Registration Dossier

Toxicological information

Exposure related observations in humans: other data

Administrative data

exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
key study
Study period:
3 MARCH 1999
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
The study is well performed by excluding skin products as much as possible (although possibly not ruled out), and it envolves a fairly large study population (107 test persons). It was not carried out according to international accepted guidelines nor was it carried out under GLP.

Data source

Reference Type:
study report

Materials and methods

Type of study / information:
1) precisely measured data on the content of musk compounds in human milk of healthy women, under optimum exclusion of contamination from the environment.
2) information on the relationship between the content of HHCB in human milk and various characteristics of the subjects as well as their habits regarding the usage of fragrance products.
Test guideline
no guideline available
Principles of method if other than guideline:
Milk from 107 mothers was taken and analysed for several polycyclic musks and nitromusks (also HHCB). A questionaire concerning the use of synthetic musk containing articles was completed by the test persons the day before taking the milk samples. Furthermore, the frequency of usage of household products as well as fish consumption were questioned.
GLP compliance:

Test material

Details on test material:
- Name of test material (as cited in study report): HHCB


Ethical approval:
not specified
Details on study design:
Milk sample were taken at the policlinic under standardized conditions:
1. Determination of the current weight of the infant with a scale designed for babies by ‘Seca Mess- und Wiegetechnik’ (Seca, Hamburg, Germany).
2. Cleaning of one breast with a cotton swab (Rauscher, Pattensen, Germany) soaked in propylene glycol (DAB) to avoid the contamination of the milk sample by musk clinging to the skin. To accomplish this, three separate swabs were used, each time beginning with the nipple and moving in circles to the surrounding skin.
3. Pumping of a milk sample from a cleaned breast using the electric milk pump ‘Medela Classic’ and its original accessories (Medela Medizintechnik GmbH, Eching, Germany). To achieve a better milk flow for the taking of the sample, the infant was breast fed simultaneously at the other breast. A. sample volume of 50 ml minimum was targeted.
4. Immediate freezing of the samples at -20°C for analysis within 2 weeks. If the analysis was possible only at a later time, the samples were immediately frozen at -70°C.

By various measures the authors tried to minimize contamination of the breast milk samples with synthetic musks from the environment:
- by wearing latex gloves free of powder (Safeskin Corp., San Diego, California, USA) while collecting and processing the samples,
- by using cleansing lotion without perfume to wash hands (Dove extra sensitive Lever Hamburg, Germany),
- by using cleansing solvent (Mucasol, Brand, Wertheim, Germany) without fragrances to clean the milk pump accessories and all the laboratory equipment needed for the lipid extraction,
- by storing the milk pump accessories in a closed metal box, cleaned with acetone immediately after drying in a drying chamber (Ehret, Dusseldorf Germany) at 80°C,
- by closing the openings of the glass flasks and pipettes with aluminium foil after drying in a drying chamber (Meinmert, München, Germany),
- by washing all laboratory equipment with acetone and n-hexane (Merck, Darmstadt, Germany) immediately before processing the samples,
- all staff working in the laboratory refrained from using perfume and other cosmetics containing fragrances.

Exposure assessment:
Details on exposure:
TYPE OF EXPOSURE: environmental


Results and discussion

In the present study HHCB was found in human milk at levels from zero to 1316 μg/kg fat (equivalent to 48 μg/kg whole milk based on a median measured fat content of 3.67%) with a mean of 80 µg/kg fat (2.9 µg/kg milk). In adipose tissue HHCB was found at levels ranging from 12 – 189 μg/kg fat.

Any other information on results incl. tables

Table 1: concentration of HHCB in human breast milk (ug/kg fat)

Median 47.8
Minimum 0
Maximum 1316.3
Interquartile range 60
Mean 80.38
Std. deviation 149.43

Applicant's summary and conclusion

HHCB was found in human milk of 107 human test persons. The mean concentration found was 80 ug/kg milk fat with a standard deviation of 149
Executive summary:

In the present study, milk from 107 women was taken and analysed for several polycyclic musks and nitromusks. A mean and a median fat content of 3.67 and 3.40%, respectively, were found in the mother’s milk. The concentration of HHCB in the milk showed a mean value of 80 ug/kg milk fat with a standard deviation of 149. The minimum and maximum values found were close to zero and 1316 mg/kg milk fat, respectively. Arrangements were made to prevent contamination.