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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:
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:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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:
Clinical signs of toxicity were non-specific and included hypokinesia, piloerection, soiled coat, ataxia, dacryorrhoea, chromodacryorrhoea, rhinorrhoea and salivation.
Body weight:
Body weight gains were in an acceptable range
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.