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Exposure related observations in humans: other data

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exposure-related observations in humans: other data
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study meets generally accepted scientific principles, acceptable for assessment.

Data source

Reference Type:
The classification of skin irritants by human patch test.
Basketter, D.A. et al.
Bibliographic source:
Food and Chemical Toxicology 35: 845-852

Materials and methods

Type of study / information:
Identification of substances with significant skin irritation potential with the human 4 hour patch test.
Endpoint addressed:
skin irritation / corrosion
Test guideline
no guideline followed
Principles of method if other than guideline:
Assessment of skin irritation potential with the human 4 hour patch test.
GLP compliance:
not specified

Test material

Test material form:
other: aqueous formulation
Details on test material:
- Name of test material (as cited in study report): N,N-dimethyl-N-dodecyl aminobetaine
- Analytical purity: 20% solution


Ethical approval:
confirmed, but no further information available
Details on study design:
The human 4 hour closed patch test was designed as part of a strategy to replace the use of animals for the identification of skin irritation/corrosion. the method was considered to be a relevant (and superior) alternative to the rabbit Draize test since the same target organ, living skin, and the same toxic effect, irritation, was measured using the same parameters. The duration of application was chosen to reflect half a normal working shift.

The patch test procedure involved application of 0.2 ml (0.2 g for solid test materials) in a 25 mm Plain Hill Top Chamber containing a Webril pad (moistened for solid test materials) to the skin of the upper outer arm of 30 volunteers for up to 4 hours. To avoid unacceptably high reactions, test materials were applied progressively from 15 and 30 min through 1, 2, 3 and 4 hours. Treatment sites were assessed for the presence of irritation using a four point scale at 24, 48 and 72 hours after patch removal. A volunteer with a "weakly positive" (characterised by mild erythema or dryness across most of the treatment site) or greater reaction at any of the readings was considered to have demonstrated a positive irritant reaction, and treatment with the causative substance did not proceed on that person.

As human skin responses to irritants show a wide interindividual variation, an irritation standard (20 % SDS) was included to assess skin iritation potential in relation to a positive control. The interpretation of results in terms of EC classification was done by statistical comparison of the data with the concurrent SDS control using Fisher's exact test (Fisher, 1935, as modified by Mehta and Patel, 1983). The minimum level of SDS classified as R38 to skin (20 %) was adopted as an appropriate pointer to this threshold in terms of the intensity and frequency of an irritant response in human skin (York et al., 1996). It was concluded that substances which when tested undiluted elicit statistically less skin irritation than this threshold should not be classified R38, whilst those that produce a similar or higher level should be classified as R38.

Inter-ethnic variations had been excluded by preliminary work on SDS demonstrating that these effects were relatively minor.

The results of the study support earlier conclusions of York et al. (1996) that the method provides an accurate 'gold standard' assessment of acute irritation potential to human skin, and in case that the human result differs from the rabbit, the human result should be considered as the correct one.
Exposure assessment:
Details on exposure:
TYPE OF EXPOSURE: Closed patch in 25 mm Plain Hill Top Chambers (Hill Top Companies, Cincinatti, OH, USA), containing a Webril pad moistened with the test substance

TYPE OF EXPOSURE MEASUREMENT: other: application of defined amount of test substance

EXPOSURE LEVELS: 0.2 ml of a 20 % solution

EXPOSURE PERIOD: 4 hours, chosen on the same basis as that used by Draize, to be half of a normal working shift.



Results and discussion

When tested at a concentration of 20 % the test substance elicited positive patch test results in 30/32 individuals (equivalent to 94 %). The corresponding positive control (20 % SDS) demonstrated positive patch test results in 27/32 individuals (equivalent to 84 %).

Therefore, the test substance at a concentration of 20 % should be classifed as irritating to the skin (R38), which is in accordance with the existing EC classification based on animal testing.

Applicant's summary and conclusion