Reaction products of n-octanol and acrylic acid, first distillation pitch

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From December 14, 2011 to January 3, 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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 8147

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:

Reaction products of n-octanol and acrylic acid, first distillation pitch

EC Number:

938-925-5

Molecular formula:

not applicable, UVCB

IUPAC Name:

Reaction products of n-octanol and acrylic acid, first distillation pitch

Details on test material:

- Physical state: Light yellow viscous liquid
- Analytical purity: UVCB
- Expiration date of the lot/batch: May 11, 2013
- Stability under test conditions: Stable
- Storage condition of test material: At room temperature in the dark

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: approx. 10-11 weeks old.
- Weight at study initiation: Given in the table
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance.
- 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 cageenrichment (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): ad libitum
- Acclimation period: Acclimatization period was at least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 +/- 3.0ºC (actual range: 19.9 - 21.7ºC)
- Humidity (%): 40-70% (actual range: 42 - 62%)
- Air changes (per hr): 15 approx.
- Photoperiod (hrs dark / hrs light):12 hours artificial fluorescent light and 12 hours darkness per day.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.081 mL/kg body weight

Doses:

2000 mg/kg (2.081 mL/kg) body weight

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: observations once daily and weighing on 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 to very severe. Maximum grade 3: grading slight to severe. Maximum grade 1: presence is scored.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured.

Clinical signs:

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

Other findings:

- Other observations:
Macroscopic findings: Two animals showed reddish discoloration of the thymus. No other 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
Males 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
MALES 2000 mg/kg
ANIMAL 1
Posture  Hunched posture	(1)	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Gait / motility Uncoordinated movements	(3)	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 2
Posture  Hunched posture	(1)	1	1	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-
Gait / motility Uncoordinated movements	(3)	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 3
Posture  Hunched posture	(1)	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Gait / motility Uncoordinated movements	(3)	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
FEMALES 2000 mg/kg
ANIMAL 4
Posture  Hunched posture	(1)	1	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 5
Posture  Hunched posture	(1)	1	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Skin/fur Piloerection	(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
MALES 2000 mg/kg	1	189	209	210
	2	174	197	210
	3	180	199	217
	MEAN	181	199	212
	ST. DEV.	8	3	4
	N	3	3	3
FEMALES 2000 mg/kg	4	197	226	229
	5	170	192	189
	6	197	244	241
	MEAN	188	221	220
	ST.DEV.	16	26	27
	N	3	3	3

Table 4. Macroscopic findings.

ANIMAL	ORGAN	FINDING	DAY OF DEATH
MALES 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	Thymus	Discolouration, reddish	Scheduled necropsy Day 15 after treatment
5		No findings noted	Scheduled necropsy Day 15 after treatment
6	Thymus	Discolouration, reddish	Scheduled necropsy Day 15 after treatment

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 value of Reaction products of n-octanol and acrylic acid, first distillation pitch in Wistar rats was determinated to be greater than 2000 mg/kg b.w.

Executive summary:

The acute oral toxicity of the substance was determinated according to the OECD 423 test guideline with GLP. The oral LD50 value of Reaction products of n-octanol and acrylic acid, first distillation pitch in Wistar rats was established to exceed 2000 mg/kg body weight. Based on these results, the test substance 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.