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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

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Endpoint:
dermal absorption
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Reason / purpose for cross-reference:
read-across source
Principles of method if other than guideline:
No guideline exists for this type of appraisal.
Radiolabelling:
other: partly
Species:
other: human, rat, guinea-pig
Details on test animals or test system and environmental conditions:
not applicable
Type of coverage:
other: Various, for details see HERA report and SIDS
Vehicle:
not specified
Duration of exposure:
Various, for details see HERA report and SIDS
Doses:
Various, for details see HERA report and SIDS
No. of animals per group:
Various, for details see HERA report and SIDS
Absorption in different matrices:
Absorption by the percutaneous route is limited, since anionic surfactants tend to bind to the skin surface (Howes, 1975; Black and Howes, 1980). Early studies with isolated human skin were unable to detect penetration of a homologous series of AS, ranging from C8 to C18 (Blank and Gould, 1961). Animal studies confirmed a low level of percutaneous absorption of AS. Less than 0.4% of a 3 μmol dose of 35S-labeled C12AS-Na was percutaneously absorbed in guinea pigs, based on recovery of the radiolabel in urine, faeces and expired air (Prottey and Ferguson, 1975). Studies with rats indicated that pre-washing of the skin with surfactant enhanced AS skin penetration (Black and Howes, 1980).For consumer exposure, actual dermal absorption is below 1% (Rice, 1977) or very low (Schäfer and Redelmeier, 1996), therefore a default assumption of 1% dermal absorption was taken for deriving the DNEL. Since the dermal absorption decreases with increasing concentration of a solution this percentage can be expanded to workers as a worst case approach.
Conversion factor human vs. animal skin:
not applicable
Endpoint:
basic toxicokinetics in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Reason / purpose for cross-reference:
read-across source
Radiolabelling:
other: partly
Species:
other: rat, dog and human
Sex:
male/female
Details on test animals or test system and environmental conditions:
not applicable
Route of administration:
oral: unspecified
Duration and frequency of treatment / exposure:
Various, for details see SIDS
Remarks:
Doses / Concentrations:Various, for details see SIDS
No. of animals per sex per dose / concentration:
Various, for details see SIDS
Control animals:
other: Various, for details see SIDS
Type:
absorption
Results:
After oral administration, alkyl sulfates are well absorbed in rats, dogs and humans.
Type:
excretion
Results:
The major path of excretion of the alkyl sulfates is the urine.
Details on absorption:
After oral administration, alkyl sulfates are well absorbed in rats, dogs and humans. This was indicated by excretion of up to 98% of the dose administered (maximum for C12ASO4Na in the urine and by comparison of excretion after oral and i.v. or i.p. application for C11ASO4K, C12ASO4K and C18ASO4Na alkyl sulfates.
Details on distribution in tissues:
After application of 14.4 mg/kg of the erythromycin salt of C16ASO4 to dogs or 250 mg/person to humans, radioactivity in plasma was maximal within 30 minutes to 2 hours of oral administration in both species indicating rapid absorption. The plasma concentration declined rapidly afterwards and reached 10% of the maximum concentration after 6 hours, indicating rapid elimination. Whole body autoradiography has been performed to follow the distribution of 35S-C10ASO4K, C12ASO4K and C18ASO4K or their metabolites within the body with time in experiments with rats after i.p. injection. For all compounds the only organs, where radioactivity was detected, were the liver and the kidney. The levels (not quantified) were highest 1 h after application. C10 AS was cleared from tissues more rapidly than C18. After 6 hours, only traces of the C10 salt remained in the kidney, whereas it took 12 hours for the C18 salt to be cleared from the kidney.
Details on excretion:
The major path of excretion of the alkyl sulfates is the urine. The data show, that there are only minor differences for the alkyl sulfates of different chain lengths in the overall excretion after i.p. application. There are also no major differences in overall excretion between male and female rats or after oral, intraperitoneal or intravenous application. The rate of excretion in the urine, however, is somewhat different. After oral as well as i.p. application, excretion of the C12 compound is complete within 6 hours after application. In contrast the excretion amounts only to about 60% (C10), 40% (C11), 15% (C18) after i.p. application, and to 25% for C11or C186 hrs after oral application. This indicates faster metabolism of the C12 compound than for the other chain lengths. Lower amounts of the alkyl sulfates are excreted via the feces within 48 hrs after oral application for the C12, C16and C18 compounds. The lowest value was obtained for the C12, while the highest values with considerable variation of 2.5 - 19.9% (2 m, 2f) were found for C11. In the bile from < 1 to 7.7% (highest amount with C11) of the dose applied was found up to 6 hours after i.v. application, indicating, that the amounts in the feces are mainly due to metabolism and not to unabsorbed compound. In addition the distribution of label in urine and feces from orally administered potassium dodecyl 35S-sulfate (C12A35SO4K) was similar in both antibiotic-treated and untreated rats, indicating that the intestinal flora does not play a significant role in the metabolism of this compound.
Metabolites identified:
yes
Details on metabolites:
Alkyl sulfates are extensively metabolized in rats, dogs and humans. This was tested with radiolabelled C10, C11, C12, C16 and C18 alkyl sulfates, potassium salts.The postulated mechanism is degradation involving omega-oxidation, followed by beta-oxidation, to yield metabolites with chain lengths of C2 and C4 for even-chain carbon alkyl sulfates. The major metabolite for even-chained alkyl sulfates was identified as the 4-carbon compound, butyric acid 4-sulfate. The 4-butyrolactone has been found as a minor metabolite which is also formed after application of butyric acid 4-sulfate. Dog and human urine also contained one other minor metabolite, glycolic acid sulfate.Metabolism of odd numbered chains (specifically, C11) in rats was postulated to follow a similar omega-, beta-degradation pathway: propionic acid-3-sulfate was the major urinary metabolite and pentanoic acid-5-sulfate and inorganic sulfate were minor metabolites.The C2 fragments enter the C2 pool of the body and are either oxidized to CO2 or found in the body. In addition about 10 to 20% of the dose usually is eliminated as inorganic sulfate.

