Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
September 1994
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
The study was not conducted in accordance with any regulatory guideline nor was it conducted in accordance with GLP. In addition the number of patients forming the investigation totalled just 6 and there were no formal controls for comparison. Similarly, confounding factors such as the exposure to measured amounts of the defined sunscreen products was not controlled. However, the information is well documented and scientifically acceptable.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Detection of UV filter substances in breast milk
Author:
J Hany and R Nagel
Year:
1995
Bibliographic source:
Deutsche Lebensmittel-Rundschau, 91(11), 341-345

Materials and methods

Objective of study:
distribution
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
It was the objective of the study to examine the potential of various sunscreen agents, including isopentyl p-methoxycinnamate and the read-across substance (2-ethylhexyl 4-methoxycinnamate, to be dermally absorbed and to appear in the breast milk of humans.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: ingredient in a UV filter formulation

Test animals

Species:
human
Strain:
not specified
Sex:
female
Details on test animals and environmental conditions:
Of the six female participants, two were from city locations, two from small town locations and two from village locations. The age range was from 27 to 34 years.

Administration / exposure

Route of administration:
dermal
Vehicle:
not specified
Duration and frequency of treatment / exposure:
One female did not use the UV filter products at all and acted as control. One female used the UV filter products daily and the remaining four individuals used the UV filter products once or twice per week throughout the summer 1994.
Doses / concentrations
Remarks:
Doses / Concentrations:
The exact quantities of UV filter product applied were not established.
No. of animals per sex per dose:
A total of 6 individuals were investigated
Control animals:
yes, concurrent no treatment
Positive control:
Not included
Details on study design:
Only six individuals were included in this assessment and, whilst one individual appeared to act as a negative control, the conditions were not necessarily similar for all six individuals.
Details on dosing and sampling:
It is unclear from the reference as to the level of exposure of each individual to the UV filter substances under investigation. One or more of the substances under test could be present in the UV screen formulation being used and there was no direct measure of the amounts of screening product being used by any of the inviduals. Details of the concentratins of the individual substances within the formulations were also not given.
Statistics:
No statistical analysis was applied

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
No details of abosrption of the identified substances were evaluated.
Details on distribution in tissues:
The distribution of substances incorporated in the UV filter formulations was investigated by the examination of breast milk samples from each individual.
Details on excretion:
No investigations on excretion were undertaken.

Metabolite characterisation studies

Metabolites identified:
not measured

Applicant's summary and conclusion

Conclusions:
Isopentyl p-methoxycinnamate was not detected in any of the breast milk samples despite being identified as an ingredient in the sunscreen formulations under test. The rlated substance, 2-ethylyhexyl 4-methoxycinnamate was detected in 2 of the four breast mik samples. It is difficult to make conclusions based upon this small data set and lack of exposure data, however, it is possible that the data is indicative of either lack of dermal absorption of isopentyl p-methoxycinnamate or absorption is sufficiently low that potential levels in tissues (such as breast milk) are undetectable.
Executive summary:

Human breast milk samples were taken from six women and examined for the presence of sunscreen agents Homosalate (HMS), Isopentyl p-methoxycinnamate (IMZ), Benzophenone-3 (BP-3), Methylbenzylidenecamphor (MBC), Octyl Dimethyl PABA (DABI) and 2 -ethylhexyl 4- methoxycinnamate (OMZ). It has been reported that up to 2% of the applied substances can be absorbed via the skin according to manufacturers information. Glass-columns filled with differently acitvated silica gel were used for the extraction of each of the 10 ml milk sampIes. The extracts were cleaned by gel permeation chromatography, afterwards reduced to a volume of 150 [ll and quantitatively analysed by Capillary Gaschromatography/ Mass Spectrometry in the SIM-mode. BP-3 and 2 -ethylhexyl 4 -methoxycinnamate were unambiguously detectable in five of the six investigated samples at a concentration range between 16 and 417 ng/g (fat basis). However, isopentyl p-methoxycinnamate was not detected in any of the samples. This information would add some support to the dermal absorption study in humans in which it was concluded that dermal absorption of isopentyl p-methoxycinnamate did not occur.