Potassium isooctadecanoate

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

basic toxicokinetics, other

Remarks:

review

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting 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:

bioaccessibility (or bioavailability)

GLP compliance:

no

Radiolabelling:

not specified

Metabolites identified:

not specified

Metabolism of BCFA

 

BCFA are normal constituents of the human neonatal gut and are metabolized by enterocytes.

To investigate human enterocyte metabolism of BCFA, we studied Caco-2 human colon carcinoma cells that differentiate into enterocyte cells [9], which, have characteristics common to fetal intestinal cells [10] and are used as a model for FA uptake [11]. Graded levels (0.1-0.5 mM) of a mixture of four pure BCFA with chain lengths of C14-C20 (iso-14:0, anteiso-17:0, iso-18:0 and iso-20:0) were delivered with bile salts in a micellar solution to simulate the postprandial intestine. Table 1 demonstrates that BCFA are taken up by Caco-2 in a dose responsive manner until they reached a plateau at around 0.50 mM. The evidence for both saturable and diffusive mechanisms for FA uptake by Caco-2 were described previously [11], and the saturable mechanism is consistent with the uptake pattern observed here. In addition, BCFA were incorporated into cell lipid classes in a selective manner (Table 2): anteiso-17:0 was unfavored in diacylglycerol (DAG) fraction compared to phospholipids (PL) and triacylglycerol (TAG). iso-18:0 was favored in PL and iso-20:0 was favored in DAG.

 

The relative uptake of dietary BCFA was calculated as the percent of a BCFA in the cells (%w/w) divided by the percent of that BCFA in the dietary mixture (%w/w), × 100. Cells were incubated for 4 hours with graded levels (0.1-0.5 mM) of a mixture of 4 BCFA (iso-14:0, anteiso-17:0, iso-18:0, and iso-20:0). BCFA were delivered to the cells in fat-free media with 10 mM Taurocholate salt and 0.2 mM mono-olein, as described by Ho et al. [11]. Control cells were treated with 10 mM Taurocholate salt and 0.2 mM mono-olein, with and without graded levels of oleic acid corresponding to doses of BCFA. BCFA were negligible in Control cells (not shown). Comparisons were made among the relative uptake of individual BCFA across treatment groups and confirm dose-dependent uptake (different superscripts (a,b,c,d) indicate a statistically significant difference, p<0.05). Cells took up BCFA from the medium in a dose responsive manner until they reached a plateau at around 0.50 mM of BCFA in the dietary mixture.

 

Table 1: Caco-2 cell relative uptake of BCFA (%; mean ± SEM) dose-response

	Amount of total BCFA in the diet
BCFA type	0.1mM	0.25mM	0.4mM	0.5mM
iso-14:0	12.6 ± 0.6 a	15.9 ± 0.2 b	22.1 ± 0.6 c	20.9 ± 0.4 c
anteiso-17:0	15.9 ± 0.2 a	18.7 ± 0.5 b	25.6 ± 0.3 c	26.1 ± 0.7 b
iso-18:0	19.2 ± 0.6 a	20.9 ± 0.5 a	26.9 ± 0.3 b	26.4 ± 0.7 b
iso-20:0	9.4 ± 0.3 a	10.7 ± 0.3 ab	17.3 ± 0.2 bc	22.4 ± 2.8 c

 

The relative uptake of dietary BCFA was calculated as the percent of a BCFA in the cells (%w/w) divided by the percent of that BCFA in the dietary mixture (%w/w), × 100. Cells were incubated for 4 hours with graded levels (0.1-0.5 mM) of a mixture of 4 BCFA (iso-14:0, anteiso-17:0, iso-18:0, and iso-20:0). BCFA were delivered to the cells in fat-free media with 10 mM Taurocholate salt and 0.2 mM mono-olein, as described by Ho et al.. Control cells were treated with 10 mM Taurocholate salt and 0.2 mM mono-olein, with and without graded levels of oleic acid corresponding to doses of BCFA. BCFA were negligible in Control cells (not shown). Comparisons were made among the relative uptake of individual BCFA across treatment groups and confirm dose-dependent uptake (different superscripts (a,b,c,d) indicate a statistically significant difference, p<0.05). Cells took up BCFA from the medium in a dose responsive manner until they reached a plateau at around 0.50 mM of BCFA in the dietary mixture.