Table 1: Data availability for toxicokinetics, metabolism and distribution

Compound

Endpoints investigated

Test substance

Counter ion

Oral absorption

 

Distribution

Metabolism

Excretion

Alkyl sulfates

C10ASO4K
CAS 7739-63-1

K

 

 

 

 

+

+

C11ASO4K
CAS not available

K

+

 

+

+

C12ASO4K
CAS 4706-78-9

K

 

+

+

+

C12ASO4Na
CAS 151-21-3

Na

 

 

 

+

+

C16ASO4Na
CAS 4706-78-9

K

 

 

 

+

+

C16ASO4Na
CAS 1120-01-0

Na

+

 

 

+

+

C18ASO4Na
CAS 1120-04-3

Na

+

 

+

+

+

Table 2: Metabolites formed from alkyl sulfates with even chain length*

HOOC-CH2-CH2-CH2-OSO3H

C4-H6-O2

HOOC-CH2OSO3H

butyric acid-4-sulfate

4-butyrolactone (ring structure)

Glycolic acid sulfate

Major Metabolite
Found in rats, dogs, humans

Minor metabolite
Found in rats, dogs, humans

Minor metabolite
Found in dogs (and humans)

* investigated substances were potassium salts of C10, C12, C14& C18alkyl sulfates

Table 3: Influence of chain length on elimination of alkyl sulfates

Compound
Shorthand

C10ASO4K
CAS 7739-63-1

C11ASO4K
CAS n.a.**

C12ASO4K
CAS 4706-78-9

C18ASO4K
CAS 7739-61-9

Number of animals, sex*

3 m

3 f

3 m

3 f

6 m

6 f

3 m

3 f

Recovery from urine at 48 h (% of dose)*

82.9

79.5

98.2

90.6

86.3

93.2

77.1

73.9

Recovery from feces at 48 h (% of dose)*

1.2

1.0

2.5

7.3

0.2

0.9

1.1

2.6

Recovery from carcass at 48 h (% of dose)*

8.1

4.0

1.6

27.6

0.4

0.4

9.4

15.6

* mean number of number of animals indicated, all values are mean values; ** n.a. = not available; 5 mg/kg bw of the35S labeled compounds was applied i.p. to MRC rats

