[2R-(2α,3Z,5α)]-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, compound with tert-butylamine (1:1)

PBT assessment

PBT assessment: overall result

PBT status:

the substance is not PBT / vPvB

Justification:

Persistence:

The test item attained 73% degradation after 28 days. Under the strict terms and conditions of OECD Guideline No. 301B the test item cannot be considered to be readily biodegradable as the test item failed to satisfy the 10-Day window validation criterion, whereby 60% degradation must be attained within 10 days of the degradation exceeding 10%. However, the test item has exhibited the potential for rapid degradation and is not considered to be persistent.

Bioaccumulation:

The log Pow for tBA Clavulanate has been calculated as -1.3, using a QSAR method (KOWWIN). The partition coefficient is well below 4.5 which suggests that the test material is not likely to bioaccumulate in the environment.

Toxicity:

The test material tBA clavulanate is not considered to be toxic and is not classified as toxic.

An acute oral study showed the test material to have an LC50 value of > 2000 mg/kg and the NOEC was set as 2000 mg/kg. The test material was determined to be not irritating to the skin or eye. A LLNA study determined the test material to be not sensitising to the skin.

The remaining toxicological testing was conducted upon a close structural analogue (potassium clavulanate).

Numerous repeat dose studies were conducted on potassium clavulanate (the surrrogate material), these included the following:

A 6 month dog study produced no adverse efects and the NOAEL was set to the highest dose group tested which was 50 mg/kg.

The NOAEL in the 90 day mouse study, also showed no adverse effects, all effects were considered adaptive responses and none of these can be associated with toxicity of the test item. The NOAEL was set to 400 mg/kg bw.

A fertility study showed very little effects and no signs of toxicity and based on the results of this study, it is thought that the maximum non-effect dose levels of potassium clavulanate for the general toxicological responses, fertility of the parent animals, and the development of the next generation under these test conditions are 25.0mg/kg/day, 75.0mg/kg/day and 75.0mg/kg/day respectively.

A developmental study was also conducted. Other than the confirmation of a slight reduction in the fetal body weight where a slight inhibition in weight gain was seen in the dam in the treatment group at 150 mg/kg, no effect was seen in the dams’ fertility, development of the fetuses, or in the development of offspring (F1) after birth. Therefore the maximum NOELs for general toxicological responses in the dams is set to 75 mg/kg due to the slight inhibition in weight gain which was seen in the Dam, for reproductive performance of the dams the NOEL is 150 mg/kg and for development of the offspring the NOEL is 150 mg/kg. The test material is therefore not considered toxic.

In conclusion, in order for the test material to be classed as a PBT substance, the test material must be classed as Persistance, bioaccumulating and toxic, our substance does not meet any of these requirements and is therefore not a PBT substance.