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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 in accordance with the Principles of Good Laboratory Practices (GLP) and was similar to OECD 402, except that it included two dose levels instead of three.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Two dose levels rather than three
Principles of method if other than guideline:
Determination of the LD50
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Liquid as received
Details on test material:
- Name of test material (as cited in study report): 1,4-CHDM DGE (ECLIPSE)
- Physical state: liquid
- Analytical purity: 78.17% 1,4-cyclohexanedimethanol diglycidyl ether
- Composition of test material, percentage of components:
- Lot/batch No.: 2013000643-51-P8

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sainath Agenesis, Hyderabad, India
- Age at study initiation: 3.5 to 4.5 months
- Weight at study initiation: 2015.6-2130g
- Fasting period before study: none
- Housing: individually in rabbit cages (approx. size: L 61 x B 46 x H 43 cm)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6to 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 22 °C
- Humidity (%): 63 to 65% relative humidity
- Air changes (per hr): 16 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial light and 12 hours darkness, light hours being 06:00-18:00h

IN-LIFE DATES: From: To: March 4, 2014 to March 20, 2014

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Based on the initial animal body weight and dose level, a calculated dose volume (1.87 to 3.95 mL) of 1,4-CHDM DGE (ECLIPSE) (undiluted, as received) was applied over the clipped area (approximately 12 × 15 cm area, corresponding to 10% of the body surface). The test item was held in contact with the skin using semi-occlusive dressing (porous gauze dressing which was not more than 8 ply) and a non-irritating tape (Medi tape 330 hypo-allergenic surgical tape) throughout the 24 h exposure period to prevent any loss of the test item and also to ensure that the rabbits did not lick or ingest it. At the end of the exposure period (24 hours), the residual test item was removed using clean towels soaked in distilled water.
Duration of exposure:
24 hours
Doses:
1000 mg/kg body weight or 2000 mg/kg body weight of 1,4-CHDM DGE (ECLIPSE)
No. of animals per sex per dose:
two groups of 5 females per dose level
Control animals:
no
Details on study design:
The rabbits were observed for signs of toxicity and mortality at 1, 2, 3 and 5 h post-dermal application on the day of dosing (day 1). Subsequently, the rabbits were observed twice a day for morbidity and mortality for a period of 14 days following dermal application. The clinical signs were recorded once a day. Individual body weights were recorded prior to dermal application on day 1 and on days 8 and 15 post-application.

At the end of observation period, all rabbits were euthanised by intravenous administration of thiopentone sodium (dose: 100 to 110 mg/kg body weight; Mfg. by: Neon Laboratories Limited, Mumbai; Lot N°: 173194). They were subjected to a gross pathological examination consisting of an external examination and opening of abdominal and thoracic cavities. Abnormalities, if any, were recorded.
Statistics:
None

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality observed during the study.
Clinical signs:
Erythema and scale formation were observed in all rabbits treated with 1,4-CHDM DGE (ECLIPSE) at various time points during the study. All animals were active and healthy during the study.
Body weight:
All animals gained body weight by the end of the study.
Gross pathology:
External examination of the rabbits at the time of sacrifice revealed scale formation at the site of test item application on rabbits N° 6, 7, 9 and 10. Visceral examination of terminally sacrificed animals did not reveal any lesions of pathological significance.
Other findings:
The acute dermal median lethal dose (LD50) of 1,4-CHDM DGE (ECLIPSE) in female rabbits was found to be greater than 2000 mg/kg body weight.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of 1,4-CHDM DGE (ECLIPSE) in female rabbits was found to
be greater than 2000 mg/kg body weight.
Executive summary:

An acute dermal toxicity study was conducted in two groups of 5 female New Zealand White rabbits (3.5 to 4.5 months old). The rabbits were dermally exposed to 1,4-CHDM DGE (ECLIPSE) at a dose of 1000 mg/kg body weight or 2000 mg/kg body weight, respectively. Based on the initial animal body weight and dose level, a calculated dose quantity of (1.87 to 3.95 mL) of 1,4-CHDM

DGE (ECLIPSE) (undiluted, as received) was applied over the clipped area (approximately 12 × 15 cm area, corresponding to 10% of the body surface). The test item was held in contact with the skin using porous gauze dressing and a non-irritating tape throughout the 24-hour exposure period. Residual test item was removed at the end of the exposure period using clean towels soaked in distilled water. Observations during the 14-day observation period included daily clinical signs and weekly body weight recordings. Necropsy

examination was performed on all animals. There was no mortality observed during the study. Erythema and scale formation were observed in all rabbits treated with 1,4-CHDM DGE (ECLIPSE) at various time points during the study. All animals were active

and healthy during the study. All animals gained body weight by the end of the study. External examination of the rabbits at the time of sacrifice revealed scale formation at the site of test item application on rabbits N° 6, 7, 9 and 10. Visceral examination of terminally sacrificed animals did not reveal any lesions of pathological significance.

The acute dermal median lethal dose (LD50) of 1,4-CHDM DGE (ECLIPSE) in female rabbits was found to be greater than 2000 mg/kg body weight.