Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 22 September 2015 to 13 November 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Reddish solid below 25°C / liquid above 25°C
Details on test material:
- State of aggregation: N/A
- Particle size distribution: N/A
- Mass median aerodynamic diameter (MMAD): N/A
- Geometric standard deviation (GSD): N/A
- Shape of particles: N/A
- Surface area of particles: N/A
- Crystal structure: N/A
- Coating: N/A
- Surface properties: N/A
- Density: 1.06 g/cm3
- Moisture content: N/A
- Residual solvent: N/A
- Activation: N/A
- Stabilisation: N/A
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Batch No.of test material: MR92143651
- Expiration date of the lot/batch: 01 January 2017
- Purity: 86.4% (No correction was made for purity of the test substance)
- Purity test date: 18 June 2015

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
- Stability under test conditions: Yes, maximum temperature: 50°C, maximum duration: unknown (until liquefaction).
- Solubility and stability of the test substance in the solvent/vehicle: no information available
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: N/A

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Prior to weighing, the test substance was heated in a water bath with a maximum temperature of 43.9ºC for 49 minutes. In order to obtain homogeneity, the formulation was heated in a water bath with a maximum temperature of 40.6ºC for 27 minutes. The formulation was allowed to cool down to a temperature of maximally 40ºC prior to dosing.
- Preliminary purification step (if any): N/A
- Final dilution of a dissolved solid, stock liquid or gel:
- Final preparation of a solid:

FORM AS APPLIED IN THE TEST (if different from that of starting material): N/A

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 10 weeks old
- Weight at study initiation: males: 256 to 280g ; females: 192 to 211g
- Fasting period before study: no
- Housing:Individually housed in labeled Makrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: Acclimatization period was at least 5 days before start of treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): 40 to 70%
- Air changes (per hr): at least 10 air changes/hour
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle

IN-LIFE DATES: From: 22 September 2015 To: 06 October 2015

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
polyethylene glycol
Remarks:
PEG 400
Details on dermal exposure:
TEST SITE
- Area of exposure: area of approximately 5x7 cm on the back of each animal (clipped)
- % coverage: approx. 10% of the total body surface i.e. approx. 25 cm² for males and 18 cm² for females.
- Type of wrap if used: The formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes using tap water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mL/kg body weight
- Concentration (if solution): 2000 mg/kg body weight
- Constant volume or concentration used: yes
- For solids, paste formed: N/A
Duration of exposure:
24 hours
Doses:
2000 mg/kg (10 mL/kg) body weight
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The time of onset, degree and duration were
recorded and the symptoms graded according to fixed scales: Maximum grade 4: grading slight (1) to very severe (4) Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).

- Necropsy of survivors performed: yes
Statistics:
Not performed

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
No mortality occurred.
Clinical signs:
Lethargy, hunched posture, shallow respiration, piloerection, ptosis, and/or chromodacryorrhoea were noted for the animals between Days 1 and 4.
General erythema, erythema maculate, scales, scabs and/or fissures were seen in the treated skin area and/or left flank of the animals during the observation period.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 value of 1-Phenyldecane-1,3-dione in Wistar rats was established to exceed 2000 mg/kg body weight.
Based on these results, 1-Phenyldecane-1,3-dione does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the GHS and CLP regulations.
Executive summary:

The objective of this study was to evaluate the potential toxicity of the test substance 1- phenyldecane-1,3-dione, following a single dermal application to rats.

The study was carried out according to OECD Test guideline No.402 and in compliance with the Good Laboratory Practices.

1-Phenyldecane-1,3-dione was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred.

Lethargy, hunched posture, shallow respiration, piloerection, ptosis, and/or chromodacryorrhoea were noted for the animals between Days 1 and 4.

General erythema, erythema maculate, scales, scabs and/or fissures were seen in the treated skinarea and/or left flank of the animals during the observation period.

The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.

No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of 1-Phenyldecane-1,3-dione in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results, 1-Phenyldecane-1,3-dione does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and Regulation (EC) No 1272/2008.