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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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study (adopted from OECD SIDS)

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
No information
Author:
PPG Ind. Inc.
Year:
1987
Bibliographic source:
TSCATS, OTS 0513463, Doc. I.D. 89-878000001
Reference Type:
secondary source
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar 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:
Purity of test material was not analytically confirmed. It was used as received from PPG Industries. Purity of that material is listed as > 98% on the MSDS

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
The animals (15 males and 15 females) were acclimated for at least one week before use. The males and females weighed 217-273 g and 180-211 g when tested, respectively. Animals were fasted for 16 hours prior to treatment. Food was available ad libitum after treatment for the duration of the
study. Animals were randomized to groups of 5 animals/sex.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
Groups of males were treated with 1000, 1500 or 2000 mg/kg, and groups of females were treated with 1000, 1250, or 1500 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Animals were observed at least 3 times on the day of treatment and at least once daily thereafter for 14 days. Body weights were recorded just prior to treatment and on Days 7 and 14 (or early as possible after death). A gross necropsy was performed on each animal that died or upon euthanization on day 14.
Statistics:
LD50 values were calculated by the method of Litchfield and Wilcoxon (J Pharm Ther 96: 99-115, 1949).

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
1 330 mg/kg bw
95% CL:
1 070 - 1 640
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 410 mg/kg bw
95% CL:
1 140 - 1 750
Sex:
male
Dose descriptor:
LD50
Effect level:
1 490 mg/kg bw
95% CL:
1 140 - 1 930
Mortality:
The number of deaths (and time of death) in the 1000, 1250 (females only), 1500, and 2000 (males only) mg/kg groups were as follows : 1 female and 1 male (the page containing time of death was missing), 1 female (Day 1), 1 male (Day 1) and 4 females (from Days 1-3), and all 5 males (from 6 hours to Day 2).
The slopes of the curves for males, females and all animals were 1.35, 1.28 and 1.35, respectively.


Clinical signs:
Toxicological effects observed during the study included activity decrease, ataxia, bradypnea, chromodacryorrhea, constricted pupils, diarrhea, dilated pupils, exophthalmos, gasping, lacrimation, nasal discharge, piloerection, polyuria, ptosis, respiratory gurgle, salivation and/or swollen tongue.

Gross pathology:
Three out of four surviving females treated with 1250 mg/kg had no abnormal findings at necropsy. The other surviving animal in this group had a stomach wall that was thickened and adhered to the liver. Three out of 4 surviving males and the one surviving female treated with 1500 mg/kg had a thickened fundus wall which adhered to the rib cage, diaphragm, spleen and adjacent lobes of the liver.
The other surviving male at this dose had no abnormal findings. Necropsy findings observed in animals that died included GI tract distended with gas, discoloration of the contents of the GI tract, serosal blood vessels pronounced along the GI tract, discoloration of the stomach mucosa, stomach wall thickened, stomach adhered to other tissues, edematous lungs, discoloration of the pancreas, liver and adrenal glands, discoloration of the contents of the urinary bladder, and/or testes drawn into abdominal cavity.

Any other information on results incl. tables

The page containing time of death and gross necropsy findings for animals treated with 1000 mg/kg was missing from the report.

Applicant's summary and conclusion