With regard to repeat dose toxicity, a suppression of body weight gain and a decrease in food consumption were observed in both sexes of the 100 mg/kg/day group and two female rats of the same group died. Increases in GOT and GPT were also observed in this group. Histopathological examination revealed fatty droplets in zona fasciculate of adrenals of both sexes and single cell necroses in liver and hyaline droplets in tubular epithelium of kidneys of male rats in the 100 mg/kg/day group. Similar histopathological changes were found in the kidneys of male rats receiving 4 and 20 mg/kg/day. The NOELs for repeat dose toxicity are considered to be less than 4 mg/kg/day for males and 20 mg/kg/day for females. In terms of reproductive/developmental toxicity, the compound had the effects on the body weight of neonates and the viability index in the 100 mg/kg/day group. The NOELs for reproductive/developmental toxicity are considered to be 100 mg/kg/day for parental males, and 20 mg/kg/day for parental females and offspring.

Dicyclopentadiene did not induce structural chromosomal aberrations or polyploidys in CHL/IU cells up to a concentration more than that causing 50% cell growth inhibition, in the absence or presence of an exogenous metabolic activation system. Structural chromosomal aberrations were marginally induced by a high concentration (0.057 mg/ml) after 24-h continuous treatment. However, negative finding were confirmed in the in vitro micronucleus test.

1. Repeat Dose and Reproductive/Developmental Toxicity1)

Purity	:	94.65%
Test species/strain	:	Rat/Crj:CD (SD)
Test method	:	OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test
Route	:	Oral (gavage)
Dosage	:	0 (Vehicle), 4, 20, 100 mg/kg/day
Number of animals	:	Males, 10; females, 10/group
Vehicle	:	Olive oil
Administration period	:	Males, 44 days Females, from 14 days before mating to day 3 of lactation
Terminal kill	:	Males, day 45 Females, day 4 of lactation
GLP	:	Yes

　Test results:

<Repeat dose toxicity>

In the 100 mg/kg group, both male and female rats showed slight suppression of body weight gain and decrease in food consumption, and two female rats died. Histopathological examination showed single cell necroses in the liver, and hyaline droplets and basophilic change in the tubular epithelium of the kidneys in male rats. The weights of these organ were also increased. An increase of fatty droplets in the fascicular zone of the adrenals was observed in both male and female rats. Blood chemistry examination in male rats showed increases in GOT and GPT. Similar histopathological changes were found in the kidneys of the 4 and 20 mg/kg male rats and in the adrenals of the 20 mg/kg/day male rats. There were no hematological changes ascribable to the compound in any group. The NOELs for repeat dose toxicity are considered to be less than 4 mg/kg/day for males and 20 mg/kg/day for females.

<Reproductive and developmental toxicity>

The compound had no effects on reproductive parameters such as the mating index, the fertility index, gestation length, number of corpora lutea or implantations, the implantation index, the gestation index, the delivery index or parturition. Two dams of the 100 mg/kg group, however, lost all their litters during the lactation period. Examination of neonates, revealed a low viability index for the 100 mg/kg group, and tendencies for lower birth weight and body weight gain. There were no significant differences in number of offspring or live offspring at birth, the sex ratio or the live birth index. No abnormal findings ascribable to the compound were found for external features, clinical signs, or on necropsy of the offspring. The NOELs for reproductive and developmental toxicity are 100 mg/kg/day for parental males, and 20 mg/kg/day for parental females and offspring.

2. Genetic Toxicity

Purity	:	95%
Type of cell used	:	Chinese hamster lung (CHL/IU) cells
Test method	:	Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
Solvent	:	Acetone
Positive controls	:	-S9, Mitomycin C +S9, Cyclophosphamide
Doses	:	-S9 (continuous treatment): 0, 0.014, 0.029, 0.057 mg/ml -S9 (short-term treatment): 0, 0.014, 0.029, 0.057 mg/ml +S9 (short-term treatment): 0, 0.03, 0.05, 0.10 mg/ml
S-9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	2
GLP	:	Yes

　Test results:

Cytogenetic effects were not seen under the conditions of this experiment.

This chemical substance marginally induced structural chromosomal aberrations at the highest concentration (0.057 mg/ml) after 24-h continuous treatment. However, it was confirmed to be negative in the in vitro micronucleus test.

	clastogenicity				polyploidy
	+	?	-		+	?	-
without metabolic activation:	[ ]	[ ]	[*]		[ ]	[ ]	[*]
with metabolic activation:	[ ]	[ ]	[*]		[ ]	[ ]	[*]

1)	The tests were performed by the Mitsubishi Chemical Safety Institute Ltd., 14 Sunayama, Hasaki-machi, Kashima-gun, Ibaraki, 314-02, Japan. Tel +81-479-46-2871 Fax +81-479-46-2874
2)	The tests were performed by the Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa, 257, Japan. Tel +81-463-82-4751 Fax +81-463-82-9627