4-methylstyrene

Endpoint summary

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

according to guideline

Guideline:

other: Federal Hazardous Substances Act , September 27, 1973

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

New Zealand White rabbits weighing 2.05 to 2.15 kg.

Type of coverage:

open

Preparation of test site:

other: abraded and non-abraded site on each rabbit

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Single dermal application of 0.5 mL to clipped and abraded rabbit skin. No occlusion. Not stated if wash off performed.

Duration of treatment / exposure:

Single application. 24 h exposure.

Observation period:

Observed at 24 and 72 h. Primary Index calculated.

Number of animals:

3 male and 3 female

Details on study design:

The site of application was clipped and abraded on all rabbits. Observations were made at 24 and 72 h following application for signs of irritation and corrosivity. Irritation scores were recorded and the primary index was calculated. The test substance was applied to the backs and occlusive wrap was not used because the test substance reacted with the dental dam creating unwanted variable. The rabbits were restrained by being put in a Newman harness for the 24 h initial exposure.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 and 72 h

Score:

1.5

Reversibility:

other: reversibility not investigated

Irritation parameter:

erythema score

Basis:

animal: 1-6

Time point:

24 h

Score:

1.5

Max. score:

2

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: for both intact and abraded skin

Irritation parameter:

edema score

Basis:

animal: 1-6

Time point:

24 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: for both intacts and abraded skin

Irritation parameter:

erythema score

Basis:

animal: 1-6

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Basis:

animal: 1-6

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Basis:

animal: 1-6

Time point:

72 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: for noth intact and abraded skin

Irritation parameter:

edema score

Basis:

animal: 1-6

Time point:

72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

other: for both intact and abraded skin

Irritant / corrosive response data:

Well defined erythema (score 2) in 3/6 rabbits with very slight edema (score 1) in other 3/6 rabbits was apparent at 24 h. At 72 h only very slight erythema (score 1) and edema (score 1) remained.
Mean value of > 1.5 - < 2.3 for erythema/eschar or for oedema from gradings in at least 2 of 3 tested animals from grades at 24, 48 and 72 h or, if reactions are delayed, from grades on 3 consecutive days after the onset of dermal reactions (when not included in the irritant category above).
In this study reactions were only measured at 24 and 72 h. However, at 24 hurs 3/6 animals had a score of 2 for erythema and 3/6 a score of 1. At 24 h 6/6 had a score of 1. Therefore the mean score for 3/6 rabbits is 1.5

Conclusions:

Under the study conditions, the calculated primary index for the test substance was 1.5.

Executive summary:

A study was conducted to determine the skin irritation/corrosion potential of the test substance in rabbits following a single dermal exposure according to Federal Hazardous Substances Act, September 27, 1973. Six New Zealand White rabbits (2.05 to 2.15 kg) were dosed dermally with a single application of 0.5 mL of the test substance. The site of application was clipped and abraded on all rabbits. Observations were made at 24 and 72 h following application for signs of irritation and corrosivity. Irritation scores were recorded and the primary index was calculated. The test substance was applied to the backs and an occlusive wrap was not used. Reactions were only measured at 24 and 72 h. At 24 h, 3/6 animals had a score of 2 for erythema and 3/6 a score of 1. At 24 h, 6/6 had a score of 1. Under the study conditions, the calculated primary index for the test substance was 1.5 (Adamik, 1997).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

summary only, lacking detail

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

New Zealand White rabbits weighing 2.00 to 2.25 kg.

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 mL instilled in to right eye. Left eye served as untreated control. Not stated if wash out performed.

Duration of treatment / exposure:

Once only. Not stated if washout performed.

Observation period (in vivo):

Observed at 1, 24, 48 and 72 hours and 4 and 7 days.

Number of animals or in vitro replicates:

3 male and 3 female

Details on study design:

Signs of ulceration of the cornea, corneal opacity, conjunctivitis, iris irritation, chemosis, tearing and refuse color were recorded.

Irritation parameter:

cornea opacity score

Basis:

animal: All

Time point:

24/48/72 h

Remarks on result:

other: information not available

Irritation parameter:

iris score

Basis:

animal: All

Time point:

24/48/72 h

Remarks on result:

other: information not available

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal: All

Time point:

24/48/72 h

Remarks on result:

other: information not available

Irritation parameter:

iris score

Basis:

mean

Time point:

7 d

Score:

0

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

7 d

Score:

0

Irritation parameter:

chemosis score

Basis:

animal: All

Time point:

24/48/72 h

Remarks on result:

other: information not available

Irritant / corrosive response data:

Immediate responses following ocular instillation – All of the rabbits closed the treated eye and preened themselves when returned to their cage. Within five minutes after instillation the rabbits had the right treated eye open. One rabbit vocalized for a few seconds when put back into its cage.

Mean Eye irritation scores for each rabbit:

Rabbit N	Mean of Score at 24, 48 and 72 Hours
	Corneal Opacity	Iris Lesion	Conjunctivae
			Chemosis	Erythema	Discharge
1	0	0	0	0	0.33
2	0	0	0	1	0.66
3	0	0	0	0.33	0
4	0	0	0	0	0
5	0	0	0	1	0
6	0	0	0	0.33	0.33

Conclusions:

Under the study conditions, there were signs of immediate discomfort (closing of eye, vocalisation) and slight chemosis, erythema and discharge, However, the maximum scores given were 1 and all signs were reversible within 7 d.

Executive summary:

A study was conducted to determine the eye irritation potential of the test substance in rabbit following a single ocular exposure according to Federal Hazardous Substances Act, September 27, 1973. Three male and 3 female New Zealand White rabbits were exposed to 0.1 mL of the test substance instilled into the right eye. It was not stated whether a wash out was performed. Under the study conditions, there were signs of immediate discomfort (closing of eye, vocalisation) and slight chemosis, erythema and discharge, However, the maximum scores given were 1 and all signs were reversible within 7 d (Adamik, 1977).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin

A study was conducted to determine the skin irritation/corrosion potential of the test substance in rabbits following a single dermal exposure according to Federal Hazardous Substances Act, September 27, 1973. Six New Zealand White rabbits (2.05 to 2.15 kg) were dosed dermally with a single application of 0.5 mL of the test substance. The site of application was clipped and abraded on all rabbits. Observations were made at 24 and 72 h following application for signs of irritation and corrosivity. Irritation scores were recorded and the primary index was calculated. The test substance was applied to the backs and an occlusive wrap was not used. Reactions were only measured at 24 and 72 h. At 24 h, 3/6 animals had a score of 2 for erythema and 3/6 a score of 1. At 24 h, 6/6 had a score of 1. Under the study conditions, the calculated primary index for the test substance was 1.5 (Adamik, 1997).

Eye

A study was conducted to determine the eye irritation potential of the test substance in rabbit following a single ocular exposure according to Federal Hazardous Substances Act, September 27, 1973. Three male and 3 female New Zealand White rabbits were exposed to 0.1 mL of the test substance instilled into the right eye. It was not stated whether a wash out was performed. Under the study conditions, there were signs of immediate discomfort (closing of eye, vocalisation) and slight chemosis, erythema and discharge, However, the maximum scores given were 1 and all signs were reversible within 7 d (Adamik, 1977).

Justification for classification or non-classification

Based on in vivo irritation testing in rabbit, the test substance does not appear to be irritating to skin or eyes to a degree triggering classification according to CLP (EC 1272/2008) criteria. However, severe irritation was noted in a 21 d repeated dose toxicity test in rabbit. Also, the read across substance vinyl toluene has been reported to be irritating to the eyes, upper respiratory tract and skin of humans at concentrations greater than 400 ppm. Based on this additional evidence, classification as Skin Irrit. 2 – H315 (causes skin irritation) and Eye Irrit. 2 – H319 (causes serious eye irritation) is therefore proposed.