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Key value for chemical safety assessment

Additional information

Cited from SIAR to SIAM 19 (Berlin, 19-22 October 2004)

In vitro Studies

In an Ames test performed according to the original publication by B. Ames (1975) with Salmonella typhimurium TA 1535, TA 1537, TA 1538, TA 98, and TA 100, test substance concentrations of 10; 50; 100; 250; 500; 1000; 5000 μg/plate were employed in the presence and absence of Aroclor induced rat liver S9 mix. Cytotoxicity was observed at > 50 μg/plate (-S9) and > 500 μg/plate (+S9), respectively. At non-toxic test substance concentrations, a significant increase in mutant frequency was not observed (Hüls AG, 1988). A negative result in the Ames test (+/- Aroclor 1254 induced rat liver S9 mix) was also obtained by Florin et al. (1980) using the same strains except TA 1538 and doses of 0.03; 0.3; 3; 30 μmol/plate (ca. 4; 40; 400; 4,000 μg/plate). These authors observed cytotoxicity at >= 3 μmol/plate (ca. 400 μg/plate). The chemical was also tested negative in an Ames test performed within the frame of the U.S. National Toxicology Program (NTP, 2004)

In a mouse lymphoma test, a negative result was obtained in the absence of a metabolic activation system (dose range 35-47.5 μg/ml), while with the addition of S-9 mix the test was equivocal (dose range 10-20 μg/ml): The only cultures exhibiting a significant increase in mutant frequency had less than 10 % total growth (National Cancer Institute / Microbiological Associates, 1992).

In vivo Studies

In a micronucleus assay in NMRI mice according to OECD TG 474 (1983) performed by Hüls AG

(1993), five mice per sex and test duration received one single application with 2,000 mg 1,2,3,4-

tetrahydronaphthalene/kg bw in corn oil (10 ml/kg bw) by gavage. The selected dose was the

maximum dose without mortalities within 48 hours. Sampling times were 24 and 48 hours after test

substance administration. 1,2,3,4-Tetrahydronaphthalene treatment did not result in an increase in

the frequency of micronucleated polychromatic erythrocytes (PCE), but it significantly reduced the

PCE/NCE ratio in male and female animals at both sampling times. This clearly indicates that the

target organ (the bone marrow) had been reached in this test.

1,2,3,4-Tetrahydronaphthalene did not induce micronuclei in peripheral erythrocytes taken from

B6C3F1 mice (10 per dose and sex) which were exposed for 13 weeks on 6 h/day, 5 days/week to

concentrations of 7.5; 15; 30; 60; 120 ppm = 41.2; 82.4; 165; 330; 660 mg/m3 (NTP, 1997 a;

NTP, 2004).

Studies in Humans

There were no studies on humans available.

Short description of key information:
Tetrahydronaphthalene was negative in a microbial mutagenicity tests with and without metabolic activation. No mutagenicity was observed in mammlian cells in vitro.
Two in vivo murine micronuceus tests following oral exposure (2000 mg/kg bw single dose) or inhalation exposure (up to 660 mg/m³ 6h/5d per week for three month) gave not indication for a genotoxic potential.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

1,2,3,4-Tetrahydronaphthalene was not genotoxic in bacterial systems in vitro (Ames test). In a Mouse Lymphoma test, results were negative and equivocal, without and with metabolic activation, respectively. In vivo, no mutagenic activity was detectable in two micronucleus assays on mice according to OECD TG 474 using the oral and inhalation routes of administration.