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study resultsAlkylsulfates have a common metabolic fate that involves hydrolysis of the ether bond between the fatty alcohol and the sulfate chain.Fatty alcohols, representing the variation in the structure of different alkylsulfates, are oxidized to the corresponding fatty acid and fed into physiological pathways like the citric acid cycle, sugar synthesis and lipid synthesis. The remaining sulfate chain is renal excreted. Regarding the different anions, it is expected that the salts will be converted to the acid form in the stomach. This means that for all types of parent chemical the same compound structure eventually enter the small intestine. Hence, the situation will be similar for compounds originating from different salts and therefore no differences in uptake are anticipated.
Executive summary:

The toxicokinetic behaviour of alkyl sulfates was assessed. Alkyl sulfates are well absorbed after ingestion. After absorption, these chemicals are distributed mainly to the liver. Alkyl sulfates are metabolized by cytochrome P450-dependent w-oxidation and subsequent beta-oxidation of the aliphatic fatty acids. End products of the oxidation are a C4sulfate and a C3or C5sulfate. In addition, for the alkyl sulfates, sulfate is formed as a metabolite. The metabolites are rapidly excreted in urine. Due to the low concentrations of the substances in consumer products and the limited uptake after dermal exposure which is the main route for consumers, significant exposure of the developing foetus via the placenta or the neonate via the breast milk is not likely. Therefore a bioaccumulation of alkyl sulfates is not expected.

