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EC number: 269-924-1 | CAS number: 68391-05-9 This substance is identified by SDA Substance Name: C12-C18 dialkyl dimethyl ammonium chloride and SDA Reporting Number: 16-047-00.
- 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:
- weight of evidence
- Study period:
- From February 10, 2004 to March 13, 2006
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 006
- Report date:
- 2006
Materials and methods
- Objective of study:
- absorption
- distribution
- excretion
- metabolism
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 417 (Toxicokinetics)
- Deviations:
- no
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- Didecyldimethylammonium chloride
- EC Number:
- 230-525-2
- EC Name:
- Didecyldimethylammonium chloride
- Cas Number:
- 7173-51-5
- Molecular formula:
- C22H48N Cl
- IUPAC Name:
- N,N-Didecyl-N,N-dimethylammonium chloride
- Test material form:
- liquid
- Details on test material:
- - Didecyldimethylammonium chloride (DDAC)
- EC number: 230-525-2
To the best of knowledge, the sample used is representative to the boundary composition shared and agreed by each registrant
Constituent 1
- Radiolabelling:
- yes
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories France, L’Arbresle, France. Caesarean Obtained, Barrier Sustained-Virus Antibody Free (COBS-VAF®).
- Age at study initiation: 7 wk old; for the bile collection group, animals were around 10 wk (males) 12 wk females).
- Weight at study initiation: 229 g males and 159 g females
- Fasting period before study: Overnight
- Housing: 2 or 3 animals/cage in oral groups and singly in dermal and bile collection group
- Diet (e.g. ad libitum): A04 C pelleted diet ad libitum
- Water (e.g. ad libitum): Filtered tap water ad libitum
- Acclimation period: At least 7 d
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 2 °C
- Humidity (%): 50±20%
- Air changes (per hr): 12 cycles/h of filtered, non-recycled air
- Photoperiod: 12 h light/ 12 h dark
Administration / exposure
- Route of administration:
- other: Oral gavage and dermal
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg
TEST SITE
- Area of exposure: Interscapular/upper back region
- % coverage: 10 % (25 -30 cm2 for 250-300 g rat)
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washed to remove all traces of test material by wiping with at least 3 cotton swabs dampened with water and diluted normal hand soap solution.
- Time after start of exposure: 6 h
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.5 mL of dosage form/kg ( Dose: 1.5 mg/kg)
USE OF RESTRAINERS FOR PREVENTING INGESTION: yes - Duration and frequency of treatment / exposure:
- 6 h
Doses / concentrations
- Remarks:
- Doses / Concentrations:
Oral: 50 and 200 mg/kg/day;
Dermal: 1.5 and 15 mg/kgbw/day
- No. of animals per sex per dose / concentration:
- 9/sex/dose - Plasma/blood pharmacokinetics (Group 1-5)
5/sex/dose - Excretion balance (Group 6-8)
5/sex/dose bile collection (Group 9) - Control animals:
- other: Yes: For the purposes of pre-dose sample analysis, plasma, blood and tissues will be collected from at least one untreated supplementary animal/sex using the above mentioned procedures.
- Positive control reference chemical:
- Not applicable
- Details on study design:
- - Rationale for animal assignment (if not random): Random
- Details on dosing and sampling:
- PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled : Blood, plasma, serum, urine, feces, cage washes, bile, skin-application site
- Time and frequency of sampling: Oral groups: 0.5, 1, 2, 4, 8, 24, 48, 72 and 96 h post gavage on Day 1 (Groups 1, 2 and 5)
Dermal group: 3, 6, 7, 8, 10, 16, 24, 48 and 72 h post dermal application (Groups 3 and 4)
Excreta and tissue collection: 0-24, 24-48, 48-72, 96-120, 120-144 and 144-168 h after the radioactive gavage/dermal application (Group 6-8)
Bile collection: 0-3, 3-6, 6-12 and 12-24 h post injection/gavage (Group 9)
METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled : urine, faeces, tissues, cage washes, bile
- Method type(s) for identification : Radio- HPLC for urine samples and LSC for biological samples - Statistics:
- None
Results and discussion
- Preliminary studies:
- None
Main ADME resultsopen allclose all
- Type:
- absorption
- Results:
- Low oral bioavailability (0.93 to 3.16 %); rapidly eliminated with a 48 h period
- Type:
- distribution
- Results:
- Radioactive levels generally decreased over time in all tissues
- Type:
- excretion
- Results:
- A mean 2.57±2.39 (males) and 1.14±0.69 % (females) of the radioactive dose was recovered over the 24 h period in the bile
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Single dose: The minimal fraction(from urine data) of the oral dose absorbed systemically was below 3.16 and 1.75 % for males and females respectively.
