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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No guideline available at the time the study was conducted, but performed comparable to current guidelines.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1973
Report date:
1973

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Animals were treated at different volumes of the test substance; no individual data presented in report
GLP compliance:
no
Remarks:
GLP was not mandatory by the time the study was conducted.
Test type:
other: non-guideline, but comparable to standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
O,O-diethyl phosphorochloridothioate
EC Number:
219-755-4
EC Name:
O,O-diethyl phosphorochloridothioate
Cas Number:
2524-04-1
Molecular formula:
C4H10ClO2PS
IUPAC Name:
O,O-diethyl chlorophosphonothioate
Details on test material:
- Name of test material (as cited in study report): EP2

Test animals

Species:
mouse
Strain:
other: CFLP
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 16-23 g
- Fasting period before study: overnight

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: aqueous solution containing 5% Tween 80
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 5%
- Amount of vehicle (if gavage): 0.4, 0.64, 1, 1.6 or 2.5 mL per kg bw

MAXIMUM DOSE VOLUME APPLIED: 2.5 mL

DOSAGE PREPARATION (if unusual):
The test substance was prepared as a 5% emulsion in 5% Tween 80 (aqueous solution).


- Rationale for the selection of the starting dose:
Doses for the full scale test were selected based on the results of a preliminary range finding study.
Doses:
full scale test: 0, 0.4, 0.64, 1, 1.6 or 2.5 mL/kg bw of a 5% solution of the test substance, corresponding to 0, 476, 762, 1190, 1380, or 2975 mg/kg bw.
(dose-range finder: 0, 0.4, 1 or 2 mL/kg bw of a 5% solution of the test substance, corresponding to 0, 476, 1190, or 2380 mg/kg bw)
No. of animals per sex per dose:
full scale test: 5/sex/dose
(dose-range finder: 2/sex/dose)
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation for mortality every hour during the first 24 hours, and daily afterwards; weight was taken at the day of dosing and then once per week
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Not applicable

Results and discussion

Preliminary study:
The results of the dose range finding study indicated that the median lethal oral dose (LD50) was in the range of 0.4 - 2mL/kg bw (corresponding to 476 - 2380 g/kg bw).
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
714 mg/kg bw
Based on:
not specified
95% CL:
> 512 - < 1 059
Mortality:
Deaths occured between one and 24 hours after dosing.
Clinical signs:
Signs of reaction to treatment, observed within a few hours after dosing included piloerection and lethargy in all animals. This was accompanied by body tremors in mice treated at dosages greater than 0.4 mL/kg bw, togehter with excess salivation in animals treated at 0.64 and 1 mL/kg bw.
Body weight:
Bodyweight gains of treated animals were comparable to those of controls, except of one female which survived treatment at 1 mL/kg bw and showed depressed bodyweight gain during the first week after treatment, but bodyweight was comparable to controls in week 2 after exposure.
Gross pathology:
Autopsy of the animals found dead after treatment revealed darkening of the liver and kidneys and injection of the intestinal blood vessels. Autopsy findings of animals surviving treatment were normal.

Any other information on results incl. tables

Mortality ratio and group mean bodyweight of mice dosed orally at EP2 - Results of the full scale test:

 

Sex

Dosage [mL/kg bw]

Bodyweight [g] at

Mortality ratio

(No. dead / No. dosed)

Time of death after dosing [h]

Dosing

Week 1

Week 2

Male

0

20

26

29

0 / 5

--

0.4

21

28

32

0 / 5

--

0.64

22

24

28

2 / 5

<23

1

21

26

31

4 / 5

<7

1.6

20

--

--

5 / 5

<5

2.5

20

--

--

5 / 5

<2

 

Female

0

20

27

32

0 / 5

--

0.4

21

28

31

1 / 5

<5

0.64

20

--

--

5 / 5

<5

1

21

24

29

4 / 5

<7

1.6

20

--

--

5 / 5

<5

2.5

20

--

--

5 / 5

<2

 

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
The acute median lethal dose (LD50) and its 95% confidence limits to mice of EP2 were calculated to be 0.6 (0.43 - 0.89) mL/kg bw, corresponding to 0.714(512 - 1059)mg/kg bw.
Executive summary:

The study was conducted in order to assess the acute oral toxicity of EP2 (O,O-diethyl chlorothiophosphate).

Therefore, mice were treated at a single dose of 0 - 2.5 mL of a 5% solution of the test substance in an aqueous solution containing 5% Tween 80 (dosage sorresponds to 0 - 2975 mg/kg bw).

During a 14 day post-exposure period, mortalities and signs of toxicity were recorded. All mice that died and those that survived the observation period were subjected to autopsy, in an attempt to identify the target organs.

Signs of reaction to treatment included piloerection and lethargy (all animals), body tremors (>0.4 mL/kg bw) and excess salivation (0.64 and 1 mL/kg bw). Death occured between one and 24 hours after test substance administration. Autopsy revealed darkening of liver and kidneys and injection of the intestinal blood vessels. Recovery of survivors was complete within one day of treatment and no adverse findings were made during autopsy. Bodyweights were not affected by treatment, except in one female which survived treatment at 1 mL/kg bw, where reduced bodyweight gain was noted during the first week after exposure, but not during week 2 after dosage.

Based on the results, the LD50 was calculated to be 0.6 mL/kg bw (corresponding to 714 mg/kg bw).