Tetrahydrothiopyran-3-carboxaldehyde

Endpoint summary

Additional information

Gene mutation in bacteria

The test substance was not mutagenic in a standard plate test with and without metabolic activation according to OECD guideline 473 (tested up to 5000 µg/plate in the standard plate test (SPT) using the purified distilled product with and without metabolic activation (BASF AG 1986). A liver S-9 mix from Aroclor-induced male Sprague-Dawley rats was used as exogenous metabolising system. A bacteriotoxic effect (reduced his- background growth, decrease in the number of his revertants) was observed from about 1500 µg/plate onward (without S-9 mix) and at 5000 µg/plate (with S-9 mix). Using E. coli WP2 uvrA a slight decrease in the number of trp+ revertants was only occasionally found at 5000 µg/plate.

TPA (lot No.: BAO-002) was also tested in a modified Ames test (modification not specified in detail) at Nippon Soda Co., Ltd. (1986). According to these results, using TA 100 the number of colonies was increased at 500 µg/plate (1^stexperiment) or at 400 µg/plate (2^ndexperiment) without metabolic activation only.

After a detailed discussion whether these increased colony numbers are real his+ revertants or only his- colonies which were allowed to undergo more cell divisions and therefore appear as small colonies, it could be verified by Nippon Soda Co. Ltd that the observed increase in the mutation rate is due to real his+ revertants (letter Nippon Soda of February 27, 1986). It was further specified that regarding the mentioned Ames test modification the preincubation method was selected. Meanwhile, an additional study with TPA (batch No.: LJ 17718-126; ZNT No.: 85/249) was carried out using only TA 100 without metabolic activation and selecting closer doses to check whether or not an increase in the colony number might occur at dose levels that had not been tested in the 1st study (BASF AG 1987). Again, no increase in the number of his+ revertants was found up to the dose of 1400 µg/plate where a slight decrease in the number of revertant colonies, paralleled by a reduced his- background growth, was observed. This was in accordance with the findings in the 1^stBASF study. The aim of the second BASF study was to investigate TPA (batch No.: LJ 17718-126; ZNT No.: 85/249) using this Ames test modification, which led to an increase in the number of mutant colonies in the studies carried out at Nippon Soda Co., Ltd. i.e. the preincubation procedure with the base-pair substitution strains TA 1535 and TA 100. Close dose levels were again selected in accordance with the Nippon Soda studies with the aim to recognize also a weakly positive effect, even if an increase in the colony number might only accurate narrow dose range. According to the results of the second BASF study, the test substance TPA (batch No.: LJ 17718-126; ZNT No.: 85/249) did not lead to any increase in the mutation rate; the number of his+ revertants was always in the range of that of the control up to that dose from which onward bacteriotoxicity was observed.

In summary, the test substance showed positive results in the Ames test at Nippon Soda (strain TA 100) while being clearly negative when tested in two independent studies at BASF laboratories. The reason for these opposing results with the same test material remains elusive.

 

Gene mutation in mammalian cells

Actually, there is no information available.

 

Cytogenicity in mammalian cells

Actually, there is no information available.

 

Other studies

Actually, there is no information available.

 

Cytogenicity in vivo

The substance Tetrahydrothiopyran-3-aldehyd was tested for clastogenicity and for the ability to have spindle poison effects in NMRI mice using the micronucleus test method. For this purpose, Tetrahydrothiopyran-3-aldehyd, dissolved in olive oil, was administered once orally to male and female animals at dose levels of 3000 mg/kg, 1000 mg/kg and 333 mg/kg body weight in a volume of 10 ml/kg body weight in each case. As negative control, mice were administered merely the solvent olive oil by the same route. As positive control for clastogenicity, 20 mg of cyclophosphamide/kg body weight was administered once orally. As positive control for spindle poison effects, 0.15 mg of vincristine/kg body weight was administered once intraperitoneally to male and female animals. The animals were sacrificed 16, 24 and 48 hours after administration and the bone marrow of the two femora was prepared in the highest dose group of 3000 mg/kg body weight. In the test groups of 1000 mg/kg and 333 mg/kg body weight, in the negative control group and in the positive control groups the 24-hour sacrifice intervals were investigated only. After staining of the preparations 1000 polychromatic erythrocytes were evaluated per animal and investigated for micronuclei. The normocytes with and without micronuclei occurring per 1000 polychromatic erythrocytes were also registered. According to the results of the study, the single oral administration of Tetrahydrothiopyran-3-aldehyd in doses of 3000 mg/kg, 1000 mg/kg and 333 mg/kg body weight did not lead to any increase in the number of polychromatic erythrocytes containing either small or large micronuclei. The rate of micronuclei was always in the same range as that of the negative control in all dose groups and at all sacrifice intervals. No inhibition of' erythropoiesis determined from the ratio of polychromatic to normochromatic erythrocytes was detected.

 

Thus, under the experimental conditions chosen, the test substance Tetrahydrothiopyran-3-aldehyd does not have any chromosome-damaging (clastogenic) effect, and there were no indications of any impairment of' chromosome distribution in the course of mitosis.

Short description of key information:
Gene mutation in bacteria
S. typhimurium TA 1535, TA 1537, TA 98, TA 100, E.coli WP2 uvrA with and without metabolic activation: negative (OECD 471, BASF AG 1986) (standard plate test)

S. typhimurium TA 1535, TA 100 with and without metabolic activation: negative (comparable to OECD 471, BASF AG 1987) (preincubation test)

S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100, E. coli WP2 uvrA with and without metabolic activation: positive (comparable to OECD 471, Nippon Soda Ltd. 1986) (preincubation test)

Gene mutation in mammalian cells
Actually, there is no information available to cover this endpoint.

Cytogenicity in mammalian cells
Actually, there is no information available to cover this endpoint.

Endpoint Conclusion:

Justification for classification or non-classification

The test results obtained with the test substance in bacteria in vitro were ambiguous when comparing results from two independent BASF studies and one study undertaken at Nippon Soda Co. Ltd. At present there are no reasons for devalidation of one the existing studies therefore the mutagenic capacity of the test substance in bacteria cannot be judged finally. When taking the results from the in vivo study into account, the test substance is considered not to be clastogenic under in vivo conditions. Therefore, based on the information currently available, there is no need for classification of the test substance for mutagenic effects according to the criteria defined by the EU and the GHS system.