Registration Dossier

Administrative data

Description of key information

In an in vitro EpiDerm™ Skin Corrosion Test (non-GLP, similar to OECD TG 431) 1,2,3,4-Tetrahydroisoquinoline was found to be moderately corrosive (viability reduced to 47% and 14% after exposure for 3 minutes and 1 hour, respectively). Skin effects indicative of corrosivity were also observed in the acute dermal toxicity test in rats (24 hours exposure, semi-occlusive, to 1000 mg/kg bw).

Key value for chemical safety assessment

Additional information

Skin irritation/corrosion:

A non-GLP in vitro EpiDerm™ Skin Corrosion Test (similar to OECD guideline 431) was available for assessment (BASF AG, 2006c). The corrosive potential of 1,2,3,4-Tetrahydroisoquinoline was predicted from the mean relative (to negative control) tissue viabilities obtained after exposure periods of 3 minutes or 1 hour (two tissues per exposure condition). The study included a concurrent positive control which showed the expected marked reduction of viability (to 20% and 9% after 3 minutes and 1 hour, respectively). A substance is considered corrosive to skin (i) if the viability after 3 minutes exposure is less than 50%, or (ii) if the viability after 3 minutes exposure is ≥ 50% and that after 1 hour exposure <15%. The test material was applied undiluted (pH undiluted: ca. 8). The mean tissue viability after exposure to the test material was 47% (3 minutes) and 14% (1 hour), indicating that the test material was corrosive to skin. Though the test method does not yet allow for the differentiation of severity of the effect, the results indicated moderate corrosivity. 


Skin effects indicative of corrosivity were also observed in a GLP-compliant acute dermal toxicity test (OECD 403) in which five male and five female Wistar rats were treated with a single dose of 1000 mg 1,2,3,4-Tetrahydroisoquinoline/kg body weight on the clipped skin, covered by a semi-occlusive dressing, for 24 hours (BASF AG, 2006b). All animals were killed in a moribund state on study day 1. On this day, the following skin effects were observed at the application site: very slight edema, induration, dryness, and red and dark-brown discoloration. Histopathological examination of the skin revealed moderate to extreme epidermal and follicular necrosis with pyknosis, and necrotic epidermis remaining in situ. Minimal inflammatory infiltrates were observed in 1 male animal.


Respiratory irritation:

Effects observed in repeated-dose inhalation toxicity studies with 1,2,3,4-Tetrahydroisoquinoline in rats (GLP-compliant 90-day study according to OECD TG 413 and pertaining 14-day range-finding study) indicated irritation of the respiratory tract (BASF SE, 2012). A summary of the methods and results of the 90-day study is given in the endpoint summary under 7.5 ‘Repeated dose toxicity’. Results indicative of respiratory irritation included clinical symptoms (salivation, reduced fur care, escape attempts) and histopathological changes at the base of the epiglottis (epithelial alteration, squamous metaplasia, submucosal lymphohistiocytic inflammation) at the mid- and/or high-concentration (24.7 and 75.1 mg/m³ , respectively). Histopathology results of the range-finding study revealed strong irritation of the upper respiratory tract at the high-concentration of 150 mg/m³ (level I nasal cavity: degeneration of squamous epithelium, in some animals with ulceration; level I larynx: epithelial alteration, mucous cell metaplasia and lympoid cell infiltration; large bronchi: mild mucous cell hyperplasia).

Justification for classification or non-classification

Skin irritation/corrosion:

Based on the in vitro skin corrosion test, 1,2,3,4-Tetrahydroisoquinoline needs to be classified as corrosive to the skin and eyes according to Directive 67/548/EEC (C; R34 Causes burns) and according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 (Cat. 1B, H314: Causes severe skin burns and eye damage).