Registration Dossier

Administrative data

Description of key information

Oral: LD50: > 2,000 mg/kg for rat (limit test, OECD 401 and GLPs compliant)

Dermal: LD50: > 2,000 mg/kg for rat (limit test, OECD 402 and GLPs compliant)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 25-JAN-1995 (animal arrived) to 17-FEB-1995 (observation period completed)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
other: CD strain (remote Sprague-Dawley origin)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River
- Age at study initiation: approximately five weeks old
- Weight at study initiation: 122-146 g for males (body weight at the day prior to dosing) and 130-146 g for females (body weight at the day prior to dosing)
- Fasting period before study: yes
- Housing: five animals (same sex/cage) were housed in stainless grid cages (R.S. Biotech, England) where the grid floors ensured rapid removal of waste material to undertrays which were cleaned out as necessary. The cages were suspended in mobile stainless steel racks.
- Diet (e.g. ad libitum): complete pelleted rodent diet (RMI(E)SQC, Special Diets Services Limited, England), ad libitum. Batch analytical data were supplied by the manufacter.
- Water (e.g. ad libitum): tap water from the public supply (Department of the Environmental regulations, England). Analytical certificates were routinely received from the suplier (Suffolk Water Company).
- Acclimation period: at least five days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 40-70 %
- Air changes (per hr): at least 10 complete air changes/hour without re-circulation.
- Photoperiod (hrs dark / hrs light): 12 hours/day


IN-LIFE DATES: From: 3-FEB-1995 To: 17-FEB-1995
Route of administration:
oral: gavage
Vehicle:
maize oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: appropriate concentration to permit administration at a constant volume-dosage of 10 mL/ kg b.w. (no other details)
- Amount of vehicle (if gavage): no data
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data
- Purity: no data


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg b.w.


DOSAGE PREPARATION (if unusual): /


Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
5 rats/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (animal sacrifice on day 15)
- Frequency of observations and weighing: the day before dosing, day 1, 8 and 15
- Necropsy of survivors performed: yes (larger organs were sectioned and the gastro-intestinal tract was opened at intervals for examination of the mucosal surfaces. No tissues were retained in fixative.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: three separate recordings of signs during the first hour after dosing and 2 further recordings during the remainder of day 1. From day 2 onwards, the animals were inspected twice daily and recordings were made once daily.
Statistics:
No data
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study.
Clinical signs:
No clinical signs were observed during the 14-day observation period.
Body weight:
All animals achieved anticipated body weight gains.
Gross pathology:
Necropsy conduted on day 15 showed no significant abnormalities.
Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 value of Rhodiastab X2 in SD 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 oral toxicity according to the GHS and CLP regulations.
Executive summary:

Rhodiastab X2 (former commercial name of the registered substance) has been tested for acute oral toxicity in CD rats according to OECD guidelines 401 and Directive 92/69/EEC method B1, and in compliance with Good Laboratory Practices. The test substance was administered at a dosage of 2000 mg/kg b.w. to a group of 5 males and 5 females, at a constant volume of 10 mL/kg in maize oil. Examinations for mortality, body weight gain and abnormal clinical signs were performed during the 14-day study period.

No death and no clinical signs were observed during the study. The general behaviour and body weight gain were not affected by treatment. At necropsy, a macroscopic examination revealed no abnormality .

Under the conditions of the test, as the LD50 is higher than 2000 mg/kg b.w., Rhodiastab X2 is not classified according to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and Regulation (EC) No 1272/2008 (CLP).

