Reaction mass of pentasodium 2-{[4-chloro-6-(ethyl{3-[(2-sulfonatoethyl)sulfonyl]phenyl}amino)-1,3,5-triazin-2-yl]amino}-5-hydroxy-6-({2-sulfonato-4-[(4-sulfonatophenyl)diazenyl]phenyl}diazenyl)naphthalene-1,7-disulfonate and tetrasodium 2-[(4-chloro-6-{ethyl[3-(vinylsulfonyl)phenyl]amino}-1,3,5-triazin-2-yl)amino]-5-hydroxy-6-({2-sulfonato-4-[(4-sulfonatophenyl)diazenyl]phenyl}diazenyl)naphthalene-1,7-disulfonate

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Remarks:

Based on available physchem and toxicology data

Type of information:

other: Expert statement based on physchem and tox data

Adequacy of study:

key study

Study period:

20 July 2006

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

Based on expert statement

GLP compliance:

no

The data presented in the this dossier only allow for a qualitative assessment of the toxicokinetic behaviour of the test item.

 

Physico-chemical data:

Red ROE805 is a dark red powder and a mixture of aromatic sulfonic acid compounds (as sodium salts) as main components, which serves as a reactive dye for cellulose and cotton. The substance has a MMD smaller than 5 µm (43% mass below 3 //m). The content of the first main component is 36.20%, and the second main component has a percentage of 27.5%. The substance is hydrolysable. At 25°C the half-life time at pH 4 is greater than 8760 hours, at pH 7.0, 90 hours and at pH 9.0, 2530 hours. The water solubility is greater than 373 g/Lat 20°C.

 

Toxicological data:

Red ROE805 was tested for its acute oral and dermal toxicity properties, for subacute oral toxicity and for irritant effects on skin and eyes. The potential to cause skin sensitization was evaluated with the Local Lymph Node Assay (LLNA). Four mutagenicity tests were performed with Red ROE805, namely Bacterial reverse mutagenic assay, the in vitro mammalian cytogenicity test, the in vitro mammalian cell gene mutation test and the mammalian bone marrow micronucleus test (in vivo).

In the tests for acute oral and dermal toxicity, the substance was applied to Wistar rats at a single dose level of 2000 mg/kg body weight. The substance was "not classified" according to the EU classification criteria. During the acute oral toxicity test, slightly ruffled fur was observed in two out 6 animals from the 2- to the 3-hour reading. However, no macroscopic findings were recorded at necropsy. In the acute dermal toxicity test a possible erythematous reaction could not be assessed, due to a red discoloration produced by the test item in all male and all female animals from test day 2 to test day 5, 6, 7, 8 or 13. Slight crusts were noted in one female from test day 8 to 10. Neither systemic signs of toxicity nor

macroscopic findings at necropsy were recorded.

In the skin irritation test, where evaluation was permitted, the test item did not elicit any skin reactions at the application site of any animal at any of the observation time. Slight to marked red staining was observed at the application site of all animals from the 1- to the 72-hour reading and persisted as slight staining in one animal until test day 7. According to EU criteria the substance is not irritating to the rabbit skin.

In the eye irritation test, no abnormal findings were observed in the cornea or iris of any animal at any of the measurement intervals. Slight reddening of the conjunctivae, slight swelling (Chemosis) of the conjunctivae, slight reddening of the sclerae were the effects observed individually at different reading times. No abnormal findings were observed in the treated eye of any animal 48 hours after treatment, the end of the observation period for all animals. Due to the irreversible coloration in only one animal after 21 days, the substance needs not to be classified as irritant.

Red ROE805 was found to be a skin sensitizer according to the LLNA skin sensitization test and was labelled with R43.

In the subacute toxicity test, the oral administration of Red ROE805 to Wistar rats at doses of 50, 200 and 1000 mg/kg/day for 28 days did not result in any test item-related findings during weekly behavioral and functional observations. No laboratory findings were recorded. No test item-related findings of toxicological relevance were noted after 4 weeks 'treatment or 2 weeks' recovery. In all rats treated with 1000 mg/kg body weight/day, rectum with reddish mucosa was observed at necropsy after four weeks of treatment. Reddish kidneys were observed in females treated with 1000 mg/kg body weight/day. These observations are considered to be test item related, because the test item is a red dyestuff, but without

toxicological relevance. Based on the results of the repeated dose oral toxicity, the no-observed-adverse-effect-level (NOAEL) of Red ROE805 was determined to be 1000 mg/kg/day.

The Bacterial reverse mutagenic assay, and the in vitro mammalian cytogenicity test gave positive results. Further tests where performed to evaluate the mutagenicity potential, the in vitro mammalian cell gene mutation test, and the mammalian bone marrow micronucleus test (in vivo), which showed that the test item does not present mutagenic properties.

No other indications on the toxicokinetic behaviour of Red ROE805 could be derived from the results of the available studies.

Conclusions:

The water solubility (greater than 373 g/l) and the partition coefficient (log Pow -5.8) of Red ROE805 indicate a negligible potential for passive absorption by diffusion through cell membranes including dermal absorption, and a negligible bioaccumulation potential. The MMD smaller than 5 µm makes it likely that inhalation into the bronchial system will occur. Metabolic degradation such as the enzymatic reduction of the azo-groups by gut bacteria, and hydroxylation of alkyl and aromatic groups are conceivable. The substance and its metabolites are anticipated to be distributed from the portal vein blood into the liver and into the kidneys where the soluble metabolites, including conjugated metabolites, are excreted via urine. Since the substance is hydrophilic, has a very low log Pow, and is ionisable, accumulation in fatty tissue is not expected.

Executive summary:

Absorption and metabolism:

The water solubility (greater than 373 g/l) and the partition coefficient (log Pow -5.8) of Red ROE805 indicate a negligible potential for passive absorption by diffusion through cell membranes including dermal absorption, and a negligible bioaccumulation potential. The MMD smaller than 5 µm makes it likely that inhalation into the bronchial system will occur. Metabolic degradation such as the enzymatic reduction of the azo-groups by gut bacteria, and hydroxylation of alkyl and aromatic groups are conceivable.

 

Distribution and excretion:

The substance and its metabolites are anticipated to be distributed from the portal vein blood into the liver and into the kidneys where the soluble metabolites, including conjugated metabolites, are excreted via urine. Since the substance is hydrophilic, has a very low log Pow, and is ionisable, accumulation in fatty tissue is not expected.

Description of key information

The water solubility (greater than 373 g/l) and the partition coefficient (log Pow -5.8) of Red ROE805 indicate a negligible potential for passive absorption by diffusion through cell membranes including dermal absorption, and a negligible bioaccumulation potential. The MMD smaller than 5 µm makes it likely that inhalation into the bronchial system will occur. Metabolic degradation such as the enzymatic reduction of the azo-groups by gut bacteria, and hydroxylation of alkyl and aromatic groups are conceivable. The substance and its metabolites are anticipated to be distributed from the portal vein blood into the liver and into the kidneys where the soluble metabolites, including conjugated metabolites, are excreted via urine. Since the substance is hydrophilic, has a very low log Pow, and is ionisable, accumulation in fatty tissue is not expected.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential