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Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
Unavailable - date of publication 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Objective of study:
metabolism
Qualifier:
no guideline followed
Principles of method if other than guideline:
The disposition of radioactivity was studied in single and repeated oral doses of [14C]LAS to rhesus monkeys.
GLP compliance:
not specified
Radiolabelling:
yes
Remarks:
[14C]LAS
Species:
monkey
Strain:
other: Macaca mulatta
Sex:
male/female
Details on test animals or test system and environmental conditions:
Four (2 male, 2 female; 5 kg average body weight) adult rhesus monkeys (Macaca mulatta)
Route of administration:
other: single or repeated oral or subcutaneous
Vehicle:
not specified
Remarks:
Doses / Concentrations:
single or repeated oral (30, 150 or 300 mg/kg) or subcutaneous (0.1, 0.5 or 1 mg/kg) doses of 14C-LAS
Dose / conc.:
30 other: mg/kg
Remarks:
single or repeated oral tests
Dose / conc.:
150 other: mg/kg
Remarks:
single or repeated oral tests
Dose / conc.:
300 other: mg/kg
Remarks:
single or repeated oral tests
Dose / conc.:
0.1 other: mg/kg
Remarks:
subcutaneous test
Dose / conc.:
0.5 other: mg/kg
Remarks:
subcutaneous test
Dose / conc.:
1 other: mg/kg
Remarks:
subcutaneous test
No. of animals per sex per dose / concentration:
2 males and 2 females
Control animals:
not specified
Details on study design:
Four adult rhesus monkeys (2 male and 2 female) of body weight approximately 5 kg each were used for all experiments. For excretion studies, single oral doses (14C-LAS of 30 mg/kg at 25 uCi) were administered by oral intubation as a solution in water. For the plasma level studies the same animals were administered single oral doses (14C-LAS of 150 mg/kg at 26 uCi and 300 mg/kg at 28 uCi) at intervals of 2 -3 weeks. About 2 -3 weeks after the last single dose each animal received 7 consecutive daily oral doses of 14C-LAS (30 mg/kg/day at 28 uCi/day) in water (6 mL). Blood samples were taken and animals were sacrificed at a different time after the last dose.

For subcutaneous dosing, single doses (14C-LAS of 1 mg/kg at 16 -40 uCi), as a solution in water, were administered by injection into the subcutaneous tissue between the shoulder blades. Similarly, for the plasma level tests, the same animals received subcutaneous doses of 0.5 and 0.1 mg/kg (8 -22 and 2 -5 uCi, respectively) at intervals of 2 -3 weeks. About 2 -3 weeks after the last single dose the animals received 7 consecutive daily subcutaneous doses of 1 mg/kg/day (about 24 uCi/day) in water. Blood samples were taken in both cases.
Details on dosing and sampling:
Blood samples were collected for the excretion and plasma studies.
Details on distribution in tissues:
When 14C-LAS was injected into the skin, most of the radioactivity remained at the site of injection. No localization of radioactivity in any tissue occurred.
Details on excretion:
After single 30 mg/kg oral doses the radioactivity was rapidly excreted, mostly during the first 24 hours. Means of 71.2% and 23.1% of the dose were excreted in the urine and feces, respectively, during 5 days. Similarly, after single 1 mg/kg subcutaneous doses, means of 64.1% and 10.9% were excreted in urine and feces, respectively, during 5 days, mostly during the first 24 hours. During the 120 hours after single oral (30 mg/kg) or subcutaneous doses (1 mg/kg) the average rate of excretion was between 63 and 74% in the urine and between 9 and 26% in the feces. No unchanged LAS was detected in urine samples after oral or subcutaneous doses (either single or repeated).
Metabolites identified:
no
Details on metabolites:
Five metabolites were excreted but they were not identified. Incubations with beta-glucuronidase/sulfatase did not affect the metabolites, indicating that the metabolites were probably not present as the corresponding conjugates.
Conclusions:
No bioaccumulation potential based on study results
Executive summary:

The disposition of radioactivity was studied in single and repeated oral or subcutaneous doses of [14C]LAS to rhesus monkeys. Results show that LAS is rapidly absorbed, then rapidly metabolized and excreted, primarily in the urine but also in the bile and feces. No accumulation or localization of radioactivity or change in elimination was observed. LAS does not bioaccumulate in the tissues.

