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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24-hour application followed by 14-day observation period
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted prior to introduction of Good Laboratory Practices; data from a summary report; limited number of animals. Study was conducted by an internal Eastman Kodak Company method, developed prior to established guidelines. The results of this study are valid for classification insofar as the conditions of exposure are at least as stringent as modern guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1964
Report Date:
1964

Materials and methods

Test guideline
Qualifier:
no guideline followed
Deviations:
not specified
Principles of method if other than guideline:
Method is an in vivo study using three guinea pigs. Following depilation of the abdomen of each animal, a single dose of the test substance was applied under an occlusive wrap for 24 hours. Animals were observed periodically for mortality, and on Days 7 and 14 for dermal reactions. In addition, 14-day weight changes were recorded.
GLP compliance:
no
Remarks:
Study conducted prior to GLPs
Test type:
other: internal Eastman Kodak method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
-Identity (according to study report): 2,2,4-trimethyl-1,3-pentanediol (TMPD)

Test animals

Species:
guinea pig
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
no data

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Following depilation of each animal's abdomen, a single dose of 0.25, 0.5, or 1.0 g/kg bw of the test substance (dose preparation: neat) was applied under an occlusive cuff and wrap. The test substance was moistened with water before administration. After a 24 hour exposure period, the cuffs and wrappings were removed.
Duration of exposure:
24 hours
Doses:
0.25, 0.50 or 1.0 g/kg bw
No. of animals per sex per dose:
1 animal/dose (sex not specified)
Control animals:
no
Details on study design:
Three guinea pigs (sex, age, and initial weights not provided) were used. Following depilation of the guinea pig abdomens, a single dose of 0.25, 0.50, or 1.0 g/kg bw of the test substance (dose preparation: neat) was applied under an occlusive wrap prepared from a pad of gauze held in place with an impervious cuff made of rubber dental dam material. The test substance was moistened with water prior to administration. The cuff was wrapped securely around the torso of the guinea pig and held in place with non-irritating tape. Animals were exposed for 24 hours; then the cuffs were removed. Animals were observed for mortality, and on Days 7 and 14 for dermal reactions. Guinea pigs were weighed prior to administration of the test substance and at termination of the 14-day observation period to measure weight changes during the study.
Statistics:
not performed

Results and discussion

Effect levels
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 1 other: g/kg bw
Mortality:
None
Clinical signs:
Signs of irritation at the application site included slight to moderate edema, erythema (grade 2), and scattered necrosis after removal of the bandage and cuff. Gross edema, eschars and little hair were noted 1 week after dose administration. Slight erythema, scarring along the edge of the patched area, sparse hair, and desquamation were noted at study termination.
Body weight:
Two animals gained weight (30 and 42 g) and one animal lost weight (17 g) during the 14-day observation period. No information was provided as to which animal lost weight.
Gross pathology:
Not performed

Applicant's summary and conclusion

Interpretation of results:
other: Not classified (NC) for any endpoint in Directive 67/548/EEC; insufficient data for UN GHS or EU CLP Regulation (EC) No. 1272/2008 acute dermal toxicity classification. NC for STOT-SE per UN GHS or EU CLP; Cat 2 for skin irritation per UN GHS and EU CLP.
Remarks:
Criteria used for interpretation of results: OECD GHS
Conclusions:
In an acute dermal toxicity test, no deaths were reported when up to 1 g/kg bw of neat 2,2,4-trimethyl-1,3-pentanediol was applied to the clipped skin of guinea pigs for twenty-four hours under occlusive wrap. No clinical signs were reported during the study. Two of three animals gained weight normally while the third lost weight. Insufficient data were provided to determine if the weight loss was dose related. Slight erythema and scarring was still evident along the top of the patch at the conclusion of the observation period. The dermal LD50 in guinea pigs was > 1.0 g/kg bw, the highest dose tested in this study.

2,2,4-Trimethyl-1,3-pentanediol was not acutely toxic by the dermal route in rats at a dose of 1000 mg/kg bw and is not classified for acute lethality by the dermal route according to Directive 67/548/EEC. There were insufficient data to determine if the test material was classifiable according to the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) or EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) 1272/2008 since Category 4 in those two classification schemes covers the dose range 1000-2000 mg/kg bw. Based on an absence of signs of systemic toxicity and/or skin absorption, 2,2,4-trimethyl-1,3-pentanediol is not classified according to the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) or EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) 1272/2008 for Specific Target Organ Toxicity – Single Exposure. Based on signs of dermal irritation still present at the conclusion of the two week observation period, 2,2,4-trimethyl-1,3-pentanediol may be classifiable for Skin Irritation/Corrosion according to the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) 1272/2008. The conditions of exposure in this study were much more stringent, both in dose used and exposure period, than what is currently used in guideline skin irritation studies.
Executive summary:

In an acute dermal toxicity study, 3 guinea pigs were exposed to 0.25, 0.5, or 1.0 g/kg bw 2,2,4-trimethyl-1,3-pentanediol under occlusive contact for 24 hours. Under the conditions of this study, no deaths occurred and the dermal LD50 was considered to be > 1 g/kg bw of the neat material. No signs of skin absorption or systemic toxicity were evident during the study. Signs of irritation at the application site included slight to moderate edema, erythema (grade 2), and scattered necrosis after removal of the bandage and cuff. Gross edema, eschars and little hair were noted at week 1 post-dose and slight erythema, scarring along the edge of the patched area, sparse hair, and desquamation was noted 2 weeks post-dose.  A body weight gain was noted in two of three animals while the remaining animal lost weight over the 2-week observation period. Based on the results of this study, 2,2,4-trimethyl-1,3-pentanediol presents a low acute toxicity hazard upon skin contact under conditions of normal use.