[No public or meaningful name is available]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From December 12, 2011 to July 26, 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was performed according to the OECD 423 Guideline, with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF guidelines 2000 (Japanese Ministry of Agriculture, Forestry and Fisheries)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Condensation products of cyclopentanone and pentaldehyde, fractionation pitch

Molecular formula:

not applicable, UVCB

IUPAC Name:

Condensation products of cyclopentanone and pentaldehyde, fractionation pitch

Details on test material:

- Physical state: Red-brownish liquid.
- Analytical purity: UVCB
- Expiration date of the lot/batch: 11 May 2013
- Stability under storage conditions: Stable.
- Storage condition of test material: At room temperature in the dark.
- Other:
Density: 0.95 g/cm3 (25°C)
pH: 8-10 at concentration of 5%

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 10 weeks old)
- Weight at study initiation: From 170 to 203 g bw. Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available ad libitum.
- Housing: Group housing of 3 animals per cage in labeled Makrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) 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: at least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0ºC
- Humidity (%): 40-70%
- Air changes (per hr): approximately 15 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From December 14, 2011 to January 3, 2012

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL.
- Amount of vehicle (if gavage): 8.39 g/kg.
- Justification for choice of vehicle: The vehicle was selected based on trial formulations and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw.

DOSAGE PREPARATION: The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle and density of the test substance.

Doses:

2000 mg/kg (10mL/kg) bw.

No. of animals per sex per dose:

6 females separated in two groups of three.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days.
- Frequency of observations and weighing:
Mortality/viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed:
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded:
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).

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Hunched posture and/or piloerection were noted in all animals on Day 1. One animal showed hunched posture on Day 2.

Gross pathology:

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

Any other information on results incl. tables

Table 1. MORTALITY DATA

TEST DAY	1	1	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15
HOURS AFTER TREATMENT	0	2	4
FEMALES 2000 mg/kg	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
FEMALES 2000 mg/kg	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-

 

 

Table 2. CLINICAL SIGNS

 

TEST DAY		1	1	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15
HOURS AFTER TREATMENT	Max Grade	0	2	4
FEMALES 2000 mg/kg
ANIMAL 1
Posture  Hunched posture	(1)	-	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Skin / fur Piloerection	(1)	-	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 2
Posture  Hunched posture	(1)	-	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Skin / fur Piloerection	(1)	-	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 3
Posture  Hunched posture	(1)	-	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Skin / fur Piloerection	(1)	-	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
FEMALES 2000 mg/kg
ANIMAL 4
Posture  Hunched posture	(1)	-	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 5
Posture  Hunched posture	(1)	-	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 6
Posture  Hunched posture	(1)	-	1	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-

-      = SIGN NOT OBSERVED / . = OBSERVATION NOT PERFORMED / + = ANIMAL DEAD

 

 

Table 3. BODY WEIGHTS (GRAM)

 

SEX/DOSE LEVEL	ANIMAL	DAY 1	DAY 8	DAY 15
FEMALES 2000 MG/KG	1	173	192	198
	2	188	206	220
	3	170	188	199
	MEAN	177	195	206
	ST. DEV.	10	9	12
	N	3	3	3
FEMALES 2000 MG/KG	4	193	226	228
	5	189	212	217
	6	203	227	237
	MEAN	195	222	227
	ST. DEV.	7	8	10
	N	3	3	3

 

 

Table 4. MACROSCOPIC FINDINGS

 

ANIMAL	ORGAN	FINDING	DAY OF DEATH
FEMALES 2000 mg/kg
1		No findings noted	Scheduled necropsy Day 15 after treatment
2		No findings noted	Scheduled necropsy Day 15 after treatment
3		No findings noted	Scheduled necropsy Day 15 after treatment
FEMALES 2000 mg/kg
4		No findings noted	Scheduled necropsy Day 15 after treatment
5		No findings noted	Scheduled necropsy Day 15 after treatment
6		No findings noted	Scheduled necropsy Day 15 after treatment

 

 

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 value of the test substance in Wistar rats was determined to be greater than 2000 mg/kg bw.

Executive summary:

Assessment of acute oral toxicity with Condensation products of cyclopentanone and pentaldehyde, fractionation pitch in the rat (Acute Toxic Class Method) was determinated according to the OECD 423 Guideline, with GLP.

The oral LD₅₀ value of the test substance in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results, Condensation products of cyclopentanone and pentaldehyde, fractionation pitch does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the:

- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011)

- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.