1,4:5,8-Dimethanonaphthalene, 2-ethylidene-1,2,3,4,4a,5,8,8a-octahydro-

Endpoint summary

Description of key information

Acute oral toxicity, Rats, LD50 = 849 mg/kg both sexes (95% CL 658 - 1068 mg/kg); 666 mg/kg males (488 - 895 mg/kg); 1089 mg/kg females (804 - 1471 mg/kg).
Acute dermal toxicity, Rats, LD50 > 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

849 mg/kg bw

Additional information

An acute oral toxicity study (CIVO-Instituten TNO, 1989) was conducted to assess the toxicity of ETD following a single oral administration to rats. The study was conducted according to OECD test guideline 401 and in compliance with GLP.

Groups of 5 males and 5 females per dose level were administered ETD as a formulation in Maize Oil by oral gavage then observed for up to 14 days post-administration. Surviving animals were sacrificed after the observation period, and a pathological examination performed. Dose levels were: 337, 506, 759, 1139, 1709, and 2562 mg/kg bodyweight.

All male animals died at the 1139, 1709 and 2562 mg/kg levels; 2 out of 5 males died at the 507 and 759 mg/kg dose levels; no males died at the 337 mg/kg level. All females died at the 2562 mg/kg level; 4 out of 5 females died at the 1709 mg/kg dose level, 2 out of 5 females died at the 759 and 1139 mg/kg levels, and no females died at the 507 mg/kg level. At each dose level, deaths occurred within 2 days of dosing. Macroscopic examination of rats after death or terminal sacrifice did not reveal any treatment related changes at any of the dose levels. The LD₅₀ (with 95% Confidence limits) was found to be 666 (488 - 895) mg/kg bw in males, 1089 (804 - 1471) mg/kg bw in females, and 849 (658 - 1068) mg/kg bw for both sexes combined.

An acute dermal toxicity study (Huntingdon Life Sciences, 2010) was conducted to assess the toxicity of ETD following a single dermal exposure to rats. The study was conducted according to OECD test guideline 402, EC test guideline B3, and US EPA OPPTS 870.1200, and in compliance with GLP.

5 Male and 5 female rats were administered a single dermal dose at a limit concentration of 2000 mg/kg bodyweight for 24 hours. The animals were observed for 14 days after administration. Surviving animals were sacrificed and a pathological examination was conducted.

No animals died during the observation period. Clinical signs were limited to reddening of the extremities (seen in all animals on the day of dosing, and fully recovered by day 4) and brown staining on the head (seen in all females on day 2 and fully recovered by day 9). No abnormalities were observed during the gross pathological examination of all animals conducted at the end of the observation period.

No inhaled toxicity study was conducted, as the requirement for an acute toxicity study by a second route of exposure was satisfied by the dermal toxicity study, noted above. It is considered unlikely that ETD will be available in a vapour or other airborne / inhalable state.

Justification for classification or non-classification

The LD50 by oral administration was determined to be 849 mg/kg bodyweight in rats (666 mg/kg bw in males; 1089 mg/kg bw in females). According to the CLP Regulation (Regulation (EC) 1272/2008), classification as Acute Toxiticy Category IV applies when the LD50 is greater than 300 mg/kg but equal to or less than 2000 mg/kg. On this basis, ETD will be classified Acute Toxicity (oral) category IV; the signal word "Warning" and the Hazard statement "H302: Harmful if swallowed" are applicable. The corresponding classification according to the Dangerous Substances Directive (Directive 67/548/EEC, DSD) is "R22, Harmful if swallowed", applicable when the acute oral LD50 is between 200 and 2000 mg/kg.

The LD50 by dermal administration to rats was determined to be greater than 2000 mg/kg; on this basis no classification is required for dermal toxicity according to either the CLP regulation, or the DSD.

Neither of the studies noted above indicated a specific target organ for toxicity. In the absence of an acute inhaled toxicity study it is not possible to state conclusively that ETD displays no Specific Target Organ Toxicity (STOT) by any exposure route (oral, dermal, or inhaled), and so although no classification for STOT (single exposure) is applied, the available data is considered inconclusive.