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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: Provides basic data. Article did not reveal if study was conducted under GLP.

Data source

Reference
Reference Type:
publication
Title:
The international Validation of a fixed dose procedure as an alternative to the classical LD50 test
Author:
Van den Heuvel et al.
Year:
1990
Bibliographic source:
Food Chem. Toxic. 28:469-482. Reprinted with permission from Elsevier.

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
Test type:
other:

Test material

Constituent 1
Chemical structure
Reference substance name:
Resorcinol
EC Number:
203-585-2
EC Name:
Resorcinol
Cas Number:
108-46-3
Molecular formula:
C6H6O2
IUPAC Name:
benzene-1,3-diol

Test animals

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

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: A vehicle was used but the name of the vehicle was not identified.
Doses:
no data
No. of animals per sex per dose:
30
Details on study design:
LD50 tests were conducted  "blind" and in accordance with OECD TG 401, 1981 rather than the 1987 test guideline  in order that information on both sexes would be available for comparision with the fixed dose test results.  The only modification in the guideline study was that, where the limit dose studies were indicated, the maximum dose used would be 2000 mg/kg by weight rather than 5000 mg/kg dose prescribed in the 1981 OECD guideline study.   One laboratory conducted the classical LD50 test following the OECD guideline as indicated above, while the remaining 31 laboratories conducted the fixed-dose testing (for comparison purposes.)  Each substance was tested at least 26 times by different laboratories using identical procedures (not all 31 laboratories were used to test for resorcinol). In the fixed dose method one of the following preset doses is to be  selected 5, 50, or 500 with an additional dose of 2000 mg/kg bw.  These  doses were selected as at the time, they matched the EC classification  system and would thus allow for appropriate classification. 

The classic LD50 study was conducted using 30 Sprague Dawley rats while  the fixed dose testing used 370 rats (a variety of rats), as laboratories  were given the freedom to select the rat strain.  This concluded in 21  laboratories performing the study using Sprague Dawley rats, 9  laboratories using Wistar and one laboratory using the Fischer 344 rats.   A total of 26 fixed dose studies was conducted using 370 rats for an  average of 14.23 rats per study. Fixed dose method:  Resorcinol was administered orally by gavage.  At least 10 animals (5 female and male) are used for each dose level.  The dose level to be used by the laboratory should be one of the four levels associated with classification, 5, 50, 500 and 2000 mg/kg/bw.  A 14 day observation period.  Animals are observed for signs of toxicity including behavioural and clinical abnormalities, gross lesions, body-weight changes, and other toxic effects.  All animals are subject to gross necropsy.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
510 mg/kg bw
95% CL:
>= 439 - <= 642
Mortality:
In the classic LD50 study: In males (only)LD50 was determined to be 533 mg/kg bw with the 95% confidence limits being (425  - 725 mg/kg bw).  In females (only) the LD50 was determined to be 489 mg/kg/bw with the 95% confidence limits being (397 -650 mg/kg bw).  In the males and females the LD50 was determined to be 510 mg/kg bw with the 95% confidence limits being (439 - 642 mg/kg bw).  The slope was determined to be 8(s.e. 2.1).  In accordance with the EC criteria at the time, resorcinol was classified as harmful.   There were no necropsy findings in the classic LD50 study.  9 animals were found dead (dose level not indicated).
In the fixed dose studies:  A total of 146 animals were found dead (dosing not indicated) for an average of 5.62 per test.  These results are only stated in general terms and are not associated with any one given chemical that was tested.
Clinical signs:
In the classic LD50 study the following clinical signs were observed:  Ptosis, posture, respiratory effects, lethargy, abnormal gait, tremors, convulsions and salivation.
In the fixed dose studies: In these studies, 26 laboratories responded in which the following number of "labs" documented the following effects:  Ptosis, 2; Posture, 5; Respiratory effects, 10; Diarrhoea and diuresis, 1; Lethargy, 10; Ataxia, 2; Abnormal gait, 3; Tremors, 13; Convulsions, 9; Prostrate Coma, 4; Salivation, 5; Lacrimation, 4; Exopthalmus,1. 
Gross pathology:
In the fixed dose studies: Autoposy findings in the fixed-dose tests with resorcinol:  Liver, kidney, stomach and intestine discoloured.  Oedma of glandular gastric mucosa.  Rapid heart beat.

Any other information on results incl. tables

Fixed Dose studies:

Results of fixed dose testing indicated that in 25 fixed dose studies conducted in separate laboratories each one of them had consistent results that resulted in a classification as harmful, in accordance with the EC
criteria at the time.  In only 1 instance did the results indicate "Unclassified."  

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information In accordance with CLP Criteria used for interpretation of results: other:
Conclusions:
The author concluded a classification of harmful is assigned to test substances that have less than 100% survival at 2000 mg/kg bw. Following the current European Classification, Labeling and Packaging Regulation (EC 1272/2008); the substance would be considered a Category IV substance for acute oral toxicity.