Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
6-hour exposure 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:
other: Eastman Kodak Company Toxicology Report
Title:
Unnamed
Year:
1959
Report Date:
1965

Materials and methods

Test guideline
Qualifier:
no guideline available
Deviations:
not specified
Principles of method if other than guideline:
Method is an in vivo study using a group of four rats (sex, strain, and weights not available) exposed to an atmosphere containing the test substance as a dust for a period of six hours. After termination of exposure, the animals were observed for mortality and adverse clinical signs for a period of 14 days. Body weights were measured prior to exposure and at termination of the 2-week observation period.
GLP compliance:
no
Remarks:
Study conducted prior to GLPs
Test type:
other: Study conducted according to an internal Eastman Kodak Company laboratory method in which rats were exposed to the test substance by whole-body inhalation exposure.
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:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
no data

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
Rats were exposed (whole-body) to an atmosphere containing 4.5 mg/L of the test substance for a period of six hours. The atmosphere was generated by a Wright Dust Mill which produced a dust particulate of the test substance; the dust was mixed with air and was directed into an 18.5 L exposure chamber at the rate of 5 L/min. The chamber temperature was maintained at 25 °C.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
6 h
Concentrations:
4.5 mg/L
No. of animals per sex per dose:
4 (sex not specified)
Control animals:
no
Details on study design:
Four rats (sex, strain, and weights not available) were exposed (whole-body) to an atmosphere containing 4.5 mg/L of the test substance for a period of six hours. The atmosphere was generated by a Wright Dust Mill which produced a dust particulate of the test substance that consisted of 34.1% respirable particles. The test substance was mixed with room air and was directed into a 18.5 L exposure chamber, maintained at 25 °C, at a rate of 5 L/min. The calculated total dose respired was 2.8 g/kg bw. Animals were observed for mortality and adverse effects for a period of 14 days. Body weights were recorded prior to exposure to the test substance and at termination of the observation period.

Results and discussion

Effect levels
Sex:
not specified
Dose descriptor:
LC50
Effect level:
> 4.5 mg/L air
Exp. duration:
6 h
Remarks on result:
other: The respirable concentration of the test substance was 1.43 mg/L. The calculated exposure to the respirable portion of the test substance was 2.8 g/kg bw.
Mortality:
None
Clinical signs:
other: Abnormal clinical signs included piloerection, vasodilatation and lacrimation 4 minutes into inhalation exposure and nose rubbing at 5 minutes into inhalation exposure. No other signs of toxicity were noted during the inhalation exposure and the 14-day o
Body weight:
All animals gained weight over the 14-day observation period (130.8 g average).
Gross pathology:
not performed

Any other information on results incl. tables

Particle determination was 34.1% respirable particles; the total dose respired was 2.8 g/kg bw.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
Under conditions used in this study, 2,2,4-trimethyl-1,3-pentanediol was not acutely toxic by the inhalation route in rats exposed to an atmospheric concentration of 4.5 mg/L (34.1% respirable particles; total dose respired: 2.8 g/kg bw) of air for 6 hours. Since no mortality was noted at this exposure level, the LC50 in rats was greater than 4.5 mg/L of air (effective respirable concentration: 1.43 mg/L) for 6 h. Treatment-related abnormal clinical signs were noted shortly after the start of exposure and were limited to piloerection, vasodilatation, lacrimation and nose rubbing. All animals gained weight over the observation period.

In accordance with Directive 67/548/EEC, 2,2,4-trimethyl-1,3-pentanediol is not classified for acute inhalation toxicity. Based on an acute inhalation LC50 value > 4.5 mg/L (effective respirable concentration: 1.43 mg/L) for 6 h in rats, 2,2,4-trimethyl-1,3-pentanediol is not expected to be classifiable for Acute Toxicity by the inhalation route 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. Based on the type and limited number of abnormal clinical signs observed during the study, 2,2,4-trimethyl-1,3-pentanediol is not classifiable for Specific Target Organ Toxicity – Single Exposure at this exposure concentration 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.
Executive summary:

In an acute inhalation toxicity study, four rats were exposed to 2,2,4-trimethyl-1,3-pentanediol at a concentration of 4.5 mg/L (effective respirable concentration: 1.43 mg/L; total respired dose: 2.8 g/kg bw) for a period of 6 hours. Under the conditions of this study, no deaths occurred and the LC50 was considered to be greater than 4.5 mg/L. Signs of toxicity included piloerection, vasodilatation, lacrimation, and nose rubbing during the first 5 minutes of inhalation exposure. No other abnormal clinical signs or signs of systemic toxicity were evident during a 14-day observation period. Based on the results of this study, 2,2,4-trimethyl-1,3-pentanediol has a low potential to cause acute toxicity by the inhalation route.