Registration Dossier

Toxicological information

Basic toxicokinetics

Currently viewing:

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
calculation (if not (Q)SAR)
Remarks:
Migrated phrase: estimated by calculation
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
A written assessment of toxicokinetic behaviour is considered appropriate for the substance. The substance displays no 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.

Data source

Materials and methods

Objective of study:
other: Assessment of toxicokinetic behaviour
Principles of method if other than guideline:
Written assessment based on toxicological profile.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Not applicable

Test animals

Species:
other: Not applicable

Administration / exposure

Details on exposure:
Not applicable
Duration and frequency of treatment / exposure:
Not applicable
Doses / concentrations
Remarks:
Doses / Concentrations:
Not applicable
No. of animals per sex per dose:
Not applicable
Positive control:
Not applicable
Details on study design:
Not applicable
Details on dosing and sampling:
Not applicable
Statistics:
Not applicable

Results and discussion

Metabolite characterisation studies

Metabolites identified:
not measured
Details on metabolites:
Not applicable

Any other information on results incl. tables

Toxicokinetic parameters such as uptake, distribution, metabolism and excretion form the essential toxicological profile of a substance. An approximate indication of the toxicokinetic pattern can be gained from the results of basic toxicity testing. The assessment of the toxicokinetic properties of Reactive Yellow FD 08064 given below is based on the results obtained for the following toxicological endpoints;

  

Acute oral toxicity

Acute dermal toxicity

Skin irritation

Skin sensitisation

Ames-Test

In vitro cytogenetic assay

Subacute (28-day) oral toxicity

 

All studies were carried out according to the principles of Good Laboratory Practice and met the requirements of the OECD an EU-Guideline for the Testing of Chemicals. Simultaneously reference to physico-chemical data such as solubility in solvents, log Pow and hydrolytic stability is included.

 

Toxicological Profile:

 

Reactive Yellow FD 08064 was tested for acute oral toxicity in male and female Wistar rats. After application of 2 000 mg/kg body weight by gavage, neither nor any clinical symptoms occurred. Based on the results of this study the median lethal dose (LD50) of Reactive Yellow FD 08064 in the rat is greater than 2 000 mg/kg body weight. Dermal treatment with 2 000 mg/kg body weight also caused no mortality or symptoms of toxicological relevance. Reactive Yellow FD 08064 is slightly irritating to the skin but is not a skin sensitiser in the maximisation test. According to the results of the acute dermal toxicity study as well as the skin irritation and sensitisation data and supported by the pronounced hydrophilic properties, Reactive Yellow FD 08064 most probably has no significant dermal absorptive potential.

 

Reactive Yellow FD 08064 was not mutagenic in a standard Ames-Test in Salmonella typhimurium TA100, TA1535, TA1537 and TA98 either with or without an exogenous metabolising system (S9-mix from Aroclor 1254 pre-treated rats) and was also not mutagenic in the preincubation method according to Prival. Reactive Yellow FD 08064 did not induce chromosome mutations (aberrations) in V79 Chinese hamster cells both in the presence as well as in the absence of a metabolic activation system.

   

Based on the results of a subacute (28-day) oral toxicity study, daily ad­ministration of doses up to 1 000 mg/kg body weight to rats has not caused compound-related lethality. Body weight development, haematological and clinical chemistry parameters as well as organ weights were unaffected. However, histopathological examinations revealed an inflammatory reaction in the submucosal layer and beyond the muscular mucosal layer of the glandular stomach. The glandular cells itself were not affected. Whereas incidence and severity of the inflammatory reaction in animals of the lowest dose group was comparable to the controls, a dose-dependent increase in severity and incidence was observed in the intermediate and high dose group. Despite this dose dependency, the effect itself is not regarded to represent a serious health hazard. Nevertheless was the 'No Observed Adverse Effect Level' (NOAEL) conservatively placed at 62.5 mg/kg body weight per day.

 

 

Evaluation and Assessment;

Based on all available data, Reactive Yellow FD 08064 does not exhibit a conspicuous toxicokinetic behaviour. Reactive Yellow FD 08064 has a very low acute toxicity potential. The results from all studies with dermal exposure indicates that Reactive Yellow FD 08064 has insignificant or no dermal absorptive potential. Additionally, taking the results of the subacute oral toxicity study into account, Reactive Yellow FD 08064 seems not to be absorbed from the gastrointestinal tract and therefore a significantbioaccumulation potential can most probably be excluded. This assumption is further supported by the marked hydrophilic character of Reactive Yellow FD 08064. The observed inflammatory changes in the glandular stomach are regarded to be a local effect and thus, do not influence the evaluation of the systemic toxic potential. Moreover, from a bistopathological point of view they are not regarded to be a serious effect. From the mutagenicity assays it appears that Reactive Yellow FD 08064 is not metabolised toward genotoxic structures.

   

Summary:

The results of basic toxicity testing give no reason to anticipate unusual characteristics with regard to the toxicokinetics of Reactive Yellow FD 08064. The data indicate that there is little or no dermal absorption. Although inflammatory changes interpreted as local effects occurred in the glandular stomach at higher doses in the subacute oral toxicity study, no signs of a significant systemic toxic potential have been observed. A bioaccumulation of Reactive Yellow FD 08064 can most probably be excluded due to the marked hydrophilic properties and lack of solubility in fat. Based on the negative mutagenicity assays, a metabolisation towards genotoxic sub-structures can be ruled out.

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: no bioaccumulation or toxicological potential based on study results
Reactive Yellow FD 08064 is not deemed to pose any bioaccumulation or toxicological hazard based on the known profile and study data available.
Executive summary:

The results of basic toxicity testing give no reason to anticipate unusual characteristics with regard to the toxicokinetics of Reactive Yellow FD 08064. The data indicate that there is little to no oral or dermal absorption. Although inflammatory changes interpreted as local effects occurred in the glandular stomach at higher doses in the subacute oral toxicity study, no signs of a significant systemic toxic potential have been observed. A bioaccumulation of Reactive Yellow FD 08064 can most probably be excluded due to the marked hydrophilic properties. Based on the negative mutagenicity assays, a metabolisation towards genotoxic sub-structures can be ruled out