Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 1981- 04 Mar 1982 (report issue date)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was not performed to modern international (OECD, EC, EPA) test guidelines and no indication of GLP compliance has been made; however the species, housing conditions and route of administration of the test substance were all appropriate to the endpoint examined, and the level of detail in the report is judged sufficient to consider the results reliable.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
Remarks:
: older proprietary study, pre-dates GLP
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Polyol PX
IUPAC Name:
Polyol PX
Test material form:
liquid: viscous
Details on test material:
- Name of test material (as cited in study report): Polyol PX- Substance type:
- Physical state: Yellow/brown viscous liquid.
- Analytical purity: Not reported.
- Impurities (identity and concentrations): Not reported.
- Composition of test material, percentage of components: Not reported.
- Isomers composition: Not reported.
- Purity test date: Not reported.
- Lot/batch No.: Not reported.
- Expiration date of the lot/batch: Not reported.
- Stability under test conditions: Not reported.
- Storage condition of test material: Not reported.
- Other:

Test animals

Species:
rat
Strain:
other: AlPk
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Animal Breeding Unit, Imperial Chemical Industries PLC, Pharmaceuticals Division, Alderley Park, Macclesfield, Cheshire.
- Age at study initiation: Not specified.
- Weight at study initiation: 120 - 240 g
- Fasting period before study: 16 - 20 hours
- Housing: The rats (a maximum of five per cage) were housed in suspended stainless steel cages (370mm length x 320mm width x 200mm
height). The floor and back of each cage were 12mm square stainless steel mesh; the sides were solid stainless steel and the front was polycarbonate (MAKROLON).
- Diet (e.g. ad libitum): The animals were fed ad libitum with BP PCD pellets.
- Water (e.g. ad libitum): The animals were allowed tap water ad libitum.
- Acclimation period: Not documented


ENVIRONMENTAL CONDITIONS
- Temperature (°C): maintained between 19 - 23ºC
- Humidity (%): approximately 50 - 60%
- Air changes (per hr): 24
- Photoperiod (hrs dark / hrs light): 12 hours light in each 24 hour period.


IN-LIFE DATES: From: Not reported.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 5, 10, 30, and 50% (w/v) aqueous solutions.
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: Not specified
- Lot/batch no. (if required): Not specified
- Purity: Not specified


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg


DOSAGE PREPARATION (if unusual): Not indicated.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: N/A
Doses:
500, 1000, 3000, and 5000 mg/kg
No. of animals per sex per dose:
Two animals per sex per dose level were used.
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days (until day 15 of test)
- Frequency of observations and weighing: Animals were observed for signs of systemic toxicity at least once between 30 and 90 minutes and again
after 4 and 6 hours and daily thereafter up to day 8. If signs of toxicity were seen on day 8 observations were made on day 11, otherwise no further
observations were necessary until day 15.
- Necropsy of survivors performed: Not reported
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: Not reported.
Statistics:
Not reported.

Results and discussion

Preliminary study:
No signs of systemic toxicity were observed in any animal at any of the dose levels
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality at any dose level
Mortality:
No animal deaths reported at any dose level.
Clinical signs:
other: No signs of systemic toxicity were observed in any animal.
Gross pathology:
Not reported.
Other findings:
Not reported.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Polyol PX was determined to have an LD50 value to male and female rats in excess of 5000 mg/kg bw
Executive summary:

A study was conducted in 1981 at the laboratories of Imperial Chemical Industries PLC, Macclesfield, Cheshire, UK, to determine the acute toxicity of the test substance Polyol PX when a single dose was administered by oral gavage to SPF albino rats. The study


was not conducted to any OECD Test Guideline, (however it is equivalent to a OECD 401 design) and no claim of GLP compliance was made. Groups of two male and two female rats were used in the range of dose levels, 500, 1000, 3000 and 5000 mg/kg bw. The animals were observed on the day of dosing at least once between 30 and 90 minutes and again between 4 and 6 hours post dose, then daily thereafter up to Day 8. No signs of systemic toxicity were observed at any time in any animal at any of the dose levels. Therefore, it was concluded that Polyol PX has an LD50 value in excess of 5000 mg/kg bw in male and female rats.