Repeated dose: The minimal fraction (from urine data) of the oral dose absorbed systemically was below 0.93 and 1.18 % for males and females respectively. - Details on distribution in tissues:
- Oral gavage:
50 mg/kg (single dose): The mean radioactivity levels were below quantifiable limits (Group 1) in all tissues except for intestines, kidneys and liver
200 mg/kg (single dose): The mean radioactivity levels were above quantifiable limits (Group 2) in half analysed tissues and organs at 24 h. Specifically high levels were present in adrenals, abdominal fat, eyes, heart, kidneys, liver, lungs, lymph nodes and pancreas.
50 mg/kg (repeated dose): The mean radioactivity levels were below quantifiable limits (Group 1) in all tissues except for intestines, kidneys, liver and mesenteric lymph nodes
Dermal application:
Single application (1.5 mg/kg): Radioactivity levels were below quantifiable limits in all tissues/organs at all time points except for the stripped skin from the application site and intestine (15 mg/kg)
Single application (15 mg/kg): Radioactivity levels were below quantifiable limits in all tissues/organs at all time points except for the stripped skin from the application site, adrenals, heart, kidneys, liver and lungs
- Details on excretion:
- Following single oral gavage at a nominal dose level of 50 mg/kg to rats, a mean 2.57±2.39 (males) and 1.14±0.69 % (females) of the radioactive dose was recovered over the 24 h period in the bile.
Toxicokinetic parametersopen allclose all
- Key result
- Toxicokinetic parameters:
- other: Oral: Mean plasma and blood radioactivity levels were all below quantifiable limits
- Key result
- Toxicokinetic parameters:
- other: Dermal: Mean plasma and blood radioactivity levels were all below quantifiable limits
Metabolite characterisation studies
- Metabolites identified:
- no
- Details on metabolites:
- No metabolites nor parent drug were found in urine samples
Any other information on results incl. tables
Conclusion: Low dermal and oral absorption. The actual
minimal fraction of the oral dose absorbed was 0.93 to
3.16%; this was eliminated rapidly, essentially within a 48-hour period.
Applicant's summary and conclusion
- Conclusions:
- Under the study conditions, the test substance was found to have low dermal and oral absorption. The total oral absorption value therefore was roughly in the range around 3-7%, based on urinary (0.93 - 3.16%) and bile (1.8-4.0%) excretion. Further, the study was flawed with respect to the dermal absorption part and did not allow a precise quantification of percutaneous absorption. Nevertheless, based on the results, it can be assumed that dermal absorption is very limited compared to absorption via the oral route.
- Executive summary:
A study was conducted to determine the blood and plasma pharmacokinetics, tissue distribution and mass balance of the test substance, 14C-test substance, DDAC (non-radiolabellled: 40.5% active, radilabelled: 98% active) following oral and dermal administrations, according to OECD guideline 417, in compliance with GLP.
Single dermal administration (at 1.5 and 15 mg/kg, as 6 h exposure over 10% of the body surface) and single (at 50 and 200 mg/kg) and repeated (at 50 mg/kg/d) oral gavage administrations of test substance were performed to male and female Sprague-Dawley rats. In addition, the elimination of radioactivity in bile after single oral administration at 50 mg/kg was investigated. Investigations included blood and plasma pharmacokinetics, tissue distribution and mass balance of total radioactivity. The animals were divided into 9 groups; groups 1 to 5 (each of 9 animals/sex) for plasma/blood pharmacokinetics of radioactivity and tissue distribution, groups 6 to 8 (each of 5 animals/sex) principally for excretion balance and group 9 (4 animals/sex) for bile collection. Animals of groups 1 to 4 and 6 and 7 were treated once with the radiolabelled test item. Animals of groups 5 and 8 were treated once per day for 6 d with the unlabelled test item, followed by a single administration of the radiolabelled test material on Day 7. All oral dosages applied 2.2 MBq/kg for radioactive dose-levels, and 3.7 MBq/kg for dermal applications. Dermal dosages were applied on clipped skin approx. 10% of the total body surface area, over the interscapular/ upper back region. The animals wore an Elizabethan collar to prevent ingestion of the test item. At the end of the exposure period, the collar was removed and kept with the swabs for analysis. After 6 h, the treated areas were washed using dampened cotton swabs with diluted hand soap followed by two dry swabs to remove all traces of the test material.
