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Endpoint:
dermal absorption
Type of information:
other: estimated by modeling on related Hydrotropes category
Adequacy of study:
key study
Study period:
2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Estimations based on state of the science modelling, not measurement
Principles of method if other than guideline:
estimation by modelling
Key result
Parameter:
percentage
Absorption:
2.8 %
Remarks on result:
other:

The modelling results show that the uptake of hydrotropes from either a diluted solution, or the concentrated product, into the stratum corneum, for short exposure durations varies between 0.36% and 0.55% of the amount applied.

- % dermal absorption is independent of concentration (i.e., the dermal flux is not saturated) and skin contact area

- % dermal absorption increases with duration exposure

- for all concentrations, the 23 hour uptake efficiency is ca 2.8% for this exposure scenario (it is unlikely if not inconceivable that anyone would be exposed to a solution containing a hydrotrope for 23 hours without removal and/or washing of the exposed surface; therefore the 2.8% uptake efficiency would represent an upper bound value)

- a 2.8% dermal absorption factor can therefore be used as an upper bound value in the exposure dose calculation

Conclusions:
Based on state-of-science modelling, a 2.8% dermal absorption factor can be used as an upper bound value in exposure dose calculations for hydrotropes.
Endpoint:
basic toxicokinetics in vivo
Type of information:
other: Read across from a member of Hydrotropes category
Adequacy of study:
key study
Study period:
Manuscript received 24th February 1971
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Objective of study:
excretion
metabolism
toxicokinetics
Qualifier:
no guideline followed
GLP compliance:
not specified
Specific details on test material used for the study:
Sodium tosylate-35S (99% purity)
Radiolabelling:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
water
Duration and frequency of treatment / exposure:
Single dose was administered.
Dose / conc.:
34.8 mg/kg bw/day (nominal)
Remarks:
Single dose.
No. of animals per sex per dose / concentration:
Two
Type:
excretion
Results:
Excretion of the unchanged parent substance: urine 82% of which 80% was excreted within the first 24 hours; Feces 13% of which the first 11.7% was excreted within the first 24 hours.
Details on absorption:
The substance is rapidly absorbed given that almost 85% of the substance was excreted in the urine within 24 hours of dosing.
Details on excretion:
The primary excretory pathway is urinary with 82 to 85% of the dose being elimited via this route.
Key result
Toxicokinetic parameters:
half-life 1st: 75 minutes
Metabolites identified:
no
Details on metabolites:
Chromatographic analysis of excreta indicated that only the unaltered tosylate-35S moeity had been excreted. In none of the three solvent systems employed was the presence of any metabolite detected.
Conclusions:
The substance is rapidly absorbed following oral gavage adminstration and then excreted unchanged primarily in the urine.
Executive summary:

In a metabolism study the substance was administered to Sprage Dawley rats (2 animals/sex/dose) by oral gavage at a dose level of 34.8 mg/kg bw (single administration). Urine and feces were collected daily for 4 days. The substance was excreted unchanged primarily in the urine.

Endpoint:
basic toxicokinetics in vivo
Type of information:
other: Read across from a member of Hydrotropes category
Adequacy of study:
key study
Study period:
Manuscript received 24th February 1971
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Objective of study:
excretion
metabolism
toxicokinetics
Qualifier:
no guideline followed
GLP compliance:
not specified
Specific details on test material used for the study:
Sodium tosylate-35S (99% purity)
Radiolabelling:
yes
Species:
dog
Strain:
Beagle
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
water
Duration and frequency of treatment / exposure:
Single administration
Dose / conc.:
17.4 mg/kg bw/day (nominal)
No. of animals per sex per dose / concentration:
1/sex/dose
Control animals:
not specified
Type:
excretion
Results:
Excretion of the unchanged parent substance measured: urine 84.5% of which 80.4% was excreted in the first 24 hours; feces 17.5% of which 12.2% was excreted in the first 24 hours.
Details on absorption:
The substance is rapidly absorbed given that almost 85% of the substance was excreted in the urine within 24 hours of dosing.
Details on distribution in tissues:
Not specified.
Details on excretion:
The substance was excreted primarily in the urine, with 84.5% being excreted over 4 days.
Key result
Toxicokinetic parameters:
half-life 1st: 75 minutes
Metabolites identified:
not specified
Details on metabolites:
Chromatographic analysis of excreta indicated that only the unaltered tosylate-35S moeity had been excreted. In none of the three solvent systems employed was the presence of any metabolite detected.
Conclusions:
The substance is rapidly absorbed following oral gavage adminstration and the substance is excreted unchanged primarily in the urine.
Executive summary:

In a metabolism study the substance was administered to beagle dogs (1 animals/sex/dose) by oral gavage at a dose level of 17.4 mg/kg bw (single administration). Urine and feces were collected daily for 4 days. The substance was excreted unchanged primarily in the urine.

