2,2,4-trimethylpentane

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study meets generally accepted scientific principles, acceptable for assessment.

Data source

Reference

Reference Type:

publication

Title:

The fate of inhaled octane and the nephrotoxicant, isooctane, in rats.

Author:

Dahl, A.

Year:

1989

Bibliographic source:

Toxicology and Applied Pharmacology 100: 334-341

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

Deviations:

yes

Remarks:

- Only male rats were used. It would have been useful to see if the excretion patterns differed in female rats for which kidney toxicity may not be of concern; limited documentation.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2,2,4-trimethylpentane

EC Number:

208-759-1

EC Name:

2,2,4-trimethylpentane

Cas Number:

540-84-1

Molecular formula:

C8H18

IUPAC Name:

2,2,4-trimethylpentane

Details on test material:

- Name of test material (as cited in study report): Isooctane (2,2,4-trimethylpentane)
- Physical state: vapour
- Analytical purity: 99.9 %
- Radiochemical purity (if radiolabelling): 99 % [4-14C]; 95 % [5-14C]
- Specific activity (if radiolabelling): 24 mCi/mmol [4-14C]; 8 mCi/mmol [5-14C]
- Locations of the label (if radiolabelling): 2,2,4-[4-14C] trimethylpentane; 2,2,4-[5-14C] trimethylpentane

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

other: F344/N

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 9-15 weeks

Administration / exposure

Route of administration:

inhalation

Vehicle:

unchanged (no vehicle)

Details on exposure:

TYPE OF INHALATION EXPOSURE: nose only

Duration and frequency of treatment / exposure:

one single dose for 2 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
nominal: 1.0 and 350 ppm (corresponding to 0.00473 and 1.7 mg/L)
analytical: 0.79 ± 0.22 and 385 ± 56 ppm

No. of animals per sex per dose / concentration:

4

Control animals:

no

Positive control reference chemical:

no data

Details on study design:

no data

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, blood, plasma, serum or other tissues, cage washes, bile
- Time and frequency of sampling: Urine and feces were collected at all times except 1 or 2 hours post-exposure.



METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled (delete / add / specify): urine, faeces, tissues, cage washes, bile
- Time and frequency of sampling:
- From how many animals: (samples pooled or not)
- Method type(s) for identification (e.g. GC-FID, GC-MS, HPLC-DAD, HPLC-MS-MS, HPLC-UV, Liquid scintillation counting, NMR, TLC)
- Limits of detection and quantification:
- Other:


TREATMENT FOR CLEAVAGE OF CONJUGATES (if applicable):

Statistics:

A Bonferroni correction was applied to each group of t-tests comparing high and low exposure groups.

Results and discussion

Metabolite characterisation studies

Metabolites identified:

not specified

Any other information on results incl. tables

Uptake rates were 3.4 and 2.2 nmol/kg/min/ppm for low and high isooctane (2,2,4 -trimethylpentane) levels, respectively. The fraction of inhaled hydrocarbon that was metabolised [sum of excreta, exhaled CO2 and carbon-14 equivalents in the carcass] was higher at low inhaled concentrations than at high inhaled concentrations. Major route of elimination was urine, for low exposure concentration 14C in urine exceeded 11% of total inhaled isooctane. The amount of inhaled 14C in the carcass at 70 hours post-exposure was less than 2% of total inhaled for both low and high concentrations. The fraction of inhaled parent compound exhaled unchanged was approx. 2%. Half of isooctane (2,2,4 -trimethylpentane) 14C retained at the end of the 2 hour exposure was eliminated within 15 hours post-exposure but elimination continued primarily by the urinary route throughout 70 hours of observation. The almost exclusive elimination of metabolites of inhaled isooctane via the kidney with little production of 14CO2 suggests that kidneys may be exposed to a higher concentration of high molecular weight metabolites of isooctane.

Applicant's summary and conclusion

Conclusions:

Interpretation of results: low bioaccumulation potential based on study results