Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

- in vitro

bacterial gene mutation:

FAT 40841/A TE was tested according to OECD Guideline 471 (study Sokolowski (2008) / Genetic toxicity in vitro ) in order to investigate the potential of the test item to induce gene mutations according to the plate incorporation assay with rat liver S9 (experiment I) and the pre-incubation test with hamster liver S9 (experiment II) using the Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100, and the Escherichia coli strain WP2 uvrA.

The plates incubated with the test item showed normal background growth up to 5000 µg/plate in the plate incorporation assay and the preincubation assay with and without metabolic activation.

No toxic effects, evident as a reduction in the number of revertants, were observed with and without metabolic activation in both experiments.

No substantial increase in revertant colony numbers of any of the five tester strains was observed following treatment with FAT 40841/A TE at any dose level, neither in the presence nor absence of metabolic activation (S9 mix). There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological relevance.

FAT 40841/A TE is considered to be non-mutagenic in this Salmonella typhimurium and Escherichia coli reverse mutation assay.

mammalian gene mutation:

covered by the negative in vivo micronucleus assay (see below)

mammalian chromosome abberation:

The test item FAT 40841/A TE, dissolved in deionised water, was assessed for its potential to induce structural chromosome aberrations in V79 cells of the Chinese hamster in vitro in one experiment up to 5000 µg/mL according to OECD TG 473 (study Bohnenberger (2009) Genetic toxicity in vitro Chromosome aberration).

Study design: Exposure period: 4 hrs, with and without S9 mix; Recovery: 14 hrs, with and without S9 mix; Preparation interval: 18 hrs, with and without S9 mix. In each experimental group two parallel cultures were set up. At least 100 metaphases per culture were evaluated for structural chromosome aberrations.

In the absence of S9 mix concentrations showing clear cytotoxicity were not scorable for cytogenetic damage. However, the cell number was markedly reduced below 60 % of control. In the presence of S9 mix cytotoxicity was observed at the highest evaluable concentration.

In the absence and presence of S9 mix statistically significant and biologically relevant increases in the number of aberrant cells excluding gaps (6.3, 6.0, and 6.5 %, respectively) were observed. These values clearly exceeded the laboratory’s historical control data range (0.0 – 4.0 % aberrant cells, excluding gaps). In addition, slight increases in cells carrying exchanges were observed.

No relevant increase in polyploid metaphases was found after treatment with the test item as compared to the frequencies of the control cultures.

In conclusion, it can be stated that under the experimental conditions reported, the test item induced structural chromosome aberrations as determined by the chromosome aberration test in V79 cells (Chinese hamster cell line) in vitro.

Therefore, FAT 40841/A TE is considered to be clastogenic in this chromosome aberration test in the absence and presence of metabolic activation.

Based on the available data it can be concluded that FAT 40841/A TE does not inflict gene mutations in vitro but causes chromosome abberations in vitro.

- in vivo

mammalian chromosome abberation:

The potential of FAT 40841/A TE to induce micronuclei in polychromatic erythrocytes (PCE) in the bone marrow of the mouse was analysed in a test (study Reichenbach (2009) Genetic toxicity in vivo Micronucleus) conducted according to OECD TG 474.

The test item was formulated in sterile water, which was also used as vehicle control. The volume administered orally was 10 mL/kg b.w.. 24 h and 48 h after a single administration of the test item the bone marrow cells were collected for micronuclei analysis.

The following dose levels of the test item were investigated:

24 h preparation interval: 500, 1000, and 2000 mg/kg b.w..

48 h preparation interval: 2000 mg/kg b.w..

(2000 mg/kg bw is the limit dose as defined by the guideline)

After treatment with the test item the number of PCEs was not substantially decreased as compared to the mean value of PCEs of the vehicle control thus indicating that FAT 40841/A TE did not exert any cytotoxic effects in the bone marrow.

In comparison to the corresponding vehicle controls there was no biologically relevant or statistically significant enhancement in the frequency of the detected micronuclei at any preparation interval after administration of the test item and with any dose level used.

In conclusion, it can be stated that under the experimental conditions reported, the test item did not induce micronuclei as determined by the micronucleus test with bone marrow cells of the mouse.

Therefore, FAT 40841/A TE is considered to be non-mutagenic in this micronucleus assay.

The negative result in the in vivo cytogenetic assay overrules the positive result from the respective in vitro test. Therefore it can be concluded that FAT 40841/A TE is not genotoxic and a classification is not necessary

Short description of key information:
- genetic toxicity in vitro: ambiguous, 1 study negative (Sokolowski (2008) / Genetic toxicity in vitro) 1 study positive (Bohnenberger (2009) Genetic toxicity in vitro Chromosome aberration)
- genetic toxicity in vivo: negative, 1 study (Reichenbach (2009) Genetic toxicity in vivo Micronucleus)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the above stated results on genetic toxicity FAT 40841/A TE does not need to be classified fort his endpoint according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.