Phthalaldehyde

Endpoint summary

Description of key information

For the target substance ortho-phthalaldehyde suitable data is available to assess the acute toxicity for two routes of exposure (oral, dermal). In an acute oral toxicity study conducted according to OECD guideline 401, the acute oral LD50 was determined to be 178.46 mg/kg bw for females, 339.67 mg/kg bw for males and the combined LD 50 was 238.12 mg/kg bw.

In an acute dermal toxicity study conducted according to OECD guideline 402, young adult Wistar rats were dermally exposed to ortho-phthalaldehyde in polyethylene glycol at a dose of 2000 mg/kg bw. Due to the absence of mortality, the dermal LD50 in rats is considered to be greater than 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

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

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

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

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.

Preliminary study:

n.a.

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.

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	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

178.46 mg/kg bw

Quality of whole database:

GLP guideline study

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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

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

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

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

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.

Preliminary study:

n.a.

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

GLP guideline study

Additional information

For the target substance ortho-phthalaldehyde suitable data is available to assess the acute toxicity for two routes of exposure (oral, dermal). In an acute oral toxicity study conducted according to OECD guideline 401, the acute oral LD50 was determined to be 178.46 mg/kg bw for females, 339.67 mg/kg bw for males and the combined LD 50 was 238.12 mg/kg bw.

In an acute dermal toxicity study conducted according to OECD guideline 402, young adult Wistar rats were dermally exposed to ortho-phthalaldehyde in polyethylene glycol at a dose of 2000 mg/kg bw. Due to the absence of mortality, the dermal LD50 in rats is considered to be greater than 2000 mg/kg bw.

Justification for classification or non-classification

Based on the available data, the target substance ortho-phthalaldehyde has to be classified for acute oral toxicity (Acute Tox. 3, H301) in accordance with CLP criteria. No classification is warranted for acute dermal toxicity.