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
Unavailable - date of publication 1968
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Objective of study:
metabolism
Qualifier:
no guideline followed
Principles of method if other than guideline:
The absorption, distribution, metabolism and elimination of LAS (radioactively labeled with 35S) were studied in male Charles River rats. LAS was administered as an aqueous solution.
GLP compliance:
not specified
Radiolabelling:
yes
Remarks:
(radioactively labeled with 35S)
Species:
rat
Strain:
other: Charles River albino
Sex:
male
Details on test animals or test system and environmental conditions:
The animals were housed in individual cages which permitted the separate collection of urine and feces. Food and water were provided ad libitum after dosing.
Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
Male rats (150-200 g) were fasted for 16 hours and given orally an aqueous solution containing LA35S. The dose was given in 1.0 mL volume. The urine was collected under toluene, removed daily, and refrigerated until it could be examined. The feces were removed each day and allowed to dry at room temperature. At the termination of the study, the animals were killed and selected organs and tissues were taken for radioassay.

Also, the route of absorption was determined by oral feeding of 40 mg of LAS to thoracic duct-cannulated rats. The lymph was collected from each animal in a single 42-hour fraction.

The enterohepatic ciruclation of the sufactant was quantifed by oral feeding of 1.2 mg of LAS to bile duct-cannulated rats and to rats prepared in a manner similar to the dual rat study described by Boquet and Fromageot. A cannula was inserted into the proximal end of the bil deuct of Rat A and into the distal end of the bile duct in Rat B such that the bile from Rat A could flow through the cannula into the bile duct, and finally into the intestin of Rat B. A second cannula was inserted into the proximal end of the bile duct of Rat B so that is bile could be collected. LA35S was fed orally to Rat A. Urine and feces of Rats A and B and bile of Rat B were collected for 90 hours after dosing.
Duration and frequency of treatment / exposure:
See details of exposure section
Dose / conc.:
0.6 other: mg
Remarks:
Excretion test (averages of three animals for the two lower doses and five animals for the two higher doses)
Dose / conc.:
1.2 other: mg
Remarks:
Excretion test (averages of three animals for the two lower doses and five animals for the two higher doses)
Dose / conc.:
8 other: mg
Remarks:
Excretion test (averages of three animals for the two lower doses and five animals for the two higher doses)
Dose / conc.:
40 other: mg
Remarks:
Excretion test (averages of three animals for the two lower doses and five animals for the two higher doses)
Dose / conc.:
1.2 other: mg/rat
Remarks:
Absorption and enterohepatic circulation tests.
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 absorption:
The compound was readily absorbed from the gastrointestinal tract (80-90% of the dose).
Details on distribution in tissues:
Primarily excreted in the urine.
Details on excretion:
Most of the absorbed 35S was eliminated within 72 hours and 60-65% of the absorbed dose was eliminated in the urine, 35% of the absorbed 35S was excreted in the bile and was reabsorbed completely from the gastrointestinal tract. Very little was found in the lymph, so transport of LAS is probably by way of portal venous blood.
Metabolites identified:
yes
Details on metabolites:
Urine - sulfophenyl butanoic and sulfophenyl pentatonic acid. These metabolites were sufficiently polar to avoid being reabsorbed from the kidney tubules. Although the metabolites in the bile were not identified, it was shown that no unchanged LAS was eliminated via this pathway.
Conclusions:
LAS is readily absorbed by the gastrointestinal track and rapidly excreted with its metabolites, primarily in the urine.
Executive summary:

The absorption, distribution, metabolism and elimination of LAS (radioactively labeled with 35S) were studied in male Charles River rats. LAS was readily absorbed by the gastrointestinal tract and rapidly metabolised and excreted in the urine.

