Octasodium 2,2'-[1,4-phenylenebis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3,6-disulphonatonaphthalene-2,8-diyl)azo]]bisnaphthalene-1,5-disulphonate

Endpoint summary

Description of key information

There are no experimental toxicokinetic data available for the substance and this statement is based on available data as physico-chemical data and toxicological data. This assumption was conducted based on the REACH ECHA “Guidance on information requirements and chemical safety assessment chapter R.7c” of the ECHA guidance document (Version 3.0, June 2017).

Available physico-chemical information taken into account:

Physical state:

The substance is a solid (brown to black, golden shiny)

Structure:

1,5-Naphthalenedisulfonic acid, 2,2’-[1,4-phenylenebis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(8-hydroxy-3,6-disulfo-1,7-naphthalenediyl)-2,1-diazenediyl]] octasodium salt (1:8) (Bayscript Magenta BB = Reactive Red 141)

Molecular mass:

C52H26CI2N14Na8O26S8: 1774 g/mol

Water solubility:

well soluble, 411.28 g/L

Log Pow:

Pow = 0.03220 at pH of 6.59; log Pow = -1.5691

Vapor pressure:

Assumed to be low based on a melting point of 275 oC. (From 25-260 °C it can be observed an endothermic curve, followed by a decomposition of the product between 275 - 389 °C (onset at 295.2 °C; enthalpy 63 J/g).

General considerations:

In general, log Kow values between 1 and 4 are favourable for absorption regarding oral/GI absorption, respiratory absorption and dermal absorption.

Based on the high water solubility (411.28 g/L), high molecular mass (1774 g/mol) and low octanol-water partition coefficient (log Pow -1.5691) absorption is likely to be limited and low. However no information of metabolic transformation of Reactive Red 141 is available.

Estimation of oral absorption:

In the key study for acute oral toxicity a discriminating dose of 5000 mg/kg bw was reported.

In a 14 days dose-range finding study no substantial toxicity was seen up to and including the limit dose of 1000 mg/kg/day. Test item-related macroscopic abnormalities were limited to the abnormal pink coloration affecting multiple tissue types at all dose levels, increase incidences were observed at the higher dose levels (800 or 1000 mg/kg/day). In addition, abnormal pink colored contents were found in the stomach, jejunum, cecum and colon. These macroscopic changes were indicative of the color of the test item.

In a combined Repeated Dose Toxicity study and Reproductive/Developmental Toxicity screening study according to OECD TG 422 three groups of ten male and ten female rats received m-phenylene di(acetate), initially at doses of 100, 330 or 1000 mg/kg/day, by oral gavage administration. Males were treated daily for two weeks before pairing, up to necropsy after a minimum of five consecutive weeks. Females were treated daily for two weeks before pairing, throughout pairing, gestation and until Day 13 of lactation. Females were allowed to litter, rear their offspring and were killed on Day 14 of lactation. The F1 generation received no direct administration of the test item; any exposure was in utero or via the milk. A similarly constituted Control group received the vehicle, purified water, at the same volume dose as treated groups.

Oral administration of Bayscript Magenta BB at 1000 mg/kg/day was not tolerated and dosing was terminated early for males and females on Days 11 and 18 of dosing, respectively. The oral administration of Bayscript Magenta BB up to and including 330 mg/kg/day for five weeks in males and for two weeks prior to pairing, throughout gestation and up to Day 13 of lactation in females, was generally well tolerated.

Test item-related histopathological changes were evident in the kidneys, consisted of tubular degeneration in both sexes, tubular regeneration predominately in females and hyaline droplets in males in animals given 330 or 1000 mg/kg/day, associated with increases in adjusted kidney weights in both sexes given 330 mg/kg/day and with gross changes of abnormal coloured kidneys seen at necropsy; these kidney changes were considered to be adverse. Test-item related histopathological changes were also evident in the stomach, spleen and liver of animals given 1000 mg/kg/day and terminated early. These included eosinophilic globules and foveolar hyperplasia in the stomach, with submucosal inflammation observed in males only, increased cellularity of the splenic white pulp and, hepatocellular apoptosis and vacuolation in the liver of females. It was therefore concluded that within the context of this study, the No Observed Adverse Effect Level (NOAEL) for systemic toxicity was 100 mg/kg/day.

There was no evidence of any adverse effects on mating performance of the adult animals or on the development of the F1 offspring. The reduction in the number of uterine implantations at 330 mg/kg/day (and as a consequence litter size) was associated with the slightly low post implantation survival index. This effect, however, was statistically significant and all parameters were outside of the Historical Control Data values (representing 11 OECD TG 422 studies). This effect is considered to be related to treatment and it is likely that the male and/or female reproductive systems have been affected, but the mechanism is undetermined and potentially adverse. It was therefore concluded that within the context of this study, the NOAEL for reproductive performance was 100 mg/kg/day.

Overall: Based on the high water solubility, high molecular weight and low octanol-water partition coefficient an absorption following ingestion is not likely. However, severe toxicity, including mortality at high doses, is seen in a combined Repeated Dose Toxicity study and Reproductive/Developmental Toxicity screening study according to OECD TG 422, indicating some oral absorption.

Estimation of dermal absorption:

There are no dermal studies available; the substance is not irritating to the skin or eyes. Based on the large molecular weight of 1774 g/mol low absorption after dermal contact is assumed.

Estimation of absorption via inhalation:

No acute or repeated dose toxicity studies are available.

Based on the physicochemical parameters it is assumed that the absorption via inhalation is low.

Estimation of distribution:

Based on the low log Pow ( -1.6) of Bayscript Magenta BB, it is likely to distribute into cells and the intracellular concentrations may be higher than extracellular concentration.

Estimation of accumulation:

In general substances with high log P values have long biological half-lives. Substances with log P values of 3 and less would be unlikely to accumulate with the repeated intermittent exposure patterns normally encountered in the workplace but may be accumulate if exposures are continuous.

Based on the low log Pow ( -1.6), accumulation of Bayscript Magenta BB is unlikely.

Estimation of metabolism:

In vitro genotoxicity data do not indicate any genotoxic metabolites. The substance is negative in the absence and in the presence of S9 extracts (Ames test (Bacterial Reverse Mutation Assay), the MNT test (in vitro mammalian cell Micronucleus Test) and the HPRT test (In Vitro Mammalian Cell Gene Mutation Tests Using the Thymidine Kinase Gene)).

Estimation of excretion:

Characteristics favourable for urinary excretion are low molecular weight (below 300 in the rat), good water solubility and ionization of the molecule at the pH of urine.

Based on the physicochemical data an excretion via feces is assumed.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

REACH Guidance default parameter for absorption after oral, dermal and inhalation expousre were considered for rout-to-route extrapolation of systemic toxicity.