.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Males and females treated on 18-FEB-92 and 20-FEB-92, respectively
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Study performed according to basic scientific principles acceptable for assessment although information is missing on test conditions (husbandry and purity of test substance).
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
Principles of method if other than guideline:
OECD guidelines were not claimed in the report however the method principles were similar to OECD 401 guidelines.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Iffa Crédo, L'Arbresle, France
- Age at study initiation: no data
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing:no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum):no data
- Acclimation period:no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data


IN-LIFE DATES: no data
Route of administration:
oral: gavage
Vehicle:
paraffin oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle (if gavage):no data
- Justification for choice of vehicle:no data
- Lot/batch no. (if required): no data
- Purity: no data


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg


DOSAGE PREPARATION (if unusual):


CLASS METHOD (if applicable): /
- Rationale for the selection of the starting dose: no data
Doses:
5000 mg/kg b.w.
No. of animals per sex per dose:
3/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: observations daily and weighting on the first day and the last day of study
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: no data
Statistics:
No data
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
other: No mortality so LD0 ≥5000 mg/kg b.w.
Mortality:
No mortality was observed.
Clinical signs:
Hypokinesia and piloerection were observed in two females after 4 and 24 hours. No clinical signs were observed in the other female and in males.

Body weight:
Body weight gain was normal.

Gross pathology:
No data
Other findings:
No data
Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 value of Rhodiastab OBM-B in SD rats was established to exceed 5000 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 oral toxicity according to the GHS and CLP regulations.
Executive summary:

Rhodiastab OBM-B (former commercial name of the registered substance) was tested for acute oral toxicity in SD rats. The test substance was administered at a dosage of 5000 mg/kg b.w. to a group of 3 males and 3 females, at a constant volume of 10 mL/kg in paraffin oil. Examinations for mortality, body weight gain and abnormal clinical signs were performed during the 7 days study period.

No death occured. No sign of reaction were observed in males during the study. Hypokinesia and piloerection were observed in 2 females, 4 and 24 hours after the treatment. No other signs were observed in the other female and in males. Body weight gain was not affected by treatment.

Under the conditions of the test, as the LD50 is higher than 5000 mg/kg b.w. Rhodiastab OBM-B is not classified according to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and Regulation (EC) No 1272/2008 (CLP).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
Study fully reliable (GLPs and OECD 401 compliant).

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
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
Reference:
Composition 0
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 information:
Composition 1
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
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
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
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.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
Study fully reliable (GLP and OECD 402 compliant).

Additional information

One Klimisch score 1 and one Klimish score 2 studies are available for the oral route and were used as key and supporting study, respectively:

In the key study (Pharmaco, 1995), perfomed according to OECD Test guideline No. 401

and in compliance with GLPs, Rhodiastab X2 (former commercial name of the registered substance) was administered at a dosage of 2000 mg/kg b.w. to a group of 5 male and 5 female rats, at a constant volume of 10 mL/kg in maize oil. No death and no clinical signs were observed during the study up to the end of the 14 -day observation period. The general behaviour and body weight gain were not affected by treatment. At necropsy, a macroscopic examination revealed no abnormality . Based on these results and under the conditions of the test, the LD50 was established to exceed 2000 mg/kg body weight.

In the supporting study (CIT, 1992), Rhodiastab OBM-B (former commercial name of the registered substance) was administered at a dosage of 5000 mg/kg b.w. to a group of 3 male and 3 female SD rats, at a constant volume of 10 mL/kg in paraffin oil. No death occured. No sign of reaction were observed in males during the study. Hypokinesia and piloerection were observed in 2 females, 4 and 24 hours after the treatment. No other signs were observed in the other female and in males up to the end of th 7 -day observation period. Body weight gain was not affected by treatment. Based on theses results and under the conditions of the test, the LD50 was established to exceed 5000 mg/kg body weight.

One Klimisch score 1 study is available for dermal route and was used as a key study:

In this study, carried out according to OECD Test guideline No.402 and in compliance with the Good Laboratory Practices, the test substance 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.

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 14 -day 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.

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

Justification for classification or non-classification

Under the conditions of these studies, the acute oral and dermal LD50 value of the registered substance was found to be above 2000 mg/kg bw in male and female rats.

According to the GHS criteria, 1 -phenyldecane-1,3 -dione can be ranked as “Unclassified” for acute oral and dermal exposure as no treatment-related mortality were reported at the tested dose of 2000 mg/kg bw.