Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29 September to 23 October 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Proprietary GLP guideline-compliant study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Details on test material:
Polyol TD, batch no. 3977901, was described as a clear liquid, and stored at ambient temperature in the dark. Stability purity and identity were confirmed by the sponsor in a material safety data sheet (not available).

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
The animals were female Sprague-Dawley Crl:CD(SD) rats. The animals were supplied by Charles River UK Ltd, Kent, UK, and were nulliparous and non-pregnant. The rats were aged 7-8 weeks old on arrival, and weighed 181-186 g. They were allowed to acclimatise to the laboratory conditions for at least 7 days prior to dosing. The rats were randomly assigned to treatment groups on arrival, and individuals were identified by ear punches.
The animals were housed in groups of 3 in polycarbonate cages (dimensions 61 x 43.5 x 24 cm) with stainless steel grid tops and solid bottoms. Wood shavings (supplied by Datesand, Manchester, UK) were used as bedding and wooden chew sticks (produced by Estap OÜ, Harjumaa, Estonia) were placed in each cage. The bedding and chew sticks were considered not to contain any additional substances in sufficient concentration to have had any influence on the outcome of the study. Certificates of analysis are included in the study data. Each cage was supplied with a water bottle and food hopper.
The environmental conditions in the room were recorded every 15 min. From animal arrival to the end of the observation period the daily average environmental temperature was recorded at approximately 21°C on each day and the relative humidity was within an approximate range of 38% to 72%. A 12 h light/dark cycle was in operation (light hours 0700 to 1900 h) with a minimum of 15 air changes per hour.
Rat and Mouse No. 1 Maintenance Diet (Special Diets Services Limited, PO BOX 705, Witham, Essex, CM8 3AD, UK) and water taken from the public supply (Scottish Water, Edinburgh, Midlothian, UK) were available ad libitum, except for a period of overnight food deprivation before dosing. Ad libitum feeding was resumed as soon as practicable after dosing. Each batch of diet is routinely analysed by the supplier for various nutritional components and chemical and microbiological contaminants. The quality of water supply is stipulated by legislation in Water Quality, Scotland, Regulations 2001 and certificates of analysis for dissolved materials, heavy metals, pesticide residues, pH, nitrates and nitrites are periodically provided. These analyses are based on water samples taken from these laboratories. The results of diet and water analyses did not provide evidence of contamination and so the outcome of the study was not prejudiced. Certificates relevant to the study are retained in the data.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test substance was already in liquid form, therefore a vehicle was not used for dosing. The test substance was maintained on a magnetic stirring throughout dosing. The administered volume of test item was calculated on the basis of each individual animal’s body weight on the day of dosing. The dose volume was 1.87 ml/kg.
Doses:
2000 mg/kg
No. of animals per sex per dose:
6 females
Control animals:
no
Details on study design:
The initial dose level of 2000 mg/kg bw was selected by the Study Director for administration to 3 females (Group 1) following a review of the available test item information. This stated that the oral LD50 values for rats of 2 of the main components of the test item exceeded 2000 mg/kg. A dose volume of 1.87 mL/kg was used in order to account for the density of Polyol TD (1068 kg/m3). A second group (Group 2) also received 2000 mg/kg. Consequently, the study was completed with no further treatment being administered. The two groups were dosed at least 2 days apart.
The animals were observed for 14 days following dosing.
All animals were checked for viability early in the morning and again as late as possible on each day. All animals were examined for reaction to treatment on the day of dosing and once daily thereafter, until Day 15. The body weight of each individual animal was recorded before dosing on Day 1 and on Days 8 and 15.
All animals were subjected to a gross necropsy at the end of the observation period on Day 15. The necropsy consisted of an examination of the cranial, thoracic and abdominal organs and tissues in situ. Carcasses were discarded after this procedure. No lesions were recorded and therefore no tissues were collected.
Statistics:
No formal statistical analysis was conducted.

Results and discussion

Preliminary study:
A preliminary study was not conducted.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality at the limit dose
Mortality:
There were no unscheduled deaths during the observation period.
Clinical signs:
Adverse signs were restricted to salivation, which was observed in all animals at 5 min post dose. No other clinical signs were seen in any animal.
Body weight:
Body weight gain was considered to be acceptable for rats of this age and strain.
Gross pathology:
Macroscopic examination revealed no abnormalities.
Other findings:
No other findings were reported.

Any other information on results incl. tables

None.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study the median lethal oral dose level (the LD50) of Polyol TD in Sprague-Dawley rats was considered to exceed 2000 mg/kg. Applying the Globally Harmonised Classification System, Polyol TD can be classified as either Category 5 (LD50 >2000 to 5000 mg/kg) or as Unclassified (CLP).
Executive summary:

This study investigated the acute oral toxicity of the test item, Polyol TD, after a single administration to Sprague-Dawley rats. Polyol TD was administered, as supplied, to 2 groups of 3 female rats at a limit dose level of 2000 mg/kg bw. Animals were observed for signs of reaction to treatment at least 6 times on the day of dosing and once daily from Day 2 until the end of the observation period on Day 15. Body weights were recorded weekly and all animals were subjected to a gross necropsy. There were no unscheduled deaths during the observation period. Adverse signs were restricted to salivation at 5 min post dose, which was observed in all animals. Body weight gain was considered to be acceptable for rats of this age and strain and there were no macroscopic abnormalities recorded at necropsy.

Under the conditions of the study the median lethal oral dose level (the LD50) of Polyol TD in Sprague-Dawley rats was considered to exceed 2000 mg/kg bw. Applying the Globally Harmonised Classification System, Polyol TD can be classified as either Category 5 (LD50 >2000 to 5000 mg/kg) or as Unclassified (CLP).