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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to an O.E.C.D. Testing Guideline under the GLP regulations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Liquid at room temperature.
Details on test material:
As per IUCLID5 Sections 1.1, 1.2. and 1.4.

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
Male or nulliparous, non-pregnant female rats of the Crl:CD.BR strain were obtained from Charles River (UK) Ltd, Margate. Healthy animals were arbitrarily allocated to the study groups one day prior to dosing. Animals placed on study were in a body weight range of 219 to 248 gm (males) and 188
to 199 gm (females) on Day -1 and were six to eight weeks old on Study Day 1. Up to five rats of the same sex were accommodated in suspended stainless steel mesh cages (dimensions 55 x 34 x 20 cm). The cages were suspended over cardboard lined trays for collection of excreta. The liners were replaced at least twice weekly.

SQC(E) Rat and Mouse Maintenance Diet No 1, from Special Diets Services Ltd, Witham was freely available to the animals at all times except for a period of overnight fasting prior to dosing which continued until approximately three hours after dosing. Each batch of diet had been analysed for specific constituents. Mains water was provided, ad libitum, via cage-mounted water bottles. The water had been periodically analysed for specific contaminants. No contaminants were present in diet or water at levels which might interfere with achieving the objective of the study.

The animal rooms were designed to permit at least 10 air changes per hour and to maintain environmental conditions of 19 to 25°C and 40 to 80% Relative Humidity. Recordings of maximum and minimum temperature and humidity were made twice daily, any minor deviations from the expected ranges were noted in the study data. The rooms were illuminated by fluorescent strip-lights for twelve hours daily (typically 0600 to 1800 hours).




Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
Individual dose volumes (mL) were calculated from the fasted body weights of the rats on the morning of dosing (Day 1) and the selected dose volume (10 mL/kg). Each rat was dosed once on Day 1, by passing the tip of a catheter along the oesophagus and instilling the test article into the gastric lumen. Doses were administered using plastic syringes and rubber catheters.
Doses:
The limit dose level of 2000 mg/kg body weight.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Treated rats were observed closely for clinical signs of reaction to treatment. Clinical signs were recorded frequently on Day 1 and regularly for the remainder of the study, (the minimum schedule being at least once within half an hour of dosing and four times within the first four hours following administration, twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period). Individual records of clinical signs were maintained for each treated rat. Rats were weighed on Day -l and Days 1, 8 and 15.

The rats were terminated by intraperitoneal injection of sodium pentobarbitone on Day 15. After exsanguination a full macroscopic necropsy was performed and all lesions recorded. The necropsy procedure included inspection of external surfaces and orifices, all viscera and tissue within the abdominal, thoracic and cranial cavities, free-hand sectioning of the liver and kidneys and examination of representative sections of mucosal surfaces of the stomach, small and large intestines.



Statistics:
No data

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
None
Clinical signs:
Clinical signs of reaction to treatment included pilo-erection. seen in one female approximately four hours after dosing. Anogenital soiling, was apparent for one male and two females on Day 2. A second male and all females had stained fur on Day 2. These signs are common following administration of an oil based formulation and were not considered to he toxicologically significant.
Body weight:
All rats gained weight normally during the first and second weeks of the observation period.
Gross pathology:
No macroscopic changes were apparent for the rats sacrificed on Study Day 15.
Other findings:
No other findings.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Single oral administration of 2,3-epoxypropyl neodecanoate at a dose level of 2000 mg/kg caused no death
in a group of ten fasted rats. no significant treatment related clinical signs were observed. The acute median lethal oral dose level (LD50) was found to exceed 2000 mg/kg body weight.
Executive summary:

The acute oral toxicity of 2,3 -epoxypropyl neodecanoate was evaluated in an O.E.C.D. Testing Guideline 420 acute rat study under the GLP regulations. No adverse findings atributed to test substance administration were observed in this study. Single oral administration of 2,3-epoxypropyl neodecanoate at a dose level of 2000 mg/kg caused no death in a group of ten fasted rats. The acute median lethal oral dose level (LD50) was found to exceed 2000 mg/kg body weight.