[2S-[2α,5α,6β(S*)]]-6-[[[[(4-ethyl-2,3-dioxopiperazin-1-yl)carbonyl]amino]phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

Endpoint summary

Description of key information

Data waiving (study scientifically not necessary / other information available): a short-term toxicity study by the oral route does not need to be conducted because appropriate intravenous studies are available and intravenous is the most appropriate route, given that the substance is not absorbed by the oral route (absorption of 0.5% in rats).

Key study. Based on a study on the sodium salt of piperacillin (analogue substance), the NOAEL of the substance is considered to be 959 mg/kg bw/d in rats.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no study available

Dose descriptor:

NOAEL

959 mg/kg bw/day

Study duration:

subacute

Species:

rabbit

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A 30-day repeated dose toxicity study via intravenous route was performed on Wistar SPF rats (no guideline available, no GLP), to determine the toxicity of the analogue substance sodium salt of piperacillin. The test item was orally administered to 15 male and 15 female rats per dose, at doses of 0 (control), 500, 1000 and 2000 mg/kg test item. Aminobenzylpenicillin (ABPC) was used as a positive control. All animals were thoroughly observed immediately after administration for the onset of any toxic signs and once daily thereafter. Survival, feed intake, and body weight were monitored. At the end of the study, the animals were sacrificed and haematology, clinical chemistry, urianalysis, gross necropsy, and histopathology was performed on 7 males and 7 females per group. During the study, mortality was observed at the highest dose tested, plus slight but significant changes in clinical signs, clinical biochemistry and organ weights. Based on the study results, the test item was found to have an intravenous NOAEL of 1000 mg/kg bw in rats. Based on the available information for the read-across approach, the target substance has a NOAEL = 959 mg/kg bw.

Justification for classification or non-classification

Based on available data (NOAEL = 959 mg/kg bw in rats), the substance is not classified for repeated dose toxicity according to CLP Regulation (EC) No. 1272/2008.