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

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral

Remarks:

other: not specified

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:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Annex V

GLP compliance:

yes

Limit test:

no

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: Rats (Sprague-Dawley)

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

corn oil

Details on oral exposure:

Method of administration:
Gavage

Duration of treatment / exposure:

Test duration: 28 days

Frequency of treatment:

Dosing regime: 7 days/week

No. of animals per sex per dose:

Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 15 mg/kg bw/day
Male: 5 animals at 35 mg/kg bw/day
Male: 5 animals at 75 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 15 mg/kg bw/day
Female: 5 animals at 35 mg/kg bw/day
Female: 5 animals at 75 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:

Clinical observations:
During week 4 of treatment, 4 males in the 75 mg/Kg/day
group were found dead or killed on humane grounds due to
their poor clinical condition.


Clinical findings were confined to the high dose level males
and were first noted on Day 27. The findings consisted of
body tremors observed among all surviving males at predose
and persisting for up to 4 hours after dosing in some
animals. In addition unsteady gait, reduced body tone,
salivation and low carriage were noted occurring in one or
two males predose, and persisted for up to 3 hours after
dosing in the worst affected animal, which was then found
dead 4 hours after dosing. On Day 28 one male exhibited body
tremors and low carriage immediately after dosing. A sudden
deterioration in clinical condition was observed for this
male and another male, characterised by body tremors,
unsteady gait, reduced body tone, salivation, wet urogenital
region, low carriage, convulsions, laboured respiration,
protruding and dark eyes.

These two animals were killed for human reasons.

Reduced body weight gain and food consumption were also
noted for these animals during Week 4 of the treatment.


The high dose level females did not exhibit any signs of a
reaction to treatment during the 4 week treatment period.

All animals receiving 15 or 35 mg/Kg/day showed no clinical
signs considered to be related to treatment with the test
substance during the 4 week treatment period.


Functional Observation Behaviour:

Treatment with the test substance was not associated with
any behavioural changes which were considered to be
indicative of neurotoxicity.

Laboratory findings:
Haematology:

Analysis of haematological parameters measured on Day 29 did
not reveal any changes that were considered to be
toxicologically significant.


Biochemistry:

Investigation performed on Day 29 revealed that the single
surviving male from the high dose level group had a slightly
increased albumin/globulin ratio, when compared to the
control and other treated groups. This was associated with a
slight reduction in the total protein for this animal, a
slightly lower GPT and calcium value and a marginally higher
potassium value. However, no similar trends were noted for
these values among the female treated groups or the
remaining treated male groups.


All other changes observed in the blood parameters of the
remaining animals were not considered to be treatment
related.

Effects in organs:
Organ weight assessment revealed an increase in absolute
thymus, epididymides and liver weight of 53%, 23% and 21%
respectively for the single surviving high dose male animal
over controls. However there were no differences from
control observed in the organ weights of the remaining
treated males or among the treated female groups.


Macroscopic findings were confined to the 4 male rats killed
in Week 4. A pale spleen was noted in 2 of the animals. A
pale spleen and dark lungs were noted in another and another
showed congested lungs and watery stomach.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

35 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day.

2

Dose descriptor:

NOEL

Effect level:

15 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Classified as: Xn - harmful