Coupling reaction products of diazotized 2-amino-6-[(2-substitued ethyl)sulfonyl]naphthalene-1-substituted acid with 4-({4-chloro-6-[ethyl(3-{[2-(substituted oxy)ethyl]sulfonyl}phenyl)amino]-heteromonocycl-2-yl}amino)-5-hydroxynaphthalene-2,7-disubstituted acid and their sodium and potassium salts

Endpoint summary

Description of key information

- Repeated dose toxicity, oral: NOAEL = 300 mg/Kg bw for the rat, (OECD 407); study “Simon (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

300 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

- Repeated dose toxicity, oral:

One fully reliable study is available (Simon (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).

The following test item related findings were noted: red stained feces and red stains in multiple organs (e. g. kidneys, mesenteric lymphnodes and stomach), noted in males and females at all dose levels (100, 300 and 1000 mg/kg/day) due to dying effect.

Effects seen in whithe blood cell count (high dose) and lymphocyte (mid and high dose), but in the absence of histopathologigal changes e.g. in the spleen, bone marrow, thymus or lymphnodes and no findings in the females, this effect is considered not to be adverse. Effects revealed in the biochemical analysis (decrease in potassium and phosphorus concentrations increased total protein level in correlation with increased albumin and increased albumin/globulin ratio) were noted only in males and as there was no dose response relationship. Therefore these changes were considered not to be of adverse nature. The increase in liver weights is considered to be caused by an adaptive reaction but, in absence of further findings, e.g. pathohistological changes in the liver, not to be of adverse nature.

Changes in kidney weights in males at 1000 mg/kg/day are in correlation with macroscopic and microscopic findings (deposit of pigment) in the high dose groups of both sexes and mid dose females. The deposits of red pigment were considered to be not adverse itself, but the secondary reactions consisting of increased severity of hyaline droplets and vacuolar degeneration of tubular epithelium were deemed to be adverse.

Based on the results of this study, a no-observed-effect-level (NOEL) of FAT 40850/A TE could not be established. The no-observed-adverse-effect-level (NOAEL) was established at 300 mg/kg/day. The guidance value for classification for specific target organ toxicity category 2 in the CLP guideline is 300 mg/kg bw/d for a 28 d study and is equivalent to a LOAEL. As here 300 mg/kg bw/d represent a NOAEL and as CLP is more conservative than DSD regarding classification for repeated dose toxicity, a classification of FAT 40850/A TE for this endpoint is not necessary.

The information available from a developmental toxicity/teratogenicity study conducted according to OECD 414 (Rudragowda, BSL, 103760, 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 40850/B 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 40850/A TE (NOAEL = 300 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.