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Description of key information

Skin Sensitizztion

DIMETOL was evaluated for its potential skin sesitization capacity prior to the availability of the LLNA protocol. A guinea pig study using an intradermal method of induction with Freund's Complete Adjuvant elicited no sensitization responses in 10 animals upon challenge with a 20% solution of DIMETOL. Three, separate human repeat patch tests were conducted with DIMETOL. In the first study, a modified Draize procedure, 10 panelists displayed no sensitization reactions to a 5% solution of DIMETOL in denatured ethanol. In the second study, also a modified Draize protocol, 53 subjects exhibited no sensitization reactions from a 2% solution of DIMETOL in dimethyl phthalate. The third and final study employed a Maximization protocol with 25 subjects and a 10% solution of DIMETOL. No sensitization reactions were reported under these conditions. The classification criteria for skin sensitization are not met.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1969
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
according to
Guideline:
other: Draize Technique
GLP compliance:
no
Remarks:
Study pre-dates introduction of GLP guidelines
Type of study:
Draize test
Justification for non-LLNA method:
LLNA not available at the time of testing.
Specific details on test material used for the study:
Giv 2-2356 Dimetol (2,6-Dimethylheptan-2-ol)
Species:
human
Sex:
male/female
Details on study design:
2% solution by weight in dimethyl phthalate
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
2%
No. with + reactions:
0
Total no. in group:
53
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
2%
No. with + reactions:
0
Total no. in group:
53
Remarks on result:
no indication of skin sensitisation

Fifty three subject, 35 female and 18 male, of representative age groups concluded a full sensitization and challenge test study in accordance with the described Draize repeated insult technique. There were no reactions manifested by any one of these subjects in the challenge test to any one of the eight prepatations in the challenge test and there were no significant reactions of either an irritative or allergenic character by any of the individuals in response to any of these preparation during the sensitization phase of the study.

Minor adhesive tape reactions were recorded but not repeated during the challenge tests.

It is therefore concluded that the eight preparations studied in this investigation are not primary irritants in the concentrations employed and that in these concentrations they were not allergenic to any of the 53 subjects who completed the full study.

Interpretation of results:
GHS criteria not met
Conclusions:
Fifty three subject, 35 female and 18 male, of representative age groups concluded a full sensitization and challenge test study in accordance with the described Draize repeated insult technique. There were no reactions manifested by any one of these subjects in the challenge test to any one of the eight prepatations in the challenge test and there were no significant reactions of either an irritative or allergenic character by any of the individuals in response to any of these preparation during the sensitization phase of the study.
Minor adhesive tape reactions were recorded but not repeated during the challenge tests.
It is therefore concluded that the eight preparations studied in this investigation are not primary irritants in the concentrations employed and that in these concentrations they were not allergenic to any of the 53 subjects who completed the full study.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
according to
Guideline:
other: an adaptation of the Draize Method
Principles of method if other than guideline:
The method of procedure is that suggested by Dr. Draize and described in 'Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics', published by the Association of Food and Drug Officials of the United States
GLP compliance:
no
Remarks:
study pre-dates GLP guidelines
Type of study:
patch test
Justification for non-LLNA method:
LLNA not available at the time of testing.
Specific details on test material used for the study:
Material: Lolitol
Date Received: June 14, 1971
Code/Lot No.: SK-08-1879 (12-5765)
Species:
human
Strain:
not specified
Sex:
male/female
Details on study design:
5.0% test material in alcohol SDA 39C
Key result
Group:
test group
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation

Results of the study are shown in the tables in the attached study as follows:

Table 1: Individual reaction scores and group totals following patch application of sample.

Table 2: Allergies, dermatitides and concomitant medication for each panelist.

The irritation and sensitizing properties of the test sample listed above were evaluated in 10 male and female panelists in a repeated insult patch test.

The 10 panelists showed little or no primary irritation.

There was no evidence of sensitization to the sample under conditions of this test.

