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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1989-06-23 to 1989-09-08
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 401 (Acute Oral Toxicity)
Version / remarks:
adopted: Fenruary, 1987
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

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:
- Name used in the report: Phthaldialdehyd
- 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: Unknown

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 Laboratory Ltd., Wölferstrasse 4, CH-4414 Fullinsdorf, Switzerland
- Age at study initiation: Males: 9 weeks, Females: 11 weeks
- Weight at study initiation: Males: 197 - 236 g, Females: 176 - 194 g
- Fasting period before study: 12-18 h
- Housing: Groups of five animals were housed in Makrolon type-3 cages with standard softwood bedding
- Diet (e.g. ad libitum): Ad libitum, pelleted standard Kliba 343, Batches 46/89 and 48/89 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

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL
DOSAGE PREPARATION (if unusual): The test article was placed into a glass beaker on a tared Mettler PE 360 balance, and the vehicle, (polyethylene glycol PEG 400) was added. A weight by volume dilution was prepared using a homogenizer.
Doses:
50, 150, 300 and 2000 mg /kg
No. of animals per sex per dose:
5 males and 5 females per dose group, 4 dose groups
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).
- Frequency of weighing: Test days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: no
Statistics:
The LOGIT-Model (COX, Analysis of Binary Data, London 1977) was applied to estimate the toxicity value. Additionally, the 90, 95 and 99 % confidence limits for the toxicity for each sex and the slope of the dose response line were estimated.

Results and discussion

Preliminary study:
n.a.
Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
178.46 mg/kg bw
Based on:
test mat.
95% CL:
>= 50.02 - <= 434.36
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
339.67 mg/kg bw
Based on:
test mat.
95% CL:
>= 152.35 - <= 1 000.76
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
238.12 mg/kg bw
Based on:
test mat.
95% CL:
>= 141.27 - <= 401.39
Mortality:
Test item related mortality was observed at at 300 and 2000 mg/kg in males and in 150, 300 and 2000 mg/kg in females. For individual results see Table 1 in box "Any other information on results incl. tables".
Clinical signs:
No clinical signs were observed for male and female rats at 50 mg/kg. At 150 mg/kg, ruffled fur was observed in male and female rats and sedated, hunched posture was observed in female rats. At 300 mg/kg, sedated, dyspnea hunched posture and ruffled fur was observed in male and female rats, ventral recumbency was observed in male rats and lateral recumbency, uncoordinated movements were observed in female rats. At 2000 mg/kg, sedated, ventral recumbency, hunched posture and dyspnea was observed in male and female rats, ruffled fur was observed in male rats and lateral recumbency was observed in female rats.
Body weight:
The body weights of the surviving males and females of group 1 (50 mg/kg) and those of the males of group 2 (150 mg/kg) were not affected by the test article treatment. The surviving females of group 2 (150 mg/kg) showed the same reactions as the males, whereas one female showed a body weight reduction after 8 days. It had recovered at termination of observation (day 15).
One surviving male of group 3 (300 mg/kg) showed no effect in body weight, whereas the second survivor showed a reduction after 8 days. It was recovered at termination of observation.
Gross pathology:
No pathological findings were observed at 50, 150 and 2000 mg/kg dose level. At 300 mg/kg, discoloration and paleness was observed in the lungs and black-brown contents were observed in the stomach of dead rats. No findings were observed in the sacrificed rats.
Other findings:
n.a.

Any other information on results incl. tables

Table 1:Number of Decendents after Treatment

Test day 1 1 1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Hours after treatment 1 2 3 5
Males Group 1 (50 mg/kg) - - - - - - - - - - - - - - - - - -
Group 2 (150 mg/kg) - - - - - - - - - - - - - - - - - -
Group 3 (300 mg/kg) - - - 2 1 - - - - - - - - - - - - -
Group 4 (2000 mg/kg) - 2 2 1 - - - - - - - - - - - - - -
Females Group 1 (50 mg/kg) - - - - - - - - - - - - - - - - - -
Group 2 (150 mg/kg) - - - - 2 - - - - - - - - - - - - -
Group 3 (300 mg/kg) - - - 4 1 - - - - - - - - - - - - -
Group 4 (2000 mg/kg) 3 2 - - - - - - - - - - - - - - - -

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
Under the conditions of this study, the oral LD50 of the test material was 178.46 mg/kg for females, 339.67 mg/kg for males and 238.12 mg/kg for both male and female rats. Thus, the test substance is classified under "Category 3" according to CLP criteria
Executive summary:

 In an acute oral toxicity study conducted according to OECD guideline 401, young adult Wistar rats (5/sex/dose) were given a single 10 mL, oral dose of the test substance, ortho-phthalaldehyde (purity: 99%) in polyethylene glycol at dose levels of 50,150, 300 and 2000 mg/kg bw and were observed for 15 days. Test item related mortality, body weight changes and clinical signs were observed in male and female rats above the 150 mg/kg dose level. Thus, the acute oral LD50 of the test material was 178.46 mg/kg for females, 339.67 mg/kg for males and 238.12 mg/kg for both male and female rats.

Based on these results, the test substance is classified under "Category 3" according to CLP criteria.