Endpoint:
basic toxicokinetics in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
Read-across approach - see read-across justification in section 13.
Reason / purpose for cross-reference:
read-across source
Objective of study:
metabolism
Principles of method if other than guideline:
The disposition of radioactivity was studied in single and repeated oral doses of [14C]LAS to rhesus monkeys.
GLP compliance:
not specified
Radiolabelling:
yes
Remarks:
[14C]LAS
Species:
monkey
Strain:
other: Macaca mulatta
Sex:
male/female
Details on test animals or test system and environmental conditions:
Four (2 male, 2 female; 5 kg average body weight) adult rhesus monkeys (Macaca mulatta)
Route of administration:
other: single or repeated oral or subcutaneous
Vehicle:
not specified
Remarks:
Doses / Concentrations:
single or repeated oral (30, 150 or 300 mg/kg) or subcutaneous (0.1, 0.5 or 1 mg/kg) doses of 14C-LAS
Dose / conc.:
30 other: mg/kg
Remarks:
single or repeated oral tests
Dose / conc.:
150 other: mg/kg
Remarks:
single or repeated oral tests
Dose / conc.:
300 other: mg/kg
Remarks:
single or repeated oral tests
Dose / conc.:
0.1 other: mg/kg
Remarks:
subcutaneous test
Dose / conc.:
0.5 other: mg/kg
Remarks:
subcutaneous test
Dose / conc.:
1 other: mg/kg
Remarks:
subcutaneous test
No. of animals per sex per dose / concentration:
2 males and 2 females
Control animals:
not specified
Details on study design:
Four adult rhesus monkeys (2 male and 2 female) of body weight approximately 5 kg each were used for all experiments. For excretion studies, single oral doses (14C-LAS of 30 mg/kg at 25 uCi) were administered by oral intubation as a solution in water. For the plasma level studies the same animals were administered single oral doses (14C-LAS of 150 mg/kg at 26 uCi and 300 mg/kg at 28 uCi) at intervals of 2 -3 weeks. About 2 -3 weeks after the last single dose each animal received 7 consecutive daily oral doses of 14C-LAS (30 mg/kg/day at 28 uCi/day) in water (6 mL). Blood samples were taken and animals were sacrificed at a different time after the last dose.

For subcutaneous dosing, single doses (14C-LAS of 1 mg/kg at 16 -40 uCi), as a solution in water, were administered by injection into the subcutaneous tissue between the shoulder blades. Similarly, for the plasma level tests, the same animals received subcutaneous doses of 0.5 and 0.1 mg/kg (8 -22 and 2 -5 uCi, respectively) at intervals of 2 -3 weeks. About 2 -3 weeks after the last single dose the animals received 7 consecutive daily subcutaneous doses of 1 mg/kg/day (about 24 uCi/day) in water. Blood samples were taken in both cases.
Details on dosing and sampling:
Blood samples were collected for the excretion and plasma studies.
Details on distribution in tissues:
When 14C-LAS was injected into the skin, most of the radioactivity remained at the site of injection. No localization of radioactivity in any tissue occurred.
Details on excretion:
After single 30 mg/kg oral doses the radioactivity was rapidly excreted, mostly during the first 24 hours. Means of 71.2% and 23.1% of the dose were excreted in the urine and feces, respectively, during 5 days. Similarly, after single 1 mg/kg subcutaneous doses, means of 64.1% and 10.9% were excreted in urine and feces, respectively, during 5 days, mostly during the first 24 hours. During the 120 hours after single oral (30 mg/kg) or subcutaneous doses (1 mg/kg) the average rate of excretion was between 63 and 74% in the urine and between 9 and 26% in the feces. No unchanged LAS was detected in urine samples after oral or subcutaneous doses (either single or repeated).
Metabolites identified:
no
Details on metabolites:
Five metabolites were excreted but they were not identified. Incubations with beta-glucuronidase/sulfatase did not affect the metabolites, indicating that the metabolites were probably not present as the corresponding conjugates.
Conclusions:
No bioaccumulation potential based on study results
Executive summary:

The disposition of radioactivity was studied in single and repeated oral or subcutaneous doses of [14C]LAS to rhesus monkeys. Results show that LAS is rapidly absorbed, then rapidly metabolized and excreted, primarily in the urine but also in the bile and feces. No accumulation or localization of radioactivity or change in elimination was observed. LAS does not bioaccumulate in the tissues.

Endpoint:
basic toxicokinetics in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
Read-across approach - see read-across justification in section 13.
Reason / purpose for cross-reference:
read-across source
Objective of study:
metabolism
Principles of method if other than guideline:
The absorption, distribution, metabolism and elimination of LAS (radioactively labeled with 35S) were studied in male Charles River rats. LAS was administered as an aqueous solution.
GLP compliance:
not specified
Radiolabelling:
yes
Remarks:
(radioactively labeled with 35S)
Species:
rat
Strain:
other: Charles River albino
Sex:
male
Details on test animals or test system and environmental conditions:
The animals were housed in individual cages which permitted the separate collection of urine and feces. Food and water were provided ad libitum after dosing.
Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
Male rats (150-200 g) were fasted for 16 hours and given orally an aqueous solution containing LA35S. The dose was given in 1.0 mL volume. The urine was collected under toluene, removed daily, and refrigerated until it could be examined. The feces were removed each day and allowed to dry at room temperature. At the termination of the study, the animals were killed and selected organs and tissues were taken for radioassay.

Also, the route of absorption was determined by oral feeding of 40 mg of LAS to thoracic duct-cannulated rats. The lymph was collected from each animal in a single 42-hour fraction.

The enterohepatic ciruclation of the sufactant was quantifed by oral feeding of 1.2 mg of LAS to bile duct-cannulated rats and to rats prepared in a manner similar to the dual rat study described by Boquet and Fromageot. A cannula was inserted into the proximal end of the bil deuct of Rat A and into the distal end of the bile duct in Rat B such that the bile from Rat A could flow through the cannula into the bile duct, and finally into the intestin of Rat B. A second cannula was inserted into the proximal end of the bile duct of Rat B so that is bile could be collected. LA35S was fed orally to Rat A. Urine and feces of Rats A and B and bile of Rat B were collected for 90 hours after dosing.
Duration and frequency of treatment / exposure:
See details of exposure section
Dose / conc.:
0.6 other: mg
Remarks:
Excretion test (averages of three animals for the two lower doses and five animals for the two higher doses)
Dose / conc.:
1.2 other: mg
Remarks:
Excretion test (averages of three animals for the two lower doses and five animals for the two higher doses)
Dose / conc.:
8 other: mg
Remarks:
Excretion test (averages of three animals for the two lower doses and five animals for the two higher doses)
Dose / conc.:
40 other: mg
Remarks:
Excretion test (averages of three animals for the two lower doses and five animals for the two higher doses)
Dose / conc.:
1.2 other: mg/rat
Remarks:
Absorption and enterohepatic circulation tests.
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 absorption:
The compound was readily absorbed from the gastrointestinal tract (80-90% of the dose).
Details on distribution in tissues:
Primarily excreted in the urine.
Details on excretion:
Most of the absorbed 35S was eliminated within 72 hours and 60-65% of the absorbed dose was eliminated in the urine, 35% of the absorbed 35S was excreted in the bile and was reabsorbed completely from the gastrointestinal tract. Very little was found in the lymph, so transport of LAS is probably by way of portal venous blood.
Metabolites identified:
yes
Details on metabolites:
Urine - sulfophenyl butanoic and sulfophenyl pentatonic acid. These metabolites were sufficiently polar to avoid being reabsorbed from the kidney tubules. Although the metabolites in the bile were not identified, it was shown that no unchanged LAS was eliminated via this pathway.
Conclusions:
LAS is readily absorbed by the gastrointestinal track and rapidly excreted with its metabolites, primarily in the urine.
Executive summary:

The absorption, distribution, metabolism and elimination of LAS (radioactively labeled with 35S) were studied in male Charles River rats. LAS was readily absorbed by the gastrointestinal tract and rapidly metabolised and excreted in the urine.

Endpoint:
dermal absorption in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
Unavailable - date of publication 1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
Radiolabelled test substance (3 mM solution) was applied to the shaved skin of female rats. The exposure lasted 15 min, after which is was rinsed off. After a 24 hr observation period during feces, urine, and expired air was collected, the animals were sacrificed and the excised skin was examined by autoradiography
GLP compliance:
not specified
Radiolabelling:
yes
Species:
rat
Strain:
other: Colworth-Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 100-120 g
- Housing: sealed metabolism cages
- Individual metabolism cages: yes

ENVIRONMENTAL CONDITIONS
- Air changes (per hr): 1.5 L/min
Type of coverage:
open
Vehicle:
other: Two test solutions were made: water, and 25% polyethylene glycol 400 in water.
Duration of exposure:
15 min
Doses:
- Nominal doses: 3 mM solution
- Dose volume: 0.2 ml
No. of animals per group:
no data
Control animals:
no
Details on study design:
DOSE PREPARATION
- Method for preparation of dose suspensions: The test substance was added to the vehicle and homogenized and equilibrated at 40 degrees C for 24 hrs. The pH was then adjusted to 9.5 by adding 0.01 n NaOH or HCl.

TEST SITE
- Preparation of test site: 24 hrs before application, hair was removed with clippers. Only animals with intact skin were used.
- Area of exposure: 7.5 cm^2

SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: yes: Animals were anesthetized during exposure. During the 24 hr observation period the animals were fitted with restraining collars or non-occlusive patches. Non-occlusive patches were made of three layers of surgical gauze 1 cm larger in each dimension than the exposure area. Over this, a stainless steel 100 mesh gauze was placed and secured with surgical strapping with holes punctured in it.

SAMPLE COLLECTION
- Collection of urine and faeces: for 24 hrs after exposure
- Collection of expired air: for 24 hrs after exposure

SAMPLE PREPARATION
- Preparation details: feces were freezed dried, carcasses were homogenized in a blender and then freeze dried

ANALYSIS
- Method type(s) for identification: Liquid scintillation counting, excised skin was examined by autoradiography
Signs and symptoms of toxicity:
not specified
Dermal irritation:
not specified
Absorption in different matrices:
- Non-occlusive cover: < 2 micrograms
- Skin wash: 135 +/- 27 micrograms
- Skin test site: Heavy deposition was seen on the skin surface, and in the upper hair follicles, 11+/-4 micrograms
- Urine: none
- Faeces: none
Key result
Time point:
24 h
Dose:
250 micrograms
Parameter:
percentage
Absorption:
< 0.3 %
Remarks on result:
other: 24 hrs after exposure

The amount of test substance that penetrated the skin was below the detection limit of 0.1 micrograms/cm2 or less than 0.3% of the initial dose.

Conclusions:
The in vivo penetration through rat skin after a 15 min exposure was < 0.3%.
Executive summary:

Radiolabelled test substance (3 mM solution) was applied to the shaved skin of female rats. The exposure lasted 15 min, after which is was rinsed off. After a 24 hr observation period during feces, urine, and expired air was collected, the animals were sacrificed and the excised skin was examined by autoradiography. Results show that the test substance, which is of low solubility, did not penetrate through the skin to any significant degree. The amount of test substance penetrating the skin was below the detection limit. The penetration through rat skin was < 0.3%.

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
Unavailable - date of publication 1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Reason / purpose for cross-reference:
reference to same study
Qualifier:
no guideline followed
GLP compliance:
not specified
Radiolabelling:
yes
Species:
human
Sex:
female
Duration of exposure:
48 hrs
Doses:
0.1 ml of 3 mM solution
No. of animals per group:
four skin samples
Details on study design:
- Method for preparation of dose suspensions: The test substance was added to the vehicle and homogenized and equilibrated at 40 degrees C for 24 hrs. The pH was then adjusted to 9.5 by adding 0.01 n NaOH or HCl.
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: human cadavars
- Ethical approval if human skin:
- Type of skin: abdominal
- Preparative technique: Epidermal samples were heated at 58 degrees C for 2 min. Samples were placed in 1 cm diamter penetration cells, and saline with 0.012% penicillin, 0.01% streptomycin was placed on both surfaces of the cells. The cells were equilibrated at 37 degrees C for 24 hrs.
- Membrane integrity check: Only cells with electrical resistance greater than 50,000 ohms were used.
- Storage conditions: -70 degree C

