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Administrative data

Description of key information

- Repeated dose toxicity, oral: NOAEL = 1000 mg/Kg bw for the rat, (OECD 407); study “Brunke (2010) Repeated dose toxicity: oral”
- Repeated dose toxicity, dermal: no study available
- Repeated dose toxicity, inhalation: no study available

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
1 000 mg/kg bw/day

Mode of Action Analysis / Human Relevance Framework

Additional information

- Repeated dose toxicity, oral:

One fully reliable study is available (Brunke (2010) Repeated dose toxicity: oral) conducted according to OECD TG 407 and GLP (28 d, oral gavage, doses: 100, 300 and 1000 mg/kg/ d, Wistar rats) showing resulted in no test item-related deaths, no adverse clinical signs during daily and weekly (weeks 1-3) observations, no effects on the functional observational battery including grip strength and locomotor activity, no effects on the mean food consumption or body weight development, no effects on the estrous stage of female animals, no adverse effects on hematology, clinical biochemistry or urinalysis parameters, no differences in mean absolute and relative organ weights, and no adverse macroscopical or microscopical findings.

Test item-related findings were generally restricted to clinical signs of bluish discoloration of the feces in animals of both sexes at 100, 300 and 1000 mg/kg bw/day along with general discoloration in animals at 1000 mg/kg bw/day, green to grey or blue discoloration of the urine in animals at 1000 mg/kg bw/day, macroscopically bluish discoloration of multiple organs such as mucosa of the gastrointestinal tract, kidneys, thymus, mesenteric lymphnodes, testes, prostrate, uterus and vagina with a dose-dependent distribution in animals at 100, 300 and 1000 mg/kg bw/day and microscopic findings of minimal deposits of fine granular brownish pigment in the tubular epithelium of the kidneys (in absence of any tubular degeneration or inflammatory lesions) in animals at 1000 mg/kg bw/day. These findings were considered to be a non-adverse dyeing effect of the test item.

For elevated methemoglobin values in the high dose group it is assumed, that the method of spectroscopic measurement of hemoglobin derivates with the hemoximeter OSM3 interferes with absorption spectra of the test item FAT 40849/A TE being present in plasma samples. Therefore, elevated methemoglobin values were considered to be an artefact and of no toxicological relevance.

The determination of a dose dependent reduction of bilirubin in LD and MD and the impossibility to determine this parameter at the HD is probably due to a bluish discoloration of the plasma samples. It is assumed, that the method of calorimetric assay of total bilirubin with the Hitachi 917 analyzer, Roche Diagnostics (nominal wavelength of 570 nm for total bilirubin) interferes with absorption spectra of the test item FAT 40849/A TE being present in plasma samples. Therefore, decreased bilirubin values were considered to be an artefact and of no toxicological relevance.

Based on the data generated from this study, The NOAEL for repeated dose toxicity of FAT 40849/A TE in Wistar rats was 1000 mg/kg body weight. As this threshold value is identical with the highest allowable dose for this study type according to the OECD TG 407, a classification of FAT 40849/A TE for repeated dose toxicity is not necessary.

The information available from a developmental toxicity/teratogenicity study conducted according to OECD 414 (Takawale, BSL, 103759, 2011, RL1; chapter 7.8.2) does not disagree with this conclusion in reporting a NOAEL for both maternal toxicity and fetal toxicity of FAT 40849/A TE in Wistar rats of 1000 mg/kg bw/day.

- Repeated dose toxicity, dermal:

No study available

- Repeated dose toxicity, inhalation:

No study available


Repeated dose toxicity: via oral route - systemic effects (target organ) urogenital: kidneys

Justification for classification or non-classification

Only data for exposure via the oral route is available, therefore the proposed classification is only valid for this route.

Based on the above stated assessment of the oral repeated dose toxicity of FAT 40849/A TE (NOAEL = 1000 mg/kg bw/d, 28 d rat, gavage, systemic effects in the kidneys) the substance does not need to be classified 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.