Stoddard solvent

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

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

Objective of study:

absorption

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

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

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.

Route of administration:

inhalation

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

See details of exposure section

Dose / conc.:

1 000 mg/m³ air

Dose / conc.:

1 250 mg/m³ air

Dose / conc.:

1 500 mg/m³ air

Dose / conc.:

2 000 mg/m³ air

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).

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.

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.

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).

 

Reference 2

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

Objective of study:

absorption

Qualifier:

no guideline followed

Principles of method if other than guideline:

21 human volunteers were exposed to white spirit at concentrations to 204, 600, 1200 and 2400 mg/m3 (34, 100, 200 and 400 ppm) (corresponding to aliphatic/aromatic levels (in mg/m3) of 172/36, 508/104, 990/203 and 1934/398),

GLP compliance:

not specified

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

Species:

other: Human

Strain:

other: healthy male volunteers

Sex:

male

Details on test animals or test system and environmental conditions:

21 human volunteers were exposed to white spirit at concentrations to 204, 600, 1200 and 2400 mg/m3 (34, 100, 200 and 400 ppm) (corresponding to aliphatic/aromatic levels (in mg/m3) of 172/36, 508/104, 990/203 and 1934/398),

Route of administration:

inhalation

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

See details of exposure section

Dose / conc.:

204 mg/m³ air

Dose / conc.:

600 mg/m³ air

Dose / conc.:

1 200 mg/m³ air

Dose / conc.:

2 400 mg/m³ air

Control animals:

not specified

Details on study design:

Study include 21 human volunteers. They noted rapid changes in the concentration of white spirit (17% aromatic hydrocarbons) in alveolar air if the exposure concentration or the pulmonary ventilation changed. Steady state in alveolar air was obtained after 20 min of exposure at rest and after 1´ h during work. The aromatic fraction reached steady state in alveolar air earlier than the aliphatic fraction. In nine students exposed to 204, 600, 1200 and 2400 mg/m3 (34, 100, 200 and 400 ppm) (corresponding to aliphatic/aromatic levels (in mg/m3) of 172/36, 508/104, 990/203 and 1934/398), the alveolar air at steady state contained 31.6-33.6% of the aliphatic exposure levels while the alveolar contents of aromatics were 8.2-11.5% of the aromatic exposure levels.

Details on absorption:

When inhaled, Stoddard solvent constituents were readily absorbed. No great differences were seen in retention at the different exposure levels. After 7 h of exposure to the above-mentioned levels the concentrations in blood of aliphatics/aromatics were found to be 0.74/0.12, 2.30/0.40, 4.07/0.91 and 9.07/2.01 mg/litre, respectively. Steady state in blood was not achieved in these experiments.

Metabolites identified:

yes

Details on metabolites:

Stoddard solvent is readily absorbed by inhalation. In a study including 21 human volunteers. They noted rapid changes in the concentration of white spirit (17% aromatic hydrocarbons) in alveolar air if the exposure concentration or the pulmonary ventilation changed. Steady state in alveolar air was obtained after 20 min of exposure at rest and after 1´ h during work. The aromatic fraction reached steady state in alveolar air earlier than the aliphatic fraction. In nine students exposed to 204, 600, 1200 and 2400 mg/m3 (34, 100, 200 and 400 ppm) (corresponding to aliphatic/aromatic levels (in mg/m3) of 172/36, 508/104, 990/203 and 1934/398), the alveolar air at steady state contained 31.6-33.6% of the aliphatic exposure levels while the alveolar contents of aromatics were 8.2-11.5% of the aromatic exposure levels. Thus, no great differences were seen in retention at the different exposure levels. After 7 h of exposure to the above-mentioned levels the concentrations in blood of aliphatics/aromatics were found to be 0.74/0.12, 2.30/0.40, 4.07/0.91 and 9.07/2.01 mg/litre, respectively. Steady state in blood was not achieved in these experiments. (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).