 

Table 2: BCFA uptake (%BCFA; mean ± SEM) into Caco-2 cells’ lipid classes

Fatty acid	Diet	Phospholipids (PL)	Diacylglycerols (DAG)	Triacylglycerols (TAG)
iso-14:0	16.8	14.2 ± 1.6 a	14.2 ± 2.7 a	20.3 ± 1.5 a
anteiso-17:0	23.7	27.5 ± 0.4 a	21.6 ± 0.6 b	28.5 ± 1.0 a
iso-18:0	27.2	37.2 ± 0.4 a	23.4 ± 0.7 b	30.0 ± 1.2 c
iso-20:0	32.2	37.2 ± 0.4 a	23.4 ± 0.7 b	20.5 ± 1.0 a

 

Cells were incubated as described in Table 1. Comparisons were made among individual BCFA across lipid classes (different superscripts (a,b,c,d) indicate a statistically significant difference between lipid classes, p<0.05). For example: anteiso-17:0 was unfavored in diacylglycerol (DAG) fraction compared to phospholipids (PL) and triacylglycerol (TAG). iso-18:0 was favored in PL and iso-20:0 was favored in DAG.

 

BCFA intake in infants and adults

 

The ingestion of BCFA is not limited to the perinatal period. The breastfed infant consumes BCFA since they are found in colostrum and mature milk at concentrations up to 1.5% w/w [23]. Taking 0.6% as a conservative estimate of mean BCFA concentration in American human milk [24] with 3.2% fat, we estimate that consumption of BCFA is about 19 mg BCFA per 100 mL human milk. Taking 600 mL as the mean intake of human milk by a one month-old infant, then a typical male infant weighing 4.5 kg (http://www.cdc.gov/growthcharts/data/who/GrChrt_Boys_24LW_100611.pdf, (Table 15-7)) consumes about 114 mg total BCFA per day, or about 25 mg BCFA per kg body weight. A three-month-old infant consumes, on average, 800 mL human milk per day, ingesting about 152 mg BCFA/day or about 23 mg BCFA/kg body weight for a male infant weighing the median of 6.5kg (http://www.cdc.gov/growthcharts/data/who/GrChrt_Boys_24LW_100611.pdf). For comparison, the mean human milk concentrations of the bioactive long chain polyun-saturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) is 0.32%w/w [25] and comparable total intakes for 1 and 3 month old infants would be 13 and 12 mg DHA per kg body weight per day, respectively. Thus, BCFA are consumed at levels that exceed DHA, a bioactive FA of great interest in infant nutrition. BCFA are not, however, a component of powdered milk formulas that use vegetable oils as their fat source, and in this sense these formula lipids differ from human milk.

BCFA are prominent in ruminant meat and milk, constituting 2% w/w of fat in the US retail cow’s milk supply [26]. Our preliminary analyses of foods from an Ithaca, New York, USA market show BCFA to be about 0.9-1.8% in various cheese and ground beef types (Ran-Ressler, et al., unpublished data). Based on these initial figures, and taking 1.3% and 0.9% as conservative estimates of the mean BCFA concentration in cheeses and in ground beef, respectively, we can estimate BCFA consumption in children. For children ages 2-11 years, the mean intake of beef is 43.5 g/d beef [27]. Children who consume a total of 28 g (1 oz) of cheese with an average of 27% fat, and 43.5 g/d of cooked beef with an average of 18% fat, consume about 168 mg BCFA per day. Addition of 1 cup of whole milk (155 mg BCFA) increases their daily BCFA intake to 323 mg. For comparison, the mean intake of DHA and arachidonic acid (ARA) in Canadian children, ages 4-7 years, was recently estimated to be 37 mg and 57mg per day [28]; both combined are only one third of the daily BCFA consumption from milk, cheese and beef.

 

Estimated BCFA content by representative serving size

			BCFA intake in common use serving sizes
Food	Fat content (% wt)	BCFA (% w/w)	Amount consumed, g	BCFA content, mg
Cow’s milk	3.2	2.0	240.0	155.0
Cooked beef	18.0	0.9 *	100.0	162.0
Cheese	27.0 **	1.3 **	28.0	98.0
Total BCFA				415.0

* Preliminary determination of BCFA concentrations in beef, purchased from a local retail store.

