Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

There are no data for TCDE.  Considering the read-across substance, DCPD, oral and inhalation exposure resulted in nephrotoxicity (alterations in renal function and kidney morphology) in male rats only and characteristic of hyaline droplet nephropathy, which is not relevant for human risk assessment. Other changes which were seen in male rats in all groups (including controls) were characteristic of chronic glomerulonephropathy. Mortality was seen in rats dosed with 100 mg/kg/day orally and in mice exposed to 51 ppm by inhalation. Apart from the effects on the kidney in (male rats only), there were few histopathological changes. Single cell necrosis in the liver and fatty changes in the adrenal glands were seen in the oral rat study only.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
4 mg/kg bw/day

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
27.6 mg/m³

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).

There are no data available for TCDE addressing the repeat dose endpoints therefore read-across to DCPD is considered below.

Non human Information


The key study is considered to be a combined repeat dose toxicity study with reproduction/developmental toxicity screening (JETOC, 1998a). Systemic toxicity at 100 mg/kg/day was indicated by the mortality of two female rats and, decreased food consumption and bodyweight gain in both males and females. There were pathological changes in the liver (single cell necrosis, males only) and adrenals (increase in fatty droplets, males and females) at 100 mg/kg/day. Similar changes were seen in the adrenals of some male rats dosed at 20 mg/kg/day. Male rat specific kidney pathology (hyaline droplet formation and basophilic changes in the tubular epithelium of the kidney) was observed in males in all dose groups. These findings are not relevant for human risk assessment.

The no effect level for systemic toxicity was therefore considered to be 20 mg/kg/day for females and 4 mg/kg/day for male rats (based on the adrenal effects at higher dose levels).

In the supporting study (Litton Bionetics, 1980), DCPD was administered by incorporation into the diet at concentrations of 100, 300 and 1000 ppm to male and female beagle dogs for 13 weeks. No significant toxicity was seen at any dose level. Minor indications of intestinal distress (vomiting and soft stools) seen at the highest dose (1000 ppm) were considered to be of no toxicological significance. The NOAEL of DCPD was therefore considered to be 1000 ppm (25 mg/kg/day) to beagle dogs following 13 weeks of dietary administration.


Key, GLP compliant studies, were conducted in Fischer 344 rats and B6C3F1 mice (Bushy Run, 1982). Vapour generation was carefully controlled and analysed to ensure that no cyclopentadiene was formed during vapour generation. Animals were exposed (whole body) to vapours of 0, 1, 5 or 50 ppm DCPD, 6 hr/day, 5 days/week for 13 weeks, followed by a 13-week recovery period. Animals were killed following completion of exposure at 2, 6, or 13 weeks and at post exposure weeks 4 or 13. 

There was no mortality in any of the rats but approximately 20% of the mice (both sexes) of the 51 ppm exposure group died during the exposure period.

In rats exposed to 51 ppm, relative liver weights were significantly increased in males.

The kidney effects seen only in male rats exposed to DCPD were reported by Bevan et al (1992) to be characteristic of alpha2u-nephropathy, which is considered to be of no relevance to human risk assessment.

The rat study indicates an overall low degree of systemic toxicity following sub-chronic inhalation exposure of DCPD at exposure levels up to 51 ppm.  As concluded by Bevan et al. (1992), increased liver weights in the absence of histopathologic changes were not considered to be an adverse effect. Excluding the male, rat-specific hyaline droplet nephropathy seen at 5.1 and 51 ppm during the exposure period, the no observed adverse effect concentration (NOAEC) in this study is therefore considered to be 51 ppm (276 mg/m3) for both males and females.  Since approximately 20% of the mice (both sexes) of the 51 ppm exposure group died during the exposure period, the NOAEC is also concluded to be 5.1 ppm (27.6 mg/m3) for male and female mice.

Human studies

In studies in human volunteers to ascertain the odour threshold of DCPD vapour for man and to determine the human sensory response (Kinkead et al, 1981), some inadvertent exposure to DCPD vapour occurred during the 5 month investigation period. Three workers experienced transitory headaches during the first 2 months, but not during the last 3 months.

Justification for classification or non-classification

3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-indene (TCDE) is not included in Annex I of the DSD. Considering the read-across candidate, DCPD, it is not classified for repeat dose toxicity under Annex I DSD or under CLP.

While some effects were seen in DCPD repeat dose studies, these are believed to be due to chronic irritation of the lungs and gastrointestinal tract with secondary stress-related effects rather specific target organ toxicity. DCPD is irritating; therefore it is biologically plausible that the mortality is mostly attributable to respiratory and gastric irritation effects rather than systemic effects. Liver effects seen in the rat oral study were not considered sufficient to warrant classification.

Repeated exposure inhalation studies in rodents show mortality at levels that would be predicted by their LC50s, and appears related to respiratory irritation/portal-of-entry effects. The original Bushy Run 90-day study showed mortality in the mice at 276 mg/m3. The LC50 in mice is about half that of rats, which might be expected for a respiratory irritant (higher ventilation rate in the mouse). This justification for non-classification for the repeat dose toxicity (mortality in mice) is supported by the existing acute inhalation classification for DCPD (Acute Cat 2).

In conclusion, as for DCPD, no classification for repeat dose toxicity is proposed for TCDE.