Blood and plasma sampling were performed as follow: (a) Oral group: 0.5, 1, 2, 4, 8, 24, 48, 72 and 96 h (b) Dermal group: 3 and 6 (i.e. during the exposure period), 7, 8, 10, 16, 24, 48 and 72 h. Following the final blood sampling/animal (i.e. at 24, 48 and 72/96 h), each sampled animal was sacrificed by cervical dislocation, under isoflurane anesthesia. The carcass were weighed and the following tissues dissected out and weighed: Adrenals, Gastro intestinal tract (complete), Lymph nodes (mesenteric and mandibular), Brain, Heart, Muscle (right leg adductor), Eyes, Kidneys, Pancreas, Fat (abdominal), Liver, Skin (lower back), Femur (right with marrow), Lungs, Spleen. In addition, for the dermal treated animals, the application site will be dissected out and weighed. Thereafter, the application site and the skin from the lower back will be each stripped completely (using tape) 13 times. No macroscopic examination was performed on the prematurely sacrificed animals or those found dead. Urine and faeces were collected from the groups 6 to 8 animals for the radioactive treatments at the following times: (a) During a period of 24 h before radioactive dosing on Day 1 (Groups 6 and 7), or Day 7 (Group 8) (b) during the periods 0-24, 24-48, 48-72, 72-96, 96-120, 120 -144 and 144-168 h after the radioactive gavage/dermal application. After each collection of faeces, the cages and trays will be carefully rinsed with not more than 20 mL of water (cage wash) (except for last collection; approximately 100 mL will be used).
Following single and/or repeated oral gavage at 50 and 200 mg/kg bw/day, the plasma and blood radioactivity levels were non-quantifiable indicating a low oral bioavailability. The actual minimal fraction of the oral dose absorbed was 0.93 to 3.16%; this was eliminated rapidly, essentially within a 48 -h period. The vast majority of the oral dose was excreted rapidly in the faeces. At the high oral dose-level only, quantifiable levels of radioactivity were found in some central organs at 24 h post- dosing (intestines, liver. kidney) ; otherwise, the vast majority of the dose was confined to the intestines and levels decreased over time. Only 2.57/1.14% (males/females) of the oral dose was eliminated in the bile in a 24-h period. No metabolites or parent drug were found in urine.
Following single dermal application at 1.5 and 15 mg/kg bw, the plasma and blood radioactivity levels were non-quantifiable at all time-points. For the 1.5 mg/kg bw group, around 1% and 50% of the dose was eliminated in the urine and faeces, respectively, mostly within a 48 h period, suggesting that the dermal dose was highly absorbed via the skin. However, as the test site was not protected with an Elizabethan collar during the main part of the collection period (the collar was worn during the exposure period only), this may have been due to the animal licking the test site. This is also supported with the finding that after oral dosing only 1-2.5% was excreted via bile back to intestines, and 2-3 % excreted via urine. At 24 h post- dosing, most of the radioactivity was in the "stripped" skin (dermis and epidermis) application site (6.07 to 21.6% of the dose) and intestines for both dose- levels, though some radioactivity was in the skin adjacent to the application site (most likely from cross- contamination due to grooming) and minor traces were in the eyes and other organs. At 72/168 h, levels in the application site were 1.06 to 2.82% of the radioactive dose, suggesting the skin acted as a drug reservoir. In the stratum corneum of the application site, the levels of radioactivity were of similar magnitude in the different layers at each time point. For all tissues/organs, the radioactivity levels essentially decreased over time. All data showed generally a low inter-animal variability. In addition, there was no evidence of gender differences.
Under the study conditions, the test substance was found to have low dermal and oral absorption. The actual minimal fraction of the oral dose absorbed roughly ranged from 0.93 to 3.16 % (based on urinary excretion) and ((1.8-4.0%) biliary excretion), which was eliminated rapidly, essentially within a 48 h period (Appelqvist, 2006). Further, the study was flawed with respect to the dermal absorption part and did not allow a precise quantification of percutaneous absorption. Nevertheless, based on the results, it can be assumed that dermal absorption is very limited compared to absorption via the oral route.
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