Conclusions:

Interpretation of results : no bioaccumulation potential based on study results
Stoddard solvent is readily absorbed by inhalation. In a study including 21 human volunteers. They noted rapid changes in the concentration of white spirit (17% aromatic hydrocarbons) in alveolar air if the exposure concentration or the pulmonary ventilation changed. Steady state in alveolar air was obtained after 20 min of exposure at rest and after 1´ h during work. The aromatic fraction reached steady state in alveolar air earlier than the aliphatic fraction. In nine students exposed to 204, 600, 1200 and 2400 mg/m3 (34, 100, 200 and 400 ppm) (corresponding to aliphatic/aromatic levels (in mg/m3) of 172/36, 508/104, 990/203 and 1934/398), the alveolar air at steady state contained 31.6-33.6% of the aliphatic exposure levels while the alveolar contents of aromatics were 8.2-11.5% of the aromatic exposure levels. Thus, no great differences were seen in retention at the different exposure levels. After 7 h of exposure to the above-mentioned levels the concentrations in blood of aliphatics/aromatics were found to be 0.74/0.12, 2.30/0.40, 4.07/0.91 and 9.07/2.01 mg/litre, respectively. Steady state in blood was not achieved in these experiments. (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).

Executive summary:

Stoddard solvent is readily absorbed by inhalation. In a study including 21 human volunteers. They noted rapid changes in the concentration of white spirit (17% aromatic hydrocarbons) in alveolar air if the exposure concentration or the pulmonary ventilation changed. Steady state in alveolar air was obtained after 20 min of exposure at rest and after 1´ h during work. The aromatic fraction reached steady state in alveolar air earlier than the aliphatic fraction. In nine students exposed to 204, 600, 1200 and 2400 mg/m3 (34, 100, 200 and 400 ppm) (corresponding to aliphatic/aromatic levels (in mg/m3) of 172/36, 508/104, 990/203 and 1934/398), the alveolar air at steady state contained 31.6-33.6% of the aliphatic exposure levels while the alveolar contents of aromatics were 8.2-11.5% of the aromatic exposure levels. Thus, no great differences were seen in retention at the different exposure levels. After 7 h of exposure to the above-mentioned levels the concentrations in blood of aliphatics/aromatics were found to be 0.74/0.12, 2.30/0.40, 4.07/0.91 and 9.07/2.01 mg/litre, respectively. Steady state in blood was not achieved in these experiments. (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).

Reference 3

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

Objective of study:

absorption

Qualifier:

no guideline followed

Principles of method if other than guideline:

12 volunteers were exposed to a vapour concentration of 600 mg/m3 (100 ppm) of three different types of white spirit for 6 h.

GLP compliance:

not specified

Specific details on test material used for the study:

Stoddard solvent contained approximately 17.8% aromatics

Radiolabelling:

no

Species:

other: Human

Strain:

other: healthy volunteers

Sex:

male

Details on test animals or test system and environmental conditions:

12 volunteers were exposed to a vapour concentration of 600 mg/m3 (100 ppm) of three different types of white spirit for 6 h.

Route of administration:

inhalation

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

See details of exposure section

Dose / conc.:

600 mg/m³ air

Control animals:

not specified

Details on study design:

12 volunteers were exposed to a vapour concentration of 600 mg/m3 (100 ppm) of three different types of white spirit for 6 h. For two of the solvents, the concentration in blood at the end of the exposure reached mean values of 3.1 and 3.2 mg/litre. These solvents consisted of 57% aliphatics, 25% alicyclics plus 17.9% aromatics, and 52% aliphatics plus 47.9% alicyclics, respectively. A significantly (p < 0.001) lower mean value of 2.3 mg/litre was obtained after exposure to the third solvent containing 98.9% aliphatic alkanes (38.7% C11 isomers and 44.4% C12 isomers) and 1.1% cycloalkanes.

Details on absorption:

When inhaled, Stoddard solvent constituents were readily absorbed. 12 volunteers were exposed by inhalation to 600 mg/m3 (100 ppm) white spirit (17.8% aromatics) for 6 hours. During the study, exercise was restricted to usual physical activity. At the end of the exposure period, the mean venous concentration of white spirit in these volunteers was 3.1 mg/L.

