Registration Dossier

Administrative data

Link to relevant study record(s)

basic toxicokinetics
Type of information:
other: written assessment based on available toxicology studies
Adequacy of study:
weight of evidence
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
A written assessment of toxicokinetic behaviour is considered appropriate for the substance. The substance displays only minor toxicological effects in any of the studies proposed, and is deemed to be be not harmful for health effects. As such, it is deemed inappropriate in terms of animal welfare to conduct a toxicokinetic assessment when no harmful effects are predicted based on known toxicology. A written assessment has therefore been prepared to address this endpoint.
Objective of study:
other: Assessment of toxicokinetic behaviour
Principles of method if other than guideline:
Written assessment based on toxicological profile.
GLP compliance:
other: Not applicable
Details on exposure:
Not applicable
Duration and frequency of treatment / exposure:
Not applicable
Doses / Concentrations:
Not applicable
No. of animals per sex per dose / concentration:
Not applicable
Positive control reference chemical:
Not applicable
Details on study design:
Not applicable
Details on dosing and sampling:
Not applicable
Not applicable
Metabolites identified:
not measured
Details on metabolites:
Not applicable
Interpretation of results (migrated information): no bioaccumulation potential based on study results

Description of key information

Based on the high water solubility, low log Kow and the results obtained in various toxicological examinations it can be concluded that Gelb Sulfatoisnot bioaccumulative.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

The assessment of the toxicokinetic properties of Gelb Sulfato given below is based on the results obtained for the following toxicological end-points with simultaneous reference to physico-chemical data such as solubility in various solvents and log Kow:

- acute oral toxicity

- acute dermal toxicity

- skin irritation

- eye irritation

- skin sensitization

- subacute (28 day) oral toxicity

- bacterial reverse mutation test

- chromosome aberration test in vitro

- rat micronucleus assay (in vivo)

Gelb Sulfato has a molecular weight of 1026.3 g/mol, a water solubility of 396.7g/l and a log Kow of -6.4.

After single oral administration of Gelb Sulfato at a dose level of 2000 mg/kg body weight neither deaths nor severe adverse symptoms occurred in female rats. Transient clinical signs of minor toxicity were seen in 1/6 of the animals. Yellow discolouration of the urine and faeces for 48 hours followed treatment. Similarly, single dermal application of 2000 mg/kg body weight onto male and female rats produced no deaths or symptoms of systemic toxicity. Test item related discoloration of skin (5/5 male; 5/5 female), were noted on the treated skin surface for 2-9 days after treatment. The median lethal dose (LD50) of Gelb Sulfato after oral and dermal administration to rats is greater than 2000 mg/kg body weight.

The administration of Gelb Sulfato into the conjunctival sac of rabbit eyes had no effect on the cornea or iris. All rabbits had slight redness of the conjunctiva with recovery at 72 hours to 7 day. Consequently, Gelb Sulfato is not irritating to skin or eyes.

Testing for sensitising properties of Gelb Sulfato was performed in guinea pigs according to the method of Magnusson & Kligman. Intradermal induction was done at 5% and dermal induction at 50%. The challenge treatment was with 50% Gelb Sulfato. No evidence of skin sensitising properties was found.

To assess the toxicity of Gelb Sulfato after repeated administration, male and female rats received the test substance at dose levels of 62.5, 250, or 1000 mg/kg body weight per day for a period of 28 days by oral gavage. 14-day recovery groups (controls and high dose animals) were included in the study.

All animal survived until scheduled study termination. No test item related clinical signs were noted. There were no differences between control and test item treated groups in the behaviour and reaction of animals to different type of stimuli. There were no test item related differences in the body weight development and in the mean food consumption between any dose levels. Haematological and clinical chemistry investigations did not reveal any toxic changes related to test item in the examined parameters. There were no relevant test item related macroscopic changes observed during necropsy. Histopathologically, there were no relevant test item related microscopic changes.

In the Ames Test, structural analogues did not cause any relevant increases in the number of revertant colonies with any of the tester strains and Gelb Sulfato is therefore assessed to be non mutagenic. In the chromosome aberration study in vitro with V79Chinese hamster cells and in the micronucleus test in rats, structural analogues proved to be non-clastogenic. Gelb Sulfato is therefore considered to be neither mutagenic nor clastogenic and does not form genotoxic metabolites.

Evaluation and Assessment

Examination of the data of the acute dermal toxicity and skin sensitisation studies gave no indication of there being any evidence for significant skin penetration of the test item (other than local colouration). In the rat dermal toxicity study, the remaining colour on the skin was not present by about 9 days.

Oral bioavailability of Gelb Sulfato was demonstrated in the acute oral study (at 2000 mg/kg bw) but there was no indication of bioaccumulation. The high water solubility and low log Kow would suggest a rapid bio-elimination and short half-life.

Based on the available data, elimination of test compound probably occurs primarily via the urine and faeces since substances with a molecular weight above 300 g/mol are generally preferentially excreted via the faeces in rodents, but the high water solubility and coloured urine would also indicate a high urinary elimination.

In summary based on the high water solubility, low log Kow and the results obtained in various toxicological examinations it can be concluded that Gelb Sulfato does not show any toxicokinetic peculiarity.