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Toxicological information

Acute Toxicity: other routes

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Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Combination of octreotride and oral glucose maintains the blood glucose level and improves survival rate in rats after monochloroacetic acid
Author:
Fujihara et al
Year:
1997
Bibliographic source:
Bulletin Osaka Medical College 53 (3): 169-173

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
After starving for 12 h, the rats were SC injected with a LD99 dose (80 mg/kg bw) of SMCA and divided into 3 groups:
1. Control group (n=20): 2 mL/h 10% glucose solution for 10 h, 60 min after SMCA treatment
2. Group A (n=20): 2 g/kg oral glucose immediately after SMCA treatment, and then 2 mL/h 10% glucose solution for 10 h, 60 min after SMCA treatment
3. Group B (n=20): sc injection of 30 ug/kg octreotide and 2 g/kg oral glucose immediately after SMCA treatment, and then 2 mL/h 10% glucose solution for 10 h, 60 min after SMCA treatment
The 10% glucose infusion was performed via a catheter under phenobarbital anaesthesia.
GLP compliance:
no
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium chloroacetate
EC Number:
223-498-3
EC Name:
Sodium chloroacetate
Cas Number:
3926-62-3
Molecular formula:
C2H2ClNaO2
IUPAC Name:
sodium chloroacetate
Specific details on test material used for the study:
SMCA was used to study effects of MCA (Monochloro acetic acid).
Supplier: Nacalai Tesque, Kyoto, Japan

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
Sixty rats of 10 week age were used. Mean weight 300 g.
Housing in air-conditioned rooms at 22 +- 1 deg. C with a 12h/day light cycle. Free access to food and water for 7 days.

Administration / exposure

Route of administration:
subcutaneous
Vehicle:
water
Details on exposure:
See at principles of method
Doses:
80 mg/kg bw SMCA
No. of animals per sex per dose:
20
Control animals:
no
Details on study design:
Capillary blood samples were obtained by ouncturing the rats' tails for determination of blood glucose and lactate. The measurements were started at the start of the infusion and at 1-h intervals during the 10-h infusion period.
Survival rates were observed for 14 days after SMCA treatment
Statistics:
Chi-square analysis was used to analyze the 140day survival rates. Mann-Whitney U-tests for differences in blood glucose and lactate.

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
other: 65% mortality
Effect level:
80 mg/kg bw
Based on:
test mat.
Mortality:
Control group: 65%
Group A: 50%
Group B: 10%
Other findings:
At the beginning of the glucose infusion blood glucose levels were:
Control group: 93 mg/dL
Group A: 144 mg/dL
Group B: 188 mg/dL
After ca. 4-5 h the levels were comparable amongst the groups
Blood lactate levels significantly different between the groups at certain time points but the values were not abnormally high.

Applicant's summary and conclusion

Conclusions:
It seesm to be important to elevate blood glucose levels within 60 min after MCA exposure. A combination of s.c. octreotide and oral glucose may be advantageous to maintain high blood glucose level at eraly stages after exposure and may be an effective therapy for MCA intoxication.