Endpoint:
dermal absorption
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Expert judgement combined with experimental data.
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Principles of method if other than guideline:
No guideline exists for this type of appraisal.
GLP compliance:
no
Radiolabelling:
other: partly
Species:
other: human, rat, guinea-pig
Details on test animals or test system and environmental conditions:
not applicable
Type of coverage:
other: Various, for details see HERA report and SIDS
Vehicle:
not specified
Duration of exposure:
Various, for details see HERA report and SIDS
Doses:
Various, for details see HERA report and SIDS
No. of animals per group:
Various, for details see HERA report and SIDS
Absorption in different matrices:
Absorption by the percutaneous route is limited, since anionic surfactants tend to bind to the skin surface (Howes, 1975; Black and Howes, 1980). Early studies with isolated human skin were unable to detect penetration of a homologous series of AS, ranging from C8 to C18 (Blank and Gould, 1961). Animal studies confirmed a low level of percutaneous absorption of AS. Less than 0.4% of a 3 μmol dose of 35S-labeled C12AS-Na was percutaneously absorbed in guinea pigs, based on recovery of the radiolabel in urine, faeces and expired air (Prottey and Ferguson, 1975). Studies with rats indicated that pre-washing of the skin with surfactant enhanced AS skin penetration (Black and Howes, 1980).For consumer exposure, actual dermal absorption is below 1% (Rice, 1977) or very low (Schäfer and Redelmeier, 1996), therefore a default assumption of 1% dermal absorption was taken for deriving the DNEL. Since the dermal absorption decreases with increasing concentration of a solution this percentage can be expanded to workers as a worst case approach.
Conversion factor human vs. animal skin:
not applicable
Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Expert judgement combined with experimental data.
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Objective of study:
toxicokinetics
Principles of method if other than guideline:
No guideline exists for this type of appraisal.
GLP compliance:
no
Radiolabelling:
other: partly
Species:
other: rat, dog and human
Sex:
male/female
Details on test animals or test system and environmental conditions:
not applicable
Route of administration:
oral: unspecified
Duration and frequency of treatment / exposure:
Various, for details see SIDS
Remarks:
Doses / Concentrations:Various, for details see SIDS
No. of animals per sex per dose / concentration:
Various, for details see SIDS
Control animals:
other: Various, for details see SIDS
Type:
absorption
Results:
After oral administration, alkyl sulfates are well absorbed in rats, dogs and humans.
Type:
excretion
Results:
The major path of excretion of the alkyl sulfates is the urine.
Details on absorption:
After oral administration, alkyl sulfates are well absorbed in rats, dogs and humans. This was indicated by excretion of up to 98% of the dose administered (maximum for C12ASO4Na in the urine and by comparison of excretion after oral and i.v. or i.p. application for C11ASO4K, C12ASO4K and C18ASO4Na alkyl sulfates.
Details on distribution in tissues:
After application of 14.4 mg/kg of the erythromycin salt of C16ASO4 to dogs or 250 mg/person to humans, radioactivity in plasma was maximal within 30 minutes to 2 hours of oral administration in both species indicating rapid absorption. The plasma concentration declined rapidly afterwards and reached 10% of the maximum concentration after 6 hours, indicating rapid elimination. Whole body autoradiography has been performed to follow the distribution of 35S-C10ASO4K, C12ASO4K and C18ASO4K or their metabolites within the body with time in experiments with rats after i.p. injection. For all compounds the only organs, where radioactivity was detected, were the liver and the kidney. The levels (not quantified) were highest 1 h after application. C10 AS was cleared from tissues more rapidly than C18. After 6 hours, only traces of the C10 salt remained in the kidney, whereas it took 12 hours for the C18 salt to be cleared from the kidney.
Details on excretion:
The major path of excretion of the alkyl sulfates is the urine. The data show, that there are only minor differences for the alkyl sulfates of different chain lengths in the overall excretion after i.p. application. There are also no major differences in overall excretion between male and female rats or after oral, intraperitoneal or intravenous application. The rate of excretion in the urine, however, is somewhat different. After oral as well as i.p. application, excretion of the C12 compound is complete within 6 hours after application. In contrast the excretion amounts only to about 60% (C10), 40% (C11), 15% (C18) after i.p. application, and to 25% for C11or C186 hrs after oral application. This indicates faster metabolism of the C12 compound than for the other chain lengths. Lower amounts of the alkyl sulfates are excreted via the feces within 48 hrs after oral application for the C12, C16and C18 compounds. The lowest value was obtained for the C12, while the highest values with considerable variation of 2.5 - 19.9% (2 m, 2f) were found for C11. In the bile from < 1 to 7.7% (highest amount with C11) of the dose applied was found up to 6 hours after i.v. application, indicating, that the amounts in the feces are mainly due to metabolism and not to unabsorbed compound. In addition the distribution of label in urine and feces from orally administered potassium dodecyl 35S-sulfate (C12A35SO4K) was similar in both antibiotic-treated and untreated rats, indicating that the intestinal flora does not play a significant role in the metabolism of this compound.
Metabolites identified:
yes
Details on metabolites:
Alkyl sulfates are extensively metabolized in rats, dogs and humans. This was tested with radiolabelled C10, C11, C12, C16 and C18 alkyl sulfates, potassium salts.The postulated mechanism is degradation involving omega-oxidation, followed by beta-oxidation, to yield metabolites with chain lengths of C2 and C4 for even-chain carbon alkyl sulfates. The major metabolite for even-chained alkyl sulfates was identified as the 4-carbon compound, butyric acid 4-sulfate. The 4-butyrolactone has been found as a minor metabolite which is also formed after application of butyric acid 4-sulfate. Dog and human urine also contained one other minor metabolite, glycolic acid sulfate.Metabolism of odd numbered chains (specifically, C11) in rats was postulated to follow a similar omega-, beta-degradation pathway: propionic acid-3-sulfate was the major urinary metabolite and pentanoic acid-5-sulfate and inorganic sulfate were minor metabolites.The C2 fragments enter the C2 pool of the body and are either oxidized to CO2 or found in the body. In addition about 10 to 20% of the dose usually is eliminated as inorganic sulfate.

