ethyl 5,5-diphenyl-2-isoxazoline-3-carboxylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 Feb - 05 May 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

Adopted in 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Version / remarks:

Adopted in 1988

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

Adopted in 1992

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Agricultural chemicals, Laws and Regulations Japan, MAFF (p. 19 - 20)

Version / remarks:

Adopted in 1985

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

443-870-0

EC Name:

-

Cas Number:

163520-33-0

Molecular formula:

C18H17NO3

IUPAC Name:

ethyl 5,5-diphenyl-4,5-dihydro-1,2-oxazole-3-carboxylate

Test animals

Species:

rat

Strain:

Wistar

Remarks:

WISKf(SPF71)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SPF breeding colony, Hoechst AG, Kastengrund, Germany
- Age at study initiation: males: approx. 6 weeks, females: approx. 7 weeks
- Body weight at study initiation: males: 183 g (mean), 169 - 199 g (range); females: 173 g (mean), 162 - 180 g (range)
- Fasting period before study: 16 h before treatment to 3 - 4 h after treatment
- Housing: Makrolon cages (Type 4) on soft wood granulate in groups of 5 animals
- Diet: Altromin 1324 rat diet (Altromin GmbH, Lage/Lippe, Germany), ad libitum
- Water: tap water in drinking water quality, ad libitum
- Acclimation period: at least 1 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Air changes: fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 6.25, 12.00, 20.00, 25.00, and 50.00% (w/v)
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: The test substance was suspended in the above stated concentrations in sesame oil with mortar and pestle and distributed homogeneously by means of a magnetic stirrer.

Doses:

625, 1250, 2000, 2500, and 5000 mg/kg bw

No. of animals per sex per dose:

5 males (625 mg/kg bw dose group)
5 males and 5 females (1250 - 5000 mg/kg bw dose groups)

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 15 days (16 days for 1250 mg/kg bw dose group for technical reasons)
- Frequency of observations and weighing: Animals were observed for mortality/moribundity and clinical signs 10, 30, 60 min and 2, 4, and 6 h after dosing, twice daily from Day 2 to 6 and daily thereafter until the end of the observation period. Individual body weights were determined weekly.
- Necropsy of survivors performed: yes

Statistics:

The LD50, the 95% limits of confidence and the equation of the probit lines were established on the basis of the mortality rates by probit analysis. The LD50 values were calculated for males and females separately. To get one probit line, a goodness-of- fit-test (Pearson) was performed with a 5% level of significance. Then the limits of confidence were calculated according to the method of FIELLER.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 740 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 251 - <= 2 245

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 611 mg/kg bw

Based on:

test mat.

Effect levels 3

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 904 mg/kg bw

Based on:

test mat.

Mortality:

625 mg/kg bw: 0/5 males died
1250 mg/kg bw: 3/5 males (48 - 72 h post-dose) and 1/5 females (6 days post-dose) died
2000 mg/kg bw: 2/5 males (48 h post-dose) and 2/5 females (48 h and 13 days post-dose) died
2500 mg/kg bw: 4/5 males (48 - 72 h post-dose) and 4/5 females (48 - 96 h post-dose) died
5000 mg/kg bw: 5/5 males (48 h post-dose) and 5/5 females (48 - 96 h post-dose) died

Clinical signs:

other: Clinical signs of intoxication did not significantly differ in type, incidence, and severity between male and female animals. Incidence and severity of clinical signs were dose-dependently increased with ascending dose. They began to emerge 1 h after admi

Gross pathology:

625 mg/kg bw:
Necropsy revealed no test substance-related findings.

1250 mg/kg bw:
- animals found dead: general autolysis, small intestine full of a reddish-black mass, positive in the faecal occult blood test
- animals sacrificed at termination: Necropsy revealed no test substance-related findings.

2000 mg/kg bw:
- animals found dead: general autolysis, liver with light discolouration, small intestine discoloured by test substance and full of test substance
- animals sacrificed at termination: Necropsy revealed no test substance-related findings.

2500 mg/kg bw:
- animals found dead: general autolysis, liver with light discolouration and lobular demarcation, lungs discoloured red, small intestine full of test substance, and reddish black mass
- animals sacrificed at termination: Necropsy revealed no test substance-related findings.

5000 mg/kg bw:
- animals found dead: general autolysis, liver with light discolouration and lobular demarcation, lungs discoloured orange, stomach full of test substance, small intestine full of test substance, and reddish black mass

Any other information on results incl. tables

Table 1. Table for acute oral toxicity.

Dose [mg/kg bw]	Toxicological results*	Duration of clinical signs	Time of death	Mortality (%)
Males
625	0/5/5	1 h – Day 2	---	0
1250	3/5/5	2 h – Day 3	Day 2 + Day 3	60
2000	2/5/5	2 h – Day 2	Day 2	40
2500	4/5/5	2 h – Day 5	Day 2 + Day 3	80
5000	5/5/5	1 h - death	Day 2	100
Females
650	0/0/0	---	---	---
1250	1/4/5	4 h - Day 6	Day 6	20
2000	2/5/5	2 h - Day 14	Day 2 + Day 13	40
2500	4/5/5	2 h - Day 4	Day 2 + Day 4	80
5000	5/5/5	2 h - death	Day 2 - Day 4	100
LD50 = 1740 mg/kg bw

* number of dead animals/number of animals with clinical signs/number of animals used  

Applicant's summary and conclusion

Interpretation of results:

other: Acute Oral Cat. 4 (H302) according to Regulation (EC) No 1272/2008

Conclusions:

In the present acute oral toxicity study in rats a LD50 value of 1740 mg/kg bw for both sexes was determined.
The LD50 value was 1611 mg/kg bw for males and 1904 mg/kg bw for females, respectively.