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EC number: 944-968-0 | CAS number: -
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1971
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Published literature in an international accepted journal. Four main experiments conducted on up to 12 Hallcomid substances using both rabbits and mice.
Data source
Reference
- Reference Type:
- publication
- Title:
- The Acute Toxicity of Dimethylamides in Several Animal Species
- Author:
- JOSEPH S. WILES and JOHN K. NARCISSE, JR
- Year:
- 1 971
- Bibliographic source:
- Association Journal (1958-1999) (1971), 32(8),539-45
Materials and methods
- Objective of study:
- toxicokinetics
Test guideline
- Qualifier:
- no guideline required
- Principles of method if other than guideline:
- No guidelines were available at the time of experimentation. However, the studies appear to have been conducted to the scientific standards of the time.
- GLP compliance:
- no
Test material
- Reference substance name:
- Hallcomid C8
- IUPAC Name:
- Hallcomid C8
- Reference substance name:
- Hallcomid C10
- IUPAC Name:
- Hallcomid C10
- Reference substance name:
- Hallcomid C12
- IUPAC Name:
- Hallcomid C12
- Reference substance name:
- Hallcomid C14
- IUPAC Name:
- Hallcomid C14
- Test material form:
- other: see attached publication
- Details on test material:
- no detailed information on source and quality of the tested chemicals
Constituent 1
Constituent 2
Constituent 3
Constituent 4
- Specific details on test material used for the study:
- Up to 12 analogue substances - N,N-dimethylamides (Hallcomids) - were tested with chain lengths from C3 to C18. See below in any other information
- Radiolabelling:
- no
Test animals
- Species:
- other: rabbits and mice
- Strain:
- not specified
- Details on species / strain selection:
- not specified
- Sex:
- not specified
- Details on test animals or test system and environmental conditions:
- Different species were used: mice, rabbit
Administration / exposure
- Route of administration:
- other: Intravenous, intraperitoneal, intraperitoneal and percutaneous routes were observed
- Vehicle:
- other: no vehicle used in the majority of experiments
- Details on exposure:
- Intravenous Toxicity Studies: test compounds were injected into rabbits through the marginal ear vein and in mice through the medial tail vein
Intraperitoneal Toxicity Studies: administered by mice and rabbit by the intraperitoneal route
Intragastric Toxicity Studies: rabbit orally via gavage (undiluted)
Percutaneous Toxicity Studies: applied to the clipped skin of mice and rabbit (undiluted) - Duration and frequency of treatment / exposure:
- The experimental groups of animals were dosed on one occasion only per experiment:
Intravenous Toxicity Studies, Intraperitoneal Toxicity Studies and Intragastric Toxicity Studies: Observations for toxic signs and death occurring over a 24-hour period.
Percutaneous Toxicity Studies: Mice were observed for 24 or 48 hours; rabbits were observed over a two-week period.
Doses / concentrations
- Remarks:
- Please see attached publication.
The dose regimen is not specifically described, however, the LD50 values provide evidence of dosages given.
Percutaneous Toxicity Studies: 1000, 2500, 5000mg/kg (mice); 100, 250, 500 mg/kg (rabbit)
- No. of animals per sex per dose / concentration:
- minimum of six mice per dose and three rabbits per dose.
- Control animals:
- no
- Positive control reference chemical:
- DMS 2,4-dimethylsulfolane ,DMAC N,N-dimethylacetamide, DMF N,N-dimethylformamide, DMSO N,N-dimethylsulfoxide
- Details on study design:
- see below in any other information
- Details on dosing and sampling:
- see below in any other information
Results and discussion
- Preliminary studies:
- Intravenous route
The LD50s for the Hallcomids and reference compounds, range from 36 mg/kg (M-8) to 1620 mg/kg
(M-4) for mice, and from 29 mg/kg (M-10) to 1000 mg/kg (M-3) far rabbits. These LD50 values indicate that the Hallcomids are more toxic by the intravenous route in rabbits and mice than are three of the four reference compounds, the exception being 2,4-dimethylsulfolane (DMS). DMSO was the least toxic of the reference compounds, and M4 was the least toxic of the Hallcomids. Hallcomids M-6 to M-12 were the most toxic of the dimethyl compounds tested intravenously in rabbits and mice.
Intraperitoneal route
The rank order of toxicity of these compounds by the intraperitoneal route is somewhat similar to that found when they were administered by the intravenous route to mice and rabbits. The reference compounds DMS and DMSO were the most toxic and the least toxic, respectively, in
mice of all the dimethyl compounds tested. M-16 was the least toxic of the Hallcomid compounds by the intraperitoneal route.
