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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 217-615-7 | CAS number: 1910-42-5
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Mar 1995 - Jul 1995
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 995
- Report date:
- 1995
Materials and methods
- Objective of study:
- distribution
- excretion
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 85-1 (Metabolism and Pharmacokinetics)
- Qualifier:
- according to guideline
- Guideline:
- other: Japanese MAFF regulations
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 417 (Toxicokinetics)
- Qualifier:
- according to guideline
- Guideline:
- other: EU Council Directive 67/548/EEC
- Qualifier:
- according to guideline
- Guideline:
- other: Commission Directive 87/302/EEC
- GLP compliance:
- yes
Test material
- Radiolabelling:
- yes
- Remarks:
- [14C]-methyl at both N-methyl positions
Test animals
- Species:
- rat
- Strain:
- other: Alpk:APfSD
- Details on species / strain selection:
- Laboratory rats were selected as standard for rodent species to comply with the corresponding toxicological studies.
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Biological Services Section, Zeneca Pharmaceuticals, Macclesfield, Cheshire, UK
- Weight at study initiation: 176g - 206g
- Housing: stock cages for same sex groups during acclimation; then individual plastic metabolic cages
- Diet: Pelleted PCD rat diet (Special Diets Services Ltd, Stepfield, Witham, Essex, UK), ad libitum, except for 12h prior and 3h after dosing
- Water: ad libitum
- Acclimation period: 5 days in stock cages; 24h in metabolic cages
ENVIRONMENTAL CONDITIONS
- Temperature (°C): between 19 and 23
- Humidity (%): between 40 and 70
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Remarks:
- sterile, double deionised
- Duration and frequency of treatment / exposure:
- single oral, bodyweight dependent dose in dose vehicle
Doses / concentrations
- Dose / conc.:
- 1 mg/kg bw (total dose)
- No. of animals per sex per dose / concentration:
- 5 male; 5 female
- Control animals:
- no
- Details on dosing and sampling:
- TOXICOKINETIC / PHARMACOKINETIC STUDY (Distribution, excretion)
- Tissues and body fluids sampled: urine and faeces collected separately, urine collected in cage washes of 5 mL water, blood and plasma, tissues (whole): brain, gonads, heart, kidneys, liver, lungs, spleen; parts of tissue: fat (abdominal), bone (femur), muscle
- Time and frequency of sampling: urine only - once, after 6h; urine (in cage washes) and faeces collected at 12, 24, 36, 48 and 72h after dosing; blood, plasma and tissues collected 3 days after dosing following killing of the rats
- All samples were taken by duplicate
Results and discussion
Main ADME resultsopen allclose all
- Type:
- excretion
- Results:
- Radioactivity in urine: males-17.9%, females-11.6% of administered dose. Radioactivity in faeces (first 24h after administration): males-63.1% and females-74.1% of the dose. Total radioactivity (including cage washings): males-92.5%, females-93.8%
- Type:
- distribution
- Results:
- Highest radioactivity tissue concentrations in males and females were found in lungs (0.023µg and 0.02µg equiv/g, respectively) and kidneys (0.01µg and 0.011µg equiv/g, respectively
Toxicokinetic / pharmacokinetic studies
- Details on distribution in tissues:
- Three days after dosing, highest radioactivity tissue concentrations in males and females were found in lungs (0.023µg and 0.020µg equiv/g, respectively) and kidneys (0.010µg and 0.011µg equiv/g, respectively). The residual carcasses of male and female rats contained 0.006µg and 0.005µg equiv/g respectively which corresponds to 0.64% and 0.54% of the dose. Remaining tissues showed concentrations equal to or less than that found in carcasses. Table 1 in "Any other information on results incl. tables" section presents a complete overview of tissue and residual carcass radioactivity measurements.
- Details on excretion:
- The rates and amounts of radioactivity excreted in urine were similar for both sexes. During the first 24h after the administration of the radiolabelled test substance, male rats excreted in urine a mean of 17.9% of administered dose and females a mean of 11.6%. The rates of excretion of radioactivity in faeces by males and females were also similar, however the total amount of radioactivity excreted by females was slightly higher. During the first 24h after administration males excreted a mean of 63.1% and females 74.1%. The total amounts of radioactivity excreted in urine and faeces (including cage washings) were 92.5% for male rats and 93.8% for female rats. The detailed results for excretion of radioactivity in urine and faeces expressed as percentages of the administered radioactivity dose, are presented as group mean results with standard deviations in Table 2 in "Any other information on results incl. tables" section.
