Ethyl 2-(dimethylamino)-1-phenylcyclohex-3-ene-1-carboxylate

Endpoint summary

Description of key information

In an acute oral toxic class method (OECD 423 guideline study, GLP compliant) the LD50 of a structural analogous of ethyl 2-(dimethylamino)-1-phenylcyclohex-3-ene-1-carboxylate was determined to be greater than 300 mg/kg bw and less than 2000 mg/kg bw. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

500 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No studies on acute oral toxicity of ethyl 2-(dimethylamino)-1-phenylcyclohex-3-ene-1-carboxylate were available. However, Article 13 of REACH states that, in case no appropriate animal studies are available for assessment, information should be generated whenever possible by means other than vertebrate animal tests, i.e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across. Four acute oral toxicity studies with two different structural analogous of ethyl 2-(dimethylamino)-1-phenylcyclohex-3-ene-1-carboxylate are available.

 

In an acute toxic class method test (OECD 423 guideline study, GLP compliant) trans Tilidine oxalate was administered to female Wistar rats by oral gavage. One group of three female rats were exposed to 300 mg/kg bw, followed by a group of three female rats exposed to 2000 mg/kg bw and another group of three female rats exposed to 300 mg/kg bw. After an observation period of 14 days surviving animals were necropsied. All animals exposed to 2000 mg/kg bw died within one day after administration. No mortality was observed in animals exposed to 300 mg/kg bw. Clinical observation in the 2000 mg/kg bw test group revealed impaired and poor general state, dyspnoea, staggering, abdominal position, ataxia, twitching, chromodacryorrhea, exophthalmos, flat respiration, high stepping gait and salivation from hour 0 up to hour 5 after administration. In the two 300 mg/kg bw test groups impaired and poor general state, dyspnoea, ataxia, staggering, abdominal position, exophthalmos, piloerection, reduced feces, exsiccosis and salivation was observed from hour 0 until study day 2 after administration. The mean body weight of the surviving animals increased throughout the study period within the normal range. Dark spotted discoloration in all lobs of the lung was observed in two animals that died in the 2000 mg/kg bw group. Two animals showed gaseous stomach, filled with liquid content and two animals were found to have red discoloration of content in the small intestine and red discoloration of the small intestine. No pathological findings were observed in animals exposed to 300 mg/kg bw. The LD50 was therefore determined to be greater than 300 mg/kg bw and less than 2000 mg/kg bw. Based on Annex 2c of OECD Guideline 423, the LD50 is 500 mg/kg bw.

 

Three acute oral toxicity studies were performed with Tilidine Hydrochloride. Ten SIV 50 male rats per dose (Hermann 1970, rat), ten NMRI male mice per dose (Hermann 1970, mouse), and 2 dogs (male/female) per dose (Hermann 1970, dog) were exposed via oral gavage. Animals were observed for 7 days, clinical signs and mortality were recorded. The typical Straub-like tail phenomenon was observed at doses ten times the analgesic dose. Tonic-clonic convulsions were observed at higher doses. In dogs ataxia, salivation and tremor were additionally observed. The LD50s were determined to be 417.7 mg/kg bw, 437 mg/kg bw, and ca. 500 mg/kg bw for male rats, male mice and male/female dogs, respectively.

Justification for selection of acute toxicity – oral endpoint
Four acute oral toxicity studies are performed with two different structural analogous of ethyl 2-(dimethylamino)-1-phenylcyclohex-3-ene-1-carboxylate. The toxic effects levels are very similar. The study with the highest Klimisch score was chosen as key study.

Justification for classification or non-classification

Because an oral LD50 of 300-2000 mg/kg bw for a structural analogous, and LD50s of 417.7 mg/kg bw, 437 mg/kg bw, and ca. 500 mg/kg bw for another structural analogous, of ethyl 2-(dimethylamino)-1-phenylcyclohex-3-ene-1-carboxylate were determined it is expected that ethyl 2-(dimethylamino)-1-phenylcyclohex-3-ene-1-carboxylate will also have similar level of toxicity.

Based on this ethyl 2-(dimethylamino)-1-phenylcyclohex-3-ene-1-carboxylate is classified for Acute toxicity Cat 4: H302: Harmful if swallowed in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008 and Xn: R22: Harmful if swallowed in accordance with EU Directive 67/548 (DSD).