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Link to relevant study record(s)

Reference
Endpoint:
dermal absorption in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: A scientific publication.
Principles of method if other than guideline:
Percutaneous absorption determined by radiolabelled substances.
GLP compliance:
not specified
Radiolabelling:
yes
Species:
mouse
Sex:
male
Duration of exposure:
1st experiment: 40 min
2nd experiment: 10 min
Doses:
3.18 mcg/mL per 3 cm2
No. of animals per group:
60 animals:
1 st experiment: 3 animals
2nd experiment: 3 animals/skin surface

1st experiment: after 10-min absorption time, maximum blood levels of all terpenes were reached. After 20 min, a decrease of terpene concentrations was observed in the blood. For isobornylacetate, the resutls were as follows: after 10 min, approximately 60 ng isobornyl acetate / mL blood (maximum), after 40 min, approx. 15 ng / mL.

2nd experiment: the terpene concentrations in the blood increase linearly with the size of the exposed skin.

Conclusions:
Maximum blood levels were achieved after 10 minutes the onset of the percutaneous absorption and this was a direct function of the size of the skin area involved.
Executive summary:

The percutaneous absorptions of isobornyl-acetate as a constituent of a foam bath was measured on animals using radioactively labelled ingredients. Pharmacokinetic measurements showed maximum blood levels 10 min after the onset of percutaneous absorption. Blood levels of all ingredients after 10 min of percutaneous absorption were a direct function of the size of the skin area involved.

Description of key information

Absorption of Isobornyl acetate extra was assessed based on physicochemical and toxicological data:

- Oral absorption is most likely.

- Inhalation absorption is likely, however it is considered to be limited.

- Dermal absorption is likely, howeer dermal penetration rate seems to be slow.

- Distribution is very likely, however there were no signs of toxicity of central nervous system. 

- Excretion via the urine, bile and breast milk are most likely. Another route of excretion may be applicable (e.g. skin after dermal application), however this is of less relevance.

- There is no clear indication of bioaccumulation potential.

The percutaneous absorptions of Isobornyl acetate as a constituent of a foam bath was measured on animals using radioactively labelled ingredients. Pharmacokinetic measurements showed maximum blood levels 10 min after the onset of percutaneous absorption. Blood levels of the substance after 10 min.of percutaneous absorption were a direct function of the size of the skin area involved.    

Key value for chemical safety assessment

Additional information

Basic toxicokinetics assessment:

Absorption of Isobornyl acetate extra was assessed as follows based on physicochemical and toxicological data:

- It is a liquid material with a molecular weight of 196.288 g/mol, water solubility = 9.7 mg/L and LogP = 3.86Vapour pressure = 0.107 mm Hg at 25 °C (~ 0.014 kPa) and Surface tension = 30.95 mN/m at 25°C.

- Acute oral and dermal toxicity are low (LD50 > 2000 mg/kg bw), however NOAEL in a 13 week repeat dose toxicity rats = 15 mg/kg/day. In male rats given 270 mg/kg bw/day there was a decrease in renal concentrating ability, an increase in water intake, exfoliation of renal tubular cells, increased kidney weight and vacuolation of the renal tubular cells. Signs of nephrotoxicity were also seen with daily doses of 90 mg/kg bw/day. Vacuolation of the epithelium of the intrahepatic bile-duct and increase in liver weights were found at 270 mg/kg bw/day. The caecum were also enlarged at this dosage level.

- Based on molecular Formula, molecular weight, water solubility, Log P and oral toxicity data, oral absorption is most likely.

- Based on Log P and oral toxicity data, inhalation absorption is likely, however due to low vapour pressure and low water solubility it is considered to be limited.

- Based on physical form, molecular weight, structure, water solubility, LogP and vapour pressure, dermal absorption is likely. However due to higher surface tension, absent skin irritation/ corrosivity/dermal toxicity and skin sensitization, dermal absorption is considered to be limited. When QSAR material was taken into consideration (Episuite, Dermwin), the dermal penetration rate seems to be slow

For the assessment of distribution, metabolism and excretion physicochemical and toxicological properties are taken into account.

- Based upon molecular weight, water solubility, Log P and target organs, distribution is very likely, however there were no signs of toxicity of central nervous system. 

- Excretion via the urine, bile and breast milk are most likely. Another route of excretion may be applicable (e.g. skin after dermal application), however this is of less relevance.

- There is no clear indication of bioaccumulation potential.

Dermal absorption data:

The percutaneous absorptions of Isobornyl acetate as a constituent of a foam bath was measured on animals using radioactively labelled ingredients. Pharmacokinetic measurements showed maximum blood levels 10 min after the onsetofpercutaneous absorption.Blood levelsof the substanceafter 10 min.ofpercutaneous absorption were a direct functionofthe sizeofthe skin area involved.