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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1989-06-22 to 1989-10-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted: 24th February 1987
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Phthalaldehyde
EC Number:
211-402-2
EC Name:
Phthalaldehyde
Cas Number:
643-79-8
Molecular formula:
C8H6O2
IUPAC Name:
phthalaldehyde
Specific details on test material used for the study:
- Appearance: Light yellow needles
- Batch No.: 1
- Purity: GC (area %) 99%
- Stablity of the test article: Stable
- Expiration date: 1989-12-31
- Stability of test article dilution: Stable for at least 48 hours

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., Wölferstrasse 4, CH-4414 Füllinsdorf, Switzerland
- Age at study initiation: males: 9 weeks, females: 11 weeks
- Weight at study initiation: males: 216 - 229 g, females: 186 - 199 g
- Housing: Animals were housed individually in Makrolon type-2 cages with standard softwood bedding
- Diet (e.g. ad libitum): Ad libitum, pelleted standard Kliba 343, Batch 46/89 rat maintenance diet
- Water (e.g. ad libitum): ad libitum, tap water
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
polyethylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: Back of the animal
- % coverage: approx. 10 % of total body surface
- Type of wrap if used: The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated skin was washed with lukewarm tap water, dried with disposable paper towels
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 mL
- Concentration (if solution): 2000 mg/kg
Duration of exposure:
15 days
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females tested at a single dose level
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations: Four times during test day 1, and daily during days 2 - 15 (mortality, viability and clinical signs). Due to the 24-hour semi-occlusive treatment, the local findings were ob erved starting with day 2 of test.
- Frequency of weighing: Test days 1 (pre-administration), 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: no
Statistics:
The LOGIT-Model could not be applied to the observed rate of death. The toxicity was estimated without use of a statistical model.

Results and discussion

Preliminary study:
n.a.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
The following local signs were observed on the back of the animals:
2000 mg/kg: males/females - edema, general erythema, necroses, skin black. Additional edema was observed in the female rats.
The symptoms as described above were partly observed until termination of test. No clinical signs were observed in the animals throughout the study.
Body weight:
A decrease in body weights was observed in 2 male and 4 female rats between days 1 and 8 of the test period. The body weight gain had recovered to normal at termination of the observation period (day 15).
Gross pathology:
The following macroscopical organ findings were observed:
2000 mg/kg: sacrificed - kidneys: discoloration, pale

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the dermal LD50 of the test material was greater than 2000 mg/kg bw.
Executive summary:

In an acute dermal toxicity study conducted according to OECD guideline 402, young adult Wistar rats (5/sex/dose) were administered with a single occlusive application of ortho-phthalaldehyde in polyethylene glycol at a dose of 2000 mg/kg bw and were observed for 15 days. Due to the absence of mortality and low adverse clinical signs, the oral LD50 in rats is considered to be greater than 2000 mg/kg. In this study, ortho-phthalaldehyde does not warrant classification for acute dermal toxicity based on CLP criteria.