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Toxicological information

Acute Toxicity: oral

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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:
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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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 levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
891 mg/kg bw
Based on:
test mat.
95% CL:
> 766 - < 1 036
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:
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:
316 mg/kg:
Body weight:
See Table
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.