Sensitization summary:

Not sensitized 10/10

Possibily sensitized 0/10

Probably sensitized 0/10

Interpretation of results:
GHS criteria not met
Conclusions:
The irritation and sensitizing properties of the test sample listed above were evaluated in 10 male and female panelists in a repeated insult patch test.
The 10 panelists showed little or no primary irritation.
There was no evidence of sensitization to the sample under conditions of this test.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Principles of method if other than guideline:
Maximization test (J.I.D.; vol. 47; No. 5; 393-409;1966)
GLP compliance:
no
Remarks:
study pre-dates GLP
Type of study:
other: Maximization test
Justification for non-LLNA method:
LLNA not available at the time of testing.
Specific details on test material used for the study:
Test substance: Dimetol
Species:
human
Strain:
not specified
Sex:
male/female
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
10%
No. with + reactions:
0
Total no. in group:
25
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 25.0.
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
10%
No. with + reactions:
0
Total no. in group:
25
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 25.0.
Interpretation of results:
GHS criteria not met
Conclusions:
There were no instances of contact-sensitization from this material on the Maximization test.
It is unlikely that this material would present a danger of contact-sensitizatioon in normal, intended use.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
no guideline available
Principles of method if other than guideline:
No guideline available in report
GLP compliance:
no
Remarks:
pre-dates GLP guidelines
Type of study:
not specified
Justification for non-LLNA method:
LLNA not available at the time of testing.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
All animal experiments were performed on albino animals of the Hartley/Dunkin strain reared by a contract breeder. The animals were housed in stainless steel wire mesh cages (five to a cage) in a room at a controlled temperature of 25 C, a relative humidity of 55% and artificially illuminated for 12 hours daily. They were fed a standard pellet guinea pig diet and water ad libitum. Female guinea pigs weighing between 350-400 g at the start of testing were used in each test.
No. of animals per dose:
10 animals were treated with the test materials (experimental group) and the same number was not treated with them (control group). For positive control, five animals were used.
Details on study design:
For both intradermal inductions, 10% test material in Freund’s Complete Adjuvant (FCA) without cinnamic acid (3%) as positive control was used. An area of 4 x 6 cm over the shoulder region is clipped with an electric clipper and shaved with an electric razor. Three pairs of intradermal injections were made simultaneously, so that on each side of the midline, there were two rows of three injections each. The injections were: (a) 0.1 ml of 50% FCA (adjuvant blended with equal amount of distilled water), (b) 0.1 ml of 10% test material in FCA and (c) 0.01 ml of 10% test material in the FCA emulsified with distilled water. One week after injections to enhance the sensitization, the same area clipped and shaved was pretreated with 10% sodium lauryl sulfate (SLS) in petrolatum 24 hours before the mild application of the test materials to provoke mild inflammatory reaction. The SLS was massaged into the skin with a glass rod. No bandage was applied. 0.2 ml of 10% test material in FCA was spread over a 2 cm x 3 cm patch of Toyo filter paper. The patch was covered by an overlapping, impermeable plastic adhesive tape (Blenderm). This is turn was firmly secured for 48 hours by means of an elastic adhesive surgical bandage which was wound around the torso of the animal. For the negative control group, distilled water was used in the same regimen instead of test materials. On the other hand, for positive control, 3% cinnamic aldehyde was used. Challenge was performed by topical application on the 21st day. The hair of the flank was removed by clipping and shaving. Challenge test was performed by applying with 0.02 ml of 20% test materials in acetone to the area of the left and right flank skin areas (1.5 x 1.5 cm2/each site). The application sites were left uncovered. Negative controls were done in the same way as the experimental group. The 2% concentration of cinnamic aldehyde in acetone or positive controls was used. The challenge sites were evaluated after 24 and 48 hours according to the criteria of Draize.
Challenge controls:
For challenge, 20% test materials in acetone without cinnamic aldehyde (3%) were used.
Positive control substance(s):
yes
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Conclusions:
Dimetol was found to be non-sensitising at 20%.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)

Respiratory sensitisation

Link to relevant study records
Reference
Endpoint:
respiratory sensitisation: in vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the available information indicates that the substance should be classified for respiratory sensitisation or corrosivity
Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The DSD and GHS classification criteria for skin sensitization are not met for DIMETOL. No evidence of sensitization was seen in an intradermal guinea pig study, and in three separate human patch tests using either a modified Draize procedure or a Maximization protocol.