glyoxal … %; ethandial … %

Repeated dose toxicity: dermal

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

Reference

Reference 1

Reference Type:

other: secondary quotation

Title:

Unnamed

Year:

1979

Reference 2

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 3

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

Test material information

Constituent 1

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 / concentrations

Doses / concentrations 1

Dose / conc.:

63 mg/kg bw/day

Remarks:

referring to the active ingredient; 1:4 dilution of each test substance in distilled water

Doses / concentrations 2

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

1

Key result

Dose descriptor:

NOAEL

Effect level:

ca. 63 mg/kg bw/day

Sex:

male

Basis for effect level:

other: referring to skin lesions

2

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