2-Ethylhexyl trans-4-methoxycinnamate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: human study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Objective of study:

absorption

excretion

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Healthy human subjects are exposed to two UV filters (Ethylhexyl Methoxycinnamate and Butyl Methoxydibenzoylmethane), investigating the absorption and excretion of the substances.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-ethylhexyl 4-methoxycinnamate

EC Number:

226-775-7

EC Name:

2-ethylhexyl 4-methoxycinnamate

Cas Number:

83834-59-7

Molecular formula:

C18H26O3

IUPAC Name:

2-​Propenoic acid, 3-​(4-​methoxyphenyl)​-​, 2-​ethylhexyl ester, (2E)​-

Details on test material:

- Name of test material (as cited in study report): Ethylhexyl methoxycinnamate, Butyl Methoxydibenzoylmethane
- Physical state: Liquid
- Specific activity (if radiolabelling): 125 uCi/ml (14C)

Specific details on test material used for the study:

4 % w/v of unlabelled material in solution

Radiolabelling:

yes

Remarks:

14C

Test animals

Species:

human

Sex:

male

Administration / exposure

Route of administration:

dermal

Vehicle:

other: carbitol

Duration and frequency of treatment / exposure:

8 hours single treatment

Doses / concentrations

Dose / conc.:

25 other: μCi

Remarks:

Doses / Concentrations: 4 %

No. of animals per sex per dose / concentration:

4 subjects, of which 1 for pilot study

Control animals:

no

Results and discussion

Preliminary studies:

Recovery Ethylhexyl Methoxycinnamate from subject 1:
Skin (by stripping): 0.18 µCi = 0.72 %
Plasma: not detectable
Urine: 0.170 µCi = 0.16 %
Faeces: not detectable

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Skin (stripping):
Subject 2: 1 %
Subject 3: 0.28 %
Subject 4: 0.48 %

Details on distribution in tissues:

Plasma: not detectable

Details on excretion:

Urine:
Subject 2: 0.16 %
Subject 3: 0.2 %
Subject 4: 0.12 %

Faeces:
Subject 2: not detectable
Subject 3: not detectable
Subject 4: not detectable

Metabolite characterisation studies

Metabolites identified:

not measured

Details on metabolites:

Not relevant

Any other information on results incl. tables

Total recovery for both the pilot and main study:

- Subject 1 (pilot): 92.3 %

- Subject 2: 90.6 %

- Subject 3: 98.2 %

- Subject 4: 93.0 %

According to OECD 427, 100 ± 10 % of test substance should be recovered in an in vivo (animal) study, this human study fulfills that requirement.

In the preliminary study an occlusive application method was used. In the main study occlusion was not used.

Occlusion (pilot study) did not appear to increase the absorption of tracer from the combined substances.

There were no clinically significant adverse reactions.

Recovery of labeled Ethylhexyl Methoxycinnamate (with unlabeled Butyl Methoxydibenzoylmethane 1789) from urine was significantly higher than that of labeled Butyl Methoxydibenzoylmethane 1789 (with unlabeled Ethylhexyl Methoxycinnamate 1789), but still extremely low.

Applicant's summary and conclusion

Conclusions:

Ethylhexyl Methoxycinnamate (containing Butyl Methoxydibenzoylmethane) shows a very low percutaneous absorption, that is indicated by very high recovery of the dose from the skin, undetectable radioactivity in plasma and faeces and a very low percentage of applied dose excreted in the urine. Therefore, it can be concluded that Ethylhexyl Methoxycinnamate does not bioaccumulate in human under the study conditions.

Executive summary:

1 healthy subject was treated with Ethylhexyl Methoxycinnamate (containing unlabelled Butyl Methoxydibenzoylmethane) for 8 hours in a preliminary study (for determination of activity to be applied), 3 healthy subjects were used in the main study. The preliminary study used occlusive application, in the main study no occlusion was applied. Subjects were screened (physical examination) and tested for derivations of haematology, serum chemistry and urinanalysis. Radioactivity (= amount of UV-Filter) was determined in skin (upper layer), plasma, urine and faeces.

No adverse effects were found after treatment in any of the subjects. Occlusion did not seem to have effect on the percutaneous absorption. In skin and urine only a very low amount of the radioactivity was recovered (maximum 1 %). In plasma and faeces no radioactivity was detectable. Therefore it is concluded that Ethylhexyl Methoxycinnamate shows only slight absorption into skin, and does not bioaccumulate.