Reaction mass of sodium 4-hydroxybenzenesulfonate and disodium 4-hydroxybenzene-1,3-disulfonate and sodium sulfate

Endpoint summary

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.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Assessment of the toxikokinetic profile of the substance is investigated using TK data on similar substances and long-term data on the substance itself, from repeated dose studies such as 90-days study, screening on reproductive and develpmental toxicity. However, data on the substance are not yet available, since the abovementioned studies are still ongoing. The TK assessment will therefore be updated as soon as results are available.

Following oral administration, p-toluene sulphonic salts 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 studied. 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 daily 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.

 

Sodium Sulphate is an inorganic salt, constituent of the blood and is a normal metabolite of sulphur-containing aminoacids and excess sulphate is excreted in the urine.

Daily sulphate excretion is reported to be 0.20 to 0.25 mmol/kg bw/day and higher in children (Health Canada, 1994).

 An adsorption study on humans reported that a very large amounts of sodium sulphate (18.1 gram as decahydrate = 8 g as Na2SO4) was administrated to voluntaries; an incomplete absorption (53% urinary recovery of sulphate in 72 hours), which was associated with severe diarrhea was recorded. The cumulative amounts of free sulphate excreted in the urine at 24, 48 and 72 hr after sodium sulphate administration were significantly larger than the amounts of free sulphate excreted during the same lengths of time in control experiments (Cocchetto and Levy , 1981). This may be explained through the consideration that the human organisms tend to eliminated the excess of sulphates, by the homeostasis mechanism.

Morris (1983) study confirms this considerationconcluding that thesaturable reabsorption facilitates sulphate homeostasis.

 

It is unlikely absorbed by skin.