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Description of key information

The available experimental data in animals displayed limited evidences of absorption and systemic distribution of the test substance and/or its metabolites or degradation products through the inhalation, oral and dermal route. Despite the absence of systemic effects reported in the acute and repeated dose toxicity studies by the oral and inhalation routes,  absorption through these routes of exposure is demonstrated by the mortality reported in the rats and/or mice acute toxicity studies (only local changes in the lung indicative of local effects were reported in the inhalation studies). Very limited distribution is expected since there was no evidence of systemic effect reported whatever the route of administration. Systemic effects observed when the test substance was dermally applied in the acute dermal toxicity study were limited and reported only at very high dose level. There was no obvious indication on the test substance metabolism or excretion from the toxicity studies.

Key value for chemical safety assessment

Additional information

No specific toxicokinetic studies are available on Reaction product of naphthalene, butanol, sulfonated and neutralized by caustic soda. A toxicokinetic assessment was made, based on the physico-chemical properties of the test substance or its close analogue “Reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda” and the results of toxicity studies (acute oral, inhalation and dermal toxicity,in vitrogenotoxicity studies and repeat dose toxicity studies).

Physico-chemical properties :

Molecular weight: approx. 300 g/mol (UVCB)

Water solubility: 604 g/L (at 20°C)

Partition coefficient in octanol/water: -0.27 (at 20°C)

Particle size: D10: >125 - <180 µm ; D50: >710 - < 1000 µm ; D95: > 1mm.

Vapour pressure: < 0.001 Pa (at 20°C)

Boiling point: >500 °C

Density: 1.525 (at 20°C)

 

Absorption and distribution :

Inhalation:

In the acute inhalation toxicity study, mortality was observed in rats exposed for 4 hours to aerosol of Reaction product of naphthalene, butanol, sulfonated and neutralized by caustic soda. Indeed, premature death was recorded in 1/10 and 9/10 rats at dose levels of 3.49 and 4.76 mg/L, respectively within 14 days post-exposure. Clinical signs such as accelerated respiration, eyelid closure, irregular and intermittent respiration, reddish discharge from nose, reduced general state and/or piloerection were reported at the mid and high dose. At necropsy dead animals from high dose group showed general congestive hyperemia and a lung filled with blood and edema. The animal which died from the mid dose group showed excessive loss of weight, empty stomach/intestines, filled with gas. Whereas the systemic toxicity is evidenced by the mortality reported at the 2 highest dose levels, this study do not permit to make considerations on the distribution of the registered substance and/or its metabolites or degradation products. Some clinical signs (effects on respiration and nose) and the macroscopic findings in the lung are rather indicative of a local effect. These results are consistent with the results obtained in the 28-day repeated dose inhalation toxicity study in rat where only local effects in the lung were reported from the mid dose of 8.1 mg/m3. The capacity of the substance to be absorbed through the respiratory tract is nevertheless supported by the significant proportion of inhalable particles (<100 µm) and the high water solubility of the registered substance.

Oral:

In the acute oral toxicity studies, mortality was observed in rats and mice exposed to one single oral (gavage) administration of Reaction product of naphthalene, butanol, sulfonated and neutralized by caustic soda from the dose of 1600 and 2500 mg/kg bw, respectively. Clinical signs such as deterioration of general health and labored breathing were reported at almost all concentrations. Mortality and clinical signs are indicative of absorption of the registered substance and/or its metabolites. The systemic distribution could not be evaluated in the absence of target organs identified in the available studies. In the 5-week oral (drinking water) rat toxicity study, no evidence of absorption and systemic distribution were identified.

Dermal route:

In the acute dermal toxicity study performed in rabbits, Reaction product of naphthalene, butanol, sulfonated and neutralized by caustic soda applied on the skin induced mortality in animals treated with 4000 mg/kg bw. There were no signs of skin irritation at any dose levels. Petechiae on the mucous membranes of the stomach seen at necropsy in 3/4 rabbits given 4000 mg/kg suggest a limited absorption and systemic distribution of the registered substance only at very high dose levels.

 

Metabolism:

Five in vitro studies assessed the potential genotoxicity of Reaction product of naphthalene, butanol, sulfonated and neutralized by caustic soda or its analogue Reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda. Three Ames tests (BASF, 1992, Herbold 1983, and CitoxLab 2012), a chromosome aberration test in cultured human lymphocytes (CitoxLab 2012) and a mouse lymphoma assay (CitoxLab 2012); all showed absence of mutagenic effects in the presence or in the absence of exogenous mammalian metabolic activation system. In the second experiment of the Ames test performed on the analogue Reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda, moderate to strong cytotoxicity was observed in all tested strains at the highest concentration only (5000 µg/plate) in the presence of metabolic activation (pre-incubation method). No cytotoxicity was observed without metabolic activation. Therefore the toxicity reported in the presence of S9 mix suggests that the analogue Reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda is metabolized and the synthesized metabolite(s) is(are) toxic to bacterial strain at this dose level. However, in the absence of specific metabolism studies and since this variation was not seen in the Ames tests conducted with the registered substance, the relevance of this variation to human is unclear. In the Mammalian mouse lymphoma assay and chromosome aberration test conducted on the analogue, cytotoxicity was observed both in the presence and absence of metabolic activation, at similar dose levels. Therefore no conclusion on the metabolism can be drawn from these two tests.

Elimination:

There is no indication of a preferred route of excretion for Reaction product of naphthalene, butanol, sulfonated and neutralized by caustic soda but its high water solubility indicate that excretion of unchanged parent substance and/or metabolites could occur by renal or biliary routes and that bioaccumulation is unlikely.