## FINAL REPORT

Toxicokinetic Assessment of

Author

Test Facility

Laboratory Project Ide ntification

- Page 1 of 8

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CONTENTS

1. INTRODUCTION

.................................................................................................................. 4

2. SUMMARY REGISTRATION DOSSIER

.............................................................................. 4

3. TO XICOKINETIC ASSESSMENT

........................................................................................ 7

4. REFERENCES

..................................................................................................................... 8- Page 4 -

1. INTRODUCTION

Sponsor

Study Monitor (on behalf of the sponsor)

Test Facility

2. SUMMARY REGISTRATION DOSSIER

Test substance information:

Identification

Structure

Molecular formula

Molecular weight

CAS Number

Description

Purity- Page 5 -

Key data given in the registration dossier include:

Physical chemistry:

Melting temperature

Boiling temperature

Relative d ensity

Vapour pressure

Surface tension

Water solubility

Partition coefficient

Dissociation constant

Hydrolysis

Particle size (MMAD)

Toxicological properties:

A limited number of studies was performed with the substance Several studies were readacross from similar substances, i.e. and , the structures of which

have been depicted below. Acute oral and dermal toxicity, skin and eye irritation are the studies

for which data from related substances was used.- Page 6 -

Acute oral toxicity LD50 >2000 mg/kg bw

Acute dermal toxicity LD50 >2000 mg/kg bw

Acute inhalation toxicity LC50 1

- 5 mg/L

Combined repeated toxicity /

reproduction/developmental

screening NOAEL parental 30 mg/kg bw/day

NOAEL reproduction 100 mg/kg bw/day

NOAEL developmental 10 mg/kg bw/day

Skin irritation test I rritating

Eye irritation test No t irritating

Sensitisation No t sensitizing

Ames test Negative

Chromosome aberration test Negative- Page 7 -

3. TOXICOKINETIC ASSESSMENT

Ba sed on similar structure and physicochemical properties and related substances are

theoretically expected to have similar adsorption, distribution, metabolism and excretion

behavior. As the relevant physicochemical properties of are available, this toxicokinetic

assessment is based on the physicochemical properties of

The low molecular weight of favours absorption in the gastro-intestinal tract by

passive diffusion, however, the low water solubility and the high log Pow

of render absorption in the gastro-intestinal tract by passive diffusion to be unlikely.

may be taken up by micellular solubilisation as is poorly soluble in water and has a high log

Pow. Therefore, for risk assessment purposes, the oral absorption of is set at 50% (1). The

results of the toxicity studies with and related substances do not provide reason to deviate

from this proposed oral absorption percentage.

Although may be expected to distribute widely throughout the body based on the small

molecular weight, the lipophilicity and low water solubility of disfavour a wide distribution.

The lipophilicity of also predicts that the intracellular concentration may be higher than the

extracellular concentration, particularly in fatty tissues. Based on the relatively high lipophilicity

may accumulate (1). Absorbed might undergo oxidation which may be followed by

conjugation (2). The conjugates are expected to be excreted via the urine as they are still

expected to be low molecular weight compounds.

The low vapour pressure indicates that is not available for inhalation as a vapour.

The low water solubility enhances penetration to the lower parts of the respiratory

tract. In combination with the high log Pow is expected to be taken up by

micellular solubilisation in the lower respiratory tract. For risk assessment purposes the

inhalation absorption of is set at 100%.

Since the log Pow is high , is expected to be taken up in the stratum corneum, but

further transfer to the epidermis is predicted to be low based on the low water solubility

According to the criteria given in the REACh guidance (1):

As

de rmal absorption is generally not expected to be higher than oral absorption, 50% dermal

absorption of is proposed.

Based on the present data, no additional conclusions can be drawn on the distribution,

metabolism and excretion of after dermal and inhalatory absorption.- Page 8 -

4. REFERENCES

1. Guidance for the implementation of REACH. Guidance on information requirements and

chemical safety assessment. Chapter R.7c: Endpoint specific guidance. European

Chemical Agency, May 2008.

2. A. Parkinson. In: Casarett and Doull’s Toxicology, The basic science of poisons. Sixth

edition. Ed. C.D. Klaassen. Chapter 6: Biotransformation of xenobiotics. McGraw-Hill,

New York, 2001.

3. Category approach fo r REACH registration of

.