Registration Dossier

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 the O.E.C.D. test guideline 402 with GLP compliance.

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:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: Colorless liquid at room temperature.
Details on test material:
As per IUCLID5 Sections 1.1. 1.2. 1.4. and 4.1. for 2,3-epoxypropyl neodecanoate, REACH Registration: 01-2119431597-33-0000.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Male and female rats of the CrI:CD.BR strain were obtained from Charles River (UK) Ltd, Margate. Animals were in a body weight range of 266 to 284 gm (males) and 232 to 248 gm (females) on Day -1. Based on information from the supplier the male rats were approximately six to eight and females, nine to ten weeks old on Day 1. The animals were housed up to five rats of the same sex in suspended stainless steel mesh cages.

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. SQC(E) Rat and Mouse Maintenance Diet No 1, from Special Diets Services Ltd, Witham was freely available to the animals at all times. Mains water was provided, ad libitum, via cage-mounted water bottles.

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. The test site of each rat was lightly brushed clean of any solid residues and swabbed with moist cotton wool before the animal was returned to it’s cage.

Duration of exposure:
24 hr
Doses:
2000 mg/kg of body weight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Following exposure to the test substance 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 condition of each dermal test site was recorded following removal of the dressing on Day 2. The time schedule for observation was similar to that for clinical observations from Day 2.

At study termination the rats were killed 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:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
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 placed on study 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 (Table 6).
Other findings:
Dermal reactions were limited to observation of slight erythema on Day 2 and 3 with isolated cases of 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:
The test substance had an acute rat dermal LD50 of > 2000 mg/kg/day with little evidence of dermal irritation at the test sites.
Executive summary:

The structural analog test substance, 2,3-epoxypropyl neodecanoate was accessed for acute dermal toxicity to the rat by an O.E.C.D. test guideline 402 study. The test substance had an acute rat dermal LD50 of > 2000 mg/kg/day with little evidence of dermal irritation at the test sites. It is anticipated that Neononanoic acid glycidyl ester will behave in a similar manner.