Any other information on results incl. tables
Table 1. Tissue and residual carcass radioactivity measurements in male and female rats three days after dosing (values are expressed as percentages of administered radioactivity and as concentrations µg equivalents of substance/g of tissue)
Tissue |
% of the dose – males |
% of the dose - females |
concentration – males |
concentration - females |
||||||||
mean |
SD |
mean |
SD |
mean |
SD |
mean |
SD |
|||||
brain |
<0.01 |
<0.01 |
<0.01 |
<0.01 |
0.005 |
0.002 |
0.004 |
<0.001 |
||||
heart |
<0.01 |
<0.01 |
<0.01 |
<0.01 |
0.006 |
0.002 |
0.004 |
<0.001 |
||||
kidney |
0.01 |
<0.01 |
0.01 |
<0.01 |
0.010 |
0.003 |
0.011 |
<0.001 |
||||
liver |
0.02 |
<0.01 |
0.02 |
<0.01 |
0.003 |
0.001 |
0.003 |
<0.001 |
||||
lungs |
0.02 |
<0.01 |
0.01 |
<0.01 |
0.023 |
0.007 |
0.20 |
0.005 |
||||
spleen |
<0.01 |
<0.01 |
<0.01 |
<0.01 |
0.005 |
0.002 |
0.005 |
0.001 |
||||
gonads |
0.01 |
<0.01 |
<0.01 |
<0.01 |
0.003 |
0.001 |
0.004 |
0.002 |
||||
abdominal fat |
- |
- |
- |
- |
0.005 |
0.001 |
<0.004 |
<0.002 |
||||
bone (femur) |
- |
- |
- |
- |
0.004 |
0.001 |
0.005 |
0.001 |
||||
muscle |
- |
- |
- |
- |
0.005 |
0.001 |
0.003 |
0.001 |
||||
blood |
- |
- |
- |
- |
0.002 |
<0.001 |
0.002 |
<0.001 |
||||
plasma |
- |
- |
- |
- |
<0.001 |
|
0.001 |
<0.001 |
||||
carcass |
0.639 |
0.186 |
0.543 |
0.105 |
0.006 |
0.002 |
0.005 |
0.001 |
||||
Total |
0.697 |
0.196 |
0.591 |
0.112 |
|
|||||||
Table 2. Excretion of radioactivity in urine and faeces, male and female rats (values are expressed as percentages of the administered radioactivity and each represents the mean of five rats with standard deviation)
Time after dosing [h] |
urine – males |
urine - females |
faeces – males |
faeces - females |
|||||||
mean |
SD |
mean |
SD |
mean |
SD |
mean |
SD |
||||
0 – 6 |
14.14 |
5.63 |
7.58 |
1.66 |
- |
- |
- |
- |
|||
6 - 12 |
2.54 |
1.15 |
2.31 |
1.35 |
- |
- |
- |
- |
|||
0 – 12 |
- |
- |
- |
- |
23.95 |
17.26 |
16.56 |
16.00 |
|||
12 -24 |
1.25 |
0.62 |
1.68 |
0.69 |
39.13 |
11.96 |
57.51 |
14.83 |
|||
24 - 36 |
0.37 |
0.22 |
0.39 |
0.12 |
3.49 |
3.40 |
3.34 |
2.10 |
|||
36 - 48 |
0.39 |
0.53 |
0.31 |
0.13 |
3.65 |
2.35 |
0.83 |
0.40 |
|||
48 - 72 |
0.37 |
0.45 |
0.28 |
0.05 |
2.14 |
1.12 |
1.63 |
0.72 |
|||
0 - 72 |
19.07 |
7.86 |
12.55 |
1.78 |
72.36 |
5.95 |
79.86 |
4.00 |
|||
|
mean (males) |
sd (males) |
mean (females) |
sd (females) |
|||||||
cage wash |
1.07 |
0.86 |
1.40 |
0.16 |
|||||||
total excreted |
92.49 |
3.40 |
93.81 |
4.04 |
Applicant's summary and conclusion
- Conclusions:
- Seventy two hours after administration of 1mg radiolabelled test substance/kg bw, low levels of radioactivity were present in the tissues and carcass. Following a single oral dose, radioactivity was rapidly eliminated in urine and faeces. The total amounts of radioactivity excreted in urine and faeces (including cage washings) were 92.5% for male rats and 93.8% for female rats.
- Executive summary:
In a GLP compliant study performed according to EPA OPP 85-1 guideline, a single oral dose of the radiolabelled test substance was administrated at 1mg/kg body weight by gavage to one group of male and one group of female rats (strain: Alpk:APfSD).
Urine, faeces and cage washes were collected at different times. After 3 days post administration the rats were sacrificed and tissues were analysed for radiolabelled content. No test substance related or otherwise unusual behaviour of the animals were observed. The rates and amounts of radioactivity excreted in urine and faeces were similar for both sexes. During the first 24 hours after the administration of radiolabeled test substance, male rats excreted in urine a mean of 17.9% and female rats a mean of 11.6% of the radioactivity. During the same period males excreted a mean of 63.1% and females a mean of 74.1% of the dose in faeces. The total amount of radioactivity excreted in urine and faeces (including cage washings) was 92.5% for males and 93.8% for females. Three days after dosing the highest tissue concentrations of radioactivity in both male and female rats were present in lungs (0.023µg and 0.020µg equiv/g respectively) and kidneys (0.010µg and 0.011µg equiv/g) In male and female rats 0.64% and 0.54% of the dose remained in the carcass which corresponds to 0.006µg and 0.005 µg equiv/g respectively. The total mean percentage recoveries, including excreta and tissue residues, for male rats was 93.2% and for females was 94.4%. In conclusion, seventy two hours after dosing only low levels of radioactivity were present in the tissues and carcass. Following a single oral dose, radioactivity was rapidly excreted in faeces and urine.
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.