Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
NOAEL
50 mg/kg bw/day
Additional information

As detailed in section 5.1.3 of the CSR (IUCLID 7.1.1),3a,4,7,7a-tetrahydro-4,7-methanoindene (DCPD) is considered an appropriate read-across candidate where data are not available for3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-indene (TCDE).

Non -human information

In a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD Guideline 422), DCPD was administered to rats by oral gavage at dose levels of 0, 4, 20 or 100 mg/kg/day. No study details have been made available other than a summary information sheet provided by the Japan Chemical Industry Ecology-Toxicology and Information Centre (JETOC, 1998a).

The study design for OECD Guideline 422 includes administration of the test substance for two weeks prior to the mating of male and female rats and, during mating (approximately 2 weeks). The females continue to be dosed throughout gestation and until termination on day 4 of lactation. The males are dosed through to approximately day 45 of the study.

Signs of systemic toxicity were seen in males and females given 100 mg/kg/day. In addition, two females lost their litters during lactation and two are reported to have died. It is not possible to establish if the rats that lost their litters are the same ones that died or were perhaps killed because of their litter loss. At this same dose level, the pups were found to have lower birth weights and lower weight gain and had a low viability index. Similar effects of treatment were not seen with the lower dose levels of 20 and 4 mg/kg/day. DCPD had no effect on mating, fertility, gestation length or parturition at any dose level tested. On the basis of this study, the oral (gavage) NOAEL for systemic and reproductive toxicity is 20 mg/kg/day.

In a three generation reproduction study (Litton Bionetics, 1980) with two litters per generation, dicyclopentadiene was administered to rats (10 males and 20 females per dose) in the diet at nominal concentrations of 0, 80 or 750 ppm (69.3, 693 ppm actual concentrations). The second and third generations were derived from the second (b) litters. No treatment-related effects were observed on the general condition of the animals or their reproductive performance. The NOAEL was 693 ppm.

According to the BG Chemie Toxicological Evaluation No. 84 (dicyclopentadiene), the highest concentration (693 ppm) was judged equivalent to a daily intake of 50 mg/kg body weight at an assumed feed intake of 70 g/kg body weight/day. Consideration of the reported food and body weight data at week 4 (when the amount of DCPD consumed would be high in relation to body weight) indicates that males of 300g body weight consuming 25g diet would receive 58 mg/kg/ body weight/day and females of 200g body weight consuming 25g diet would receive 87 mg/kg/ body weight/day. The value for females would not be exceeded during pregnancy. On the basis of this study, the oral (dietary) NOAEL for systemic and reproductive toxicity is therefore at least 50 mg/kg/day.

On the basis of these reproduction studies, the oral NOAEL for reproductive toxicity for DCPD is at least 50 mg/kg/day.


Short description of key information:
There are no human data available for effects of TCDE or the read-across substance, DCPD, on fertility. A potential key study on DCPD conducted to OECD guideline 422 has been conducted although only minimal study details have so far been made available. This study uses the oral (gavage) route of administration. Data from a three generation reproduction study for DCPD (dietary route of exposure) are also available. There are no reproduction studies available using the dermal or inhalation routes of exposure to TCDE or the read-across substance, DCPD.

Effects on developmental toxicity

Description of key information
There are no human data available for developmental effects of TCDE or the read-across substance, DCPD, in humans.  A key developmental toxicity study using the dietary rout of exposure to DCPD is available together with data from dose range finding studies in pregnant rats and rabbits using the oral (gavage) route of exposure.  These latter studies do not include foetal examination. There are no developmental toxicity studies available using the dermal or inhalation routes of exposure to TCDE or DCPD.  
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
60 mg/kg bw/day
Additional information

As detailed in section 5.1.3 of the CSR (IUCLID 7.1.1), 3a,4,7,7a-tetrahydro-4,7-methanoindene (DCPD) is considered an appropriate read-across candidate where data are not available for 3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-indene (TCDE).

Non-human information

No data are available for TCDE.

A developmental toxicity study in rats was conducted using the dietary route of oral exposure to DCPD (Litton Bionetics, 1980). This is considered to be the key study and includes standard (guideline) methods of evaluation. Dietary concentrations of 0, 80, 250 or 750 ppm were fed to groups of 20 time-mated rats on days 6-15 of gestation(where day 0 was the day of confirmation of mating). There was no maternal toxicity and no developmental toxicity at any dietary level and therefore 750 ppm was a NOAEL.

According to the BG Chemie Toxicological Evaluation No. 84 (Dicyclopentadiene), the highest concentration (750 ppm) was judged equivalent to a daily intake of 150 mg/kg body weight at an assumed feed intake of 200 g/kg body weight/day. Consideration of the reported food and body weight data for days 6-15 of gestation indicates that females of 250g body weight consuming 20g diet would receive 60 mg DCPD/kg body weight/day.

On the basis of this study, the oral (dietary) NOAEL for maternal and developmental toxicity is 60 mg/kg/day.

Limited data are available for the oral (gavage) route of administration of DCPD. Dose range finding studies have been conducted in pregnant rats and rabbits (Gulati, 1993). These provide data on maternal toxicity but little information on developmental toxicity because there was no visceral or skeletal examination of the foetuses. Groups of 11 time-mated rats were dosed with 0, 50, 200, 300, 400 or 500 mg/kg/day on days 6-15 of gestation (where day 0 was the day of confirmation of mating). Dose levels of 300mg/kg/day or more caused maternal lethality; a single death occurred in the 200mg/kg/day group. Reduced body weight gain was observed in females given 50 or 200 mg/kg/day. Lower foetal weight was associated with 200 mg/kg/day but not with 50 mg/kg/day. A NOAEL for maternal toxicity was not established in this study.Groups of 10 mated New Zealand White rabbits were dosed with 0, 25, 100, 200, 300 or 400 mg/kg/day on days 6-19 of gestation (where day 0 was the day of mating). Signs of systemic toxicity and lethality were observed in the 300 and 400 mg/kg/day groups. Maternal body weight gain was reduced in the 200 mg/kg/day group. One animal from the 100 mg/kg/day group aborted its litter and on the basis of this, the NOAEL for maternal toxicity was considered to be 25 mg/kg/day. 

Justification for classification or non-classification

Considering the read across substance, DCPD, is not toxic to reproduction and has no effect on fertility or development, it is concluded that TCDE does not warrant classification under DSD or CLP.