Table 1: Data availability for toxicokinetics, metabolism and distribution

Compound

Endpoints investigated

Test substance

Counter ion

Oral absorption

 

Distribution

Metabolism

Excretion

Alkyl sulfates

C10ASO4K
CAS 7739-63-1

K

 

 

 

 

+

+

C11ASO4K
CAS not available

K

+

 

+

+

C12ASO4K
CAS 4706-78-9

K

 

+

+

+

C12ASO4Na
CAS 151-21-3

Na

 

 

 

+

+

C16ASO4Na
CAS 4706-78-9

K

 

 

 

+

+

C16ASO4Na
CAS 1120-01-0

Na

+

 

 

+

+

C18ASO4Na
CAS 1120-04-3

Na

+

 

+

+

+

Table 2: Metabolites formed from alkyl sulfates with even chain length*

HOOC-CH2-CH2-CH2-OSO3H

C4-H6-O2

HOOC-CH2OSO3H

butyric acid-4-sulfate

4-butyrolactone (ring structure)

Glycolic acid sulfate

Major Metabolite
Found in rats, dogs, humans

Minor metabolite
Found in rats, dogs, humans

Minor metabolite
Found in dogs (and humans)

* investigated substances were potassium salts of C10, C12, C14& C18alkyl sulfates

Table 3: Influence of chain length on elimination of alkyl sulfates

Compound
Shorthand

C10ASO4K
CAS 7739-63-1

C11ASO4K
CAS n.a.**

C12ASO4K
CAS 4706-78-9

C18ASO4K
CAS 7739-61-9

Number of animals, sex*

3 m

3 f

3 m

3 f

6 m

6 f

3 m

3 f

Recovery from urine at 48 h (% of dose)*

82.9

79.5

98.2

90.6

86.3

93.2

77.1

73.9

Recovery from feces at 48 h (% of dose)*

1.2

1.0

2.5

7.3

0.2

0.9

1.1

2.6

Recovery from carcass at 48 h (% of dose)*

8.1

4.0

1.6

27.6

0.4

0.4

9.4

15.6

* mean number of number of animals indicated, all values are mean values; ** n.a. = not available; 5 mg/kg bw of the35S labeled compounds was applied i.p. to MRC rats

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study resultsAlkylsulfates have a common metabolic fate that involves hydrolysis of the ether bond between the fatty alcohol and the sulfate chain.Fatty alcohols, representing the variation in the structure of different alkylsulfates, are oxidized to the corresponding fatty acid and fed into physiological pathways like the citric acid cycle, sugar synthesis and lipid synthesis. The remaining sulfate chain is renal excreted. Regarding the different anions, it is expected that the salts will be converted to the acid form in the stomach. This means that for all types of parent chemical the same compound structure eventually enter the small intestine. Hence, the situation will be similar for compounds originating from different salts and therefore no differences in uptake are anticipated.
Executive summary:

The toxicokinetic behaviour of alkyl sulfates was assessed. Alkyl sulfates are well absorbed after ingestion. After absorption, these chemicals are distributed mainly to the liver. Alkyl sulfates are metabolized by cytochrome P450-dependent w-oxidation and subsequent beta-oxidation of the aliphatic fatty acids. End products of the oxidation are a C4sulfate and a C3or C5sulfate. In addition, for the alkyl sulfates, sulfate is formed as a metabolite. The metabolites are rapidly excreted in urine. Due to the low concentrations of the substances in consumer products and the limited uptake after dermal exposure which is the main route for consumers, significant exposure of the developing foetus via the placenta or the neonate via the breast milk is not likely. Therefore a bioaccumulation of alkyl sulfates is not expected.

