2-methylpentane-2,4-diol

Repeated dose toxicity: dermal

Administrative data

Endpoint:

sub-chronic toxicity: dermal

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

This study is considered invalid due to the high incidence of death due to respiratory infection in all test groups. Also the method of application was unusual and the actual dose level could not be accurately determined. There was potential for ingestion as the site of application was uncovered abdominal skin.

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

SIDS Initial Assessment Report for SIAM 13

Author:

OECD

Year:

2001

Bibliographic source:

UNEP PUBLICATIONS

Reference 2

Reference Type:

review article or handbook

Title:

Toxicity profile Hexylene glycol.

Author:

British Industrial Biological Research Association (BIBRA)

Year:

1991

Reference 3

Reference Type:

review article or handbook

Title:

Chapter Fifty. Glycols

Author:

Rowe VK and Wolf MA

Year:

1981

Bibliographic source:

Patty's Industrial Hygiene and Toxicology. Third Revised Edition. Clayton GD and Florence FE (Eds). John Wiley & Sons, New York.

Reference 4

Reference Type:

study report

Title:

Unnamed

Year:

1950

Report date:

1950

Materials and methods

Test guideline

Qualifier:

no guideline followed

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-methylpentane-2,4-diol

EC Number:

203-489-0

EC Name:

2-methylpentane-2,4-diol

Cas Number:

107-41-5

Molecular formula:

C6H14O2

IUPAC Name:

2-methylpentane-2,4-diol

Test material form:

other: liquid

Test animals

Species:

rabbit

Strain:

not specified

Sex:

male

Administration / exposure

Type of coverage:

open

Vehicle:

unchanged (no vehicle)

Details on exposure:

Repeated uncovered applications, 5 days/week for 90 applications. Groups of 10-12 rabbits were exposed at each dose level. The test material was gently rubbed into the clipped belly of each rabbit for 1 minute in every 15 minutes over a period of 1 hour. At the end of this time excess liquid was blotted off. The initial dose levels were 1 ml/kg and 2 ml/kg/day. The control animals received glycerol at 2 ml/kg. Due to mortality, unrelated to treatment, a second study was started using hexylene glycol at 1.0 and 0.5 ml/kg/day and glycerol at 1.0 ml/kg/day.

Duration of treatment / exposure:

15 weeks

Frequency of treatment:

5 days/week

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0.5, 1.0 and 2.0 ml/kg bw/d
Basis:
nominal per unit area

Doses / concentrations 2

Remarks:

Doses / Concentrations:
461, 923 and 1846 mg/kg bw/d
Basis:
other: Assuming a density of 923 mg/cm3

No. of animals per sex per dose:

10-12

Control animals:

other: glycerol

Details on study design:

Post-exposure period: none

Examinations

Sacrifice and pathology:

Sections of skin from the treatment site plus liver and kidney were examined microscopically.

Results and discussion

Results of examinations

Details on results:

In the first experiment 2/11 rats receiving 2 ml/kg and 8/10 rats given 1 ml/kg hexylene glycol died due to respiratory infection or diarrhoea. 5 survivors at the higher dose level showed slight cloudy swelling of the liver. The two survivors at 1 ml/kg/day showed no histopathological changes in the liver or kidneys. 8/12 rabbits receiving glycerol also died. In the second study mortality was also high with 6/10 rabbits at 1 ml/kg and 4/11 at 0.5 ml/kg dying of lung infection. None of the survivors at 1 ml/kg showed any histopathological change in the liver or kidney. One survivor at 0.5 ml/kg showed cloudy swelling of the liver but the kidneys appeared normal. The effects on the skin were described as 'loss of epithelium and scrappy epidermis' for all treated and control groups. The authors considered this due to friction rather than a toxic effect.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The study gives limited information concerning the effect of repeated inunction due to intercurrent infection amongst the test animals and the method of application. Changes in the skin at all dose levels were not attributed to the test compound. There were no effects considered treatment related at dose levels of 1 ml/kg/day.