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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP and Guideline study, limited but acceptable documented (no raw data given)

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2003

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
N-Phenyl-N'-isopropyl-p-phenylenediamine, purity: 99.5%

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% sodium carboxymethylcellulose
Doses:
0, 269, 350, 455, 592, 769, 1000 mg/kg
No. of animals per sex per dose:
5 per dose and sex
Control animals:
yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
522 mg/kg bw
Based on:
test mat.
95% CL:
224 - 1 154
Remarks on result:
other: Clinical signs and death observed

Any other information on results incl. tables

Mortality:

Animals died from two days to four days after admnistration in the group receiving 269 mg/kg and above for males and 592 mg/kg and above for females.

Clinical signs observed: brownish urine, a crouching position, eyelid closure, decrease of fecal volume, pale skin, yellowish urine and abdominal distention; in addition some of animals which subsequently died showed adoption of a prone postion, straggering, decreased respiration, lacrimation and hypothermia.

Body weight: decreased body weights or recreased body weight gain were observed in dosed groups; return to normal was apparent at day 8 or later during the observation period.

Gross Pathology:

Decedents showed: enlargement of the liver, enlargement and pale coloration of the kidney, pleural effusion, ascites, edematous lung, shrinking and pale coloration of the spleen,detachment or red colored areas in the forestomach mucosa, thickening and pale coloration in the mucosa of glandular stomach and yellowish colored change of the subcutis

Survivor exhibited: Thickening and pale coloration in the muscosa of forestomach

Histopathology:

Decedents: necrosis or degeneration of centrilobular hepatocytes and hypertrophy of hepatocytes, necrosis or degeneration in the proximal tubular epithelium of the kidneys, alveolar edema in the lung, hemorrhage and edema in the submucosa of the forestomach and in the mucosa of glandular stomach.

Survivors: hypertrophy of centrilobular hepatocytes, increased mitosis of hepatocytes and regeneration in the tubular epithelium of kidney; some animals with cellular infiltration of foam cells and neutrophils in the lung, brown pigment deposition in the forestomach and regeneration in the epithelium of the glandular stomach, in males which survived, extramedullary hematopoiesis was increased in the spleen

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria