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EC number: 203-396-5 | CAS number: 106-42-3
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Non-GLP, non-guideline animal experimental study, published in peer reviewed literature, minor restrictions in reporting but otherwise adequate for assessment.
Cross-reference
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- publication
- Title:
- The role of toxicokinetics in xylene-induced ototoxicity in the rat and guinea pig
- Author:
- Gagnaire F, Marignac B, Blachere V, Grossman S and Langlais C
- Year:
- 2 007
- Bibliographic source:
- Toxicology 231, 147-158
Materials and methods
- Objective of study:
- toxicokinetics
Test guideline
- Qualifier:
- no guideline followed
- GLP compliance:
- not specified
Test material
- Reference substance name:
- o-xylene
- EC Number:
- 202-422-2
- EC Name:
- o-xylene
- Cas Number:
- 95-47-6
- Molecular formula:
- C8H10
- IUPAC Name:
- o-xylene
- Details on test material:
- - Source: Acros, Geel, Belgium
- Purity: 99% (for all)
Constituent 1
- Radiolabelling:
- no
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Iffa Credo, Saint-Germain-sur-l'Arbresle, France
- Age at study initiation: approx. 7 wk
- Housing: group housed, 4/cage in polypropylene cages with woodchip bedding
- Diet : UAR-Alimentation, Epinay-sur Orge, France, sterilised by gamma irradiation ad libitum
- Water : filtered tap water ad libitum
- Acclimation period: 6 days
ENVIRONMENTAL CONDITIONS
- Temperature: 22°C
- Humidity: 50-60%
- Photoperiod (lights on): 07.00 - 19.00 hr
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- olive oil
- Details on exposure:
- Each isomer dosed by gavage - single dose of 8.47 mmol/kg, dissolved in olive oil (dose volume 4 mL/kg bw).
- Duration and frequency of treatment / exposure:
- Single dose
Doses / concentrations
- Remarks:
- Doses / Concentrations:
8.47 mmol/kg (899 mg/kg)
- No. of animals per sex per dose / concentration:
- 60
- Control animals:
- no
- Details on study design:
- Blood and brain concentrations of ortho, meta and para-xylene (one isomer per experiment) determined in SD rats following a single oral dose of 8.47 mmol/kg bw. Results for o-xylene only are reported here. Comment: 8.47 mmol p-xylene / kg bw shown previously to cause histopathological lesions in the organ of Corti in rats whereas m- and o-xylenes ineffective (see Gagnaire and Langlais (2005) Arch. Toxicol. 79, 346-354).
- Details on dosing and sampling:
- - Tissues and body fluids sampled: blood (abdominal aorta), brain
- From how many animals: 6-8 per timepoint
- Time and frequency of sampling: 10, 20 and 30 min; 1, 2, 5, 8, 11, 15 and 24 hr
- Other: samples taken under deep anaesthesia (sodium pentobarbital) and stored frozen until analysis
- Method type(s) for identification: GC-FID - Statistics:
- Elimination half-life was estimated during the linear phase post-treatment. Maximum blood and brain concentrations were compared by one-way ANOVA followed by Scheffe's multiple range test if results were significant.
Results and discussion
Toxicokinetic / pharmacokinetic studies
Toxicokinetic parametersopen allclose all
- Toxicokinetic parameters:
- Cmax: Blood: o-xylene = 39 µg/mL
- Toxicokinetic parameters:
- Cmax: Brain: o-xylene = 116 µg/g
- Toxicokinetic parameters:
- half-life 1st: Blood: o-xylene = 213 min
- Toxicokinetic parameters:
- half-life 1st: Brain: o-xylene = 238 min
- Toxicokinetic parameters:
- AUC: Blood: o-xylene = 28242
- Toxicokinetic parameters:
- AUC: Brain: o-xylene = 88083
Any other information on results incl. tables
Graphical data showed that o-xylene appeared rapidly in blood and brain, peaked after 2 hr, remained steady for 3 hr and then declined steadily over time. Levels in brain (Cmax, AUC) were around 3-fold greater than those for blood.
Applicant's summary and conclusion
- Conclusions:
- Blood and brain concentrations of o-xylene were determined in young adult male Sprague-Dawley rats following oral gavage administration of 8.47 mmol/kg. o-xylene appeared rapidly in blood and brain, peaked after 2 hr, remained steady for 3 hr and then declined steadily over time. Levels in brain (Cmax, AUC) were around 3-fold greater than those for blood.
- Executive summary:
Blood and brain concentrations of o-xylene were determined in young adult male Sprague-Dawley rats following oral gavage administration of 8.47 mmol/kg. o-xylene appeared rapidly in blood and brain, peaked after 2 hr, remained steady for 3 hr and then declined steadily over time. Levels in brain (Cmax, AUC) were around 3-fold greater than those for blood.
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