Description of key information

Absorption: 100% via oral route, 1% via dermal route
Distribution: Unquantified amounts of three different alkyl sulfates were found only in the kidney and the liver.
Metabolism: Alkylsulfates have a common metabolic fate that involves omega- and beta-oxidation to the respective C2 and C4 (even numbered AS) and the C3 and C5 (odd numbered AS). The oxidation products are mainly sulfated and excreted. C2-fragments may enter the C2 pool of the body and are either oxidized to CO2 or found in the body. Hydrolysis of the ether bond between the fatty alcohol and the sulfate chain may occur to a small degree. About 10 to 20% of the dose usually is eliminated as inorganic sulfate.
Excretion: The majority was excreted via urine. Only smaller amounts are excreted via the faeces. Elimination is fastest for C12 (complete within approx. 6 h) but decreases for other chain length.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
1

Additional information

To draw a coherent picture of the toxicokinetic, metabolism and distribution of the various members of the alkyl sulfates this endpoint is covered by read across to structurally related alkyl sulfates (AS). The possibility of a read-across to other alkyl sulfates in accordance with Regulation (EC) No 1907/2006 Annex XI 1.5. Grouping of substances and read-across approach was assessed. In Annex XI 1.5 it is given that a read-across approach is possible for substances, whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity. The AS reported within the AS category show structural similarity. The alkyl chain length in the alkyl sulfate category varies from C8 to C18. In addition most chemicals of this category are not defined substances, but mixtures of homologues with different alkyl chain lengths (UVCBs). The most important common structural feature of the category members is the presence of a predominantly linear aliphatic hydrocarbon chain with a polar sulfate group, neutralized with a counter ion. This structural feature confers the surfactant properties of the alkyl sulfates. The surfactant property of the members of the AS category in turn represent the predominant attribute in mediating effects on mammalian health. Due to the structural similarities also the disposition within the body is comparable throughout the category. The AS of the AS category also have similar physico-chemical, environmental and toxicological properties, validating the read across approach within the category. The approach of grouping different AS for the evaluation of their toxicokinetics, metabolism and distribution as well as their effects on human health and the environment was also made by the OECD in the SIDS initial assessment profile [1] and by a voluntary industry programme carrying out Human and Environmental Risk Assessments (HERA [2). Data reported within the discussion below summarize the information of the SIDS and HERA reports.

Absorption:

After oral administration, alkyl sulfates are well absorbed in rats, dogs and humans (SIDS, 2007). This was indicated by excretion of up to 98% of the dose administered (maximum for C12AS Na) in the urine and by comparison of excretion after oral and i.v. or i.p. application for several alkyl sulfates. Hence, oral absorption is assumed to be 100%.

Absorption by the percutaneous route is limited, since anionic surfactants tend to bind to the skin surface (SIDS, 2007). Early studies with isolated human skin were unable to detect penetration of a homologous series of AS, ranging from C8 to C18 carbon chain lengths. Animal studies confirmed a low level of percutaneous absorption of AS. Less than 0.4% of a 3 μmol dose of 35S-labeled C12 ASO4Na was percutaneously absorbed in guinea pigs, based on recovery of the radiolabel in urine, faeces and expired air. Studies with rats indicated that pre-washing of the skin with surfactant enhanced AS skin penetration. Early studies with isolated human skin (not specified further) were unable to detect dermal penetration of C12AS Na.

Based on experimental data on animals and humans, a default assumption of 1% dermal absorption was taken for deriving the DNEL. Since dermal absorption decreases with increasing concentration of a solution, this percentage can be used for workers as a worst case approach.

Distribution:

After oral administration of 14.4 mg/kg bw of the erythromycin salt of C16AS to dogs or 250 mg/person to humans, radioactivity in plasma was maximal within 30 minutes to 2 hours of exposure in both species indicating rapid absorption (SIDS, 2007). The plasma concentration declined rapidly afterwards and reached 10 % of the maximum concentration after 6 hours, indicating rapid elimination.

