Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
other: In accordance with REACH Annex VIII (8.8) an assessment of toxicokinetic behavior has been conducted to the extent that can be derived from the relevant available information.
Adequacy of study:
key study
Study period:
The assessment was conducted in May 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Relevant studies were reviewed by a qualified toxicologist with a view to fulfilling the requ irements of Annex VIII (8.8).

Data source

Reference
Reference Type:
other:
Title:
Unnamed
Year:
2018

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
n accordance with REACH Annex VIII (8.8) an assessment of toxicokinetic behaviour has been
conducted to the extent that can be derived from the relevant available information.The assessment
is based on the Guidance on information requirements and chemical safety assessment R.7c:
Endpoint specific guidance (ECHA, November 2014)
GLP compliance:
no
Remarks:
No relevant for assessment

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
Identification: OK (640-2) (Furoxy Hydroxy)
Batch: G316533
Purity: 94.032% w/w
Physical state/Appearance: cream colored solid
Expiry Date: 25 March 2018
Storage Conditions: Store cold at 4° C in the dark
Radiolabelling:
no

Results and discussion

Metabolite characterisation studies

Metabolites identified:
not measured

Any other information on results incl. tables

TOXICOKINETIC BEHAVIOUR

OK Furoxy Hydroxy is a white to brown colored powder with physico-chemical properties which imply the risk of particle inhalation of OK Furoxy Hydroxy to be minimal. Furthermore, the supporting toxicological information suggests any inadvertent inhalation is unlikely to lead to an elevation in systemic toxicity. OK Furoxy Hydroxy was identified to be a transient ocular irritant based upon its effects on conjunctival tissues upto 24 hours post exposure ; the in vitro genotoxicity panel indicates that there are limited concerns for genotoxicity, with weak positive effects noted in two strains (TA100 and TA 1538) of Salmonella.

The results from a single dermal dose toxicity study (irritation) , in conjunction with the molecular weight and log Pow indicate that absorption occurs via the dermis. Acute oral toxicity results showed the LD50 to be >2000 mg/kg body weight, and the Oral (Gavage) Repeated Dose Toxicity Study in the rat did not result in any adverse toxicological findings, based upon the molecular weight and log Pow, absorption form the Gastrointestinal tract can be anticipated.

Absorption

The general physico-chemical properties of OK Furoxy Hydroxy including the molecular

weight and log Pow would indicate that significant absorption is possible.

Distribution

Information relating to the distribution of OK Furoxy Hydroxy is limited; however, the chemical

characteristics and findings from the Oral (Gavage) Repeated Dose Toxicity Study implies

systemic distribution would most likely occur via the serum following oral administration and gastric

absorption. Furthermore while the properties (i.e. poor water solubility) of OK Furoxy Hydroxy suggest a

potential to accumulate in adipose tissue, none of the studies conducted showed any evidence of this.

Metabolism

There is limited evidence of test item or metabolite influenced hepatic metabolism from the Oral (Gavage) Repeated Dose Toxicity Study, with moderate increases in ASAT in high dose female rats only.

Excretion

The most plausible route of clearance for relatively low water soluble chemicals would be by transfer of

test material and/or metabolites from the plasma to the bile through the hepatocytes leading to clearance

of any metabolic breakdown products primarily via the faeces.

Applicant's summary and conclusion

Conclusions:
The available information suggests that absorption of substance from the gastrointestinal tract following oral ingestion is likely given the test items physico-chemical characteristics.
These characteristics together with the noted dermal irritation of OK Furoxy Hydroxy also indicate absorption dermal exposure of test item is likely. Absorption via the inhaltion route is not likely given the particle size distribution of the substance and low vapour pressure, however it can be anticipated that any respirable fraction will be readily absorbed. Any absorbed test material has the potential to undergo hepatic transformation and subsequent renal clearance, however the physical characteristics of the substance also indicate that clearance can also be expected to be via the bile with subsequent excretion in the faeces.