** Preliminary determination of the mean fat and BCFA concentrations in different cheeses, purchased from a local retail store.

 

Based on the same preliminary food data, the BCFA intake of an adult who consumes 28g (1oz) of cheese, 100 g of cooked beef and 1 cup of whole milk will total approximately 415 mg/day (Table 4) (Ran-Ressler, et al., unpublished data). BCFA intake is greater than the 100 mg average daily consumption of the DHA and eicosapentaenoic acid (EPA) reported in a survey of 8604 Americans between 1999 and 2000 and by women of child-bearing age, based on NHANES III data [29,30]. Thus, BCFA are being consumed in substantial amounts by most non-vegans, during all life stages.

In conclusion, BCFA are normal constituents in the gut from very early age, and they are present in the gut throughout the human life cycle. Studies in human cell and animal models show that BCFA are not inert components of the GI tract but are metabolized by enterocytes.

 

References

9. Pinto M, Robine-Leon S, Maric-Dominique A, et al. Enterocyte-like differentiation and polarization of the human colon carcinoma cell line caco-2 in culture. Biol Cell. 1983;47:323–330.

10. Blais A, Bissonnette P, Berteloot A. Common characteristics for na+-dependent sugar-transport in caco-2 cells and human-fetal colon. Journal of Membrane Biology. 1987;99:113–125.

11. Ho SY, Storch J. Common mechanisms of monoacylglycerol and fatty acid uptake by human intestinal caco-2 cells. Am J Physiol Cell Physiol. 2001;281:C1106–1117.

24. Aitchison JM, Dunkley WL, Canolty NL, et al. Influence of diet on trans fatty acids in human milk. Am J Clin Nutr. 1977;30:2006–2015.

25. Brenna JT, Varamini B, Jensen RG, et al. Docosahexaenoic and arachidonic acid concentrations in human breast milk worldwide. Am J Clin Nutr. 2007;85:1457–1464.

26. Ran-Ressler RR, Sim D, O’Donnell-Megaro AM, et al. Branched chain fatty acid content of united states retail cow’s milk and implications for dietary intake. Lipids. 2011;46:569–576.

27. Daniel CR, Cross AJ, Koebnick C, et al. Trends in meat consumption in the USA. Public Health Nutr. 2011;14:575–583.

28. Lien VW, Clandinin MT. Dietary assessment of arachidonic acid and docosahexaenoic acid intake in 4-7 year-old children. J Am Coll Nutr. 2009;28:7–15.

29. Ervin RB, Wright JD, Wang CY, et al. Dietary intake of fats and fatty acids for the united states population: 1999-2000. Adv Data. 2004:1–6.

30. Brenna JT, Lapillonne A. Background paper on fat and fatty acid requirements during pregnancy and lactation. Ann Nutr Metab. 2009;55:97–122.

Conclusions:

Branched chain fatty acids (BCFA) are primarily saturated fatty acids (FA) with a methyl branch, usually near the terminal methyl group. BCFA are abundant in bacteria, skin, and vernix caseosa but have seldom been studied with respect to human nutrition. They are constituents of the term newborn infant gut lumen, being swallowed as vernix particulate components of amniotic fluid in the last trimester of normal pregnancy. The few published reports of BCFA in human milk enable an estimate that breast fed infants consume 19 mg BCFA per 100ml milk. Dietary BCFA consumption from milkfat and other ruminant products, the main sources of dietary BCFA, is more than 400 mg BCFA per day in adult Americans. This estimate exceeds by several fold the average dietary intake of bioactive FA, such as docosahexaenoic acid. In conclusion, BCFA are normal constituents in the gut from very early age, and they are present in the gut throughout the human life cycle. Studies in human cell and animal models show that BCFA are not inert components of the GI tract but are metabolized by enterocytes.

Reference 2

Endpoint:

basic toxicokinetics in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

The study was conducted with sodium salts of palmitic and stearic acid. Sodium soaps of long chain C16 and C18 fatty acids are to a certain degree considered structural analoguous with regard to excretion taking into account the physico-chemical properties (surface active properties, logKow, water solubility) and the chemical structure of the test item (mainly potassium soap of iso branched long chain C17 fatty acid) and therefore the results of the source substance are considered relevant for risk assessment.

