the update of OECD TG 429. Direct LLNA (NMRI mice, female, 6 animals/group) Groups Weight index Cell count index (index of mean +/-SD in %) Gr.1 1.00 +/- 26.52 1.00 +/- 26.46 Gr.2 1.06 +/- 31.38 1.06 +/- 38.46 Gr.3 0.91 +/- 16.23 0.91 +/- 23.67 Gr.4 0.97 +/- 43.54 0.98 +/- 65.67 Gr.5 1.80 +/- 29.30 2.16 +/- 36.11 Ear swelling (NMRI mice, female, 6 animals/group, in 0.01 mm) Groups day 1 day 4 Index day 4 (mean +/- SD in %) Gr.1 17.50 +/- 3.85 19.08 +/- 5.22 1.00 Gr.2 17.25 +/- 2.62 18.83 +/- 5.92 0.99 Gr.3 17.50 +/- 2.98 18.83 +/- 5.47 0.99 Gr.4 17.33 +/- 2.84 18.58 +/- 5.36 0.97 Gr.5 17.42 +/- 4.55 22.00 +/- 7.99 1.15 Ear weight (NMRI mice, female, 6 animals/group, in mg per 8 mm diameter punch) Groups day 4 Index day 4 (mean +/- SD in %) Gr.1 11.69 +/- 6.23 1.00 Gr.2 12.36 +/- 9.60 1.06 Gr.3 12.13 +/- 6.90 1.04 Gr.4 11.36 +/- 8.03 0.97 Gr.5 14.17 +/- 7.12 1.21 Group 1 Vehicle (A/OO = acetone/olive oil) Group 2 10% dimethyl propylphosphonate (in A/OO) Group 3 30 % dimethyl propylphosphonate (in A/OO) Group 4 100 % dimethyl propylphosphonate Group 5 40 % Alpha Hexyl Cinnamic Aldehyde (in A/OO)
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: Modified LLNA. Measurement of cell counts instead of radioactive labelling.
Any other information on results incl. tables
Stimulation indices (weight and cell counts; ear swelling and ear weight)
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.
Based on results obtained in validation studies and general experiences with this test system groups of mice were treated with vehicle, 10 %, 30% or 100% dimethyl propylphosphonate in acetone/olive oil (A/OO).
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 dimethyl propylphosphonate.
The "positive level", which is 1.4 for the cell count index, was never reached or exceeded in any dose group.
The "positive level" of ear swelling, which is 2xl0E-2 mm increase, i.e. about 10% of the control values, has not been reached or exceeded in any dose group.
No substance specific effects were determined for ear weights either.
After treatment with Alpha Hexyl Cinnamic Aldehyde (group 5) the NMRI mice showed clear increases in the weights of the draining lymph nodes and in the stimulation indices for cell counts compared to control animals, which are of statistical significance. The "positive level", which is 1.4 for cell count indices, has clearly been exceeded.
The "positive level" of ear swelling, which is 2x 10E-2 mm increase, i.e. about 10 % of the control values, has been exceeded in the positive control group. This increase is of statistical significance. A significant increase compared to vehicle treated animals regarding ear weights was detected, too.
Body weights
The body weights of the animals were not affected by any treatment.
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LLNA was negative. Dimethyl propylphosphonate shows no sensitizing potential in the modified Local Lymph Node Assay (IMDS) in female NMRI mice after dermal application of up to and including a 100 % concentration of dimethyl propylphosphonate.
- Executive summary:
The modified Local Lymph Node Assay (IMDS) was performed in 2012 on 24 female NMRI mice of the strain HsdWin: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 dimethyl propylphosphonate.
A concurrent control of 6 animals treated with Alpha Hexyl Cinnamic Aldehyde (alpha-HCA) was included.
The study was conducted according to OECD Guidelines No. 429 and No. 406, EC Guideline 2004/73/EC (29th Adaptation of Guideline 67 /548/EEC, B.42)/Health Effects Test Guideline and OPPTS 870.2600 (EPA) with the following test item concentrations:
Test item: 0% (vehicle control), 10%, 30% and 100%.
Positive control: 40% Alpha Hexyl Cinnamic Aldehyde
The test item and the positive control were formulated in acetone/olive oil ( 4:1) (A/OO) to yield a solution.
Compared to vehicle-treated animals, none of the parameters measured in the substancetreated 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 up to and including 100 % dimethyl propylphosphonate in this test system.
In conclusion, these results show that the test item dimethyl propylphosphonate has no sensitizing potential in mice after dermal application of up to and including a 100 % concentration. No indication for a non-specific (irritant) activation was detected, too. Therefore, the concentration of 100 % turned out to be the NOEL for the parameters investigated in this study with respect to skin sensitization. These results are verified by the comparison with the results of the positive control group (Alpha Hexyl Cinnamic Aldehyde).
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.