Diethyl thiophosphoryl (Z)-(2-aminothiazol-4-yl)methoxyimino acetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

other: Body responsible for the test

Title:

Unnamed

Year:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Annex V Method (B1.bis)

GLP compliance:

yes

Test type:

fixed dose procedure

Test material

Test material information

Constituent 1

Reference substance name:

Diethyl thiophosphoryl (Z)-(2-aminothiazol-4-yl)methoxyimino acetate

EC Number:

426-790-0

EC Name:

Diethyl thiophosphoryl (Z)-(2-aminothiazol-4-yl)methoxyimino acetate

Cas Number:

162208-27-7

Molecular formula:

Hill formula: C10 H16 N3 O5 P S2

IUPAC Name:

diethoxy(sulfanylidene)-lambda5-phosphanyl (2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetate

Test animals

Species:

other: Rat (Sprague-Dawley origin)

Administration / exposure

Vehicle:

other: Corn oil.

No. of animals per sex per dose:

Preliminary sighting study: 2 (female)
Main study: 10 (male)
Main study: 10 (female)

Details on study design:

Preliminary sighting study:
A preliminary sighting study was carried out by dosing
female rats at 500 and 2000 mg/kg bodyweight.

Main study:
A group of ten rats (five male and five female) were dosed
at 500 mg/kg bodyweight. A further group of ten rats (five
males and five females) was dosed at 50 mg/kg bodyweight.

Results and discussion

Preliminary study:

Species/strain: Rats (Sprague-Dawley origin)
2000 mg/kg bw: Evident toxicity: Y; Mortality: Y
500 mg/kg bw: Evident toxicity: Y; Mortality: N
Observations:
Initially one animal was dosed at 500 mg/kg bodyweight.
Clinical signs in this animal comprised piloerection,
hunched posture, waddling/unsteady gait, increased
respiration, soft to liquid yellow/brown discoloured faeces,
increased/clear urine and ungroomed appearance (ano/genital
region). Recovery was complete by Day 8. Bodyweight gain was
considered satisfactory and the animal was sacrificed on Day
8. No macroscopic abnormalities were observed at post mortem
examination.

A further female was treated at 2000 mg/kg bodyweight.
Clinical signs noted in this animal prior to death comprised
of piloerection only. This animal died within one hour of
dosing. Macroscopic examination of this animal revealed
congestion (characterised by dark appearance) of the liver
and spleen. Fluid contents were noted in the stomach.

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

50 mg/kg bw

Effect levels 2

Dose descriptor:

other: 500 mg/kg bw (fixed dose initial)

Remarks on result:

other: No. with evident toxicity: 5; No. of deaths: 5; No. of animals used: 5

Effect levels 3

Dose descriptor:

other: 50 mg/kg bw (fixed dose initial)

Remarks on result:

other: No. with evident toxicity: 5; No. of deaths: 0; No. of animals used: 5

Effect levels 4

Dose descriptor:

other: 500 mg/kg bw (fixed dose initial)

Remarks on result:

other: No. with evident toxicity: 5; No. of deaths: 4; No. of animals used: 5

Clinical signs:

Signs of toxicity:
Five males and four females dosed at 500 mg/Kg bodyweight
died within 3 hours of dosing. Piloerection was observed in
all rats within six minutes of dosing and was accompanied in
rats later on Day 1 and/or at later intervals during the
study by:


Hunched posture and abnormal faeces, seen in all animals at
50 and 500 mg/kg;

Waddling/unsteady gait, lethargy, abnormal respiration and
pallid extremities in all males and one female at 500 mg/kg;

Partially closed eyelids and increased lacrimation in one
male and one female at 500 mg/kg;

Walking on toes in all rats at 500 mg/kg;

Discoloured urine, body tremors and blue/cold extremities in
one female at 500 mg/kg;

Ungroomed appearance in all rats at 500 mg/kg and one male
and one female at 50 mg/kg.

Recovery of the surviving female treated at 500 mg/kg was
complete by Day 9. For rats treated at 50 mg/kg, all signs
with the exception of piloerection had resolved by Day 2.
Recovery of all rats treated at 50 mg/kg was complete by Day
5.

Gross pathology:

Effects on organs:
Macroscopic examination of the nine animals which died
within three hours of dosing revealed congestion of the
subcutaneous tissue, brain, heart, lungs, liver, kidneys,
stomach and alimentary tract. Pallor was noted in the
subcutaneous tissue, brain, stomach and small intestine.
Enlargement of the heart and stomach were also noted.
Congestion with fluid contents and gaseous distension were
also noted in the stomach and alimentary tract.

Macroscopic examination of the one surviving female treated
at 500 mg/kg and all rats at 50 mg/kg, killed at Day 15
revealed no abnormalities.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information