Ethyl 3-[[bis(1-methylethoxy)phosphinothioyl]thio]propionate

Neurotoxicity

Administrative data

Endpoint:

neurotoxicity: acute oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From May 28, 1982 to June 8, 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non GLP (performed in 1982), no positive control but well documented

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Principles of method if other than guideline:

A single oral administration (by gavage) of the test material at doses of 0, 500 and 2500 mg/kg was administered to male and female rats.
Laboratory investigations were carried out in all rats of each sex and each group at 4 and 24 hours after the administration to determine cholinesterase inhibitory activity of the test material.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl 3-[[bis(1-methylethoxy)phosphinothioyl]thio]propionate

EC Number:

275-965-6

EC Name:

Ethyl 3-[[bis(1-methylethoxy)phosphinothioyl]thio]propionate

Cas Number:

71735-74-5

Molecular formula:

C11H23O4PS2

IUPAC Name:

ethyl 3-{[bis(propan-2-yloxy)(sulfanylidene)-λ⁵-phosphanyl]sulfanyl}propanoate

Details on test material:

- Name of test material (as cited in study report): TK 11950
- Substance type: Organic
- Physical state: Liquid
- Analytical purity: not determined
- Lot/batch No.: 013 IV
- Expiration date of the lot/batch: December 1982

Test animals

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animal Production Stein, CIBA-GEIGY AG
- Age at study initiation: approximately 7-8 weeks
- Weight at study initiation: males: 246 +/- 10 g, females: 207 +/- 8 g
- Fasting period before study:
- Housing: by number of cage, in Macrolon cages type 2 with standardised granulated soft wood bedding (Société Parisienne des sciures Pantin)
- Diet (e.g. ad libitum): Pelleted, certified standard diet Nafag No. 890 Tox, ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: 11 days (from May 28, 1982 to June 7, 1982)
Neither insecticides not chemicals were applied in the animal room with the exception of disinfectant: Fungitex SB (Prod. No. 30071, CIBA-GEIGY AG)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2°C
- Humidity (%): 55+/-10%
- Air changes (per hr): 15-17 air changes/hour
- Photoperiod (hrs dark / hrs light): 12h dark / 12h light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
The solutions were freshly prepared immediately prior to the dosing of the animals and administered within 2 hours.
Vehicle: CMC


VEHICLE
- Concentration in vehicle: 0, 500 and 2500 mg test material/kg
- Amount of vehicle (if gavage): 10 mL/kg

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

Laboratory investigations carried out at 4 and 24 hours after the administration

Frequency of treatment:

Single dose

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

500 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

2 500 mg/kg bw/day (nominal)

No. of animals per sex per dose:

PRETEST:
for control: 4 (2 males and 2 females)
for test: 4 (2 males and 2 females)

MAIN TEST:
for control: 8 (4 males and 4 females)
for test: 8 (4 males and 4 females)

Control animals:

yes, concurrent vehicle

Examinations

Observations and clinical examinations performed and frequency:

The activity of acetylcholinesterase (in plams and red blood cells) was checked by colorimetry (modified acetylthiocholine DTNB method. Voss G. et al. Toxicol. Appl. Pharmacol. 16, 764 (1970))

The blood chemistry was also checked
HYLMD I (Normal) Travenol
HYLAND I I (Abnormal) Travenol
MCNI-TRCL I (Normal) Merz + Dade
MCNI-TOCL I I (Abnormal) Merz + Dade
ROCHE "N" NORMAL Roche Diagnostica

Results and discussion

Results of examinations

Details on results:

A single oral administration of the test article to male and female rats at a dose of 500 mg/kg had no inhibitory effect on plasma and RBC cholinesterase activity.
At 2500 mg/kg a slight inhibition of the plasmachollinesterase activity was recorded.
One of the males in the contrl group died during the blood withdrawal procedure.

Applicant's summary and conclusion

Conclusions:

A single oral administration of test material to male and female rats at a dose of 500 mg/kg had no inhibitory effect on plasma and RBC cholinesterase activity. A single oral administration of test material to male and female rats at a dose of 2500 mg/kg induced a slight inhibition of the plasma cholinesterase activity.