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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From January 12, 2012 to January 26, 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 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF Guidelines (2000)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

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:

male/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 weeks old.
- Weight at study initiation: Given in the table
- 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. During the acclimatization period the animals were group housed in Makrolon cages (MIV type, height 18 cm).

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 +/- 3.0ºC (actual range: 19.8 - 22.1ºC)
- Humidity (%): 40-70% (actual range: 39 - 66%)
- Air changes (per hr): 15 approx.
- Photoperiod (hrs dark / hrs light):12 hours artificial fluorescent light and 12 hours darkness per day.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: approx. 25 cm² for males and 18 cm² for females.
- % coverage: 10% of the total body surface.
- Type of wrap if used: 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): the skin was cleaned of residual test substance using tap water.
- Time after start of exposure: 24 h.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (2.081 mL/kg) bw.
- Constant volume or concentration used: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg (2.081 mL/kg) bw.

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Observation once daily; weighing days 1 (pre-administration), 8 and 15.
- Other examinations performed:
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).

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured.

Clinical signs:

other: Chromodacryorrhea and/or piloerection were noted among the animals on Days 1 and/or 2.

Other findings:

One male showed dark red discolouration of the lungs at macroscopic post mortem examination. No further 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	(1)
ANIMAL 1 Skin/fur piloerection		-	-	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 2 No clinical signs noted		-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 3 Skin/fur Scales (treated skin)	(3)	-	-	-	-	-	-	-	1	-	-	-	-	-	-	-	-	-
ANIMAL 4 Secretion/excretion Chromodacryorrhoea (Snout)	(3)	-	1	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 5 Secretion/excretion Chromodacryorrhoea (Snout)	(3)	-	-	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-
FEMALES 2000 mg/kg
ANIMAL 6 No clinical signs noted		-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 7 Skin/fur Scales (treated skin)	(3)	-	-	-	-	-	-	1	1	1	-	1	1	-	-	-	-	-
ANIMAL 8 Skin/fur Piloerection	(1)	-	-	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-
Secretion/excretion Chromodacryorrhoea (Snout)	(3)	-	-	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 9 Skin/fur Piloerection	(1)	-	-	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-
Secretion/excretion Chromodacryorrhoea (Snout)	(3)	-	1	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 10 Skin/fur Piloerection	(1) (3)	- -	- -	1 -	1 -	- -	- 1	- 1	- 1	- 1	- -	- -	- -	- -	- -	- -	- -	- -
Secretion/excretion Chromodacryorrhoea (Snout)	(3)	-	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-

Table 3. Body weigh (grams)

SEX/DOSE LEVEL	ANIMAL	DAY 1	DAY 8	DAY 15
MALES 2000 mg/kg	1	288	290	325
	2	270	273	300
	3	282	290	314
	4	283	292	324
	5	271	282	305
	MEAN	279	285	314
	ST. DEV.	8	8	11
	N	5	5	5
FEMALES 2000 mg/kg	6	196	194	210
	7	211	209	221
	8	194	188	204
	9	188	185	201
	10	198	196	214
	MEAN	197	194	210
	ST.DEV.	8	9	8
	N	5	5	5

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
4	Lungs	Discolouration, dark red	Scheduled necropsy Day 15 after treatment
5			Scheduled necropsy Day 15 after treatment
FEMALES 2000 mg/kg
6		No findings noted	Scheduled necropsy Day 15 after treatment
7		No findings noted	Scheduled necropsy Day 15 after treatment
8		No findings noted	Scheduled necropsy Day 15 after treatment
9		No findings noted	Scheduled necropsy Day 15 after treatment
10		No findings noted	Scheduled necropsy Day 15 after treatment

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal 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 bw.

Executive summary:

The acute dermal toxicity of the substance was determinated according to the OECD 402 test guideline with GLP. The dermal 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 dermal 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.