Metabolites identified:

yes

Details on metabolites:

When inhaled, Stoddard solvent constituents were readily absorbed. 12 volunteers were exposed by inhalation to 600 mg/m3 (100 ppm) white spirit (17.8% aromatics) for 6 hours. During the study, exercise was restricted to usual physical activity. At the end of the exposure period, the mean venous concentration of white spirit in these volunteers was 3.1 mg/L.

Conclusions:

Interpretation of results : no bioaccumulation potential based on study results
When inhaled, Stoddard solvent constituents were readily absorbed. 12 volunteers were exposed by inhalation to 600 mg/m3 (100 ppm) white spirit (17.8% aromatics) for 6 hours. During the study, exercise was restricted to usual physical activity. At the end of the exposure period, the mean venous concentration of white spirit in these volunteers was 3.1 mg/L.

Executive summary:

Stoddard solvent is readily absorbed by inhalation.12 volunteers were exposed to a vapour  concentration of 600 mg/m3 (100 ppm) of three different types of  white spirit for 6 h. For two of the solvents, the concentration in   blood at the end of the exposure reached mean values of 3.1 and   3.2 mg/litre. These solvents consisted of 57% aliphatics, 25%   alicyclics plus 17.9% aromatics, and 52% aliphatics plus 47.9%   alicyclics, respectively. A significantly (p < 0.001) lower mean value of 2.3 mg/litre was obtained after exposure to the third solvent  containing 98.9% aliphatic alkanes (38.7% C11 isomers and 44.4% C12  isomers) and 1.1% cycloalkanes.

Reference 4

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

Objective of study:

distribution

excretion

Qualifier:

no guideline followed

Principles of method if other than guideline:

Distribution of white spirit to adipose tissue has been demonstrated. Seven volunteers were exposed to 600 mg/m3 (100 ppm) of white spirit (99% aliphatics) 6 h/day for 5 days. The concentration of white spirit was determined in biopsies from adipose tissue, in venous blood and in alveolar air immediately after each exposure and up to 66 h after the last exposure.

GLP compliance:

not specified

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

Species:

other: Human

Strain:

other: healthy volunteers

Sex:

male

Details on test animals or test system and environmental conditions:

Seven volunteers were exposed to 600 mg/m3 (100 ppm) of white spirit (99% aliphatics) 6 h/day for 5 days. The concentration of white spirit was determined in biopsies from adipose tissue, in venous blood and in alveolar air immediately after each exposure and up to 66 h after the last exposure.

Route of administration:

inhalation

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

See details of exposure section

Dose / conc.:

600 mg/m³ air

Control animals:

not specified

Details on study design:

Seven volunteers were exposed to 600 mg/m3 (100 ppm) of white spirit (99% aliphatics) 6 h/day for 5 days. The concentration of white spirit was determined in biopsies from adipose tissue, in venous blood and in alveolar air immediately after each exposure and up to 66 h after the last exposure.

Details on distribution in tissues:

Distribution of Stoddard solvent to adipose tissue has been demonstrated. Seven volunteers were exposed to 600 mg/m3 (100 ppm) of white spirit (99% aliphatics) 6 h/day for 5 days. The concentration of white spirit was determined in biopsies from adipose tissue, in venous blood and in alveolar air immediately after each exposure and up to 66 h after the last exposure. The level of white spirit in adipose tissue gradually rose (after the last exposure on day 5) to a value of 41 mg/kg fat, but had declined to 32 mg/kg fat 66 h later. From a mathematical fit using a three-compartment model and the data from blood and fat measurements, a fat:blood partition coefficient of 47 was calculated. The redistribution phase was estimated to be 20 h and the half-life of white spirit in adipose tissue was calculated to be 46-48 h. From these data white spirit maximum and minimum steady-state fat concentrations of 55 and 35 mg/kg, respectively, were calculated in the case of occupational exposure to 600 mg/m3 (100 ppm) (maximum level: Friday afternoon; minimum level: Monday morning). Finally,steady-state maximum and steady-state minimum brain concentrations of5 and 0.6 mg/kg, respectively, were estimated.