Objective of study:

excretion

Qualifier:

no guideline followed

Principles of method if other than guideline:

Turnover of [14C] surfactants in the rat

GLP compliance:

no

Specific details on test material used for the study:

Name of test material (as cited in study report): Sodium salts of Decanoic acid (C10:0), Dodecanoic acid (C12:0), Tetradecanoic acid (C14:0), Hexadecanoic acid (C16:0), Octadecanoic acid (C18:0)
Analytical purity: Pure biochemical grade
Specific activity (if radiolabelling): 14 mCi/mM
Locations of the label (if radiolabelling): 1-Alkyl position with 14C (1-14C)

Radiolabelling:

yes

Species:

rat

Strain:

Wistar

Details on species / strain selection:

Test animals
Weight at study initiation: 100-120 g
Individual metabolism cages: yes

Sex:

female

Route of administration:

other: intraperitoneal (3 animals) and subcuntaneous (3 animals)

Vehicle:

other: The test materials were applied as sodium soap solutions (sodium salts).

Duration and frequency of treatment / exposure:

6 h

Remarks:

Doses / Concentrations of fatty acid sodium soaps:
C10:0: ca. 1.09 mg/kg bw;
C12:0: ca. 1.18 mg/kg bw;
C14:0: ca. 1.36 mg/kg bw;
C16:0: ca. 1.55 mg/kg bw;
C18:0: ca. 1.64 mg/kg bw;

No. of animals per sex per dose / concentration:

6: 3 animals injected intraperitoneally, 3 animals injected subcutaneously

Control animals:

no

Details on dosing and sampling:

Pharmacokinetics study (excretion)
Tissues and body fluids sampled: urine, faeces, expired air
Time and frequency of sampling: single sampling at 6 h post-application

Details on excretion:

The rate and route of excretion of 14C from intraperitoneally administered [14C] surfactant solutions were the same as that from subcutaneously administered solutions. The specific recoveries are shown in the results section. These results showed that at 6 h after administration, the C10:0 and C12:0 soaps were readily metabolized and the main route of excretion was as 14CO2, The C14:0 soap was readily incorporated into the body and the 14C excretion was slow. The C16:0 and C18:0 soaps showed some metabolism with subsequent 14CO2 excretion but most of the 14C was recovered in the carcass at 6 h. From the results the route of excretion of 14C surfactant giving the most sensitive indication of percutaneously absorbed surfactant was indicated.

Metabolites identified:

yes

Remarks:

14CO2

Recoveries of 14C from rats after injection with [14C] surfactants.

	Dose		% Applied dose
[14C] Surfactant	µCi	(mg)	CO2	Urine	Faeces	Carcass
C10:0	7.25	0.12	57 ± 5	< 0.1	< 0.1	37 ± 6
C12:0	10.49	0.13	65 ± 7	< 0.1	< 0.1	30 ± 7
C14:0	8.13	0.15	5 ± 3	2.1 ± 1.2	< 0.1	85 ± 9
C16:0	7.74	0.17	21 ± 4	< 0.1	< 0.1	71 ± 8
C18:0	8.49	0.18	38 ± 9	< 0.1	< 0.1	56 ± 16

Each result is the mean from six animals ± SD – three animals injected intraperitoneally and three animals subcutaneously. The collection time was 6 h after injection.

Conclusions:

The turnover of the [14C] surfactants in the rat showed that there was no significant difference in the rate or route of excretion of 14C given by intraperitoneal or subcutaneous administration. The main route of excretion was as 14CO2 in the expired air at 6 h after administration. The remaining material was incorporated in the body. Longer fatty acid chains are more readily incorporated than shorter chains. At ca. 1.55 and 1.64 mg/kg bw, 71% of the C16:0 and 56% of the C18:0 was incorporated and 21% and 38% was excreted as 14CO2, respectively.

Reference 3

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

Publication on percutaneous absorption of anionic surfactants (soaps) is presented due to presence in and potential release of fatty acids C16-18 from the registered substance due to metabolic activation and presence of small quantities within the UVCB.

