Reaction mass of glycerol and methanol and Fatty acids, vegetable-oil

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

According to the OECD SIDS document for potassium hydroxide (30 January 2002), a Klimisch 2 reliability score was assigned since the test procedure in accordance with national standard methods with acceptable restrictions. The OECD 425 guideline (acute oral toxicity, up-and-down procedure) is based on a revised ASTM version of the described procedure.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

A confirmatory study for the up-and-down method for acute oral toxicity testing

Author:

Bruce RD

Year:

1987

Bibliographic source:

Fund. Appl. Toxicol., 8, 97-100

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Version / remarks:

This guideline is based on the procedure used in this study, but adopted en revised by ASTM (1987)

Principles of method if other than guideline:

* 14-day survival population conventional LD50 (conventional test) data were analyzed by the probit procedure of the SAS system (SAS Institute Inc., 1985)
* 1-week survival population conventional LD50 (up-and-down method)
data were analyzed by the method of maximum likelyhood (Dixon, 1965) using the SAS procedure NLIN

GLP compliance:

not specified

Test type:

other: up-and-down method and conventional dosing

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Potassium hydroxide

EC Number:

215-181-3

EC Name:

Potassium hydroxide

Cas Number:

1310-58-3

Molecular formula:

HKO

Details on test material:

- Name of test material (as cited in study report): potassium hydroxide

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: no data
- Weight at study initiation: 190-300 g (weight variance is greater than the +/- 20% limit stated in OECD guideline 425)
- Fasting period before study: 18-20 hr prior to dosing
- diet after exposure: access to food ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

dose is based on fasted body weight

Doses:

- conventional protocol (bruce 1985):
animals are dosed in groups of 10
geometric progression of 1.4 between successive dose groups
doses per time period: single dose

- up-and-down procedure:
animals are dosed singly (at least 1 day apart)
if animal dies or appears to be moribund the day after dosing, dose of next animal is decreased by a factor 1/1.3
if not, dose is increased by a factor 1.3

No. of animals per sex per dose:

10 animals per dose (conventional programme)
1 animal per dose (up-and-down method)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (conventional programme), 1 week (up-and-down method)
- Necropsy of survivors performed: no data
- Other examinations performed: no data

Statistics:

* conventional test: data were analyzed by the probit procedure of the SAS system (SAS Institute Inc., 1985)
* up-and-down method: data were analyzed by the method of maximum likelyhood (Dixon, 1965) using the SAS procedure NLIN

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

333 mg/kg bw

95% CL:

270 - 376

Remarks on result:

other: conventional method, 1 week observation (without taking into account deaths during 2nd week)

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

388 mg/kg bw

95% CL:

288 - 523

Remarks on result:

other: up-and-down procedure (1 week observation)

Mortality:

-Number of deaths at each dose level: no data
-Some deaths observed during the second week after dosing. An LD50 of 273 mg/kg bw/d (214-324) was calculated based on the conventional method after a 2 weeks observation period. Since KOH is a strong alkaline substance, effects may occur even after a longer observation period due to the corrosive effects of the substance, leading to organ damage. However, this effect can not be considered as an acute effect.

Body weight:

-bw: 190-300 g
- Weight variation of rats was greater than the +/- 20% limit stated in OECD guidleine 425.

Other findings:

- Potential target organs: no data

Applicant's summary and conclusion

Interpretation of results:

other: no data

Remarks:

Criteria used for interpretation of results: not specified

Conclusions:

on the basis of one week observations: LD 50 for potassium hydroxide = 333 mg/kg (conventional method) and 388 mg/kg (up-and-down method)

Executive summary:

on the basis of one week observations: LD 50 for potassium hydroxide = 333 mg/kg (conventional method) and 388 mg/kg (up-and-down method).