Details on excretion:

After exposure had stopped there was a short phase with rapid elimination from blood resulting from distribution to other tissues. This phase was followed by a long phase with a rather slow elimination and a half-life of 46 h.
The half-life of Stoddard solvent in adipose tissue was calculated to be 46-48 h

Metabolites identified:

yes

Details on metabolites:

Distribution of Stoddard solvent to adipose tissue has been demonstrated. Seven volunteers were exposed to 600 mg/m3 (100 ppm) of white spirit (99% aliphatics) 6 h/day for 5 days. The concentration of white spirit was determined in biopsies from adipose tissue, in venous blood and in alveolar air immediately after each exposure and up to 66 h after the last exposure. The level of white spirit in adipose tissue gradually rose (after the last exposure on day 5) to a value of 41 mg/kg fat, but had declined to 32 mg/kg fat 66 h later. From a mathematical fit using a three-compartment model and the data from blood and fat measurements, a fat:blood partition coefficient of 47 was calculated. The redistribution phase was estimated to be 20 h and the half-life of white spirit in adipose tissue was calculated to be 46-48 h. From these data white spirit maximum and minimum steady-state fat concentrations of 55 and 35 mg/kg, respectively, were calculated in the case of occupational exposure to 600 mg/m3 (100 ppm) (maximum level: Friday afternoon; minimum level: Monday morning). Finally,steady-state maximum and steady-state minimum brain concentrations of5 and 0.6 mg/kg, respectively, were estimated.

Conclusions:

Interpretation of results : no bioaccumulation potential based on study results
The half-life of Stoddard solvent in adipose tissue was calculated to be 46-48 h
Distribution of Stoddard solvent to adipose tissue has been demonstrated. Seven volunteers were exposed to 600 mg/m3 (100 ppm) of white spirit (99% aliphatics) 6 h/day for 5 days. The concentration of white spirit was determined in biopsies from adipose tissue, in venous blood and in alveolar air immediately after each exposure and up to 66 h after the last exposure. The level of white spirit in adipose tissue gradually rose (after the last exposure on day 5) to a value of 41 mg/kg fat, but had declined to 32 mg/kg fat 66 h later. From a mathematical fit using a three-compartment model and the data from blood and fat measurements, a fat:blood partition coefficient of 47 was calculated. The redistribution phase was estimated to be 20 h and the half-life of white spirit in adipose tissue was calculated to be 46-48 h. From these data white spirit maximum and minimum steady-state fat concentrations of 55 and 35 mg/kg, respectively, were calculated in the case of occupational exposure to 600 mg/m3 (100 ppm) (maximum level: Friday afternoon; minimum level: Monday morning). Finally,steady-state maximum and steady-state minimum brain concentrations of5 and 0.6 mg/kg, respectively, were estimated.

Executive summary:

Distribution of Stoddard solvent to adipose tissue has been demonstrated. Seven volunteers were exposed to 600 mg/m3 (100 ppm) of white spirit (99% aliphatics) 6 h/day for 5 days. The concentration of white spirit was determined in biopsies from adipose tissue, in venous blood and in alveolar air immediately after each exposure and up to 66 h after the last exposure. The level of white spirit in adipose tissue gradually rose (after the last exposure on day 5) to a value of 41 mg/kg fat, but had declined to 32 mg/kg fat 66 h later. From a mathematical fit using a three-compartment model and the data from blood and fat measurements, a fat:blood partition coefficient of 47 was calculated. The redistribution phase was estimated to be 20 h and the half-life of white spirit in adipose tissue was calculated to be 46-48 h. From these data white spirit maximum and minimum steady-state fat concentrations of 55 and 35 mg/kg, respectively, were calculated in the case of occupational exposure to 600 mg/m3 (100 ppm) (maximum level: Friday afternoon; minimum level: Monday morning). Finally,steady-state maximum and steady-state minimum brain concentrations of5 and 0.6 mg/kg, respectively, were estimated.

Reference 5

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

Objective of study:

distribution

excretion

toxicokinetics

Qualifier:

no guideline followed

Principles of method if other than guideline:

In this study rats exposed to 0, 2290 or 4580 mg/m3 (0, 400 or 800 ppm) of white spirit (20% v/v aromatics) for 6 h/day,5 days/week, for 3 weeks. This study also measured the distribution of aromatic and aliphatic components; aliphatics seemed to accumulate more than aromatics.

