Tris[2-chloro-1-(chloromethyl)ethyl] phosphate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study generated according to internationally accepted testing guidelines and according to GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): Tolgard TDCP MK1
- Physical state: colourless liquid
- Purity: not stated

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) limited.
- Age at study initiation: 6 -8 weeks
- Weight at study initiation: 136 - 197 g
- Fasting period before study: 19h prior to the study and 3-4h post dosing.
- Housing: Rats were housed by sex in polypropylene cages with mesh floors suspended over absorbent paper lined trays with a maximum of 6 animals per cage for the dose ranging study and 5 animals per cage for the main study.
- Diet: Rat and mouse maintenance diet (Special diets services)
- Water: ad libitum
- Acclimation period: At least 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21
- Humidity (%): 47%
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12h/12h

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Doses:

1000, 2000, 3000, 4000 and 5000mg/kg (Range finding study);
2000mg/kg (Main Study)

No. of animals per sex per dose:

2 males and 2 females at each of 5 dose levels (Range finding study);
5 Males and 5 Females (Main Study)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 17 days
- Frequency of observations and weighing: on the day of dosing and once daily for 17 days following dosing, animals were weighed immediately prior to dosing , 7 days after dosing and at sacrifice.
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight, post-mortem examination.

Results and discussion

Preliminary study:

In the dose ranging study both pairs of males and females died at dosing levels 3000, 4000 and 5000 mg/kg, death was 1-2 days after dosing.
Clinical signs in survivors, noted 1-5 days after dosing included coma, piloerection, soiled coat, clonic convulsions, dacryorrhoea, chromodacryorrhea, rhinorrhoea and excess salivation.
No abnormalities were noted at post mortem examination.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Two female animals died on day 4.

Clinical signs:

other: Clinical signs of toxicity were non-specific and included hypokinesia, piloerection, soiled coat, ataxia, dacryorrhoea, chromodacryorrhoea, rhinorrhoea and salivation.

Gross pathology:

No abnormalities were detected at post-mortem examination.

Applicant's summary and conclusion

Interpretation of results:

other: Low acute toxicity

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 > 2000mg/kg under these experimental conditions.