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Toxicological profile :

Adverse effects of Uronium hydrogen sulphate:

No toxicity was observed after acute exposure by oral and dermal route in the rats. The LD50 was in both case higher than 2000 mg/kg bw. No effect was observed after dermal administration, whereas some effects were noted by oral route (one rat died at 2000 mg/kg bw and some clinical signs were observed (huntched posture, piloerection).

Uronium hydrogen sulphate is not considered as irritant to the skin, but is severely irritating to the eyes.

Uronium hydrogen is considered as not sensitising to the skin, but a non-specific (irritant) effect was observed during the test. This irritant effect is probably due to the used of a solvent (acetone/olive oil, recommended by OECD guideline 429 as standard vehicle), that promotes penetration of the test item through the skin barrier.

 

Toxicokinetic analysis of Uronium hydrogen sulphate:

No information is available with Uronium hydrogen sulphate as an aduct of urea and sulphuric acid.

As Uronium hydrogen sulphate readily degrades to urea and sulfuric acid and/or sulfate ions in the human body, the assessment of the repeated toxicity of urea sulphate is based on the data available on the degradation products:

- Sulfates (as calcium salt): no severe toxicological effect was observed after oral administration of (calcium) sulfate. In a Combined Repeated Dose and Reproduction/Developmental Toxicity Screening Test in rats [OECD TG 422] with calcium sulphate dihydrate, the LOAEL and NOAEL were determined to be 300 mg/kg bw/day and 100 mg/kg bw/day for male rats, and the NOAEL for females was 1000 mg/kg bw/day.

- Urea: 12-month carcinogenicity screening studies in the rat and mouse demonstrate that urea is of very low chronic toxicity by the oral route. Similarly, no evidence of local or systemic toxicity was seen in 4-week and 25-week dermal toxicity studies in the rat.

 

An’s test in S. typhimurium according to OECD TG 471 (with and without metabolic activation) is negative. No other data are available with urea sulphate.

As urea sulfate readily degrades to urea and sulfuric acid and/or sulfate ions in the human body, the results obtained with these substances are considered:

- Sulfates (as calcium salt): no positive results were obtained in-vitro (, mouse lymphoma assay) or in-vivo (micronucleus test) ;

- Urea: urea is considered extremely unlikely to be genotoxic. Negative results are reported in threetests. Positive results are reported in assays for mutagenicity and clastogenicity in mammalian cells, however the value of these studies are limited by the extremely high test concentrations. A positive result is reported in a mouse bone marrow assay of unconventional design, however this study is not considered to be reliable.

 

No data are available on uronium hydrogen sulphate.

However data available on its degradation products (sulphate salt and urea) in the human body show that urea sulfate is very unlikely to be a reproductive toxin:

- Calcium sulfate dihydrate showed no signs of reproduction/developmental toxicity in an OECD 422 reproduction/developmental screening test (NOAEL = 790 mg/kg bw/day, as anhydrous).

- Urea is very unlikely to be a reproductive toxin; it is naturally produced in large quantities in the human body as a consequence of normal protein catabolism and has no effects after long term exposure, especially regarding reproductive organs.

Thus testing cannot be justified scientifically.

 

Absorption:

No data is available, but the absence of systemic toxicity after exposure indicates that the substance is of low toxicity.

A low potential of absorption by passive diffusion is predicted based on low LogPow values of the degradation products.

Uronium hydrogen sulphate is not considered as ahighly volatile substance, thus inhalation as a vapour is not a probable route of exposure.

Regarding dermal uptake, it is predicted to be low as the water solubility is very high and the Log P value is below 0. Uronium hydrogen sulphate and its degradation products may be too hydrophilic to cross the lipid rich environment of the stratum corneum.

In view of the pH of the substance, damage to the skin surface may enhance penetration. However no skin irritation was observed in the in-vivo irritation test in the rabbit. The use of a solvent may promote penetration of the test item through the skin barrier, as observed during the skin sensitisation test (LLNA).

 

Distribution:

No data is available.

If uronium hydrogen sulphate and its degradation compounds are absorbed, these water-soluble molecules and ions will diffuse through aqueous channels and pores.

No target organ has been identified, as no systemic toxicity was observed.

 

Bioaccumulative potential:

Uronium hydrogen sulphate and its degradation compounds are not predicted to bioaccumulate in the body as these compounds are not Lipophilic substances and are hydrosolubles.

 

Metabolism:

In the “Tolerance Reassessment Eligibility Decision for Urea Sulfate” (EPA, 2005), theEnvironmental Protection Agency (EPA) has determined that uronium hydrogen readily degrades to urea and sulfuric acid and/or sulfate ions in the environment and in the human body. Therefore, the tolerance reassessment for the active ingredient urea sulfate was based on the tolerance reassessments performed on both urea and sulfuric acid and its salts.

Urea is naturally produced in large quantities in the human body as a consequence of normal protein catabolism.

Reference:EPA (2005). Tolerance Reassessment Eligibility Decision for Urea Sulfate.http://www.epa.gov/oppsrrd1/REDs/urea_sulfate_tred.pdf

 

Excretion:

No data is available.

The major routes of excretion for substances from the systemic circulation are in the urine and/or the faeces.