GLP compliance:

not specified

Specific details on test material used for the study:

Stoddard solvent contained approximately 20% aromatics)

Radiolabelling:

no

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

In this study male rats exposed to 0, 2290 or 4580 mg/m3 (0, 400 or 800 ppm) of white spirit (20% v/v aromatics) for 6 h/day,5 days/week, for 3 weeks.

Route of administration:

inhalation

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

6 h/day,5 days/week, for 3 weeks.

Dose / conc.:

2 290 mg/m³ air

Dose / conc.:

4 580 mg/m³ air

Control animals:

not specified

Details on study design:

In this study male rats exposed to 0, 2290 or 4580 mg/m3 (0, 400 or 800 ppm) of white spirit (20% v/v aromatics) for 6 h/day,5 days/week, for 3 weeks. The total aromatic hydrocarbon fraction concentration in the brain at the high exposure level was about twice the concentration at 2290 mg/m3 (1.54 and 0.73 mg/kg), whereas the concentration in brain of the total aliphatic fraction at 4580 mg/m3 exceeded the 2290 mg/m3 level by more than three times (8.65 and 2.39 mg/kg). The authors concluded that accumulation may occur during long-term exposure to high levels of aliphatic hydrocarbons.

Details on distribution in tissues:

At the end of the exposure period, white spirits had accumulated in the brain (3.4 and 10.2 mg/kg wet weight, respectively). This study also measured the distribution of aromatic and aliphatic components; aliphatics seemed to accumulate more than aromatics. The total aromatic hydrocarbon fraction concentration in the brain at the higher exposure level was about twice the concentration found at the lower exposure level (i.e.,1.54 and 0.73 mg/kg, respectively), whereas the concentration in the brain of the total aliphatic fraction at the higher exposure level exceeded the concentration found at the lower concentration by more than three times (i.e., 8.65 and 2.39 mg/kg, respectively). This may be due to an increased metabolic elimination of the aromatic components.

Details on excretion:

Stoddard solvent components are rapidly eliminated from the blood and brain.

Metabolites identified:

yes

Details on metabolites:

Distribution of Stoddard solvent to adipose tissue has been demonstrated. At the end of the exposure period, white spirits had accumulated in the brain (3.4 and 10.2 mg/kg wet weight, respectively). This study also measured the distribution of aromatic and aliphatic components; aliphatics seemed to accumulate more than aromatics. The total aromatic hydrocarbon fraction concentration in the brain at the higher exposure level was about twice the concentration found at the lower exposure level (i.e.,1.54 and 0.73 mg/kg, respectively), whereas the concentration in the brain of the total aliphatic fraction at the higher exposure level exceeded the concentration found at the lower concentration by more than three times (i.e., 8.65 and 2.39 mg/kg, respectively). This may be due to an increased metabolic elimination of the aromatic components.

Conclusions:

Interpretation of results : no bioaccumulation potential based on study results
Distribution of Stoddard solvent to adipose tissue has been demonstrated. At the end of the exposure period, white spirits had accumulated in the brain (3.4 and 10.2 mg/kg wet weight, respectively). This study also measured the distribution of aromatic and aliphatic components; aliphatics seemed to accumulate more than aromatics. The total aromatic hydrocarbon fraction concentration in the brain at the higher exposure level was about twice the concentration found at the lower exposure level (i.e.,1.54 and 0.73 mg/kg, respectively), whereas the concentration in the brain of the total aliphatic fraction at the higher exposure level exceeded the concentration found at the lower concentration by more than three times (i.e., 8.65 and 2.39 mg/kg, respectively). This may be due to an increased metabolic elimination of the aromatic components.
Stoddard solvent components are rapidly eliminated from the blood and brain.

Executive summary:

Distribution of Stoddard solvent to adipose tissue has been demonstrated. At the end of the exposure period, white spirits had accumulated in the brain (3.4 and 10.2 mg/kg wet weight, respectively). This study also measured the distribution of aromatic and aliphatic components; aliphatics seemed to accumulate more than aromatics. The total aromatic hydrocarbon fraction concentration in the brain at the higher exposure level was about twice the concentration found at the lower exposure level (i.e.,1.54 and 0.73 mg/kg, respectively), whereas the concentration in the brain of the total aliphatic fraction at the higher exposure level exceeded the concentration found at the lower concentration by more than three times (i.e., 8.65 and 2.39 mg/kg, respectively). This may be due to an increased metabolic elimination of the aromatic components.

