Copper, [29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]-, sulfonated

Endpoint summary

Description of key information

Introduction

No specific toxicokinetic or ADME studies on potential metabolites, were available at the time of this review. However, physico-chemical and mammalian toxicity data were available for evaluation from which a reasoned scientific opinion on the ADME parameters of this substance may be predicted. The data were generated specifically on the UVCB substance in GLP and regulatory compliant studies. An online literature search (primarily PubChem, TOXNET, ChemIDplus) did not reveal any further data that might be used to aid in this prediction.

 

Physico–chemical data

The test substance was poorly soluble in water (≤9.3 E-02 g/L). Following OECD Method 117, the test substance eluted as three peaks on the ultraviolet (UV) detector and the corresponding Log POW for the test substance was a range from < thiourea to 2.98. The n-Octanol/water partition coefficient for thiourea is reported by BUA to be -1.61 to -0.92 [BUA (1995) Thiourea. German Chemical Society (GDCh) Advisory Committee on Existing Chemicals of Environmental Relevance (BUA). Stuttgart, S. Hirzel, Wissenschaftliche Verlagsgesellschaft (BUA Report 179)]. The vapour pressure (3.97E-03 Pa at 20 °C) and melting point >350 °C) do not suggest that this substance would present a risk of inhalation exposure under ambient environmental conditions. The surface tension (73.4 mN/m at 20 °C) indicates that the substance is not considered to be surface active.

 

Available studies

The acute toxicity studies, by either the oral route (based on read across substance) or dermal route (based on test substance), revealed no toxicity, each presenting the same LD₅₀ of greater than 2000 mg/kg bw. The substance was also not a skin or eye irritant. Furthermore, the substance was not mutagenic or clastogenic in any of the genotoxicity assays conducted. LLNA results (based on read across substance) indicated that the test substance was not a skin sensitiser; there were no pathological or other clinical signs of systemic toxicity in this assay.

 

Combined repeated 28-day toxicity and reproductive/developmental toxicity studies (OECD 422) were completed by administration via oral gavage to rodents. Doses included 100, 350, 600, and 1000 mg/kg bw/day of the test substance. While blue discoloration was observed on the fur and in stomach and intestinal tissues, there were no adverse systemic effects reported for both parents and neonates at the highest dose level. Therefore, the NOAEL was considered to be 1000 mg/kg bw/day.

 

The data from these studies indicate a substance with no acute or adverse sub-chronic systemic or adverse reproductive/developmental toxicity and no genotoxicity.

 

Absorption and distribution

The low water solubility of the test material and the lack of toxicity in the acute and subacute oral toxicity studies and the acute dermal toxicity study indicate that the substance would not be expected to be absorbed across the lipid bilayers of cell membranes after oral exposure or be absorbed dermally Further, in the OECD 422 study, after repeated 28-day dosing, the lack of oral absorption and systemic exposure is evidenced by reported blue discoloration of the stomach, intestinal tissues and rectum of test animals, as well as blue faeces in the treated animals, which appeared to be dose-dependent; however, no other organs outside of the digestive system were reported to be similarly discoloured (e.g., liver, kidneys, etc.).

 

The physico-chemical properties and physical state of the test substance suggest that it is unlikely to result in acute inhalation exposure and consequently, risk. This is supported by the absence of toxicity observed following acute oral or repeated 28-day dose studies.  

 

Metabolism

In the genotoxicity studies, no adverse effects were seen either with or without the addition of metabolic activation (+/- liver S9-mix), this favours the view that potential metabolites, should they exist, were likely to be of no or limited mammalian toxicity. The evidence (lack of toxicity) from the OECD 422 study would support this.

 

Excretion

Given the physical chemical properties of the substance, the nature of the effects seen in the repeat dose toxicity study and probable limited bioaccumulation, it is predicted that excretion (of parent and potential metabolites) would mostly be via the faeces and possibly the urine; however, no report of discoloured urine was indicated in the study report.

 

Conclusion

The physico-chemical characteristics of the test substance and the data from the repeat dose toxicity study suggest and demonstrate that the substance is not likely to be rapidly absorbed, distributed or metabolised. The substance appears to be excreted in the faeces, as demonstrated by blue discoloration in intestinal tissues and the dose-dependent blue discoloration of faeces. The toxicity of metabolites is likely to be limited, as no overall toxicity was present, in any study, and in the genotoxicity studies metabolic activation was without demonstrable effect.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential