3a,4,7,7a-tetrahydro-4,7-methanoindene

Endpoint summary

Description of key information

Dicyclopentadiene is of slight - moderate acute toxicity by the oral and inhalation routes (oral LD50 590 mg/kg, inhalation 4 hour LC50 1972 mg/m3) and is practically non-toxic by the dermal route (dermal LD50 > 2000 mg/kg). The NOAEC for irregular breathing, stereotypic behaviour in rats and mice has been reported to be 248.74 mg/m3 (Bushy Run, 1981).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 September 1988 - 18 October 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Principles of method if other than guideline:

n/a

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): DCPD 75%
- Physical state: clear, yellow-coloured liquid
- Composition of test material, percentage of components: 71.1% endo dicyclopentadiene, 0.8% exo dicyclopentadiene, 1.4% m-bicyclozonadiene, 15.2% CPD-MCPD codimers, 0.3% tricyclopentadiene, 1.3% CPD-butadiene codimer, 0.3% CPD-piperylene codimer, 0.3% CPD-isoprene codimer, <0.1% benzene , remainder misc. hydrocarbons.
- Specific gravity: 0.971
- Storage condition of test material: room temperature

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna (UK) Ltd., Wyton, Huntingdon, Cambridgeshire, UK
- Age at study initiation: 5-8 weeks
- Weight at study initiation: males 120-146 g; females 120-150 g
- Fasting period before study: overnight
- Housing: In groups of up to 5, sexes separately in solid floor polypropylene cages with sawdust bedding
- Diet: Rat and Mouse Expanded Diet No. 1 (Special Diet Services Ltd., Witham, Essex, UK) ad libitum (except for overnight fast immediately prior to dosing and approximately 2 hours after dosing)
- Water: Mains drinking water ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20-21°C
- Humidity: 45-68%
- Air changes (per hr): approx 15
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 22 September 1988 To: 18 October 1988

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Maximum dose volume applied: 2.06 mL/kg
Minimum dose volume applied: 0.51 mL/kg

Doses:

500, 794, 1260 and 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed 1 and 4 hours after dosing and once daily thereafter.
- Body weights: recorded on day of dosing (day 0), days 7, 14 or at death.
- Necropsy of survivors performed: yes

Statistics:

The acute oral LD50 and 95% confidence limits calculated using the probit method.

Preliminary study:

n/a

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

590 mg/kg bw

95% CL:

393 - 886

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

512 mg/kg bw

95% CL:

227 - 1 155

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

676 mg/kg bw

95% CL:

444 - 1 030

Mortality:

All deaths occurred one or two days following dosing. There were 2, 4, 5 and 5 male deaths and 1, 2, 5 and 5 female deaths in the 500, 794, 1260 and 2000 mg/kg bw groups, respectively.

Clinical signs:

other: other: Hunched posture, piloerection, lethargy and decreased respiratory rate were present in all animals during the day of dosing. Ptosis was occasionally noted in animals dosed with 794 or 1260 mg/kg during this period and inall rats dosed with 2000 mg/

Body weight:

other body weight observations

Gross pathology:

Haemorrhagic lungs, dark liver and sloughing of the non-glandular gastric epithelium were seen in decedents. No abnormalities were seen in animals killed at the end of the study.

Other findings:

n/a

n/a

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 and 95% confidence limits of dicyclopentadiene 75% were calculated to be 590 (393-886) mg/kg bw for males and females combined; 512 (227-1155) mg/kg bw for males and 676 (444-1030) mg/kg bw for females.

Executive summary:

In this OECD 401 study, groups of 5 male and 5 female Sprague Dawley rats (fasted overnight) were dosed by gavage at levels of 500, 794, 1260 or 2000 mg/kg dicycolpentadiene and were observed daily for 14 days after dosing. At the 4 hour observation period rats dosed with high levels of dicyclopentadiene (1260 or 2000 mg/kg bw) had hunched posture, piloerection, lethargy and decreased respiratory rate, with ptosis and occasional signs of ataxia seen in those dosed at 2000 mg/kg bw. All rats dosed at 1260 or 2000 mg/kg bw died one or two days after dosing. Haemorrhagic lungs, dark liver and sloughing of the non-glandular gastric epithelium was seen in decedents. The LD50 was calculated to be 590 mg/kg bw (male/female), 512 mg/kg (male) and 676 mg/kg/bw (female).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

590 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Remarks:

GLP compliant, near guideline study, available as unpublished report, adequate for assessment

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

6 hour exposure

Principles of method if other than guideline:

n/a

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

- Supplier: Exxon (Baton Rouge, LA)
- Batch number (assigned Chemical Hygiene Fellowship (CHF) Sample Number): 41-379
- Name of test material (as cited in study report): Dicyclopentadiene (DCPD)
- Physical state: clear colourless liquid at room temperature
- Analytical purity: ~97% endo- and ~1% cyclopentadiene

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Microbiological Associates, Walkersville, Maryland, USA
- Age at study initiation: no data
- Weight at study initiation: no data
- Fasting period before study: no
- Housing: 2 per cage in stainless steel cages
- Diet: powdered chow diet ad libitum except during exposure
- Water: ad libitum except during exposure
- Acclimation period: approximately 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature: 69-74°F
- Humidity: 30-63%
- Photoperiod: 12 hrs dark /12 hrs light

IN-LIFE DATES: no data

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: air

Remark on MMAD/GSD:

n/a

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Dicyclopentadiene vapour was generated inside a heated Pyrex tube to achieve complete vaporization while keeping temperature below the point (35°C) at which fracturing to monomer occurred.

TEST ATMOSPHERE
- Chamber concentrations of dicyclopentadiene and cyclopentadiene (CPD) were monitored by gas chromatography/flame ionization detection with detection limit of 0.05 ppm for both compounds.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

by gas chromatography/flame ionization detection

Duration of exposure:

6 h

Concentrations:

Target concentrations were 50, 150, 300 and 600 ppm.
Actual exposure concentrations were 46, 130, 260 and 557 ppm.

No. of animals per sex per dose:

6

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: animals were observed daily for clinical signs
- Necropsy of survivors performed: yes

Statistics:

LC50 was calculated by the method of moving averages.

Preliminary study:

n/a

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

284 ppm

95% CL:

>= 236 - <= 341

Exp. duration:

6 h

Remarks on result:

other: 1536 mg/m3 air (analytical)

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

353 ppm

95% CL:

>= 322 - <= 387

Exp. duration:

6 h

Remarks on result:

other: 1910 mg/m3 air (analytical)

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1 723 mg/m³ air (analytical)

Exp. duration:

6 h

Sex:

male/female

Dose descriptor:

other: NOAEC for irregular breathing, stereotypic behaviour

Effect level:

46 ppm

Remarks on result:

other: 248.74 mg/m3

Mortality:

There were mortalities in male and female rats exposed to 557 or 260 ppm. (The actual numbers of rats dying at the various exposure levels were not presented in the report).

Clinical signs:

other: Male and female rats at 557 ppm showed loss of righting reflex, impaired gait, stereotypic behaviour, laboured breathing, nasal discharge, convulsions and death. At 260 ppm, both sexes showed stereotypic behaviour, respiratory difficulty and nasal dischar

Body weight:

No data

Gross pathology:

There were no gross pathological effects noted at necropsy

Other findings:

n/a

Incidence of mortality following single 6-hour inhalation exposure

Target Concentration (ppm)	Dead/dosed		Comment
	male	female
600	6/6	6/6	Males: One died during exposure. 3 died immediately post-exposure. 2 found dead on the day after exposure. Females: All found dead on the day after exposure.
300	2/6	0/6	Males: 2 found dead the day after exposure.
150	0/6	0/6
50	0/6	0/6

 

Interpretation of results:

Category 2 based on GHS criteria

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Following a 6 hour whole body, inhalation exposure to dicyclopentadiene vapour, the LC50 was 284 (236-341) ppm (male) and 353 (322-387) ppm (female). The results were not confounded by the fracturing of dicyclopentadiene into cyclopentadiene. The male/female 6 hour LC50 is equivalent to 1723 mg/m3.

Executive summary:

In this study, groups of 6 male and 6 female Fischer 344 rats were exposed (whole body) to 46, 130, 260 or 557 ppm dicyclopentadiene vapour for 6 hours and then observed daily for up to 14 days. At 557 ppm, one male died during exposure, 3 died immediately post-exposure and 2 were found dead on the day after exposure; all females were found dead on the day after exposure. At 260 ppm, two males were found dead on the day after exposure, all females survived. Clinical signs included loss of righting reflex, impaired gait, stereotypic behaviour, laboured breathing, nasal discharge and convulsions. The LC50 was 284 ppm (male) and 353 ppm (female), equivalent to 1536 and 1910 mg/m3, respectively.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

1 972 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 September 1988 - 6 October 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Principles of method if other than guideline:

n/a

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Supplier: Dow Chemical Europe SA
- Batch number (Sponsor's identification): DCPD 75%- Name of test material (as cited in study report): DCPD 75%
- Physical state: clear, yellow-coloured liquid
- Composition of test material, percentage of components: 71.1% endo dicyclopentadiene, 0.8% exo dicyclopentadiene, 1.4% m-bicyclozonadiene, 15.2% CPD-MCPD codimers, 0.3% tricyclopentadiene, 1.3% CPD-butadiene codimer, 0.3% CPD-piperylene codimer, 0.3% CPD-isoprene codimer, <0.1% benzene , remainder misc. hydrocarbons.
- Specific gravity: 0.971
- Storage condition of test material: room temperature

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna (UK) Ltd., Wyton, Huntingdon, Cambridgeshire, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: males 231-256 g; females 210-255 g
- Fasting period before study: None
- Housing: Solid floor polypropylene cages with sawdust bedding
- Diet: Rat and Mouse expanded Diet No. 1 (Special Diet Services Ltd., Witham, Essex, UK) ad libitum
- Water: Mains drinking water ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20-21°C
- Humidity: 45-68%
- Air changes: approximately 15 per hour
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 22 September 1988 To: 6 October 1988

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: shorn skin on back and flanks
- % coverage: 10%
- Type of wrap if used: aluminium foil occluded with double layers of adhesive strapping wound around trunk of animal

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with moist cotton wool
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.06 mL/kg bodyweight
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bodyweight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed 1 and 4 hours after dosing and daily thereafter for 14 days. Bodyweights recorded on day of treatment and on days 7 and 14
- Necropsy of survivors performed: no

Statistics:

None, acute LD50 estimated.

Preliminary study:

n/a

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

None

Clinical signs:

other: other: Vocalisation, lasting up to 30 minutes, noted in all animals after dosing. Hunched posture, lethargy, piloerection, erythema and oedema present in all animals on day 1. Continued in 'Any other information on results'

Body weight:

other body weight observations

Gross pathology:

No abnormalities were seen.

Other findings:

n/a

Clinical signs continued:

Isolated incidences of red/brown staining of snout and ptosis observed. These reactions regressed and by Day 3 all animals showed signs of eschar which persisted until Day 10 and Day 12 in two animals. All treatment sites appeared normal by the end of the study period.

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The acute dermal LD50 of dicyclopentadiene 75% to the rat was greater than 2000 mg/kg body weight.

Executive summary:

The acute dermal toxicity of dicyclopentadiene 75% was assessed in a group of 5 male and 5 female rats. 2.06 mL/kg body weight was applied to the shorn flank and held in place with an occlusive dressing. Animals were observed at 1 and 4 hours after dosing and then daily for 14 days. Clinical signs present on day 1 included vocalisation lasting up to 30 minutes (noted in all animals after dosing), hunched posture, lethargy, piloerection, erythema and oedema, . Isolated incidences of red/brown staining of snout and ptosis were seen. All animals showed signs of eschar by day 3 which persisted until days 10 or 12. All treatment sites appeared normal by the end of study. All animals gained weight and there were no gross abnormalities at necropsy. The acute dermal LD50 of dicyclopentadiene 75% in the rat was greater than 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Non human information

Acute toxicity : oral

In what is considered to be the key study (Safepharm, 1989a), groups of fasted Sprague Dawley rats were dosed by gavage at dose levels of 500, 794, 1260 or 2000 mg/kg of resin grade dicyclopentadiene with a purity of 75% dicyclopentadiene and observed daily for 14 days after dosing. Signs of toxicity (including lethargy and decreased respiratory rate) were seen after dosing with 1260 or 2000 mg/kg bw, with ptosis and occasional signs of ataxia seen 4 hours after dosing with 2000 mg/kg bw. All rats dosed with 1260 or 2000 mg/kg bw died one or two days after dosing. Haemorrhagic lungs, dark liver and sloughing of the non-glandular gastric epithelium were seen in decedents. The LD50 was calculated to be 590 mg/kg bw (male/female); 512 mg/kg for males and 676 mg/kg/bw for females.

In supporting studies by Litton Bionetics (1976c) the oral LD50 in the Sprague Dawley rat was 449 mg/kg (male/female); 520 mg/kg for males and 378 mg/kg for females. Slightly lower LD50 values were found in Swiss Webster mice: 220 mg/kg (male/female); 190 mg/kg for males and 250 mg/kg for females. Although the mouse acute oral LD50 values are slightly lower than the rat, the mouse acute toxicity studies have a Klimisch code of 2 while the key study in the rat was assigned a Klimisch code of 1. Furthermore, OECD guideline 401 states that although several mammalian test species may be used, the rat is the preferred rodent species.

 

Acute toxicity : inhalation

Key, near-guideline studies assessing the acute inhalation toxicity of dicyclopentadiene exposure in rats and mice for 6 hours have been reported (Bushy Run, 1981). These studies were conducted to obtain a definitive LC50 value that was not confounded by fracturing of the dicyclopentadiene (previous publications have given conflicting LC50 values that might have been caused by loss of dicyclopentadiene via fracturing). Chamber concentrations of dicyclopentadiene and cyclopentadiene were monitored by gas chromatography/flame ionization detection with a detection limit for both chemicals of 0.05 ppm; cyclopentadiene was below the detection limit in both studies.  

In the rat study, groups of Fischer 344 rats were exposed for 6 hours to vapours containing 46, 130, 260 or 557 ppm and then observed daily for up to 14 days. At 557 ppm, all females were found dead on the day after exposure and all males died within 24 hours of exposure. At 260 ppm, two males were found dead on the day after exposure, all females survived. Clinical signs included loss of righting reflex, impaired gait, stereotypic behaviour, laboured breathing, nasal discharge and convulsions. The 6 hour LC50 was 284 ppm for males and 353 ppm for females, equivalent to 1723 mg/m3 (male/female). Conversion of this result using Haber's rule (n=3) gives a 4 hour LC50 equivalent of 1972 mg/m3 for males and females.  The NOAEC for irregular breathing and stereotypic behaviour was 46 ppm (248.74 mg/m3).

In the mouse study, groups of B6C3F1 mice were exposed for 6 hours to the same vapour concentrations of dicyclopentadiene and then observed daily for up to 14 days. At 557 ppm, all mice died within 24 hours of exposure. At 260 ppm, all males were found dead on the day after exposure and all females died during exposure or within 24 hours. At 130 ppm, 2 males and 3 females died within 24 hours of exposure. There were no deaths at 46 ppm. Clinical signs included loss of righting reflex, impaired gait, stereotypic behaviour, laboured breathing, clear nasal discharge, loss of coordination and convulsions prior to death. The 6 hour LC50 was 143 ppm for males and 126 ppm for females, equivalent to 738.5 mg/m3 (male/female). The NOAEC for irregular breathing and stereotypic behaviour was 46 ppm (248.74 mg/m3).

Supporting studies assessed the acute inhalation toxicity of dicyclopentadiene exposure for 4 hours in rats, mice, dogs and rabbits (Kinkead et al, 1971).  The LC50 in the male albino rat was 359.4 ppm (1943 mg/m3) and in the female was 385.2 ppm (2083 mg/m3). These values are consistent with the LC50 equivalent of 1972 mg/m3 for males and female rats calculated using Haber's rule from the Bushy Run, (1981) study. For the male mouse the 4 hour LC50 was 145.5 ppm (787 mg/m3) and for the male rabbit was 771 ppm (4171mg/m3).  For the female dog, the 4 hour LC50 was between 458 and 773 ppm (2473-4174 mg/m3).  Poor coordination and convulsions were seen in all species, especially prior to death and eye and nose irritation, lachrymation and tremors were observed in the dog study.

Acute toxicity : dermal

In what is considered to be the key study (Safepharm 1989b), the acute dermal toxicity of resin grade dicyclopentadiene with a purity of 75% dicyclopentadiene was assessed in a group of 5 male and 5 female rats. 2000 mg/kg bodyweight of the chemical was applied to an area of clipped, intact dorsal skin and held in place with an occlusive dressing. Animals were observed at 1 and 4 hours after dosing and then daily for 14 days. Clinical signs present in all animals on day 1 included vocalisation for up to 30 minutes, hunched posture, lethargy, piloerection, erythema and oedema.  All animals showed signs of eschar by day 3 which persisted until days 10 or 12 but all treatment sites appeared normal by the end of the study. The acute dermal LD50 of dicyclopentadiene 75% to the rat was greater than 2000 mg/kg bodyweight.  In two rabbit studies, the acute dermal LD50 of undiluted dicyclopentadiene was 4460 mg/kg bw (Smyth et al, 1962) and 6720 mg/kg bw (Smyth et al, 1954). No observations of systemic toxicity were reported.

Human information

No relevant information

Justification for classification or non-classification

Dicyclopentadiene is harmful by the oral route with an LD50 value of 590 mg/kg which justifies classification Category 4 (H302) under CLP (Harmonised classification).

Considering the data presented, the calculated 4 hr LC50 of 1972 mg/m3 justifies classification as Category 2 classification under CLP H330 (Fatal if inhaled).

Dicyclopentadiene is of low acute toxicity by the dermal route with an LD50 greater than 2000 mg/kg and therefore does not warrant classification under CLP for dermal exposure.