Oral route
The Halllcomids (M-12, M-14, M-180L) were of a similar order of toxicity as the reference compounds when administered by the intragastric route in rabbits. Clinical observations disclosed evidence of diarrhoea, and all animals showing a marked decrease in activity.
Dermal route
Following application of these materials, there was reddening and irritation over the entire area of application within 2 to 3 hours in both species. During the longer observation period with rabbits, moderate to severe thickening and wrinkling of the skin was seen by the fifth day, necrosis and cracking of the skin by the eighth day, sloughing at 9 to 13 days, and recovery by the fifteenth day. The toxic signs displayed were the same as those induced by these compounds when administered by the other routes. Decreased activity was evidence of systemic absorption in both species, and death in most groups of mice receiving the highest dose.
Main ADME results
- Type:
- absorption
- Results:
- evidence of absorption by all routes tested
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- See Executive Summary. Absorption was evident via all routes of administration. Least toxicity was evident via the dermal route.
- Details on distribution in tissues:
- not specified
Transfer into organs
- Observation:
- not determined
- Details on excretion:
- not specified
Toxicokinetic parameters
- Toxicokinetic parameters:
- other: clear evidence of exposure
Metabolite characterisation studies
- Metabolites identified:
- not specified
Bioaccessibility (or Bioavailability)
- Bioaccessibility (or Bioavailability) testing results:
- not specified
Any other information on results incl. tables
See attached publication.
The article leads to the following main results:
- The mid range chain length Hallcomids are the most toxic when intravenous applied. 24h LD50 40mg/kg (C10; mice) and 36mg/kg (C8;mice) which marks also the highest toxicity in the series of homologues.
- For the intraperitonial application the C5-6 Hallcomids are the most toxic substances directly followed by C8 (LD50 620mg/kg) and C10 (LD50 800mg/kg)
- In the intragastric study the C6 Hallocomid shows the most toxic effect directly followed by the C8-10 mixture (pure C10 was not tested) (LD50 3530mg/kg)
- Percutaneous application shows the highest toxicity for C6 Hallcomid followed by C8 and C10.
- The investigation of the lethal time (Lt) if VX is applied with different Hallcomids as enhancer reveals to the result that C8/10 mixtures are most shortening to the lifetime when applied in combination with VX followed by C10 and C6.
- When Lt and LD50 is plotted against the chain length of the Hallcomids the C8-10 mixture markes the minimum of the curve followed by the pure C8 and C10.
Applicant's summary and conclusion
- Conclusions:
- The data provide clear evidence of absorption and systemic exposure to the N,N-dimethylamides (Hallcomids) tested (see table in Executive Summary) via all routes of administration tested. Toxicity was far less profound via the dermal route, and delayed, but nonetheless the data suggest dermal penetration and systemic exposure.
- Executive summary:
The following Hallcomids (N,N-dimethylamides) of varying chain lengths were used in this study:
Code number*
Chemical Name
M-3
N,N-dimethylproprionamide
M-4
N, N-dimethylbutyramide
M-5
N,N-dimethylpentanamide
M-6
N, N-dimethylcaproamide
M-8
N,N-dimethylcaprylamide
M8-10
N,N-dimethylcaprylamide capramide
M-10
N, N-dimethylcapramide
M-12
N,N-dimethyllauramide
M-14
N,N-dimethylmyristamide
M-16
N,N-dimethylpalmitamide
M-18
N,N-dimethylstearamide
M-l8OL
N,N-dimethyloleamide
* Chain length
When the N,N-dimethylamides (Hallcomids) were administered parenterally, the onset time of the various toxic signs varied with the amount given; the higher the dose, the earlier was the occurrence of a slight to moderate decrease in activity (30 to 60 minutes). The degree was related to the dose. A period of anaesthesia followed until the animals began to convulse and die 2 to 6 hours after administration. Percutaneously exposed animals exhibited a similar pattern of toxic signs, but onset times were very much more delayed, death occurring 15 to 22 hours following application. The reference compounds studied did not cause responses which were significantly different from those with the Hallcomids; however, for equal closes the effects were slightly less severe for the reference compounds.
The data provide clear evidence of absorption and systemic exposure to the N,N-dimethylamides tested (see table above) via all routes of administration tested. Toxicity was far less profound via the dermal route, and delayed, but nonetheless the data suggest dermal penetration.
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