Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 12 June to 27 June 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study in compliance with international recognized guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: crystalline powder
Details on test material:
Name : DICYCLOHEXYLPHTHALATE
Alternative names : DCHP
Dicyclo hexyl phthalate solid
Diciclo esil ftalato solido
Ftalato di cicloesile solido
Batch number : 031-12
Expiry date : 27 January 2013
Description (by the Sponsor) : White crystalline powder
Appearance at first use : White crystalline powder
Storage at RTC : Ambient condition
RTC reference number : 13219
Certificate of analysis : Supplied by the Sponsor and presented in Addendum I Test item characterisation : Not undertaken at the testing facility. The determination of the identity, strength, purity, composition, stability was the responsibility of the Sponsor.

Test animals

Species:
rat
Strain:
other: Sprague Dawley SD
Sex:
male/female
Details on test animals and environmental conditions:
Animal supply and acclimatisation

Species and strain: Rat, Sprague Dawley SD
Sex: Males and females (nulliparous and non-pregnant)
Age and weight range (at order): 6 to 8 weeks old, 176 to 200 grams
Supplier : Charles River Italia S.p.A., Calco (Lecco), Italy
Breeder : Charles River Italia S.p.A., Calco (Lecco), Italy
Date of arrival : 31 May 2012
Weight range at arrival: 197 to 203 grams
Acclimatisation period: At least 5 days
Veterinary health check: After arrival


Caging

No. of animals/cage: 5/cage (during acclimatisation ) and individually caged (during study)
Housing: Polycarbonate cages measuring 42.5x26.6x18 cm (during both acclimatisation and study periods) with stainless steel mesh lid and floor. Nesting material was provided inside suitable bedding bags.
Cage tray control: Daily inspected and changed as necessary (at least twice times/week)


Water and diet

Water : Drinking water supplied to each cage via a water bottle
Water supply : Ad libitum
Diet : 4 RF 18 (Mucedola S.r.l., Via G. Galilei, 4, 20019, Settimo Milanese (MI) Italy)
Diet supply : Ad libitum throughout the study


Housing conditions (parameters set)

Room lighting: : Artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours
Air changes: : Approximately 15 to 20 air changes per hour
Temperature range: 22°C ± 2°C
Relative humidity range: 55% ± 15%
Actual conditions were monitored, recorded and records retained. No relevant deviations occurred.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
corn oil
Details on dermal exposure:
A single group of 5 male and 5 female animals was dosed at a level of 2000 mg/kg.
Duration of exposure:
24 hours
Doses:
Frequency of treatment: Once only, on the day of dosing (Day 1).
Treatment area preparation: On the day before dosing (Day –1).
A single area was clipped free of hair (by an electric clipper equipped with a suitable blade) on the dorsal surfaces of the trunk of each animal (approximately 10% of body surface).
Care was taken to avoid damage to the skin.
Dose calculation: Aliquots were weighed according to the body weight of each animal measured prior to dosing.
Dosing procedure: An aliquot of the supplied test item was spread evenly over an area of approximately 10% of the body surface area. A patch of sur gical gauze covered by a strip of synthetic film was placed over the treated site and the whole assembly held in place by encirclin g the trunk of the animal with a length of elastic adhesive bandage, this forming a semi-occlusive barrier.
Exposure time : 24 hours
Washing procedure: After exposure, the adhesive bandage and gauze patch were removed. The treatment area was cleaned by gentle swabbing of the skin with cotton wool soaked with lukewarm water.
No. of animals per sex per dose:
5 animals/sex/group
Control animals:
no
Details on study design:
Dose level Animal number
mg/kg Males (even) Females (odd)

2000 2, 4, 6, 8, 10 1, 3, 5, 7, 9

Males and females were identified by even and odd numbers, respectively.
Statistics:
not applicable

Results and discussion

Preliminary study:
not applicable
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred in male or female animals after treatment during the observation period.
Clinical signs:
Clinical signs were limited to scab on the neck seen in one animal from Day 8 to Day 15 (not confirmed at post mortem examination). This sign is not considered toxicologically relevant.
Body weight:
The body weight changes were within the expected range for this species and age of animals at the end of the study.
Gross pathology:
At necropsy examination, no abnormalities were found in any animals, including the examination of the treatment site.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute toxicity of DICYCLOHEXYLPHTHALATE was investigated following dermal administration of a single dose to the rat at 2000 mg/kg.

No mortality occurred following dosing and no toxicologically relevant signs of toxicity were observed.

These results indicate that the test item, DICYCLOHEXYLPHTHALATE, has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg.
Executive summary:

The acute toxicity of DICYCLOHEXYLPHTHALATE was investigated following dermal administration of a single dose to the rat. A single dose of 2000 mg/kg was administered to a group of 5 male and 5 female animals for 24 hours. After 14 days all animals were killed and subjected to necropsy examination. No mortality occurred and no toxicologically relevant clinical signs were observed in male or female animals during the observation period.

The body weight changes observed during the study were within the expected range for this species and age of animals.

No abnormalities were found at necropsy in the animals at termination of the study. No abnormalities were observed at the treated site.

These results indicate that the test item, DICYCLOHEXYLPHTHALATE, has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg.