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Toxicological information

Endpoint summary

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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

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
590 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
1 972 mg/m³

Acute toxicity: via dermal route

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% dicylcopentadiene 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 asssigned 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% dicylcopentadiene 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.