Registration Dossier

Administrative data

Description of key information

Skin Irritation

in vitro Skin irritation data do not need to be conducted as adequate in vivo skin irritation data exist to classify DIMETOL.

Two in vivo rabbit skin irritation studies are available to consider in a weight of the evidence apporach. Both pre-date GLP guidelines. The first study is an acute dermal toxicity study performed in 10 rabbits with a dose of 5 g/kg. Observations included moderate edema and moderate erythema in a majority of the animals. The second study used 6 rabbits to determine the primary irritant properties of DIMETOL applied neat. The primary irritation index was 5.13.

Both studies indicate DIMETOL can be irritating to the skin.

Eye Irritation

in vitro Eye irritation data do not need to be conducted as adequate in vivo eye irritation data exist to classify DIMETOL.

Two in vivo rabbit eye irritation studies are available to consider in a weight of the evidence approach. Both pre-date GLP guidelines. The first study instillation of 0.1 mL of 5% test material into the right eye of each of three rabbits, in the manner described, produced a moderate conjunctival irritation. On the seventh day of observation these eyes were normal. In the second study neat material instilled into the rabbits' eyes produced a primary irritation index: 536 / 18 = 29.8. The pathological findings on the eye and the irritations on the mucous membrane were not reversible within 8 days. Based on the findings the substance must be considered to be moderately irritant.

Taken together, these studies justify classification of DIMETOL as a serious eye irritant under GHS and as an eye irritant DSD schemes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: 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:
Method in Federal Register 38(187)1500.41, S.27019,1973.
GLP compliance:
no
Remarks:
study pre-dates GLP introduction
Specific details on test material used for the study:
Product: 2,6-Dimethylheptanol -2 (liquid)
Substance No.: 77/278
Species:
rabbit
Strain:
not specified
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Remarks on result:
probability of moderate irritation
Irritant / corrosive response data:
Primary irritation index: 20.5 / 4 = 5.13
Alterations were observed already after a short period of exposure. The irritations were reversible within 8 days after a short period of exposure, but not so after a 24-hour exposure. Based on the findings the substance must be considered to be strongly irritant (light redness and swelling. Flaking and overlapping redness were observed.)
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Based on the findings the substance must be considered to be moderately irritant.
Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Reason / purpose:
data waiving: supporting information
Reason / purpose:
data waiving: supporting information
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1976
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Documentation insufficient for assessment: Non-GLP study; no data about purity and no certificate of analysis of the test substance; no details on age, gender, weight and strain of rabbits and housing conditions
Qualifier:
no guideline available
Principles of method if other than guideline:
No information on method available
GLP compliance:
no
Remarks:
study pre-dates introduction of GLP
Specific details on test material used for the study:
- Name of test material (as cited in study report): Dimetol
Species:
rabbit
Strain:
not specified
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
not specified
Controls:
no
Remarks on result:
positive indication of irritation

Ten rabbits were dosed with 5 g/kg, irritant effects were observed. Slight redness in 2, moderate redness in 8, slight edema in 1, and moderate edema in 9 of the animals were observed.

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Ten rabbits were dosed with 5 g/kg, irritant effects were observed. Slight redness in 2, moderate redness in 8, slight edema in 1, and moderate edema in 9.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation
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:
Method in Federal Register 38(187)1500.41, S.27029,1973.
GLP compliance:
no
Remarks:
study pre-dates GLP introduction
Specific details on test material used for the study:
Product: 2,6-Dimethylheptanol -2 (liquid)
Substance No.: 77/278
Species:
rabbit
Strain:
not specified
Vehicle:
unchanged (no vehicle)
Details on study design:
Primary eye irritation was measured in 6 rabbits. Readings at 24, 48 & 72 hrs and 8 days.
Remarks on result:
probability of moderate irritation
Irritant / corrosive response data:
Primary irritation index: 536 / 18 = 29.8
The pathological findings on the eye and the irritations on the mucous membrane were not reversible within 8 days. Based on the findings the substance must be considered to be moderately irritant.
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Based on the findings the substance must be considered to be moderately irritant.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1971
Reliability:
4 (not assignable)
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
Specific details on test material used for the study:
Material: Lolitol
Product: 12-5765
Species:
rabbit
Strain:
other: albino
Vehicle:
other: Alcohol SDA 39C
Controls:
yes
Amount / concentration applied:
Each animal has 0.1 mL of the test sample instilled into the right eye with no further treatment.
Observation period (in vivo):
Both the treated and control eyes were examined every twenty-four hours for four days and then again on the seventh day.
Number of animals or in vitro replicates:
Three normal, healthy, albino rabbits were used.
Details on study design:
The scorings recorded were made according to the Draize scale for scoring ocular lesions.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
A x B x 5
Time point:
other: Day 1, 2, 3, 4 and 7
Score:
0
Max. score:
80
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
A x 5
Time point:
other: Day 1, 2, 3, 4 and 7
Score:
0
Max. score:
10
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
(A + B + C) x 2
Time point:
other: Day 1, 2, 3, 4 and 7
Score:
10.67
Max. score:
20
Reversibility:
fully reversible
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Instillation of 0.1 mL of 5% test material into the right eye of each of three rabbits, in the manner described, produced a moderate conjunctival irritation. On the seventh day of observation these eyes were normal.
Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Reason / purpose:
data waiving: supporting information
Reason / purpose:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on a weight of the evidence approach DIMETOL is classified as irritating to the skin.

Based on a weight of the evidence approach DIMETOL is classified as a serious eye irritant for GHS and as an eye irritant for DSD.