Distillates (Fischer-Tropsch), C8-10-branched and linear

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

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: Basic data given.

Data source

Reference

Reference Type:

publication

Title:

Uptake of 19 hydrocarbon vapor inhaled by F344 rats.

Author:

Dahl, A.R. et al.

Year:

1988

Bibliographic source:

Fundamental and applied toxicology 10: 262-269

Materials and methods

Objective of study:

absorption

Principles of method if other than guideline:

The comparative rates of uptake of 19 hydrocarbon (including normal-heptane) vapours by rats were determined by a dual-column gas chromatography method.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Heptane

EC Number:

205-563-8

EC Name:

Heptane

Cas Number:

142-82-5

Molecular formula:

C7H16

IUPAC Name:

heptane

Details on test material:

- Name of test material (as cited in study report): heptane (Aldrich Chemicals, Milwaukee, Wisconsin)
- Analytical purity: >99%

Radiolabelling:

no

Test animals

Species:

rat

Strain:

other: F344/N

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Lovelace ITRI colony
- Age at study initiation: 12 to 15 weeks
- Weight at study initiation: mean 298 g
- Housing: Before exposure, animals were housed in polycarbonate cages (2 animals/cage) with hardwood chip bedding and filter caps.
- Individual metabolism cages: yes/no
- Diet (e.g. ad libitum): AM. Food (Lab Blox, Allied Mills, Chicago, IL, USA); ad libitum
- Water (e.g. ad libitum): water from bottles with sipper tubes; ad libitium


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 22.2
- Humidity (%): 20 to 50
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: vapour

Vehicle:

unchanged (no vehicle)

Details on exposure:

TYPE OF INHALATION EXPOSURE: nose only

The exposure apparatus, exposure procedures, and method for handling data were described in detail by Dahl et al., 1987 (Amer Ind Hyg Assoc J 48:505-510)

The vapour was pumped at 400 mL/min from a Teflon supply bag through one sampling loop of a dual-column gas chromatograph, past the nose of a rat confined in a nose-only exposure tube, through the second sampling loop of the dual column gas chromatograph and, finally, into an exhaust bag.
The amount of hydrocarbon vapour absorbed was calculated from the output of the gas chromatograph and the flow rate past the rat´s nose. Rat exposures were preceded by a 10-15 min pre-exposure equilibration/calibration period without a rat in the system.

Duration and frequency of treatment / exposure:

80 min for 5 consecutive days (totally 450 min)

Doses / concentrations

Remarks:

Doses / Concentrations:
on day 1: 1 ppm
on day 2: 10 ppm
on day 3: 100 ppm
on day 4: 1000 ppm
on day 5: 5000 ppm
See also "any other information on materials and methods".

No. of animals per sex per dose / concentration:

at 100 ppm: 10 male rats (not further specified)

Control animals:

not specified

Positive control reference chemical:

no data

Details on study design:

All animals were exposed for 80 min/day for 5 consecutive days with escalation of vapour concentration daily.

Details on dosing and sampling:

During the exposures (80 min/day), respiratory and gas chromatographic data were collected at 1 min intervals.

Statistics:

The calculation of vapour uptake from gas chromatography data see attached document.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Only data from one exposure at 100 ppm were available. Uptake of inhaled heptane vapour was 4.5 ± 0.3 nmol/kg/min/ppm (N=10). The value is given for uptake during minutes 60 to 70 from start of exposure.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
Taking into account all data of the report, a number of trends relating uptake to chemicals properties were observed. Among these, highly volatile hydrocarbons are less well-absorbed than less volatile hydrocarbons; unsaturated compounds are better absorbed than saturated ones; and branched hydrocarbons are less well-absorbed than unbranched ones. These trends can be used to predict relative uptake rates within classes of hydrocarbons.

Executive summary:

Taking into account all data of the report, a number of trends relating uptake to chemicals properties were observed. Among these, highly volatile hydrocarbons are less well-absorbed than less volatile hydrocarbons; unsaturated compounds are better absorbed than saturated ones; and branched hydrocarbons are less well-absorbed than unbranched ones. These trends can be used to predict relative uptake rates within classes of hydrocarbons.