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Toxicological information

Basic toxicokinetics

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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
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other 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

Reference
Name:
Unnamed
Type:
Constituent
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)
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
human
Strain:
other: not relevant
Sex:
male

Administration / exposure

Route of administration:
dermal
Vehicle:
other: carbitol
Duration and frequency of treatment / exposure:
8 hours single treatment
Doses / concentrations
Remarks:
Doses / Concentrations:
4%
No. of animals per sex per dose:
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 uCi = 0.72%
Plasma: not detectable
Urine: 0.170 uCi = 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 Methoxydibenzoylmethane1789) 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:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
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.