Registration Dossier

Toxicological information

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:
direct observations: clinical cases, poisoning incidents and other
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study in 50 human volunteers. Protocol well described (no international guideline). No clear information on the actual observations, only scores available.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974
Report Date:
1974

Materials and methods

Study type:
study with volunteers
Endpoint addressed:
skin irritation / corrosion
skin sensitisation
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A group of 50 individuals volunteered to participate in the evaluation. On the upper arm of each individual, 3 sites were designated for contact with 3 test materials, one of which being DBPP. A series of 16 applications, each of 24 hours duration were carried out. The test substance was applied to a pad, the pad was placed on the contact site and sealed with overlapping strips of Blenderm tape (occlusive). At the end of the 24h period, the patches were removed and the sites examined. The sites were then rested for 24 hours and re-examined. If the contact sites manifested no changes the test material was re-applied to the same site. After 2 application cycles, the test material was diluted to 5% in water and the exposure was continued in this manner for the remainder of the study
After the 15th application, the participants rested for 2 weeks before being challenged. The sites of contact used previously were challenged with the test material diluted to 5% concentrations in water for 24 hours under occlusion. After removal the contact sites were examined immediately and following at intervals of 24 hours for 48 hours.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Liquid
Details on test material:
- Name of test material (as cited in study report): dibutyl phenyl phosphate

Method

Type of population:
general
Subjects:
- Number of subjects exposed: 50
- Sex: not specified
- Age: not specified
- Race: not specified
- Demographic information: not specified
- Criteria for qualifying:
* general well-being
* absence of any skin disease which might be confused with skin reactions from the test materials
* willingness to cooperate
* dependability and intelligence in following directions
* reading, understanding and signing an informed-consent contract
Ethical approval:
not specified
Route of exposure:
dermal
Reason of exposure:
intentional
Exposure assessment:
measured
Details on exposure:
A lintine disc was moistened with 0,4 mL of the test material. The treated pad was placed on the predesignated site, covered and sealed by overlapping strips of Blenderm tape. The patch was kept intact for 24 hours.
Examinations:
At the end of the 24 hours the seal was broken and the patch removed. The skin sites were examined and gross changes, if present, were graded on a scale of 1 to 4. Absence of any visible skin changes was assigned a 0 value. The sites were again examined 24 hours later, just prior to the next application of test substance.
Medical treatment:
None.

Results and discussion

Results of examinations:
For DBPP, no significant reactions were observed after a first 24 h exposure. Visible skin changes signifying reaction to injury were observed in 2 out of 50 subjects after the second exposure to undiluted test substance. Both reactions were scored 1 on the scale of 1-4. Subsequent exposures to 5% solutions of DBPP in water did not result in any further observations on skin irritation. Furthermore, no visible skin changes were noted following the challenge application in any of the 50 subjects.

Applicant's summary and conclusion

Conclusions:
The test substance DBPP was significantly less irritating than the other 2 test substances involved in the test (tributyl phosphate and tributyl phosphate / tricresyl phosphate), which are considered primary irritants in their undiluted form.
At 5% concentrations, none of the test substances are primary irritants, fatiguing agents or sensitizers.

In so far as sensitization is concerned, the extrapolation of these results to a general population is limited statistically by the number of subjects used. In this case, since 50 subjects were used, we may predict with 95% certainty that at least 92,89% of a general population will not be sensitized by these test materials.