Diallyl phthalate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

not specified

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Diallyl phthalate

EC Number:

205-016-3

EC Name:

Diallyl phthalate

Cas Number:

131-17-9

Molecular formula:

C14H14O4

IUPAC Name:

1,2-bis(prop-2-en-1-yl) benzene-1,2-dicarboxylate

Details on test material:

- Name of test material (as cited in study report): diallylphthalate
- Physical state: pale yellow liquid
- Analytical purity: 99% (thin-layer and gas chromatographic analysis)
- Lot/batch No.: 25-121 (Hardwicke Chemical Co., Elgin. SC)
- Storage condition of test material: 4°C
- Storage of reference samples at -20°C
- Diallylphthalate was found to be stable for 2 weeks at temperatures up to 60°C in the presence of light.

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Frederick Cancer Research Center (Frederick, MD)
- Acclimation period: 6 wk
- Age at study initiation: 10 wk
- Method of Identification: Ear tag
- Housing: 2-3 per cage, Polycarbonate (Lab Same as single- Products. Garfield, NJ. administration studies and Hazleton Systems, Aberdeen, MD)
- Bedding:Ab-sorb-dri ( Lab Products; Garfield, NJ)
- Diet: Purina Lab Chow@ (ground); provided ad libitum except for the night before dosing
- Water (e.g. ad libitum): Tap water in bottles, acidified to pH 2.5 with HCl; provided ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 1;
- Humidity (%):30-70;
- Air changes (per hr): 12-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: necropsy dates: 18 January 1976- 26 January 1976

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

Dosing solution: 50 mg/ml

Doses:

Male: 464, 681, 1000 & 1470 mg/kg
Female: 316, 464, 681, 1000 & 1470 mg/kg

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: every half hour on the day of dosing and daily thereafter;
- Frequency of weighing: on the day of dosing (0) and on days 7 and 14;
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,gross pathology

Statistics:

Spearman-Karber method (Finney, D, 1964, Statistical Method in Biological Assay, 2nd ed. London: Charles Griffin and Co., Ltd., p.27.)

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

891 mg/kg bw

Based on:

test mat.

95% CL:

> 766 - < 1 036

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

656 mg/kg bw

Based on:

test mat.

95% CL:

> 545 - < 789

Mortality:

1470 mg/k: all rats dead during the study
1000 mg/kg: 4/5 males and 3/5 females dead
681 mg/kg: 0/5 males dead and 5/5 females dead
464 mg/kg: 0/5 males dead and 0/5 females dead
316 mg/kg: 0/5 females dead

Clinical signs:

other: 1470 mg/kg, males and females: diarrhea, inactivity, hunched posture, hyperpnea, watery secretions around the nose nd mouth 1000 mg/kg, males and females: same effects but less frequently 681 mg/kg female: reduced activity on the day of dosing 464 mg/kg:

Gross pathology:

1470 mg/kg: apparent hemorrhagic lesions in the urinary bladder, darkened lungs
1000, 681 & 464 mg/kg: darkened appearance of the lungs
1000 mg/kg female: reddened intestines in 2 females that died early

Any other information on results incl. tables

SURVIVAL AND MEAN BODY WEIGHTS OF RATS IN THE SINGLE-ADMINISTRATION GAVAGE STUDIES OF DIALLYLPHTHALATE

Dose (mg/kg)	Survival	Mean Bods Weights (grams)
MALE		Initial	Final	Change
464	5/5	246	252	+6
681	5/5	250	275	+25
1,000	(b)1/6	247	245	-2
1,470	(c) 0/5	247	(d)	(d)
FEMALE
316	5/5	151	154	+3
464	5/5	150	161	+11
681	(e) 0/5	154	(d)	(d)
1,000	(f) 2/5	151	146	-5
1,470	(g) 0/5	149	(d)	(d)

(a) Number surviving/number initially in group

(b) Days of death: 1,2,2,4

(c) Days of death: 2,2,2,2,2

(d) Nodata are presented due to the 100% mortality in this group.

(e) Days of death:2,2,2,2,3

(f) Days of death: 2,2,3

(g) Days of death: 2,2,2,2,3

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information

Conclusions:

The 14-day LD50 values for diallylphthalate administered once, by gavage in corn oil, were 891 mg/kg for male rats and 656 mg/kg for female rats. These values are within or close to the range of 0.77-1.7 g/kg for acute oral LD50 values reported in the literature.

Executive summary:

In single-oral-administration studies with DAP in male and female Fischer 344 rats, all rats that received 1,470 mg/kg, 4/5 males and 3/5 females that received 1,000 mg/kg, and 5/5 females that received 681 mg/kg diallylphthalate died during the study. Diarrhea, inactivity, hunched posture, hyperpnea, and watery secretions around the nose and mouth were observed in nearly all animals of both sexes at 1,470 mg/kg before they died. These clinical signs occurred less frequently at 1,000 mgikg. Female rats receiving 681 mg/kg exhibited reduced activity on the day of dosing only.

At necropsy, apparent hemorrhagic lesions were noted in the urinary bladder, and the lungs appeared dark in animals receiving the 1,470 mg/kg dose (chemical-induced deaths). The darkened appearance of the lungs was also noted frequently at 1,000, 681, and 464 mg/kg. Fluid was found in the thoracic cavity, and the intestines appeared to be reddened in two females in the 1,000 mg/kg group that died early.

The calculated LD50 values and 95% confidence intervals were 891 (95%-conf. limits: 766-1,036) mg/kg and 656 (95%-conf. limits:

645-789) mg/kg for male and female rats, respectively.