2-propanol and 2-butanol production, distn. residues

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13. September 2010 - 28. September 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study under GLP, according to international guidelines and with full documentation

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2-propanol and 2-butanol production, distn. residues, sample 2010

Molecular formula:

UVCB substance

IUPAC Name:

2-propanol and 2-butanol production, distn. residues, sample 2010

Test material form:

liquid

Details on test material:

- The analysis was performed for the reference sample "Sample 2010" as defined in Section 1.4
- Lot/batch No.: 10013593
- Expiration date of the lot/batch: March 2011
- Storage condition of test material: For several days, the test item was stored in the test facility at room temperature protected from light and kept under inert gas. As soon as a fridge with explosion prevention was available, the test item was stored at 2 – 8 °C. No relevant changes in composition were detected before and after storage at room temperature (GC chromatograms).

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage de Gérome (Quartier Labaste –F40260 Linxe)
- Age at study initiation: 11 or 15 weeks old
- Weight at study initiation: between 1.93 kg and 3.53 kg
- Housing: individual box

- Diet (e.g. ad libitum), Water (e.g. ad libitum): Drinking water (tap-water from public distribution system) and foodstuff (SDS - C15) were supplied freely.
- Acclimation period: a minimal 5-day acclimatisation period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): approximately fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (07.00 to 19.00) and twelve hours darkness

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

amount: 0.1 mL

Observation period (in vivo):

Ocular examinations were performed on both right and left eyes 1 hour, 24, 48 and 72 hours following treatment.
NOTE: As persistent reactions were noted at 72 hours post-dose, additional observations have been carried out from day 4 daily for up to 9 days in order to determine the reversible character of the lesions observed.

Number of animals or in vitro replicates:

3 males

Details on study design:

Eye examinations were carried out using the scale of lesion scores according to OECD 405.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: between days 7 and 9

Remarks on result:

other: a moderate redness noted 1 hour after the test item instillation

Results 2

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.8

Max. score:

4

Reversibility:

fully reversible within: between days 7 and 8

Remarks on result:

other: a moderate to important chemosis noted 1 hour after the test item instillation

Results 3

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: one day

Remarks on result:

other: a congestion, noted 1 hour after the test item instillation in two animals

Results 4

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

mean

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 2 days

Remarks on result:

other: a moderate corneal opacity

Any other information on results incl. tables

INDIVIDUAL AND MEAN SCORES OF CONJUNCTIVAE, IRIS AND CORNEA

Animal n°	Time after treatment	Conjunctivae		Iris	Cornea
		Chemosis (A)	Redness (C )	Lesion (D)	Opacity (E )
A0356	24 hours	2	2	0	2
	48 hours	1	2	0	0
	72 hours	1	2	0	0
Total		4	6	0	2
Mean		1.3	2	0	0.7
A0374	24 hours	2	2	0	2
	48 hours	2	2	0	0
	72 hours	2	1	0	0
Total		6	5	0	2
Mean		2	1.7	0	0.7
A0375	24 hours	2	3	0	2
	48 hours	2	2	0	0
	72 hours	2	2	0	0
Total		6	7	0	2
Mean		2	2.3	0	0.7
Classificationin accordance with the European regulation		According to the calculated means, the test item has to be classified R36 "irritating to eyes".
Classificationin accordance with the GHS regulation		According to the calculated means, the test item has to be classified in category 2 "irritating to eyes" with the hazard statement H319 "causes serious eye irritation".

TOTAL AND INDIVIDUAL SCORES OF OCULAR IRRITATION

Animal No: A0356

Observation time	Conjunctivae				Iris		Cornea			Individual irritation index
	A	B	C	(A+B+C)x2	D	Dx5	E	F	ExFx5
				X=		Y=			Z=	X+Y+Z=
1 hour (D0)	2	3	2	14	1	5	0	0	0	19
24 hours (D1)	2	0	2	8	0	0	2	1	10	18
48 hours (D2)	1	0	2	6	0	0	0	0	0	6
72 hours (D3)	1	0	2	6	0	0	0	0	0	6
Day 4 (D4)	1	0	2	6	0	0	0	0	0	6
Day 5 (D5)	1	0	2	6	0	0	0	0	0	6
Day 6 (D6)	1	0	2	6	0	0	0	0	0	6
Day 7 (D7)	0	0	2	4	0	0	0	0	0	4
Day 8 (D8)	0	0	1	2	0	0	0	0	0	2
Day 9 (D9)	0	0	0	0	0	0	0	0	0	0

Animal No: A0374

Observation time	Conjunctivae				Iris		Cornea			Individual irritation index
	A	B	C	(A+B+C)x2	D	Dx5	E	F	ExFx5
				X=		Y=			Z=	X+Y+Z=
1 hour (D0)	3	3	2	16	1	5	0	0	0	21
24 hours (D1)	2	0	2	8	0	0	2	1	10	18
48 hours (D2)	2	0	2	8	0	0	0	0	0	8
72 hours (D3)	2	0	1	6	0	0	0	0	0	6
Day 4 (D4)	1	0	1	4	0	0	0	0	0	4
Day 7 (D7)	1	0	0	2	0	0	0	0	0	2
Day 8 (D8)	0	0	0	0	0	0	0	0	0	0

Animal No: A0375

Observation time	Conjunctivae				Iris		Cornea			Individual irritation index
	A	B	C	(A+B+C)x2	D	Dx5	E	F	ExFx5
				X=		Y=			Z=	X+Y+Z=
1 hour (D0)	3	3	2	16	0	0	0	0	0	16
24 hours (D1)	2	0	3	10	0	0	2	1	10	20
48 hours (D2)	2	0	2	8	0	0	0	0	0	8
72 hours (D3)	2	0	2	8	0	0	0	0	0	8
Day 4 (D4)	1	0	1	4	0	0	0	0	0	4
Day 7 (D7)	1	0	0	2	0	0	0	0	0	2
Day 8 (D8)	0	0	0	0	0	0	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

Category 2A (irritating to eyes) based on GHS criteria

Conclusions:

In conclusion, the results obtained, under these experimental conditions, enable to conclude that the test item „2-propanol and 2-butanol production, distn. residue“ has to be classified in accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures, in category 2 “Irritating to eyes”. The signal word “Warning” and hazard statement H319 “Causes serious eye irritation” are required.

Executive summary:

Acute eye irritation was assessed for „2-propanol and 2-butanol production, distn. residue“ according to OECD guideline No 405. The test item was instilled as supplied, into the eye of 3 New Zealand rabbits at the dose of 0.1 mL. The experimental protocol was established on the basis of the official method as defined in the OECD guideline No 405 dated April 24th, 2002 and the test method B.5 of the Council regulation No 440/2008. The ocular reactions observed during the study have been moderate to important and totally reversible in the three animals:

- at the conjunctivae level: a moderate redness noted 1 hour after the test item instillation and totally reversible between days 7 and 9, associated with a moderate to important chemosis noted 1 hour after the test item instillation and totally reversible between days 7 and 8,

- at the iris level: a congestion, noted 1 hour after the test item instillation in two animals, and totally reversible on day 1.

- at the corneal level: a moderate corneal opacity, noted 24 hours after the test item instillation, and totally reversible on day 2.

In accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures, the test item has to be classified in category 2 “Irritating to eyes”. The signal word “Warning” and hazard statement H319 “Causes serious eye irritation” are required.