Whole body autoradiography has been performed to follow the distribution of 35S-C10AS K, C12AS K and C18AS K or their metabolites within the body with time in experiments with rats after i.p. injection. For all compounds the only organs, where radioactivity was detected were liver and kidney. The levels (not quantified) were highest 1 h after application. C10AS K was cleared from tissues more rapidly than C18AS K. After 6 hours, only traces of the C10AS K salt remained in the kidney, whereas it took 12 hours for the C18AS K salt to be cleared from the kidney.

Metabolism/Excretion:

Alkyl sulfates are extensively metabolized in rats, dogs and humans. This was tested with radiolabelled C10, C11, C12, C16 and C18 alkyl sulfates, potassium salts (SIDS, 2007).

The postulated mechanism is degradation involving omega-oxidation, followed by beta-oxidation, to yield metabolites with chain lengths of C2 and C4 for even-chain carbon alkyl sulfates. The major metabolite for even-chained alkyl sulfates was identified as the 4-carbon compound, butyric acid 4-sulfate. The 4-butyrolactone has been found as a minor metabolite which is also formed after application of butyric acid 4-sulfate. Dog and human urine also contained one other minor metabolite, glycolic acid sulfate.

Metabolism of odd numbered chains (specifically, C11) in rats was postulated to follow a similar omega-, beta-degradation pathway: propionic acid-3-sulfate was the major urinary metabolite and pentanoic acid-5-sulfate and inorganic sulfate were minor metabolites.

The C2 fragments enter the C2 pool of the body and are either oxidized to CO2 or found in the body. About 10 to 20% of the dose usually is eliminated as inorganic sulfate.

The major path of excretion of the alkyl sulfates is the urine. The data show, that there are only minor differences for the alkyl sulfates of different chain lengths in the overall excretion after i.p. application. There are also no major differences in overall excretion between male and female rats or after oral, intraperitoneal or intravenous application. The rate of excretion in the urine, however, is somewhat different. After oral as well as i.p. application, excretion of the C12 compound is complete within 6 hours. In contrast the excretion amounts only to about 60% (C10), 40% (C11), 15% (C18) after i.p. application, and to 25% for C11 or C18 6 hours after oral application. This indicates faster metabolism of the C12 compound than for the other chain lengths.

Lower amounts of the alkyl sulfates are excreted via the faeces within 48 hours after oral application for the C12, C16 and C18 compounds. The lowest value was obtained for the C12, while the highest values with considerable variation of 2.5 - 19.9% (2 m, 2f) were found for C11. In the bile from <1 to 7.7% (highest amount with C11) of the dose applied was found up to 6 hours after i.v. application, indicating, that the amounts in faeces are mainly due to metabolism and not to unabsorbed compound. In addition the distribution of label in urine and faeces from orally administered potassium dodecyl-35S-sulfate (C12A35S K) was similar in both antibiotic-treated and untreated rats, indicating that the intestinal flora does not play a significant role in the metabolism of this compound.

Based on the above mentioned data, tissue accumulation can be excluded.

Influence of counter ions on ADME

Due to dissociation, there is no effect of the counter ion on absorption, distribution, metabolism and excretion of the alkyl sulfate moiety expected (Hera, 2002). This is supported by comparable results achieved with alkyl sulfates having different counter ions reported within this section.

 

Discussion on absorption rate:

Absorption by the percutaneous route is limited, since anionic surfactants tend to bind to the skin surface (SIDS, 2007). Both, studies with isolated human skin and animal tests confirmed a low level of percutaneous absorption. Based on experimental data on animals and humans, a default assumption of 1% dermal absorption was taken for deriving the DNEL. Since the dermal absorption decreases with increasing concentration of a solution this percentage can be used for workers as a worst case approach.

[1] SIDS initial assessment profile, (2007);
http://www.aciscience.org/docs/Alkyl_Sulfates_Final_SIAP.pdf

[2] (HERA Draft report, 2002);
http://www.heraproject.com/files/3-HH-04-%20HERA%20AS%20HH%20web%20wd.pdf