O,O-diethyl phosphorochloridothioate

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

other information

Study period:

1970

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

The subacute inhalation toxicity of 109 industrial chemicals

Author:

Gage, J. C.

Year:

1970

Bibliographic source:

Brit. J. industr. Med., 27, 1 - 18

Materials and methods

Test guideline

Qualifier:

no guideline followed

Deviations:

not applicable

Principles of method if other than guideline:

Inhalation toxicity of 109 substances, including O,O-diethyl phosphorochloridothionate, was studied by exposing rats to known concentrations in air for periods of up to 4 weeks (4-5 hours/day, 5 days/week). The air used for for the atmosphere was filtered, dried to a relative humidity of less than than 10% and supplied at a line pressure of 1 atm. The vapour concentration was generated by injecting a liquid at a known rate into a metered stream of air by means of a controlled fluid-feed atomizer. Concentration was calcuated based on the known rate of introduction of the substances into the air stream.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

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): O,O-diethyl phosphorochloridothionate
-Physical state: liquid

Test animals

Species:

rat

Strain:

other: Alderley Park, specific-pathogen-free

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 200 g on average
- Diet: ad libitum
- Water: ad libitum

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

clean air

Remarks on MMAD:

MMAD / GSD: not applicable

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

not applicable

Duration of treatment / exposure:

4-5 hours/day, 5 days/week over up to 4 weeks

Frequency of treatment:

5 days per week

Doses / concentrations

Remarks:

Doses / Concentrations:
5, 20 and 104 ppm
Basis:
nominal conc.

No. of animals per sex per dose:

4 males/dose

Control animals:

yes, concurrent no treatment

Details on study design:

- Dose selection rationale: Dosages were selected based on a preliminary study.

Positive control:

not applicable; 109 chemicals were tested in total in the investigation

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes; daily

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes; daily

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes; at the end of the study period

CLINICAL CHEMISTRY: No

URINALYSIS: Yes; samples were taken daily

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (lung, liver, kidneys, spleen, adrenals, heart, jejunum, ileum, thymus)

Other examinations:

No other examinations

Statistics:

not applicable

Results and discussion

Results of examinations

Details on results:

5 ppm (4 male rats treated on 14 days for 5 hours each):
slight nose irritation, respiratory difficulty, weight loss;
histology: slight thickening of alveolar walls of lungs

20 ppm (4 male rats treated on 14 days for 5 hours each):
severe nose irrritation, respiratory difficulty, weight loss;
histology: alveolar thickening and areas of collapse in lungs, degeneration of kidney tubular cortex

104 ppm (4 male rats treated on 2 days for 4 hours each):
nose and eye irritation, salivation, respiratory difficulty;
autopsy: lungs swollen, gut digested with gas
histology: lung emphysema

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

No other information.

Applicant's summary and conclusion

Conclusions:

O,O-dietyl phosphorochloridothionate is primarily an irritant, presumably due to the reactive chlorine atom.

Executive summary:

A subacute inhalation toxicity study was performed for 109 industrial chemicals, including O,O-diethyl phosphorochloridithionate.

Rats were exposed for 4 -5 hours per day for 2 (high dose) or 14 days (medium and low dose) towards 104, 20 or 5 ppm of O,O-diethyl phosphorochloridothionate. The test atmosphere was generated by injecting the liquid at a known rate into a metered stream of air. Rats were weighed and observed for condition and behaviour each day and urine was collected overnight for biochemical analysis. At the end of the study, blood was taken for haematological tests and gross examination of organs and histopathology were performed.

Results revealed that even at the lowest concentration, O,O-diethyl phosphorochloridothionate resulted in irritation of the nose and thickening of alveolar walls in the lungs. With rising concentration of the test substance, more signs of irritation and breathing difficulties were observed.

It is concluded that O,O-diethyl phosphorochloridothionate is an irritant at concentrations of 5 - 104 ppm (corresponding to 0.5 - 10.4 mg/mL) in air.