Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 7th June to 24 th 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 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class 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:
female
Details on test animals and environmental conditions:
Animal supply and acclimatisation

Species and strain: Rat, Sprague Dawley SD
Number and sex: Females (nulliparous and non-pregnant)
Age and weight range (at order): 6 to 7 weeks old, 150 to 174 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: 160 to 171 grams
Acclimatisation period: At least 5 days
Veterinary health check: After arrival

Caging

No. of animals/cage: 3 during the study; up to 5 during acclimatisation
Housing: polisulphone solid bottomed cages measuring 42.5x26.6x18.5 cm (during acclimatisation) and 59x38.5x20 (during the study) cm with nesting material
Cage tray control: Daily inspected and changed as necessary (at least 3 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 except for dosing procedure indicated in section 4.2.2


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 and recorded and records retained. No relevant deviations occurred.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The acute toxicity of DICYCLOHEXYLPHTHALATE was investigated following a single oral administration (10 mL/kg in corn oil) to the Sprague Dawley rat followed by a 14-day observation period.
Doses:
Frequency of treatment: Once only, on the day of dosing (Day 1).
Fasting procedure: Overnight prior to dosing (Day –1) up to 4 hours after dosing.
Dose calculation: Dose volume of 10 mL/kg of body weight for each animal.
Dosing method: By gavage, using a plastic feeding tube attached to a graded syringe.
No. of animals per sex per dose:
3 females per doses
Control animals:
no
Details on study design:
A first sub-group of 3 female animals was dosed at a level of 2000 mg/kg (Step 1). Mortality did not occur. A second sub-group, similarly composed, was then dosed at the same dose level (Step 2). No mortality occurred.
No further doses were investigated since the objective of the study had been achieved.
Statistics:
not applocable

Results and discussion

Preliminary study:
not applicable
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred in the 6 animals dosed in two sub-groups treated at 2000 mg/kg (Steps 1 and 2).
Clinical signs:
No clinical signs were recorded in the 6 animals dosed in two sub-groups treated at 2000 mg/kg (Steps 1 and 2).
Body weight:
Changes in body weight observed during the study were within the expected range for this strain and age of animals.
Gross pathology:
At necropsy examination, no abnormalities were observed in any animal of the study (Steps 1 and 2).

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 a single oral administration (10 mL/kg in corn oil) to the Sprague Dawley rat followed by a 14-day observation period.

No mortality occurred and no signs of toxicity were observed in the 6 animals following dosing at 2000 mg/kg.

These results indicate that the test item DICYCLOHEXYLPHTHALATE did not induce effects of toxicological relevance in the rat following oral administration of a single dose at a level of 2000 mg/kg. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg body weight.
Executive summary:

The acute toxicity of DICYCLOHEXYLPHTHALATE was investigated following a single oral administration to the Sprague Dawley rat. The test item (batch 031-12) was administered at 2000 mg/kg (dose volume of 10 mL/kg using corn oil as vehicle).

Animals were observed for a 14 day period, then subjected to necropsy examination.

A first sub-group of 3 female animals was initially dosed at 2000 mg/kg (Step 1). No mortality occurred and no clinical signs were observed.

A second sub-group of 3 female animals was then dosed at the same dose level (Step 2). No deaths occurred and no clinical signs were noted.

Body weight changes recorded during the study were within the expected range for this strain and age of animals.

No abnormalities were observed in any animal treated at necropsy examination performed at the end of the observation period.

These results indicate that the test item DICYCLOHEXYLPHTHALATE did not induce effects in the rat following oral administration of a single dose at a level of 2000 mg/kg. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg body weight.