Reaction mass of 2,4-dimethyl-6-phenyl-3,6-dihydro-2H-pyran and 2-methyl-4-methylene-6-phenyltetrahydro-2H-pyran and 4,6-dimethyl-2-phenyl-3,6-dihydro-2H-pyran

Endpoint summary

Description of key information

Skin irritation
Eye irritation
A weight of evidence approach was used, with three in vivo studies performed on the target substance available.  From the three studies it can be concluded that the test item does not meet the criteria for classification according to Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

Key value for chemical safety assessment

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

The study was conducted between 30 May 1977 and 16 June 1977.

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Documentation insufficient for assessment.

Qualifier:

according to guideline

Guideline:

other: Modified Federal Hazard Substances labelling Act Method

Deviations:

no

GLP compliance:

no

Remarks:

Study pre-dates GLP.

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

No data

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

No data

Observation period (in vivo):

22 days

Number of animals or in vitro replicates:

Three

Details on study design:

Test substances are applied to one eye each of three rabbits by gently pulling the lower lid away from the eyeball and placing 0.1 mL in the sac so formed. Standards for comparison are applied to further rabbits in the same manner.
Eyes are examined 24 hours after treatment and thereafter at daily intervals and graded for corneal, conjunctival and iridial damage. Eyes are examined before application of the materials and at daily intervals afterwards with a slit lamp and corneal swelling is measured.

Modification of standard method
Area of cornea and iris affected was assessed as well as intensity.

Irritant / corrosive response data:

The test substance, as supplied, caused no corneal, conjunctival or iridial lesions when assessed at 24 h. One rabbit showed signs of discomfort when treated.

Summary of results

Substance	No. of rabbits	Number of rabbits with stated ocular lesion
		Discomfort	Positive conjunctival reactions (1)	No. with iritis	No with pannus	Corneal opacity grade (2)					Duration (3)		Maximum corneal swelling % (4)
						0.5	1	2	3	4	Opacity≥1 Day 8	Opacity≥0.5 day 22	-10 % to +19 %	+ 20 % to +39 %	+40 % to +59 %	+60 % to + 79 %	+80 % to + 79 %	+100 %
Test substance	3	1	-	-	-	-	-	-	-	-	-	-	3

1)   Positive conjunctival reactions – number of rabbits with conjunctival erythema or chemosis grades ≥2.

2)     Corneal opacity - maximum grade obtained during period of observation.

3)     Duration – number of animals with corneal opacity grades ≥1 on 8^thday of observation or with any ocular lesions on the 22^ndday of the test.

4)     Corneal swelling - maximum swelling attained during period of observation.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance, as supplied, is not an eye irritant. This material may cause pain if accidentally splashed into the eye.

Executive summary:

The test substance was assessed for eye irritation using an in vivo method. The test substance, as supplied, caused no corneal, conjunctival or iridial lesions when assessed at 24 h. One rabbit showed signs of discomfort when treated.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Eye Irritation

Serious eye damage is defined as the production of tissue damage in the eye, or serious physical decay of vision following application of a test substance to the anterior surface of the eye, which is not fully reversible within 21 days of application. Eye irritation means the production of changes in the eye following application of test substance to the anterior surface of the eye, which are fully reversible within 21 days of application.

The classification system for substances involves a tired testing and evaluation scheme and a number of factors are considered in determining eye irritation or serious eye damage.

A weight of evidence approach was used, with three in vivo studies performed on the target substance available.

In the first study a 50 % solution of the test substance caused corneal lesions affecting between half and all the corneal surface in all the animals. The lesions were associated with moderate corneal swelling, moderate to severe conjunctivitis and slight to moderate discharge. Two animals developed iritis affecting a quarter to three quarters of the iris. The lesions had healed within 10 days. One animal showed signs of discomfort when treated. 

However, in the second study, the test substance, administered undiluted to three rabbits, caused no corneal, conjunctival or iridial lesions when assessed at 24 h. One rabbit showed signs of discomfort when treated.

In the third study no corneal, conjunctival or iridial lesions that were observable 24 h after application of the neat substance to the eye. The test substance was essentially non-irritant to the eye when applied undiluted to the eyes of six rabbits. It caused some slight conjunctivitis immediately after application to the eye but had no other effect.

From the three studies it can be concluded that the test item does not meet the criteria for classification according to Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

Justification for selection of eye irritation endpoint:
The study was conducted on the target substance in vivo in an appropriate test species and is submitted as weight of evidence with several other studies.

Justification for classification or non-classification

Skin irritation

Eye Irritation

The classification for substances involved a tired testing and evaluation scheme and a number of factors are considered in determining eye irritation or serious eye damage. A weight of evidence approach was used, incorporating three in vivo studies performed on the target substance. 

Classification for eye irritation is divided into two categories. Category 1 is used when the test substance causes irreversible effects to the eye; category 2 is used when there are reversible effects to the eye. The criteria for classification as Category 2 is required when a substance produces corneal opacity≥1 and /or iritis≥1, and / or conjunctival redness≥2 and / or conjunctival oedema (chemosis)≥2 in at least two if three animals tested, calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test item and which fully reverses within 21 days.

One study performed using a 50 % solution of the test substance in Tween 80 did produce some corneal opacity and chemosis. The extent to which these effects were observed could lead to a classification as a Category 2 eye, irritant based on the corneal opacity and conjunctival redness. However, two further studies which were both performed on the neat substance lead to minor discomfort and slight conjunctivitis, but no corneal, conjunctival or iridial lesions were observed.

Therefore the weight of evidence concludes that the test substance is not classified as an eye irritant, as two studies which were both performed using neat applications of the test substance, provided no evidence for classification for the test substance.