The reported study was conducted with sodium salts of palmitic and stearic acid. Sodium soaps of long chain C16 and C18 fatty acids are considered structural analoguous with regard to dermal absorption taking into account the physico-chemical properties (surface active properties, logKow, water solubility) and the chemical structure of the test item (mainly potassium soap of iso branched long chain C17 fatty acid) and therefore the results of the source substance are considered relevant for risk assessment.

Reason / purpose for cross-reference:

read-across source

Qualifier:

no guideline followed

Principles of method if other than guideline:

In vitro penetration through rat skin

GLP compliance:

no

Specific details on test material used for the study:

The reported study was conducted with sodium salts of palmitic and stearic acid. Sodium soaps of long chain C16 and C18 fatty acids are considered structural analoguous with regard to dermal absorption taking into account the physico-chemical properties (surface active properties, logKow, water solubility) and the chemical structure of the test item (mainly potassium soap of iso branched long chain C17 fatty acid) and therefore the results are considered relevant for risk assessment.

Radiolabelling:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Weight at study initiation: 100-120 g

Type of coverage:

open

Vehicle:

water

Remarks:

The test materials were applied as soap solutions (sodium salts).

Duration of exposure:

24 h

Doses:

Nominal doses: 300 µg C10:0, 325 µg C12:0, 375 µg C14:0, 425 µg C16:0 and 450 µg C18:0/4.9 cm² skin- Dose volume: 0.051 ml/cm²

No. of animals per group:

not specified

Control animals:

no

Details on study design:

Source of skin: rat dorsal skin
Type of skin: full thickness skin
Preparative technique: Dorsal skin was clipped 24 h before cervical dislocation. The skin was excised and mounted in 2.5 cm penetration cells similar to those described by Ainsworth (J Soc Cosmet Chem 11:69 (1960)).
Assay: Diffusion cell, similar to those described by Ainsworth (J Soc Cosmet Chem 11:69 (1960))
Receptor fluid: saline

Signs and symptoms of toxicity:

no effects

Dermal irritation:

no effects

Key result

Time point:

24 h

Dose:

86.73 µg fatty acid C16:0/cm²

Parameter:

percentage

Absorption:

0.2 %

Key result

Time point:

24 h

Dose:

91.84 µg fatty acid C18:0/cm²

Parameter:

percentage

Absorption:

< 0.1 %

The results show no measurable penetration of the C18:0 soap through rat skin up to 24 h after application, but 0.2 µg/cm² of the C16:0 soap had penetrated at 24 h. At the end of the experiment,i .e. 24 h after application, between 60 and 70% of the applied [14C] soaps were rinsed from the skin and 30-40% was associated with the skin.

Conclusions:

The in vitro penetration of C16 and C18 fatty acids (as aqueous sodium salt solutions) through rat skin decreases with increasing chain length. At 86.73 µg fatty acide C16/cm² and 91.84 µg fatty acid C18/cm², about 0.2% and less than 0.1% of the C16 and C18 sodium soap solutions is absoberd after 24 h exposure, respectively.

Executive summary:

The in vitro penetration of C16 and C18 fatty acids (as aqueous sodium salt solutions) through rat skin decreases with increasing chain length. At 86.73 µg fatty acide C16/cm² and 91.84 µg fatty acid C18/cm², about 0.2% and less than 0.1% of the C16 and C18 sodium soap solutions is absoberd after 24 h exposure, respectively.

Reference 4

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

The reported study was conducted with sodium salts of palmitic and stearic acid. Sodium soaps of long chain C16 and C18 fatty acids are considered structural analoguous with regard to dermal absorption taking into account the physico-chemical properties (surface active properties, logKow, water solubility) and the chemical structure of the test item (mainly potassium soap of iso branched long chain C17 fatty acid) and therefore the results of the source substance are considered relevant for risk assessment.

Reason / purpose for cross-reference:

read-across source

Qualifier:

no guideline followed

GLP compliance:

no

Specific details on test material used for the study:

The reported study was conducted with sodium salts of palmitic and stearic acid. Sodium soaps of long chain C16 and C18 fatty acids are considered structural analoguous with regard to dermal absorption taking into account the physico-chemical properties (surface active properties, logKow, water solubility) and the chemical structure of the test item (mainly potassium soap of iso branched long chain C17 fatty acid) and therefore the results are considered relevant for risk assessment.

