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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
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 402 and 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 402 (Acute Dermal Toxicity)
Deviations:
not specified
GLP compliance:
yes
Test type:
fixed dose procedure
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 CrI:CD.BR strain were obtained from Charles River (UK) Ltd, Margate. All animals were given a clinical inspection for ill health on arrival and a sample was weighed. An interval of approximately one week elapsed between arrival of the animals and study initiation. Healthy animals were arbitrarily allocated to the study groups at least one day prior to dosing. Animals placed on study were in a body weight range of 266 to 284 gm (males) and 232 to 248 g m (females) on Day -1. The male rats were approximately six to eight and females, nine to ten weeks old on Day 1 of the study. 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. Each batch of diet had been analysed for specific constituents. SQC(E) Rat and Mouse Maintenance Diet No 1, from Special Diets Services Ltd, Witham was freely available to the animals at all times. 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

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Electric clippers were used to remove all hair from an area of the dorsum measuring approximately 6 x 8 cm on the day before dosing. The dermal test site was an area approximately 5 x 5 cm (10% of the total body surface) on the clipped dorsum of the rat. The test article was spread as uniformly as possible across the dermal test site. A 5 x 5 cm dense gauze patch was placed over the treated skin and was retained in place by an elasticated, open-weave, adhesive bandage “Steroban” from Steroplast Ltd. Bredbury. This was wrapped securely around the torso of the animal to form a semi- occlusive dressing. The bandage and patch were removed 24 hours afier application.
Duration of exposure:
24 hr
Doses:
A single dermal application of the test sustance at 2000 mg/kg of body weight.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Individual dose volumes (mL) were calculated from the body weights of the rats on the morning of dosing (Day 1) and the test article density. 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. The rats were weighed on Day -l and Days 1, 8 and 15. The condition of each dermal test site was recorded following removal of the dressing on study Day 2. The rats were sacrificed 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 dermal test site, liver and kidneys.



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 chromodacryorrhoea for two males and two females on Day 2; the same two females also had soiled anogenital regions on Day 2.
Body weight:
All rats gained weight normally during the first and second weeks of the study.
Gross pathology:
Terminal examination revealed unilateral renal pelvic dilatation in one female and pale kidneys in a second female and pale areas on the spleen of one male. These findings are considered to be insignificant.
Other findings:
Dermal reactions were limited to observation of slight erythema on Day 2 and 3 in all alnimls. Two animals exhibited well defined erythema apparent shortly after removal of the semi- occlusive dressing. All reactions had resolved by Day 4.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Single (24 hour) semi occluded topical application of the test substance, 2,3-epoxypropyl neodecanoate at a dose level of 2000 mg/kg caused no death in a group of ten rats. No toxicologically significant clinical signs were observed and the slight erythematous reactions were transient resolving by Day four. The acute median lethal dermal dose level (LD50) for the test substance was found to exceed 2000 mg/kg body weight.
Executive summary:

The acute dermal toxicity of 2,3 -epoxypropyl neodecanoate to male and female rats was assessed in a GLP, O.E.C.D. Testing guideline 402 "Acute Dermal Toxicity" study. No mortalities or significant adverse clinical signs were observed. The slight erythematous reactions observed were transient resolving by Day four. The acute median lethal dermal dose level (LD50) for the test substance was found to exceed 2000 mg/kg body weight.