Reference 6

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

Objective of study:

excretion

Qualifier:

no guideline followed

Principles of method if other than guideline:

In this study was measured the concentration of aliphatics and aromatics in the alveolar air of six volunteers during and after 7 hours of exposure to either 300 or 600 mg/m3 (50 or 100 ppm) white spirit vapor (17% aromatics).

GLP compliance:

not specified

Specific details on test material used for the study:

Stoddard solvent contained approximately 83% aliphatics and 17% aromatic components.

Radiolabelling:

no

Species:

other: Human

Strain:

other: healthy volunteers

Sex:

male

Details on test animals or test system and environmental conditions:

In this study was measured the concentration of aliphatics and aromatics in the alveolar air of six volunteers during and after 7 hours of exposure to either 300 or 600 mg/m3 (50 or 100 ppm) white spirit vapor (17% aromatics).

Route of administration:

inhalation

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

See details of exposure section

Dose / conc.:

300 mg/m³ air

Dose / conc.:

600 mg/m³ air

Control animals:

not specified

Details on study design:

In this study was measured the concentration of aliphatics and aromatics in the alveolar air of six volunteers during and after 7 hours of exposure to either 300 or 600 mg/m3 (50 or 100 ppm) white spirit vapor (17% aromatics).

Details on excretion:

Ten minutes after exposure had ceased, the expiratory concentration levels of aliphatics and aromatics were found to be about 12% of the initial exposure level for both fractions. Sixteen hours later, the levels in expiratory air had fallen to 2% (aliphatics) and 4% (aromatics) of the initial exposure level. These results indicate that steady state in adipose tissue will be reached after approximately 3 weeks following continuous exposure.
Absorbed Stoddard solvent vapour is eliminated by the lungs.

Metabolites identified:

yes

Details on metabolites:

In this study was measured the concentration of aliphatics and aromatics in the alveolar air of six volunteers during and after 7 hours of exposure to either 300 or 600 mg/m3 (50 or 100 ppm) white spirit vapor (17% aromatics). Ten minutes after exposure had ceased, the expiratory concentration levels of aliphatics and aromatics were found to be about 12% of the initial exposure level for both fractions. Sixteen hours later, the levels in expiratory air had fallen to 2% (aliphatics) and 4% (aromatics) of the initial exposure level. These results indicate that steady state in adipose tissue will be reached after approximately 3 weeks following continuous exposure.

Conclusions:

Interpretation of results : no bioaccumulation potential based on study results
In this study was measured the concentration of aliphatics and aromatics in the alveolar air of six volunteers during and after 7 hours of exposure to either 300 or 600 mg/m3 (50 or 100 ppm) white spirit vapor (17% aromatics). Ten minutes after exposure had ceased, the expiratory concentration levels of aliphatics and aromatics were found to be about 12% of the initial exposure level for both fractions. Sixteen hours later, the levels in expiratory air had fallen to 2% (aliphatics) and 4% (aromatics) of the initial exposure level. These results indicate that steady state in adipose tissue will be reached after approximately 3 weeks following continuous exposure.
Absorbed Stoddard solvent vapour is eliminated by the lungs.

Executive summary:

In this study was measured the concentration of aliphatics and aromatics in the alveolar air of six volunteers during and after 7 hours of exposure to either 300 or 600 mg/m³(50 or 100 ppm) white spirit vapor (17% aromatics). Ten minutes after exposure had ceased, the expiratory concentration levels of aliphatics and aromatics were found to be about 12% of the initial exposure level for both fractions. Sixteen hours later, the levels in expiratory air had fallen to 2% (aliphatics) and 4% (aromatics) of the initial exposure level. These results indicate that steady state in adipose tissue will be reached after approximately 3 weeks following continuous exposure. 

