Registration Dossier

Toxicological information

Repeated dose toxicity: dermal

Currently viewing:

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

Referenceopen allclose all

Reference Type:
secondary source
Title:
SIDS Initial Assessment Report for SIAM 13
Author:
OECD
Year:
2001
Bibliographic source:
UNEP PUBLICATIONS
Reference Type:
review article or handbook
Title:
Toxicity profile Hexylene glycol.
Author:
British Industrial Biological Research Association (BIBRA)
Year:
1991
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 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

Reference
Name:
Unnamed
Type:
Constituent
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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0.5, 1.0 and 2.0 ml/kg bw/d
Basis:
nominal per unit area
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.