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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:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: In accordance with OECD 401 with non-GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report Date:
1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
purity: >99.9%
particle size: >355 um

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: arabic gum solution
Doses:
284, 227, 182, 145, 116, 93, 74 mg/kg
No. of animals per sex per dose:
10
Control animals:
no
Statistics:
Probit method of C.I.Bliss

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
128 - 148.3 mg/kg bw
Based on:
test mat.
95% CL:
> 114 - <= 165
Sex:
male
Dose descriptor:
LD50
Effect level:
128 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
148.3 mg/kg bw
Based on:
test mat.
Mortality:
Dose mortality (%)
ml/kg mg/kg male female
7.44 88.5 0 0
9.30 111 10 0
11.63 138 40 30
14.54 173 60 30
18.18 216 100 80
22.73 270 100 100
28.41 338 100 100
Clinical signs:
In group 182 mg/Kg or more, spontanious activity was markedly decreased and colonic respiration was observed from several minutes after administration.
No marked changes were observed in surviving animals throughout the seven day observation period.
Body weight:
no data
Gross pathology:
The liver of the dead animal in high dose groups were brownish-yellow  Stomach showed diffused blood-spot In the mucous membrane.
There were no reportable macroscopic abnormalities in major organs in surviving animals.

Any other information on results incl. tables

The number of dead animals per day (total N=10)

ml/kg 1d. 2d. 3d. 4d. 5d. 6d. 7d. Dead No.

male 28.41 10 10

22.73 10 10

18.18 10 10

14.54 4 - 1 1 - - - 6

11.63 4 - - - - - - 4

9.30 1 - - - - - - 1

7.44 0 - - - - - - 0

female 28.41 10 10

22.73 10 10

18.18 7 1 - - - - - 8

14.54 3 - - - - - - 3

11.63 3 - - - - - - 3

9.30 0 - - - - - - 0

7.44 0 - - - - - - 0

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
LD50 = 128.0 mg/kg-male rat
LD50 = 148.3 mg/kg-female rat
Executive summary:

There are two studies on acute oral toxicitty using quite similar testing method, one is achieved at Y1984 using the submitter's sample and the other one is achieved at Y2000 under Japanese Govermental inspection program using another company's sample.

In an first acute oral toxicity study , groups of SD rats, 10/sex were given a single oral dose of PMI (provided by NIPPON SHOKUBAI on 1984.08.20) in arabic gum at doses of  0, 74.4 , 93.0, 116.3, 145.4, 181.8, 227.3, 284.1 mg/kg bw and observed for 7 days.

 

Oral LD50Males =  128 mg/kg bw (95% C.I. 114.8 - 141.3 mg/kg bw)

      Females =  148.3 mg/kg bw (95% C.I. : 133.4 - 165.0 mg/kg bw)

The other study's results are;

LD50 for oral rat male = 153 mg/kg (95% C.I. 100 -237 mg/kg)

LD50 for oral rat female = 188 mg/kg (95% C.I. no data)

From a top level review, the first study has a lower K rating but is the most sensitive and gives lowest LD50.

The conclusion is that;

LD50 = 128.0 mg/kg-male rat

LD50 = 148.3 mg/kg-female rat

PMI is classified as the category 3 in accordance with GHS for acute oral toxicity based on the LD50.          

No marked changes were observed in surviving animals throughout the seven day obsevation period.

There were no reportable macroscopic abnormalities in major organs in surving animals.