Stoddard solvent

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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Exposure to white spirit. I. Concentration in alveolar air and blood during rest and exercise.

Author:

Aastrand I, Kilbom Aa, & Övrum P

Year:

1975

Bibliographic source:

Scand J Work Environ Health, 1: 15-30.

Materials and methods

Objective of study:

absorption

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Healthy male volunteers were exposed to white spirit at concentrations up to 2500 mg/m3 in inspiratory air during rest and exercise on a bicycle ergometer. The white spirit contained approximately 83% aliphatics and 17% aromatic components. The duration of each exposure period was 30 minutes. The pulmonary ventilation, the cardiac output, and the concentration of white spirit (subdivided into aromatic and aliphatic components) in alveolar air and arterial blood were determined during and after exposure.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Stoddard solvent

EC Number:

232-489-3

EC Name:

Stoddard solvent

Cas Number:

8052-41-3

Molecular formula:

C10H22

IUPAC Name:

stoddard solvent

Test material form:

liquid

Specific details on test material used for the study:

Stoddard solvent (boiling range, 150-200°C; ) contained approximately 83% aliphatics and 17% aromatic components.

Radiolabelling:

no

Test animals

Species:

other: Human

Strain:

other: healthy male volunteers

Sex:

male

Details on test animals or test system and environmental conditions:

healthy male volunteers were exposed to white spirit at concentrations up to 2500 mg/m3 in inspiratory air during rest and exercise on a bicycle ergometer.

Administration / exposure

Route of administration:

inhalation

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

See details of exposure section

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

1 000 mg/m³ air

Doses / concentrations 2

Dose / conc.:

1 250 mg/m³ air

Doses / concentrations 3

Dose / conc.:

1 500 mg/m³ air

Doses / concentrations 4

Dose / conc.:

2 000 mg/m³ air

Doses / concentrations 5

Dose / conc.:

2 500 mg/m³ air

No. of animals per sex per dose / concentration:

Three or five males per dose for the excretion test, six males for the absorption and enterohepatic tests.

Control animals:

not specified

Details on study design:

Human volunteers were exposed for 30 min during rest or during exercise to 1250 and 2500 mg/m3 of white spirit (boiling range, 150-200°C; 83% aliphatics and alicyclics, 17% aromatics). At the end of the exposure period the concentration of aliphatics and aromatics in alveolar air was found to be about 25% and 15%, respectively, of the concentration in the inspired air.

Statistics:

(The aliphatic fraction was analysed by gas chromatography as a "total aliphatic fraction", whereas the aromatic fraction was calculated on the basis of analytical determination of 1,2,4-trimethylbenzene, which was chosen to represent the aromatic fraction).

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

When inhaled, Stoddard solvent constituents were readily absorbed. After a 30-minute exposure at rest to approximately 1040 mg/m3 of the aliphatic components, the concentration in alveolar air was 255 mg/m3 (25 % of the concentration in the inspiratory air). The corresponding arterial blood concentration was 1.7 mg/kg. When alveolar ventilation tripled (50 W exercise), the alveolar concentration increased to 515 mg/ m3 (50 % of the concentration in inspiratory air), whereas the arterial concentration rose to 3.5 mg/kg. When alveolar ventilation was raised to 60 L/min (150 W exercise), the alveolar concentration rose to about 60 % of the concentration in inspiratory air. Thirty minutes following exposure, alveolar concentration was ~180 mg/m3 and arterial concentration was near 0 mg/kg.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Stoddard solvent is readily absorbed by inhalation. Human volunteers were exposed for 30 min during rest or during exercise to 1250 and 2500 mg/m3 of white spirit (boiling range, 150-200°C; 83% aliphatics and alicyclics, 17% aromatics). At the end of the exposure period the concentration of aliphatics and aromatics in alveolar air was found to be about 25% and 15%, respectively, of the concentration in the inspired air.

Applicant's summary and conclusion

Conclusions:

Interpretation of results : no bioaccumulation potential based on study results
Stoddard solvent is readily absorbed by inhalation. Human volunteers were exposed for 30 min during rest or during exercise to 1250 and 2500 mg/m3 of white spirit (boiling range, 150-200°C; 83% aliphatics and alicyclics, 17% aromatics). At the end of the exposure period the concentration of aliphatics and aromatics in alveolar air was found to be about 25% and 15%, respectively, of the concentration in the inspired air.

Executive summary:

Human volunteers were exposed for 30 min  during rest or during exercise to 1250 and 2500 mg/m3of white spirit (boiling range, 150-200°C; 83% aliphatics and alicyclics, 17%   aromatics). At the end of the exposure period the concentration of   aliphatics and aromatics in alveolar air was found to be about 25% and   15%, respectively, of the concentration in the inspired air. With   exposure during exercise (load of 50 watts, corresponding to light   work), the pulmonary ventilation tripled and the concentrations of the  aliphatics and the aromatics in the alveolar air increased to about   50% and 20%, respectively, of the concentrations in the inspired air.    However, the total amount of retained vapour was considerably  increased because of the three-fold rise in pulmonary ventilation.   Measurements of the concentrations in venous and arterial blood were  found to reflect the exposure level quite well. Thus the amount in   blood doubled as the exposure level doubled. Exposure to 1250 mg/m3   during hard exercise (load of 150 watts) resulted in a seven-fold rise   in pulmonary ventilation, an increase in aliphatics in venous blood   from 1.3 mg/kg (rest level) to 5.4 mg/kg, and an increase in aromatics   from 0.2 to 2.6 mg/kg. The total uptake over a period of 30 min was   measured in one subject during exposure to 1000, 1250, 1500 and   2000 mg/m3white spirit vapour. Of the total amount of the inspired   aliphatic fraction, 59% was retained at the lowest and 46% at the  highest level. The uptake of the aromatics was found to be 70% at   the lowest level and 58% at the highest. (The quantitative   analytical determinations were carried out on n-decane and   1,2,4-trimethylbenzene as markers for the aliphatic and the aromatic   fractions, respectively).