[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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1977

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[[[[(4-ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino]phenylacetyl]amino]-3,3-dimethyl-7-oxo-, monosodium salt, [2S-[2α,5α,6β(S*)]]-

EC Number:

261-868-6

EC Name:

4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[[[[(4-ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino]phenylacetyl]amino]-3,3-dimethyl-7-oxo-, monosodium salt, [2S-[2α,5α,6β(S*)]]-

Cas Number:

59703-84-3

Molecular formula:

C23H26N5O7S.Na

IUPAC Name:

sodium;(2S,5R,6R)-6-[(2S)-2-[4-ethyl-2,3-dioxopiperazin-1-yl)carbonylamino]-2-phenylacetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate

Test material form:

solid

Specific details on test material used for the study:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: dilution with water.

Test animals

Species:

rat

Strain:

Wistar

Remarks:

SPF

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Nippon CLEA Co., Ltd.
- Age at study initiation: 6 or 8 weeks, 12 or 16 weeks and 1 week old. The LD50 were compared in the three stages of growth.
- Weight at study initiation: 6-8 weeks: (6 weeks old: males =1 80-200 g, females = 110-130 g ; 8 weeks old: males = 220-290 g, females = 160-195 g), 12-16 weeks (body weight: 12 to 23 weeks old male 300 to 350 g, female 200 to 240 g, 16 week old male 400 to 450 g); 1 week: one male, 13 to 25 g.
- Diet: ad libitum
- Water: tap water ad libitum
- Acclimation period: one week.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2ºC
- Humidity (%): 60 ± 5%

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

water

Doses:

8 and 10 g/kg-bw

No. of animals per sex per dose:

7 animals per sex per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 7 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, macroscopic observations.

Statistics:

Litchfield-Wilcoxon's method.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 8 weeks old rats

Mortality:

No mortalities occured.

Clinical signs:

other: Mild locomotor suppression was the only transient effect observed.

Gross pathology:

No macroscopic abnormalities.

Any other information on results incl. tables

Table 1. Death rate in acute toxicity tests of T-1220.

Dose (g/kg)	Male									Female
	Time in days								Death Rate	Time in days								Death Rate
	0	1	2	3	4	5	6	7		0	1	2	3	4	5	6	7
8.00	0	0	0	0	0	0	0	0	0/7	0	0	0	0	0	0	0	0	0/7
10.00	0	0	0	0	0	0	0	0	0/7	0	0	0	0	0	0	0	0	0/7

Table 2. Summary of results.

Animal	Route	Age	LD50 (g/kg)
			Male	Female
Rat	p.o.	8w	> 10	> 10

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

EU criteria

Conclusions:

The oral LD50 of the test item in rats was > 10000 mg/kg-bw.

Executive summary:

An acute oral toxicity study was conducted in order to determine the toxicological properties of the sodium salt of piperacillin with a method similar to OECD guideline 401 (non-GLP). The test item was administered p.o. to two groups of 7 rats per sex at doses of 8.0 and 10.0 g/kg-bw test item. Mortalities and clinical signs were monitored during 7 days post-dosing after which animals were necropsied and subjected to a gross examination. No mortalities occured, the clinical signs were limited to mild transient locomotor suppression, no gross abnormalities were observed at necropsy. The oral LD50 was found to be > 10 g/kg-bw in rats.