Radiolabelling:

yes

Species:

other: human

Sex:

female

Type of coverage:

open

Vehicle:

other: The test materials were applied as soap solutions (sodium salts).

Duration of exposure:

24 h

Doses:

- Nominal doses: 300 µg C10:0, 325 µg C12:0, 375 µg C14:0, 425 µg C16:0 and 450 µg C18:0/4.9 cm² skin- Dose volume: 0.051 ml/cm²

No. of animals per group:

not specified

Control animals:

no

Details on study design:

Skin penetration

Source of skin: human abdominal skin

Type of skin: epidermis

Preparative technique: Female abdominal skin samples obtained at autopsy were frozen and stored at -70°C. Samples of the skin were allowed to thaw out and were heated at 58°C for 2 min and the epidermis removed in sheets.
Membrane integrity check: The electrical resistance of the cells was measured and only cells with a resistance greater than 50 000 Ohm were used.

Principled of the assay

Diffusion cell: The epidermal samples were mounted in 1 cm diameter penetration cells similar to those describedb y by Ainsworth (J Soc Cosmet Chem 11:69 (1960)).

Receptor fluid: Saline containing 0.012% Pencillin and 0.01% Streptomycin

Occlusion: no

Key result

Time point:

24 h

Dose:

217.95 µg C16:0/cm²

Parameter:

percentage

Absorption:

ca. 0.14 %

Remarks on result:

other: 0.3 ± 0.2 µg C16:0/cm² absorbed (n=4)

Key result

Time point:

24 h

Dose:

230.77 µg C18:0/cm²

Parameter:

percentage

Absorption:

ca. 0.04 %

Remarks on result:

other: 0.1 ± 0.1 µg C18:0/cm² absorbed (n=4)

Conversion factor human vs. animal skin:

no data available

The results show no measurable penetration of the C18:0 soap through rat skin up to 24 h after application, but 0.2 µg/cm² of the C16:0 soap had penetrated at 24 h. Some 7.5 µg of the C10:0, C12:0 and C14:0 soaps had penetrated per cm² at 24 h but the results were not significantly different for the three soaps. For the three soaps which penetrated the skin there was a lag time of 1 h before any measurable penetration occurred, but after this the rate of penetration steadily increased. At the end of the experiment,i .e. 24 h after application, between 60 and 70% of the applied [14C] soaps were rinsed from the skin and 30-40% was associated with the skin.

Conclusions:

The in vitro penetration of C16 and C18 fatty acids (as sodium salt solutions) through human epidermis decreases with increasing chain length. At 217.95 µg C16/cm² and 230.77 µg C18/cm², about 0.14% and 0.04% of the C16 and C18 soap solutions is absoberd after 24 h exposure, respectively.

Reference 5

Endpoint:

dermal absorption in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

The reported study was conducted with sodium salts of palmitic and stearic acid. Sodium soaps of long chain C16 and C18 fatty acids are considered structural analoguous with regard to dermal absorption taking into account the physico-chemical properties (surface active properties, logKow, water solubility) and the chemical structure of the test item (mainly potassium soap of iso branched long chain C17 fatty acid) and therefore the results of the source substance are considered relevant for risk assessment.

Qualifier:

no guideline followed

GLP compliance:

no

Specific details on test material used for the study:

The reported study was conducted with sodium salts of palmitic and stearic acid. Sodium soaps of long chain C16 and C18 fatty acids are considered structural analoguous with regard to dermal absorption taking into account the physico-chemical properties (surface active properties, logKow, water solubility) and the chemical structure of the test item (mainly potassium soap of iso branched long chain C17 fatty acid) and therefore the results are considered relevant for risk assessment.

Radiolabelling:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Test animals
Weight at study initiation: 100-120 g
Individual metabolism cages: yes

Type of coverage:

open

Vehicle:

other: The test materials were applied as soap solutions (sodium salts).

