Naphtha (Fischer-Tropsch), light, C4-10-branched and linear

Neurotoxicity

Administrative data

Endpoint:

neurotoxicity: sub-chronic inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: peer reviewed international scientific journal

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Health assessment of gasoline and fuel oxygenate vapors: Neurotoxicity evaluation

Author:

J.P. O’Callaghan et al.

Year:

2014

Bibliographic source:

Regulatory Toxicology and Pharmacology (2014; in press). doi: 10.1016/j.yrtph.2014.05.002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.6200 (Neurotoxicity Screening Battery)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: EPA GFAP determination (GFAP Assay 79.67, CFR Vol. 59, No. 122, 27 June 1994)

Deviations:

not specified

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Baseline gasoline vapor condensate

IUPAC Name:

Baseline gasoline vapor condensate

Details on test material:

- Name of test material (as cited in study report): Baseline gasoline vapor condensate (BGVC)
- Composition of test material, percentage of components: see below "Any other information on materials and methods incl. tables", Tables 1 and 2
- Other: Test substance is closely related to 'Naphtha (Fischer-Tropsch), light, C4-10 - branched and linear', but it contains a higher level of aromatics, olefins and cycloparaffins. It can be assumed that the level of toxicity of 'Naphtha (Fischer-Tropsch), light, C4-10 - branched and linear', mainly consisting of branched and linear hydrocarbons is, however, considerably less (or at least the same) than that seen with the test material.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: vapour

Vehicle:

air

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

6 h/day, 5 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 2000, 10000, 20000 mg/m3/day
Basis:
nominal conc.

No. of animals per sex per dose:

5 males and 5 females

Control animals:

yes, concurrent vehicle

Applicant's summary and conclusion

Conclusions:

Overall, administration of the gasoline substances at the concentrations tested were not associated with changes in motor activity or with any change in counts of the 25 nominal FOB measures, or the 4 continuous FOB measures.
All substances (and consequently, the closely related test material ‘Baseline gasoline vapor condensate'’ (BGVC) as well) showed no statistically significant increases in GFAP (Glial Fibrillary Acidic Protein) levels in male or female rats. Under the exposure conditions employed, treatmentinduced astrogliosis i.e. an induction in brain region levels of GFAP, did not occur in the representative areas of the adult rat brain.

Executive summary:

Sprague–Dawley rats were exposed via inhalation to vapor condensates of either gasoline or gasoline combined with various fuel oxygenates to assess potential neurotoxicity of evaporative emissions. Test articles included vapor condensates prepared from ‘‘baseline gasoline’’ (BGVC), or gasoline combined with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA). Target concentrations were 0, 2000, 10,000 or 20,000 mg/mg3 and exposures were for 6 h/day, 5 days/week for 13 weeks. The functional observation battery (FOB) with the addition of motor activity (MA) testing, hematoxylin and eosin

staining of brain tissue sections, and brain regional analysis of glial fibrillary acidic protein (GFAP) were used to assess behavioral changes, traditional neuropathology and astrogliosis, respectively.

Functional observation battery (FOB) and motor activity (MA) data for all agents, except G/TBA, were negative. G/TBA behavioral effects resolved during recovery. Neuropathology was negative for all groups. Analyses of GFAP revealed increases in multiplebrain regions largely limited to males of the G/EtOH group, findings indicative of minor gliosis, most significantly in the cerebellum. Small changes (both increases and decreases) in GFAP (Glial Fibrillary Acidic Protein) were observed for other test agents but effects were not consistent across sex, brain region or exposure concentration.