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

Endpoint summary

Description of key information

Skin irritation/corrosion: Key study: OECD Guideline 404. GLP study. The primary skin irritation/corrosion of the test substance was determined to be not irritating.
Eye irritation: Key study: OECD Guideline 405. GLP study. The acute eye irritation/corrosion of the test substance was determined to be not irritating.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From March 15, 2012 to March 23, 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF Guidelines (2000)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: At least 6 weeks old
- Weight at study initiation: At least 1.0 kg
- Housing: Animals were individually housed in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm).
- Diet (e.g. ad libitum): Pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy) approximately 100 grams per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) and wooden sticks (Swedish aspen wood, Bioservices, Uden, The Netherlands)
- 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): 18 to 24ºC
- Humidity (%): 40 to 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle.

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: Adjacent areas of the untreated skin of each animal served as controls.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours after the removal of the dressings and test substance

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: 2x3 cm
- Type of wrap if used: Micropore tape

SCORING SYSTEM:
Erythema and eschar formation:
No erythema .......................................................................................................................... 0
Very slight erythema (barely perceptible) ......................................................................... 1
Well-defined erythema ......................................................................................................... 2
Moderate to severe erythema............................................................................................... 3
Severe erythema (beet redness) *........................................................................................ 4
*. Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the maximum grade for erythema (= 4) is given.

Oedema formation:
No oedema ................................................................................................................................................. 0
Very slight oedema (barely perceptible) ................................................................................................ 1
Slight oedema (edges of area well-defined by definite raising) ......................................................... 2
Moderate oedema (raised approximately 1 millimeter) ....................................................................... 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure)..... 4

Irritation parameter:

erythema score

Basis:

animal: #1, 2, 3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks:

24 hours

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal: #1, 2, 3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks:

24 hours

Remarks on result:

no indication of irritation

Table 1. Individual skin irritation scores

Animal	240^1			246			250
Time after exposure	Erythema (0-4)	Oedema (0-4)	comments	Erythema (0-4)	Oedema (0-4)	comments	Erythema(0-4)	Oedema (0-4)	comments
1 hour	1	1	-	1	1	-	1	1	-
24 hours	0	0	-	0	0	-	0	0	-
48 hours	0	0	-	0	0	-	0	0	-
72 hours	0	0	-	0	0	-	0	0	-

¹Sentinel.

Table 2. Mean value irritation scores

Animal	Mean 24, 48 and 72 hours
	Erythema	Oedema
240	0.0	0.0
246	0.0	0.0
250	0.0	0.0

 

Table 3. Animal specifications

 

Animal	Sex	Age at start (weeks)	Body weighs (grams)
			prior to application	at termination
240	male	10	2289	2356
246	male	11	2508	2608
250	male	11	2453	2504

 

Interpretation of results:

GHS criteria not met

Conclusions:

The substance was found not irritating in the skin of rabbits.

Executive summary:

The skin irritation of the substance was determinated according to OECD 404 guideline with GLP. The substance was found to be not irritating for the rabbits' skin. Slight irritation was observed in all three animals (both score: oedema and erythema) after four hours with the score 1, this result was fully reversible after 24 hours in all animals.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From April 3, 2012 to July 27, 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No. 8147, April 2011; including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany.
- Age at study initiation: at least 6 weeks old.
- Weight at study initiation: at least 1.0 kg.
- Housing: Animals were individually housed in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm).
- Diet (e.g. ad libitum): Pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy) approximately 100 grams per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) and wooden sticks (Swedish aspen wood, Bioservices, Uden, The Netherlands).
- 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): 18 to 24°C.
- Humidity (%): 40 to 70%.
- Air changes (per hr): approximately 15 room air changes/hour.
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle.

IN-LIFE DATES: From: April 23, 2012 To: May 10, 2012

Vehicle:

unchanged (no vehicle)

Controls:

other: The other eye remained untreated and served as the reference control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL.

Duration of treatment / exposure:

24-hour

Observation period (in vivo):

Approximately 1, 24, 48 and 72 hours after instillation of the test substance.

Number of animals or in vitro replicates:

3 Males

Details on study design:

STUDY DESING
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner two weeks later, after considering the degree of eye irritation observed in the first animal.

TREATMENT
Each animal was treated by instillation of 0.1 mL of the test substance, in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control.
Immediately after the 24-hour observation, a solution of 2% fluorescein (Merck, Darmstadt, Germany) in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.
After the final observation, the animals were sacrificed by intra-venous injection of Euthasol® 20% (AST Farma BV, Oudewater, The Netherlands).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM:

CORNEAL IRRITATION

Opacity: degree of density (area most dense taken for reading)
No ulceration or opacity (may include slight dulling of normal luster) ............................................ 0
Scattered or diffuse areas of opacity, details of iris clearly visible................................................. 1
Easily discernible translucent area, details of iris slightly obscured............................................... 2
Nacreous area, no details of iris visible, size of pupil barely discernible........................................ 3
Opaque cornea, iris not discernible through the opacity .............................................................. 4

Area of cornea involved:
No ulceration or opacity................................................................................................................ 0
One quarter or less but not zero .................................................................................................. 1
Greater than one quarter, but less than half ................................................................................. 2
Greater than half, but less than three quarters ............................................................................. 3
Greater than three quarters, up to whole area .............................................................................. 4

IRIS
Normal ....................................................................................................................................... 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia,
or injection, any of these or combination thereof, iris still reacting to light
(sluggish reaction is positive) ....................................................................................................... 1
No reaction to light, hemorrhage, gross destruction (any or all of these)....................................... 2

CONJUNCTIVAL IRRITATION

Redness (refers to palpebrae and sclera, excluding cornea and iris):
Blood vessels normal .................................................................................................................. 0
Some blood vessels definitely hyperaemic (injected).................................................................... 1
Diffuse, crimson color, individual vessels not easily discernible.................................................... 2
Diffuse beefy red.......................................................................................................................... 3

Chemosis (refers to lids and/or nictitating membranes):
No swelling ………………………………………… ........................................................................ 0
Any swelling above normal (includes nictitating membranes) ...................................................... 1
Obvious swelling with partial eversion of lids................................................................................ 2
Swelling with lids about half closed ............................................................................................. 3
Swelling with lids more than half closed ....................................................................................... 4

Discharge:
No discharge (may include small amounts observed in inner canthus of normal animals) ........... 0
Any amount different from normal and/or lacrimation ................................................................... 1
Discharge with moistening of the lids and hairs just adjacent to lids ............................................. 2
Discharge with moistening of the lids and hairs (considerable area around the eye) ................... 3
Where standard lighting was considered inadequate for observing minor effects, eye examinations were performed using an ophthalmic examination lamp.

Irritation parameter:

cornea opacity score

Basis:

animal: #1, 2, 3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal: #1, 2, 3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal: #1, 2, 3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48h

Irritation parameter:

chemosis score

Basis:

animal: #1, 2, 3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 h

Irritant / corrosive response data:

Irritation:
Instillation of approximately 0.1 mL of the test substancee into one eye of each of three rabbits resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 48 hours in all animals.
No iridial irritation or corneal opacity were observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.
Corrosion:
There was no evidence of ocular corrosion.

Other effects:

Coloration / Remnants:
No staining of (peri) ocular tissues by the test substance was observed and no test substance remnants were seen.
Toxicity / Mortality:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Table 1. Individual eye irritation scores.

Animal	Time after dosing	Cornea			Iris	Conjunctivae			Comments
		Opacity (0-4)	Area (0-4)	Fluor area (%)^2	(0-2)	Redness (0-3)	Chemosis (0-4)	Discharge (0-3)
263^1	1 hour	0	0	0	0	1	1	1	-
	24 hours	0	0		0	1	0	0	-
	48 hours	0	0		0	0	0	0	-
	72 hours	0	0		0	0	0	0	-
279	1 hour	0	0	0	0	1	1	1	-
	24 hours	0	0		0	1	0	0	-
	48 hours	0	0		0	0	0	0	-
	72 hours	0	0		0	0	0	0	-
285	1 hour	0	0	0	0	1	1	1	-
	24 hours	0	0		0	1	0	0	-
	48 hours	0	0		0	0	0	0	-
	72 hours	0	0		0	0	0	0	-

 ¹Sentinel,²Green staining after fluorescein treatment (percentage of total corneal area).

 

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance does not have to be classified for eye irritation.

Executive summary:

Acute eye irritation/corrosion study with the test substance in the rabbit was determined according to OECD 405 guideline and EU B5 Method with GLP.

Single samples of 0.1 mL of the test substance were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours after instillation.

Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 48 hours in all animals.

Based on these results, Reaction products of n-octanol and acrylic acid, first distillation pitch does not have to be classified and has no obligatory labelling requirement for eye irritation 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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Key study:

Skin irritation/corrosion:

The possible corrosive and irritative potential of the test substance was carried out according to the OECD Guideline 404 (GLP study). 0.5 mL of the test substance was applicated onto clipped skin for 4 hours using a semi-occlusive dressing.

Irritation: The test substance caused a very slight erythema and very slight oedema in the treated skin areas. The skin irritation resolved within 24 hours after exposure in all animals.

Corrosion: There was no evidence of a corrosive effect on the skin.

Eye irritation:

The possible corrosive and irritative potential of the test substance was carried out according to the OECD Guideline 405 (GLP study). 0.1 mL of the test substance was instilled into one eye of each of three rabbits.

Irritation: The test substance caused a irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 48 hours after exposure in all animals.

Corrosion: There was no evidence of ocular corrosion.

Justification for selection of skin irritation / corrosion endpoint:
Only one study available. GLP compliant and of high quality (Klimisch 1).

Justification for selection of eye irritation endpoint:
Only one study available. GLP compliant and of high quality (Klimisch 1).

Justification for classification or non-classification

 Based on these results Reaction products of n-octanol and acrylic acid, first distillation pitch does not have to be classified and has no obligatory labelling requirement for skin irritation 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.