Reference 7

Endpoint:

dermal absorption

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

QSAR prediction: US EPA accepted QSAR method for organic chemicals properties assessment.

Qualifier:

no guideline required

Principles of method if other than guideline:

Using the DERMWIN v2.01 QSAR model

GLP compliance:

no

Remarks:

not applicable to QSAR models

Radiolabelling:

no

Species:

other: QSAR model,

Strain:

other: QSAR model,

Sex:

not specified

Type of coverage:

other: QSAR model

Vehicle:

other: QSAR model

Duration of exposure:

not applicable to QSAR models

Doses:

not applicable to QSAR models

No. of animals per group:

not applicable to QSAR models

Control animals:

no

Details on study design:

not applicable to QSAR models

Details on in vitro test system (if applicable):

not applicable to QSAR models

Signs and symptoms of toxicity:

not specified

Dermal irritation:

not specified

Absorption in different matrices:

A QSAR model predicts that the permeability of Stoddard solvent to human skin is quite low. The permeability coefficient was determined to be 0.00115 mg/cm2, which is around 1% of the skin penetration rate.Predicted dermally absorbed coefficient was determined to be Kp (est)=0.362 cm/hr.

A QSAR model predicts that the permeability of Stoddard solvent to human skin is quite low. The permeability coefficient was determined to be 0.00115 mg/cm2, which is around 1% of the skin penetration rate.Predicted dermally absorbed coefficient was determined to be Kp (est)=0.362 cm/hr.

Conclusions:

A QSAR model predicts that the permeability of Stoddard solvent to human skin is quite low. The permeability coefficient was determined to be 0.00115 mg/cm2, which is around 1% of the skin penetration rate.Predicted dermally absorbed coefficient was determined to be Kp (est)=0.362 cm/hr.

Executive summary:

A QSAR model predicts that the permeability of Stoddard solvent to human skin is quite low. The permeability coefficient was determined to be 0.00115 mg/cm2, which is around 1% of the skin penetration rate.Predicted dermally absorbed coefficient was determined to be Kp (est)=0.362 cm/hr.

Description of key information

Interpretation of results : no bioaccumulation potential based on study results

Kinetics and metabolism

 

Stoddard solvent vapour is readily absorbed by inhalation. In humans 59% of the aliphatic and alicyclic hydrocarbons and 70% of thearomatic hydrocarbons were absorbed at a Stoddard solventvapour level of 1000 mg/m³. The hydrocarbons are distributed from blood to othertissues, and a human fat:blood partition coefficient of 47 has been calculated. Stoddard solventis widely distributed throughout the body in humans.Experiments performed with single hydrocarbon exposure to rats revealed higher brain:blood partition ratios for aliphatics and alicyclics than for aromatic hydrocarbons.

 

Stoddard solvent is eliminated from the blood in a biphasic manner after exposure. After an initial and very short distribution phase with rapid elimination from the blood, a long phase with a considerably slower elimination (half-life of about 46 h) follows. ThusStoddard solventhas been detected in blood 66 h after a single inhalation exposure. The half-life in adipose tissue has been estimated to be 46-48 h.

 

Only sparse data on elimination and metabolism of Stoddard solvent exist, but urinary excretion of metabolites and elimination of parent compounds through expiration have been demonstrated in humans.

 

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - dermal (%):

1

Additional information

Interpretation of results : no bioaccumulation potential based on study results

When inhaled, Stoddard solvent constituents were readily absorbed. 12 volunteers were exposed by inhalation to 600 mg/m3 (100 ppm) white spirit (17.8% aromatics) for 6 hours. During the study, exercise was restricted to usual physical activity. At the end of the exposure period, the mean venous concentration of white spirit in these volunteers was 3.1 mg/L.  

 

The half-life of  Stoddard solvent in adipose tissue was calculated to be 46-48 h

Distribution of Stoddard solvent to adipose tissue has been demonstrated. Seven volunteers were exposed to 600 mg/m3 (100 ppm) of white spirit (99% aliphatics)   6 h/day for 5 days. 

 

Stoddard solvent components are rapidly eliminated from the blood and brain.

Absorbed Stoddard solvent vapour is eliminated by the lungs.