FINAL REPORT

Toxicokinetic Assessment of

Author

Test Facility

 

Laboratory Project Identification

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CONTENTS 

1. INTRODUCTION .................................................................................................................. 4

2. SUMMARY REGISTRATION DOSSIER .............................................................................. 4

3. TOXICOKINETIC ASSESSMENT ........................................................................................ 7

4. REFERENCES ..................................................................................................................... 8

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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

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Key data given in the registration dossier include: 

Physical chemistry: 

Melting temperature

Boiling temperature

Relative density

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. 

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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

NOAELparental 30 mg/kg bw/day

NOAELreproduction 100 mg/kg bw/day

NOAELdevelopmental 10 mg/kg bw/day

Skin irritation test Irritating

Eye irritation test Not irritating

Sensitisation Not sensitizing

Ames test Negative

Chromosome aberration test Negative

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3. TOXICOKINETIC ASSESSMENT 

Based 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 

dermal 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. 

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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 for REACH registration of 

. 

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