Duration of exposure:

15 min

Doses:

Nominal doses: 116 µg C10:0, 131 µg C12:0, 150 µg C14:0, 167 µg C16:0 and 184 µg C18:0/7.5 cm² skin
Dose volume: 0.013 ml/cm²

No. of animals per group:

3

Control animals:

no

Key result

Time point:

6 h

Dose:

22.27 µg C16:0/cm²

Parameter:

percentage

Absorption:

0.3 %

Remarks on result:

other: 0.53 ± 0.18 µg C16:0/7.5 cm² absorbed without prewash (n=3)

Key result

Time point:

6 h

Dose:

24.53 µg C18:0/cm²

Parameter:

percentage

Absorption:

ca. 0.3 %

Remarks on result:

other: 0.53 ± 0.14 µg C16:0/7.5 cm² absorbed without prewash (n=3)

Conversion factor human vs. animal skin:

no data available

The amount of the [1-14C] labelled soaps penetrating through 7.5 cm² of treated skin was calculated from the levels of 14C recovered in the expired CO2, urine, faeces and in the carcass, after excision of the treated area of skin, at 6 h after application. The terminal skin was examined by autoradiography which showed heavy deposition of 14C on the stratum corneum, especially at the entrances of the hair follicles, and in the hair follicles for all soaps. Traces of 14C were seen in the epidermis from all the soaps but only with the C12:0 and C14:0 soaps could detectable amounts of 14C be seen in the upper regions of the dermis.

The amounts of [14C] soap present in the skin at 6 h after application were between 2 and 5 µg/cm² of skin, but there were no statistically significant differences between the five soaps even after the prewashing regime with unlabelled soap solution.

The amounts of 14C recovered in the expired CO2, urine, faeces and carcass from rats washed for 15 min with the [14C] soap solutions are summarized in the table below where the effect of prewashing the skin is compared with a single wash.

The results show that from a single wash and rinse the order of penetrability of the soaps was C12:0 > C10:0 ≈ C14:0 > C16:0 ≈ C18:0. Approximately 10 times more C12:0 penetrated than the C16:0 soap. The results from the prewashed animals are only indications as to the actual amounts penetrating since inactive soap deposited on the skin would have diluted the [14C] soap applied. The results, however, showed an increase in the penetration of C10:0 and C12:0 and no significant change for the other soaps. Thus since the true specific activity of the soaps penetrating must be lower than the test solution the amounts penetrating must be greater than the figures given in all cases.

		Amount penetrating over 7.5 cm² of skin (µg)
		Number of prewashes with 300 mM soap solutions
[1-14C] Soap	Application (µg)	0	1	3
C10:0	116	1.78 ± 0.70	2.99 ± 1.71	8.92 ± 4.26
C12:0	131	5.06 ± 2.59	5.29 ± 3.44	9.04 ± 2.57
C14:0	150	2.04 ± 0.39	1.52 ± 0.42	1.60 ± 0.18
C16:0	167	0.53 ± 0.18	0.55 ± 0.17	0.63 ± 0.16
C18:0	184	0.53 ± 0.14	0.36 ± 0.13	0.35 ± 0.02

Conclusions:

The in vivo penetration of C10, C12, C14, C16 and C18 fatty acids (as sodium salt solutions) through rat skin decreases with increasing chain length. At 22.27 µg C16/cm² and 24.53 µg C18/cm², about 0.3% of both the C16 and C18 soap solutions is absoberd after 6 h exposure.

Description of key information

Branched chain fatty acids (BCFA) are primarily saturated fatty acids (FA) with a methyl branch, usually near the terminal methyl group. BCFA are abundant in bacteria, skin, and vernix caseosa but have seldom been studied with respect to human nutrition. They are constituents of the term newborn infant gut lumen, being swallowed as vernix particulate components of amniotic fluid in the last trimester of normal pregnancy. BCFA protect against Necrotizing Enterocolitis (NEC) in the rat pup model. Dietary BCFA at levels similar to those found in human vernix reduced NEC incidence by more than 50%, increased the abundance of BCFA-containing bacteria, and increased the expression of ileal anti-inflammatory IL-10. The few published reports of BCFA in human milk enable an estimate that breast fed infants consume 19 mg BCFA per 100ml milk. Dietary BCFA consumption from milkfat and other ruminant products, the main sources of dietary BCFA, is more than 400 mg BCFA per day in adult Americans. This estimate exceeds by several fold the average dietary intake of bioactive FA, such as docosahexaenoic acid. BCFA are bioactive, abundant but neglected components of the human food supply.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

0.3

Absorption rate - inhalation (%):

0