Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: Toxicokinetic Assessment
Adequacy of study:
weight of evidence
Reliability:
other:
Rationale for reliability incl. deficiencies:
other: toxickokinetic assessment based not on specific toxicokinetik data but on the available experimental data

Data source

Reference
Reference Type:
other: toxicokinetic assessment
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Any other information on results incl. tables

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 like skin irritation/corrosion, eye irritation, skin sensitization, in vitro mutagenicity and acute and repeated dose oral toxicity studies. This assumption follows the procedure indicated in the “Guidance on information requirements and chemical safety assessment chapter R.7c” of the ECHA guidance document (version 1.1, November 2012).

Available physico-chemical information taken into account:

Physical state:

The substance is an organic solid.

Particle size distribution:

MMAD (Mass Median Aerodynamic Diameter) was determined for the fraction (< 100 µm, 0.22 % of total sample) and reported to be 10.57 µm with two fractions of 40.94 and 52.32 % distributing in the range of 4 -100 µm.

Structure:

8,9,10,11 -tetrachloro-12H-phthaloperin-12 -one

Molecular weight: 408 g/mol

Water solubility: Insoluble; water solubility was not detectable with a value lower than 0.00003 g/l.

Log Pow: 7.1 at 25°C (pH 7.3).

Surface tension:

Based on the chemical structure surface activity is not expected. Vapor pressure: Anticipated to be low because the melting point is >300 C.

Estimation of oral absorption:

Oral absorption is considered to be low, based on the physico-chemical data: molecular weight 408 g/mol, insoluble in water, log Pow above 4. No toxicity or absorption was seen in 1) an acute oral toxicity study; the discriminating dose was the highest dose tested: 5000 mg/kg; 2) a sub-acute toxicity study according to OECD TG 407. At the limit dose, 1000 mg/kg/day no adverse effects were observed and the NOAEL was 1000 mg/kg/day. Starting at the mid dose of 300 mg/kg bw, all animals of both sexes showed changes in feces color (reddish particles), which is a consequence of the strong red color of the test item and thus is not considered as adverse effect. Overall: oral absorption is assumed to be low based on physicochemical properties and oral toxicity experiments. Estimation of dermal absorption:

Dermal absorption is likely to be low because it is a solid with a molecular mass above 100, insoluble in water and a log Pow value above 4. In addition based on the chemical structure surface activity is not expected. Dermal toxicity data also does not indicate relevant dermal absorption: Skin irritation: Not irritating and no systemic effects Skin sensitization: Not sensitizing in LLNA Dermal toxicity data: Not available Overall: dermal absorption is assumed to be low based on physicochemical properties and dermal irritation and sensitization data.

Estimation of absorption via inhalation:

Vapor pressure is anticipated to be low because the melting point is >300 oC. In humans, particles with aerodynamic diameters below 100 μm have the potential to be inhaled. The fraction of particles below 100 µm was reported to be only 0.22 % of total sample. No absorption or toxicity was seen in an acute inhalation toxicity study conducted in accordance with OECD TG 403. A group of male and female rats was nose-only exposed to the dry powder aerosol of the test article at an actual concentration of 2868 mg/m³. No animal died, no clinical findings and no pathotlogical changes were noted. Therefore, the discriminating dose was > 2868 mg/m³, the maximum technically attainable concentration. Overall: absorption by inhalation is assumed to be low based on physicochemical properties and acute inhalation data in rats.

Overall estimation on absorption:

absorption is anticipated to be similar and very low by oral, dermal and inhalation route.

Estimation of distribution:

Based on the high log Pow (7.1) and the the insolubility in water it is not likely that the substance distributes into cells. This assumption is supported by the oral sub-acute toxicity study in which no adverse effects were observed and the limit dose 1000 mg/kg/dya. Starting at the mid dose of 300 mg/kg bw,. all animals of both sexes showed changes in feces color (reddish particles), which is a consequence of the strong red color of the test item.

Estimation of accumulation:

Poorly water soluble particles have the potential to accumulate in the lung. Based on the particle size distribution only 0.22% of the sample have a MMAD >100µm. Overall, the particle size distribution is not in favor of substantial accumulation.

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, in-vitro Chromosome Aberration test and gene mutation assay in mammalian cells (HPRT)).

Estimation of excretion:

Based on the low absorption potential of the compound excretion is anticipated mainly (exclusively) via the feces; this is supported by the sub-acute toxicity study. Starting at the mid dose of 300 mg/kg bw, all animals of both sexes showed changes in feces color (reddish particles), which is a consequence of the strong red color of the test item.

Applicant's summary and conclusion