Registration Dossier

Administrative data

Description of key information

Dicyclopentadiene is considered to be irritating to skin and the respiratory system and slightly irritating to eyes. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion, other
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.22-2.54kg
- Housing: Individually in suspended metal cages
- Diet: Rabbit Diet ad libitum (Preston Farmers Ltd., New Leake, Boston, Lincolnshire, UK)
- Water: Mains water ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 16-22°C
- Humidity: 54-67%
- Air changes (per hr): Approximately 15/hour
- Photoperiod: 12 hrs dark / 12 hrs light):

IN-LIFE DATES: From: 9 November 1988 To: 16 November 1988
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: not specified
- Type of wrap if used: gauze patch held in place with surgical adhesive tape under a Tubigrip corset

REMOVAL OF TEST SUBSTANCE
- Washing (if done): swabbed with water
- Time after start of exposure: 4 hr after application

SCORING SYSTEM: Draize scale
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 & 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days.
Remarks on result:
other: possible hyperkeratinisation at 7 days in all 3 animals.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 & 72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 7 days

Skin irritation scores according to the Draize scheme

Time

Erythema (Test/Control sites)

Oedema (Test/Control sites)

 Animal number

34F

43F

80M

34F

43F

80M

after 1 hour

1

2

1

1

2

1

after 24 hours

2

2

2

4

4

3

after 48 hours

2

2

2

2

2

1

after 72 hours

2

2

2

2

2

1

mean scores 24-72h

2

2

2

2.6

2.6

1.7

Overall mean score (24-72 h)

2

2.3

Well-defined erythema persisted at all treated skin sites at 24, 48 and 72 hour observations. Signs of possible hyperkeratinisation were noted on day 7. No oedema was noted on day 7. No other adverse dermal reactions were noted during the study.

Interpretation of results:
moderately irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a skin irritation study with dicyclopentadiene 75% in rabbits, overall mean scores (24, 48 & 72 hr) were 2 for erythema and 2.3 for oedema. Dicyclopentadiene 75% was therefore considered to be a moderate irritant to rabbit skin.
Executive summary:

Skin irritation was assessed in a group of 3 New Zealand white rabbits. 0.5 mL of dicyclopentadiene 75% was applied to an area of clipped, intact skin under a semi-occlusive dressing for 4 hours. Animals were observed at 1 and 4 hours after removal of the patch and then daily for 7 days. Well-defined erythema and slight to severe oedema was present at skin sites of all rabbits at 24, 48 and 72 hour observations. On day 7 no oedema was noted but there were signs of possible hyperkeratinisation. No other adverse dermal reactions were noted during the study. The overall mean scores (24, 48 & 72 hr) were 2 for erythema and 2.3 for oedema, and the mean oedema score exceeded 2.3 for two of the three animals. DCPD 75% was a therefore considered a moderate irritant to rabbit skin and, according to EEC labelling regulations, the symbol "Xi" and risk phrase R38 "IRRITATING TO SKIN" are required.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation, other
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.45-2.67 kg
- Housing: Individually in suspended metal cages
- Diet: Rabbit Diet ad libitum (Preston Farmers Ltd., New Leake, Boston, Lincolnshire, UK)
- Water: Mains water ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 15-20°C
- Humidity: 40-66%
- Air changes (per hr): Approximately 15/hour
- Photoperiod: 12 hrs dark / 12 hrs light):

IN-LIFE DATES: From: 14 November 1988 To: 22 November 1988
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
Single application
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- The eyes were not washed

SCORING SYSTEM:
- According to the numerical system of Draize JH, 1959 and a modified version of the Kay and Calandra system, 1962

TOOL USED TO ASSESS SCORE:
- Standard ophthalmoscope
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24-72 hour
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24 -72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24-72 hours
Score:
0.43
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: slight redness present in 1 animal at 72 h.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 -72 hours
Score:
0.1
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: slight chemosis in 1 rabbit at 24 h

Dicyclopentadiene 75%: Eye irritation scores according to the Draize scheme

Time

Cornea

Iris

Conjunctiva

 

 

 

Redness

Chemosis

Animal number

545

544

547

545

544

547

545

544

547

545

544

547

after 1 hour

0

d

d

1

1

1

3

2

2

2

2

2

after 24 hours

0

0

0

0

0

0

1

1

0

0

1

0

after 48 hours

0

0

0

0

0

0

0

1

0

0

0

0

after 72 hours

0

0

0

0

0

0

0

1

0

0

0

0

mean scores 24-72h

0

0

0

0

0

0

0.3

1

0

0

0.3

0

d = dulling of corneal surface

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Dicyclopentadiene 75% was a moderate irritant to the rabbit eye at 1 hour but was practically non-irritating at 24, 48 and 72 hours.
Executive summary:

Eye irritation was assessed in 3 New Zealand white rabbits. 0.1 mL dicyclopentadiene 75% was instilled into the conjunctival sac and the eyes were scored for irritation responses at 1, 24, 48 and 72 hours and at 7 days after instillation. At 1 hour, corneal dulling was present in 2 eyes, iridial inflammation and moderate conjunctival irritation were present in all 3 eyes, giving an overall mean score of 18.5 at 1 hour, which corresponds to moderate irritation (Kay and Callandra, 1962). Signs of irritation regressed to minimal in 2 eyes at 24 hours but persisted in 1 animal at 48 and 72 hours. All effects were fully reversible within 7 days. Dicyclopentadiene 75% was a moderate irritant to the rabbit eye at 1 hour but was practically non-irritating at 24, 48 and 72 hours. According to EEC and GHS labelling regulations dicyclopentadiene is a non-irritant and requires no symbol or risk phrase.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Non human information

 

Skin

In what is considered to be the key skin irritation study in New Zealand White rabbits (Safepharm, 1989c) 0.5 mL of dicyclopentadiene 75% was applied to an area of clipped, intact skin under a semi-occlusive dressing for 4 hours. Animals were observed at 1 and 4 hours after removal of the patch and then daily for 7 days. Well-defined erythema and slight to severe oedema was present at all sites and for all rabbits at 24, 48 and 72 hour observation times. On day 7, no oedema was noted but there were signs of possible hyperkeratinisation. No other adverse dermal reactions were noted during the study. The overall mean scores (24, 48 and 72 h) were 2 for erythema and 2.3 for oedema; dicyclopentadiene 75% was a therefore considered to be a moderate irritant of rabbit skin.

In an older supporting study. New Zealandwhite rabbits were used to assess skin irritation following a 24 hour, uncovered, application of 0.01 mL undiluted dicyclopentadiene (Smyth 1962).  The overall irritation score (on a scale of 1 -10) was 5 and confirmed that undiluted dicyclopentadiene was moderately irritating to rabbit skin.

Eye

In what is considered to be the key eye irritation study in New Zealand White rabbits (Safepharm 1989d) 0.1 mL dicyclopentadiene 75% was instilled into the conjunctival sac and the eyes were scored for irritation responses at 1, 24, 48 and 72 hours and at 7 days after instillation. Moderate irritation was present at 1 hour in all 3 rabbit eyes; iridial inflammation and conjunctival irritation were present in all cases and corneal dulling was present in 2. However, signs of irritation regressed to minimal in 2 eyes at 24 hours. Although corneal redness persisted in 1 animal at 72 hours, all effects were fully reversible within 7 days.

In a supporting study (Litton Bionetics, 1976a) using undiluted dicyclopentadiene, initial conjunctival irritation was present in 7 out of 9 rabbits but had recovered by day 3. Undiluted dicyclopentadiene was practically non-irritating at 24, 48 and 72 hours in this study. 

Respiratory

Whilst there are no specific studies assessing respiratory irritation, laboured/ irregular breathing, nasal discharge and haemorrhagic lungs post mortem were evident in acute inhalation exposures of rats and mice (Bushy Run, 1981) and dose-dependent eye irritation was observed in a variety of species during acute inhalation exposures to neat dicyclopentadiene vapour (Kinkead et al, 1971).

Human information

Very little information has been reported on the irritation effects of dicyclopentadiene in humans. However, in a study in volunteers to determine the human sensory response to dicyclopentadiene vapour, 2 subjects inhaled analysed concentrations of 1 ppm and 5.5 ppm for 30 minutes (Kinkead et al, 1971). Both concentrations caused sporadic eye and throat irritation and one subject could taste dicyclopentadiene for 1 hr after the 5.5 ppm exposure. Human exposure to vapours of dicyclopentadiene is considered likely to result in respiratory and ocular irritation. The literature was reviewed (Amoore et al, 1983) to provide quantitative data on the odour thresholds of 214 chemicals including dicyclopentadiene. Data on the volatility, solubility, ionisation and water-air distribution ratio at 25ºC were collected and a safe dilution factor and an odour safety factor were calculated. For dicyclopentadiene the threshold limit value was 5 ppm v/v, the volatility at 25ºC was 3600 ppm v/v, the air odour threshold was 0.0057±1.9 ppm. The calculated safe dilution factor was 720 and the odour safety factor was 870. On the basis of these results, dicyclopentadiene was placed in odour safety class A (i. e. more than 90% of distracted persons perceived warning of TLV concentration in the air).

Effects on skin irritation/corrosion: moderately irritating

Effects on eye irritation: slightly irritating

Effects on respiratory irritation: irritating

Justification for classification or non-classification

The animal studies of both undiluted dicyclopentadiene and dicyclopentadiene 75% demonstrate moderate skin irritation and justify the classification of Category 2 (Irritant) with the hazard statement" H315 causes skin irritation" under CLP.

In the key study of eye irritation, dicyclopentadiene 75% was non-irritant but undiluted dicyclopentadiene showed slight eye irritation in a supporting study. Maintenance of the classification as Category 2 "H319 Causes serious eye irritation" under CLP is proposed.

The observations of respiratory tract irritation in animals and humans means that dicyclopentadiene warrants classification as Category 3 for transient target organ toxicity under STOT-RE under CLP.