Description of key information

Short description of key information on bioaccumulation potential result:

Given the high polarity and water solubility , the substance is expected to be rapidly excreted and minimally absorbed into systemic circulation

Short description of key information on absorption rate:

No data available.  Not required under REACH.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Following oral administration, p-toluene sulphonic acid is rapidly absorbed. In dogs were given 17.4 mg of radiolabelled 35S sodium tosylated/kg body weight, maximum radioactivity was measured in the blood after just 30 minutes (Dreifuss et al., 1971).


In rats and dogs which were given oral doses of p-toluene sulphonate as sultamicillin tosylate (100 mg/kg and 50 mg/kg body weight, respectively), maximum serum concentrations were measured 2 hours after administration (Kano et al., 1985)


 


In situ studies of intestinal absorbtion with Sprague-Dawley rats showed that at pH 7.5 /thus, in dissociated form) PTSA was not absorbed after 10 minutes (Ho et al., 1982)


 


The dispersion of PTSA in the tissues also occurs rapidly. Its half life in the plasma of both dogs and rats was found to be 75 minutes (Dreufuss et al., 1971; Ho et al., 1982). Studies with sultamicillin tosylate produced a half life value in dogs of 60 minutes and in ratd of 100 minutes (Kano et al., 1985).


 


The distribution of PTSA in the tissues following intravenous injection (no information on dose size) has been studies.. The highest concentration after 35 minutes were found in urine and kidneys (Ho et al., 1982). Following adinistration as Sultamicillin tosylate to rats, its concentration was measured after 2 and 6 hours. After 6 hours, p-toluene sulphonate was no longer detectable in any tissues apart from the kidney (1.2 ug/g), heart (0.1 ug/g) and serum (0.3 ug/ml) (Kano et al., 1985)


 


As can be seen from these studies, elimination is very rapid and occurs mainly via the kidneys. Within four days, following oral administration of 34.8 mg of PTSA/kg body weight to rats, 82% was escreted in the urine and 13% in the faeces. For dogs, which were given 17.4 mg PTSA/kg body weight, the respective values were 84,5% and 17.5%. In both cases by far the greater part of the administerd dose was eliminated after just one day (Dreyfuss et al., 1971).


 


In rats, within 24 hours sultamicillin tosylate (200 mg/kg bw) was eliminated to 87% in the animal's urine and to 1.2% in the faeces (Kano et al., 1985). Analyses of urine and faeces showed that in both cases the substance had been eliminated unaltered. The excretion profiles for dogs which were administerd 17.4 mg sodium tosilate-35S/kg bw i.p. or p.o. and for rats which where administerd 34.8 mg/kg of the same substance p.o. were found to be very similar (Dreyfuss et al., 1971) . After 5 days, excretion of labelled sodium tosilate in the dogs was below the detection limit. In rats, too, even at a dose of 200 mg/kg, after 4 days 95% of the dose has been excreted (Dreyfuss et al., 1971).


 


Also when p-toluene sulphonate was administerd to rats in the form of sultamicillin tosylate in dayli doses of 100 mg/kg bw over a period of 21 days, no accumulation of p-toluene sulphonate in the animal was found. The highest p-toluene suklphonate concentrations were found in the kidneys (14 ug/g) and serum (2.9 ug/ml) 4 hours following administration of the last dose, while the concentration in other tissues was under 1 ug/g. These concentrations were of the same order of magnitude as those found 4 hours after administration of a single dose of the substance. 24 hours afteradministration of the final dose, p-toluene sulohinate was no longer detectable in the animals' organs (Kano et al., 1985)


 


 


Regarding dermal adsorption it can be evaluated the result of a model build to evaluate the dermal penetration for hydrotopes.


A multiple homogeneous layer model was used to derive an estimate of dermal penetration for hydrotropes. The mathematical model simulates the uptake of a chemical substance through the skin into a central sink compartment below the skin. The model uses the substance's diffusion and partitioning coefficients and calculates the total (cumulative) fraction of the substance that enters the stratum corneum for a specific exposure duration. The model does not include any metabolism and the model is believed to represent an upper bound estimate of the potential uptake of the substance through the skin.


Dermal penetration simulations based on a mechanistic model of the process of uptake of chemical substances in skin predicts that the dermal penetration of a generic hydrotrope is less than 0.6% of the applied amount (over a wide range of exposure scenarios). Simulations show that for an exposure extending to 23 hours, the dermal uptake does not exceed 2.8% of the applied amount, regardless of the applied amount (concentration) within the range of 0.0002% to 10%. 10% is considered an upper bound of the concentration of hydrotropes in consumer products.


 


Although polarity of the aromatic sulfonic acids is less than hydrotopes, the low Kow can help in supporting a very low penetration of acids too. The dermal pathway is in any case not included in the exposure scenarios because of the corrosivity of the substance.