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Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
The present data are from a preliminary test conducted for the purpose of dosage estimation for a main dermal carcinogenicity study (see 7.7). The data are available as secondary peer-reviewed quotation, reported in following acknowledged reviews, the CICAD 57 (2004) and the Toxicological Dossier of Glyoxal of the EFfCI (2004).

Data source

Referenceopen allclose all

Reference Type:
other: secondary quotation
Title:
Unnamed
Year:
1979
Reference Type:
secondary source
Title:
The Toxicological Dossier of Glyoxal
Author:
Schilling K
Year:
2004
Bibliographic source:
The European Federation for Cosmetic Ingredients, EFfCI
Reference Type:
secondary source
Title:
CICAD 57: Glyoxal, Concise International Chemical Assessment Document, 1st draft
Author:
Kiehlhorn J, Pohlenz-Michel C, Schmidt S and Mangelsdorf I
Year:
2004
Bibliographic source:
prepared by the Fraunhofer Institute for Experimental Medicine, Hanover, Germany for the WHO (Geneva)

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The present study was a preliminary test conducted for the purpose of dosage estimation for a main dermal carcinogenicity study reported in chapter 7.7.
GLP compliance:
no
Remarks:
GLP was not compulsory at the time the study was conducted
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Glyoxal
EC Number:
203-474-9
EC Name:
Glyoxal
Cas Number:
107-22-2
Molecular formula:
C2H2O2
IUPAC Name:
oxalaldehyde
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: BRRC sample number 41-400, identification number R9195-160 and BRRC sample number 41-429, identification number R9516-43

OTHER
- Impurities (identity and concentrations): 0.7% acid (calc. as acetic), 5.9% formaldehyde, 0.3% glycolaldehyde, 0.9% ethylene glycol (first batch)
- Impurities (identity and concentrations): 0.1% acid (calc. as acetic), 0.7% formaldehyde, 0.2% glycolaldehyde, traces of ethylene glycol (second batch)

Test animals

Species:
mouse
Strain:
C3H
Sex:
male

Administration / exposure

Type of coverage:
not specified
Vehicle:
water
Details on exposure:
-Each substance was tested as 1:4 and 1:8 dilutions in distilled water. 
-Taking into account a density of 1.27g/cm3 and a mean body weight for the mice of 25 g, the dosage for the 1:4 dilution was calculated to be about 317 mg/kg bw/day referring to the test substance containing ca. 40% glyoxal, and ca. 125 mg/kg bw/day referring to the  active ingredient as such. 
- For the 1:8 dilution, the dosage was about 158 mg/kg bw/day referring to the test substance containing ca. 40% glyoxal, i.e. ca. 63 mg/kg bw/day referring to the active ingredient.
Duration of treatment / exposure:
2 week
Frequency of treatment:
each animal received one application/day, and a total of 10 applications.
Doses / concentrationsopen allclose all
Dose / conc.:
63 mg/kg bw/day
Remarks:
referring to the active ingredient; 1:4 dilution of each test substance in distilled water





Dose / conc.:
125 mg/kg bw/day
Remarks:
referring to the active ingredient; 1:8 dilution of each test substance in distilled water

No. of animals per sex per dose:
Five animals per group were used
Control animals:
yes, concurrent no treatment
Details on study design:
Male C3H /HeJ mice were randomized into 5 groups of 5 animals each and received a series of 10 applications of diluted test substance onto the clipped skin of the back throughout a period of 2 weeks. The application  volume was 25 µL. No further details were provided. Negative control animals received similar treatment with distilled water alone.

Examinations

Observations and examinations performed and frequency:
- The animals were observed and examined for mortality, health state and skin lesions. 
- Body weight was recorded at  test initiation and thereafter,following the first, third, fourth, sixth, eighth, ninth and tenth application; a semi-automatic weighing system was used. Body weight changes were assessed statistically.
Sacrifice and pathology:
After the last application, all animals were sacrificed for the purpose of necropsy.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
effects observed, treatment-related
Description (incidence and severity):
Both substances tested as 1:4 dilutions in water resulted in open lesions of the skin; no such lesions were seen in the animals treated with the 1:8 dilutions of both test substances.
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined

Effect levels

open allclose all
Key result
Dose descriptor:
NOAEL
Effect level:
ca. 63 mg/kg bw/day
Sex:
male
Basis for effect level:
other: referring to skin lesions
Key result
Dose descriptor:
NOAEL
Effect level:
ca. 125 mg/kg bw/day
Sex:
male
Basis for effect level:
other: referring to systemic toxicity

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

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