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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: limited documentation but sufficient for evaluation

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2008

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 417 (Toxicokinetics)
Deviations:
no
GLP compliance:
not specified

Test material

Constituent 1
Details on test material:
- Name of test material (as cited in study report): 1-Butyl-3-methylimidazolium Chloride
- Physical state:
- Analytical purity: Bmim-Cl reference standard (98% Bmim-Cl)
- Radiochemical purity (if radiolabelling): [14C] Bmim-Cl was 97.5%
- Specific activity (if radiolabelling): 27.5 mCi/mmol.
- Locations of the label (if radiolabelling): RTI International (Research Triangle Park, NC)
- Stability under test conditions: stable
- Storage condition of test material: 8°C
- Lot/batch No.: 9719-75
Radiolabelling:
yes
Remarks:
C14

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: rat: Harlan Sprague-Dawley, Inc. (Indianapolis, IN)
- Age at study initiation: 8–9 weeks ;
- Weight at study initiation: 161–200 g
- Fasting period before study: 12 h Animals used in the dermal or the repeated dose study were not fastened
- Acclimation period: 5-7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25 °C
- Photoperiod (hrs dark / hrs light): 12 h

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Duration and frequency of treatment / exposure:
once for the absorbtion study (iv and oral)
once/ day in the 5 day accumlation study
Doses / concentrations
Remarks:
Doses / Concentrations:
50 mg/kg was administered by oral gavage (single administration)
0.5, 5 and 50 mg/kg/day by oral gavage (repeated administration)
5 mg/kg was selected for the i.v. route of administration.
No. of animals per sex per dose / concentration:
4
Control animals:
no
Details on study design:
- Dose selection rationale: oral 1/10 of the LD50; Iv 1/100 of the LD50
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
iv application
- Tissues and body fluids sampled : urine, faeces, blood, cage washes
- Time and frequency of sampling:
Blood: 0.7.5 min h; 15 min ; 30 min; 45 min; 1 h, 1,5 h 3h; 6 h; 9h; 12 h; 24 h; 36 h; 48 h.
Other samples 6h 12 h 24 h, 48 h,

oral application (single application)
- Tissues and body fluids sampled : urine, faeces, blood, cage washes adipose tissue, blood, heart, intestine, intestinal contents, kidneys, lung, liver, muscle, spleen, stomach, stomach contents, skin, and testes.
- Time and frequency of sampling: 6h (urine only), 12 h 24 h, 48 h, 72 h


METABOLITE CHARACTERISATION STUDIES

- Tissues and body fluids sampled: urine
- Time and frequency of sampling: 6 h and 12 h
- From how many animals: Not pooled
- Method type(s) for identification: HPLC-UV/vis-radiometric analysis and LC/MS for non radioactive samples

Statistics:
mean +/- SD

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Systemic bioavailability was determined to be 62.1% of a 50 mg/kg oral dose in rats.
Details on distribution in tissues:
Cumulative Dose recovered from all tissues 24 h after the final dose following one or five serial daily oral administrations of Bmim-Cl (50 mg/kg/day) to male F-344 rats was 1.1 +/- 0.2 %. This is even less the cumulative dose recovery from all tissues 24 h after one administration (5.3 +/- 2.4 %). This suggest that bioaccumulation potential of BMIM Cl is low. distribution to dissues to single organs was not reported.
Details on excretion:
Urinary excretion of the parent compound by rats was the major route of elimination (i.v.: 91% in 24 h; oral: 55–74% in 24 h). The rates and routes of elimination were not affected by escalation of dose (0.5–50 mg/kg) or repeated oral administration (five daily administrations, 50 mg/kg) and were similar in male rats and B6C3F1 female mice (86–95% of dose eliminated in 24 h).

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
94.7 +/- 10 % of the iv applied radiactivity were recoverd as Butyl-3-methylimidazolium Chloride, no other peak was detected HPLC-UV Vis- radiometric analysis in blood and urine samples.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results