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Description of key information

No specific information on toxicokinetic, metabolism or distribution of Nigrosin WLF in animals or in humans are available. 
Therefore, statements on toxicokinetics of Nigrosin WLF are based on the physico--chemical data as well as on the toxicological studies described in IUCLID within the REACH process.

Key value for chemical safety assessment

Additional information

No specific information on toxicokinetic, metabolism or distribution of Nigrosin WLF in animals or in humans are available. Therefore, the following statements on toxicokinetics of Nigrosin WLF are based on the physico--chemical data as well as on the toxicological studies described in IUCLID within the REACH process. The criteria outlined in the Reach Guidance on Information Requirements and Chemical Safety Assessment, Chapter R7c. Section R7.12: Guidance on Toxicokinetics, will be applied throughout the statement.

The Chemical name of Nigrosin WLF is Hydrochloric acid, reaction products with aniline and nitrobenzene, sulfonated, sodium salts. This organic UVCB substance contains aniline as an impurity. Since the concentration on Aniline is very low, below 0.2% (w/w), this impurity is not further evaluated in this assumption. The molecular weight of this black solid could not be determined. The calculated vapour pressure values are extrapolated at 0.000005 Pa at 20 °C, 0.0000095 Pa at 25 °C and 0.00017 Pa at 50 °C. The melting point was determined according to the guideline "EC-A 1"and the Differential thermal analysis (DTA) showed no melting point The boiling point was determined according to the guideline "EC-A 2"and the Differential thermal analysis (DTA) showed no boiling point. The sample decomposed at 310 °C. The water solubility is 100 g/liter, the log Pow is unknown.

Due to this information inhalation exposure is unlikely

ABSORPTION

The molecular weight cannot be determined but can be assumed to be >500 g and the log Pow is not known. However the substance is soluble in water. Therefore the guidance document proposes that the substance is likely to absorbed from GI tract. However, from the acute oral toxicity no clinical findings are reported (LD50 >2000 mg/kg bw , Report No. T5050442, Löser 1975) . From the available repeated oral dose toxicity study neither hematology nor clinical chemistry gave evidence for treatment related effects up to 1000 mg/kg bw/day . The only test item related microscopic and macroscopic changes at terminal sacrifice are slight grey or black discolorations in a dose-related manner in all treated groups, predominantly in the lymph nodes and less frequently in the intestine and /or Peyer’s patches. Corresponding to these findings at clinical observations it was noted that the color of feces was changed (black) in cages of treatment groups (Report No T2082697, Schladt 2013). These observations indicate poor absorption after oral ingestion.

Referring to dermal absorption, as the substance is a solid and the molecular weight is supposed to be high ( > 500 g) and the water solubility is 100 g/l and log Pow is unknown, therefore it is anticipated that dermal absorption is low to moderate. The acute dermal toxicity study (LD50 >2000 mg/kg bw, Report No. AT06430, Gillissen 2012) as well as the skin irritation (Report No. T1048720, Mihail 1976) or the skin sensitization study (Report No. AT06456, Vohr 2012) do not provide information on dermal absorption because no systemic effects are reported thus confirming the assumption-of a low absorption rate.

There are no animal experiments available using the inhalation route. The substance is a solid with very low volatility based on vapor pressure below 0.5 kPa and a boiling point above 150 °C (decomposition by >300 °C), In humans, particles with aerodynamic diameters below 100 µm have the potential to be inhaled; particles with aerodynamic diameters below 50 µm may reach the thoracic region and those below 15 µm the alveolar region of the respiratory tract. According to OECD guideline 110, the particle size distribution of Hydrochloric acid, reaction products with aniline and nitrobenzene, sulfonated, sodium salts was determined by scanning electron microscopy method for the sieved fraction (100 µm, 0.15 % of total sample) and presented on the basis of calculated mass fractions. The median diameter was 78.22 µm with the main fraction of 76 % distribution in the range of 10 - 100 µm; and hence the tested Hydrochloric acid, reaction products with aniline and nitrobenzene, sulfonated, sodium salts with sieved size smaller than 100 µm are mainly dominated by inhalable fraction as defined in EN 481. Thus it is unlikely that large quantities of the compound are inhaled.

As the log Pow is unknown no statement can be given for the absorption directly across the respiratory tract epithelium. The compound is soluble in water (100 g/l) and may be retained within the mucous membranes. For absorption of deposited material similar criteria as for GI tract may apply. Based on the physico-chemical properties the potential tor respiratory absorption is low. Taking into account the lack of observed effects after oral ingestion it is likely that the absorption rate via inhalation and oral dosing is low and absorption vial inhalation is considered to be comparable to that via gastrointestinal tract.

DISTRIBUTION

There are no specific data available. The compound is soluble in water and may be retained within the mucous. In the available repeated dose toxicity study (Schladt 2013) neither hematology nor clinical chemistry gave evidence for treatment related effects up to 1000 mg/kg bw/day . Test item related microscopic and macroscopic changes observations at terminal sacrifice were slight grey or black discolorations in a dose-related manner in all treated groups, predominantly in the lymph nodes and less frequently in the intestine and /or Peyer’s patches. Corresponding to these findings at clinical observations it was noted that the color of feces was changed (black) in cages of treatment groups. As no other findings are noted these observations indicate the low absorption rate and the consecutive distribution of the compound in the body.

METABOLISM

There are no specific investigations available. Based on the results of the in vitro mutagenicity tests with Nigrosin WLF [Ames test (Report No. AT06550, Nern 2012), HPRT (Harlan CCR Study No. 1469000, Harlan CCR 2012) and MNT in vitro (Report No. AT06519, Nern 2013)] it is concluded that DNA-reactive metabolites of the substance will probabely not be generated in mammals in the course of hepatic transformation.

EXCRETION

There is no specific information available. However, in the sub-acute oral study in rats at clinical observations, it was noted that the color of feces was changed (black) in cages of treatment groups, indicating that the compound might be mainly excreted via feces