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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
sub-chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Book section. Because of 1) the uncertainties in the significance of the effects reported, 2) the study was conducted without collar or occlusion to prevent oral intake of compound making it impossible to determine actual exposures and 3) the area of application was not reported, this study should not be used to determine a dermal NOAEL.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Safety Evaluation of Four Bicyclic Musk Fragrance-Chemicals Relative to the Neurotoxin, Acetyl Ethyl Tetramethyl Tetralin (AETT).
Author:
Gressel, Y., Troy, W.R., Foster, G.V.
Year:
1980
Bibliographic source:
Mechanisms of Toxicity and Hazard Evaluation (B. Holmstedt, R. Lauwerys, M. Mercier, and M.|Roberfroid, Eds.) Elsevier/North-Holland Biomedical Press,|New York, pp.53-58.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
In the 13 week study, groups of 15 female rats (Crl:COBS CD (SD) BA strain; weight 156-232 g) were exposed topically unoccluded (gentle inunction to the anterior dorsal shaven skin) to dose levels of 1, 10 and 100 mg Galaxolide (65% HHCB in DEP) /kg bw per day as a 2% (w/v) solution in ethanol.
GLP compliance:
no
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The test substance was the commercially available grade of HHCB which is ca. 65% HHCB in DEP

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female

Administration / exposure

Type of coverage:
open
Vehicle:
ethanol
Details on exposure:
Route of Administration: dermal
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
1, 10, 100 mg/kg bw/d
Basis:
nominal per unit body weight
No. of animals per sex per dose:
15 females
Control animals:
yes

Results and discussion

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

The only effect reported was an increase in liver weights at
the highest dose level.  No neurotoxic effects were seen.

Applicant's summary and conclusion

Conclusions:
Clear evidence of neurotoxicity, both clinically and pathologically, was seen with the positive control but no such evidence for HHCB was seen at any dose level
Executive summary:

In the 13 week study, groups of 15 female rats (Sprague-Dawley; weight 156-232 g) were exposed topically unoccluded (gentle inunction to the anterior dorsal shaven skin) to dose levels of 1, 10 and 100 mg Galaxolide (65% HHCB in DEP) /kg bw per day as a 2% (w/v) solution in ethanol. Untreated controls and ethanol controls were included. Observations included mortality, clinical signs, behavioural and motor function and (limited) haematology, serum chemistry, organ weights, macroscopy and histopathology. Special neuropathological examination of brain, spinal cord, and peripheral nerves was included for 2 animals per dose group. In the 13-week study, there were no reported adverse clinical signs, no variation in biochemistry or haematological parameters, no effects on bodyweight and no histological changes at any dose. However, increased absolute and relative liver weights were seen at 100 mg Galaxolide/kg bw per day, but no actual data were presented so the degree of these changes is unknown. This study was primarily designed to screen for neurotoxicity and a positive control, 7-Acetyl-6-ethyl-1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphthalene (AETT) a known rat neurotoxin, was similarly dosed at 0.1, 0.3, 1, 3, 10, 30 or 100 mg/kg bw/day for 13 weeks. Clear evidence of neurotoxicity, both clinically and pathologically, was seen with the positive control but no such evidence for HHCB was seen in either study at any dose level