Signs and symptoms of toxicity:
not examined
Dermal irritation:
yes
Remarks:
some swelling was seen after 48 hrs of contact
Absorption in different matrices:
Only 30% of the test substance was removed by rinsing, with 70 % remaining associated with the skin.
Key result
Time point:
2 h
Dose:
152.9 micrograms/cm^2
Parameter:
percentage
Absorption:
< 0.07 %
Key result
Time point:
6 h
Dose:
152.9 micrograms/cm^2
Parameter:
percentage
Absorption:
< 0.07 %
Key result
Time point:
24 h
Dose:
152.9 micrograms/cm^2
Parameter:
percentage
Absorption:
< 0.07 %
Key result
Time point:
48 h
Dose:
152.9 micrograms/cm^2
Parameter:
percentage
Absorption:
< 0.07 %
Conclusions:
The in vitro penetration through human skin after a 48 hr exposure was < 0.07%.
Executive summary:

Radiolabelled test substance was applied (0.1 ml of a 3 mM solution) to samples of human abdominal skin from four female cadavars. Exposure time was 48 hrs. Analysis by liquid scintillation counting was done at 0.5, 1, 2, 3, 4, 6, 7, 8, 24, and 48 hrs. Penetration through human skin was negligible, with < 0.07% absorbed in 48 hrs.

Description of key information

No information is available on the toxicokinetics of benzenesulfonic acid, 4-C10-13-sec-alkyl derivs., compds. with 2-propanamine (LAS IPA).

The endpoint of toxicokinetics was addressed with data for LAS Na and IPA (see read-across statement). Overall the substance is not expected to have a bioaccumulation potential.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

IPA:

One study with limited information is available on the toxicokinetics of IPA (Cavender et al., 2000). The study concludes that ingested isopropylamine partly may undergo methyl or N-oxidation. A substantial part is expected to be excreted unchanged in the urine. If oxidative deamination occurs, acetone will be formed. This is usually exhaled as well as excreted into the urine. Small amounts of acetone are normally formed in the intermediary metabolism through spontaneous or enzymatic decarboxylation of acetoacetate. The substance does not show a bioaccumulation potential.

LAS Na:

The absorption, distribution, metabolism and elimination of LAS (radioactively labelled with 35S) were studied in male Charles River rats. LAS was readily absorbed by the gastrointestinal tract (80-90% of the dose)and rapidly metabolized and excreted in the urine. Most of the absorbed 35S was eliminated within 72 hours and 60-65% of the absorbed dose was eliminated in the urine, 35% of the absorbed 35S was excreted in the bile and was re-absorbed completely from the gastrointestinal tract. Retention of radioactivity was not observed in any organ (Michael, 1968).

The disposition of radioactivity was studied in single and repeated oral or subcutaneous doses of [14C]LAS to rhesus monkeys. Results show that LAS is rapidly absorbed, then rapidly metabolized and excreted, primarily in the urine but also in the bile and feces. No accumulation or localization of radioactivity or change in elimination was observed. LAS does not bioaccumulate in the tissues (Cresswel et al., 1978).

Radiolabelled test substance (3 mM solution) was applied to the shaved skin of female rats. The exposure lasted 15 min, after which is was rinsed off. After a 24 hr observation period during feces, urine, and expired air was collected, the animals were sacrificed and the excised skin was examined by autoradiography. Results show that the test substance, which is of low solubility, did not penetrate through the skin to any significant degree. The amount of test substance penetrating the skin was below the detection limit. The penetration through rat skin was < 0.3% (Howes, 1975a).

Radiolabelled LAS was applied (0.1 ml of a 3 mM solution) to samples of human abdominal skin from four female cadavars. Exposure time was 48 hrs. Analysis by liquid scintillation counting was done at 0.5, 1, 2, 3, 4, 6, 7, 8, 24, and 48 hrs. Penetration through human skin was negligible, with < 0.07% absorbed in 48 hrs (Howes, 1975b).