Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
05.-25. February 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was performed according to OECD Guideline No. 402 "Acute Dermal Toxicity" (adopted: 24 February 1987)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Huntingdon Life Science Ltd., Wooley Road, Alconbury, Huntingdon Cambridgeshire, PE28 4HS, England
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Glyoxylic Acid 50.5 %
- Lot/batch No.: SCA200104-2
- Stability under test conditions: Not advised, but assumed to be stable for six months from the date of receipt
- Storage condition of test material: Room temperature
- Physical state: liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- The rat was chosen as it has been shown to be a suitable model for this type of study and is the animal
recomended in the test guidelines.
- Source: Sprague Dawley (CD), obtained from Harlan U.K. Ltd., Bicester, Oxon, England
Each animal was identified by tail marking. Each cage was identified by a coloured label displaying the dose level,
study number and animal mark
- Age at study initiation: approx. 8 to 12 weeks of age prior to dosing (day 1)
- Weight at study initiation: 168-207 g
- Housing: The rats were allocated without conscious bias to cages within the treatment group.
They were housed individually from day 1 in metal cages (RS Biotech Sub-Dividable Rodent Cages - polished stainless steel) until day 5 when they
were returned to group housing.
The cages were fitted with grid floors to ensure rapid removal of waste material to undertrays.
- Diet (e.g. ad libitum): A standard laboratory rodent diet (Special Diet Services RM1(E) SQC expanded pellet) was provided ad libitum.
The batches of diet used for the study were analysed by the supplier for certain nutrients, possible contaminants and micro-organisms.
- Water: drinking water was provided ad libitum and routinely analysed by the supplier for physical and chemical quality.
- Acclimation period: All the rats were acclimatised to the experimental environment for a period of six days prior to the start of treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): within the range of 21 +/- 2°C
- Humidity (%): 40-70 %
- Photoperiod (hrs dark / hrs light): 12 hrs of artificial light in each 24-hour period


Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Test substance preparation
Glyoxylic Acid 50.5% was administered, as supplied, at a dose volume of 1.53 ml/kg bw
(specific gravity as measured by this testing facility was 1.307 g/ml).

The absorption of the test substance was not determined. Characterisation of homogeneity, stability and purity of the test substance
was not undertaken in this study and remained the responsibility of the sponsor.

Administration of test substance
On day 1 prior to treatment, hair was removed from the dorso-lumbar region of each rat with electric clippers taking care to avoid damaging the skin,exposing an area equivalent to approximately 10 % of the total body.

The test substance was applied by spreading it evenly over the prepared skin. The treatment area (approx. 50 x 50 mm) was covered
with porous gauze held in place with a non-irritating dressing, and further covered by a waterproof dressing encircled firmly around the trunk of the animal.

Treatment in this manner was performed on day 1 (day of dosing) of the study only.

At the end of the 24 hrs exposure period the dressing was carefully removed and the treated area of skin was washed with warm water (30-40 °C) to remove any residual substance. The treated area was blotted dry with absorbent paper.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
A group of ten rats (five males and five females) was treated with a single topical application of the test substance, as supplied,
at a dose level of 2000 mg/kg bw.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Clinical signs:
Animals were observed soon after dosing and at frequent intervals for the remainder of day 1. On subsequent days animals were
observed once in the morning and again at the end of the experimental day (with the exception of day 15 - morning only). The nature
and severity of the clinical signs and time were recorded at observation.

- Bodyweight:
The bodyweight of each rat was recorded on days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean
bodyweights were calculated

Terminal studies
- Termination:
All animals were killed on day 15 by carbon dioxide asphyxiation.

- Macroscopic pathology:
All animals were subjected to a macroscopic examination which consisted of opening the cranial, and thoracic and abdominal cavities.
The macroscopic appearance of all tissues was recorded.
Statistics:
no statistical analysis necessary

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Cages of rats were checked at least twice daily for mortalities and there were no deaths and no systemic response to treatment in any animal throughout the study.
Clinical signs:
There were no systemic response to treatment following a single dermal application of Glyoxylic Acid 50.5% to group of ten rats (five males and five females) at a dose level of 2000 mg/kg bw.
Body weight:
Low bodyweight gains were recorded for four females on Day 8 and three females on Day 15.
All other animals were considered to have achieved satisfactory bodyweight throughout the study.
Gross pathology:
No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.
Other findings:
Dermal responses:
No dermal reactions were observed in any animal during the study.

Applicant's summary and conclusion

Executive summary:

The acute dermal toxicity of Glyoxylic Acid 50% was studied in the rat according to OECD TG 402 (adopted: 24 Feb. 1987). There were no deaths and no systemic response to treatment in any animal throughout the study. No dermal reactions were observed in any animal during the study. Low bodyweight gains were recorded for four females on day 8 and three females on day 15. All other animals were considered to have achieved satisfactory bodyweight gains throughout the study.

Based on these results the acute lethal dermal dose to rats of Glyoxylic Acid 50.5% was demonstrated to be greater than 2000 mg/kg bw.