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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:
1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data

Data source

Reference
Reference Type:
publication
Title:
1-Naphthol – Single and Repeated Dose (30-Day) Oral Toxicity Studies In The Mouse
Author:
Poole, A., and Buckley, P.
Year:
1989
Bibliographic source:
Food and Chemical Toxicity, 27, 233-238

Materials and methods

Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
- Principle of test: Standard acute method
- Short description of test conditions: Four mice (2/sex) were exposed to 1-naphthol at doses of 500, 1000 and 2000 mg/kg bw in propane-1,2-diol by gavage.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
No data
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: No data
- Expiration date of the lot/batch:No data
- Purity test date: No data
- Purity : no data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: No data
- Stability under test conditions: No data
- Solubility and stability of the test substance in the solvent/vehicle: No data
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING No

FORM AS APPLIED IN THE TEST : Suspension

Test animals

Species:
mouse
Strain:
CD-1
Remarks:
Cr1: CD-1 (ICR)BR)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK limited
- Age at study initiation: 6-7 weeks old
- Weight at study initiation: No data
- Housing: solid-bottomed cages
- Diet (ad libitum): Porton rat Diet Pellets (Labsure Animal Food Ltd. Poole, Dorset)
- Water (ad libitum): filtred tap-water
- Acclimation period: yes - 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 22°C
- Humidity (%): 40-60%
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12h light/ 12h black

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: propane-1,2-diol-water (1:1 v/v)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 1/1
- Amount of vehicle (if gavage): 10 ml/kgbw
- Justification for choice of vehicle: No data
- Lot/batch no. (if required): No data
- Purity: No data

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kgbw
Doses:
500, 1 000 and 2 000 mg/kgbw
No. of animals per sex per dose:
2 per sex per dose
Control animals:
yes
Remarks:
one untreated and one with the vehicle
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: No data
- Necropsy of survivors performed: yes (colon, duodenum, gall bladder, heart, ileumn kidneys, liver, lungs, parathyroid, gland, stomach (forestomach and glandular region) and thyroid gland
- Other examinations performed: clinical signs, body weight,, clinical chemistry (ALT, ALP, GLDH, TP, ALB, BUN, CREA, GLU) and heamatology analyses (Hgb, RBC, Hct, Plt, WBC)
Statistics:
From the heamatology and clinical chemistry data generated in these studies, arithmetic means and standard deviations were calculated.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 000 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The mice dosed at 2000 mg/kgbw became subdued shortly after treatment developed abnormal respiration and tremors and finally suffered total collapse. All of the animals in this dose group were killed in extremis between 15 and 90 min after dosing.
One male in the low-dose (500 mg/kgbw) group was killed in extremis approximately 2 hours after dosing.
Clinical signs:
The animals treated at 1000 mg/kgbw also showed subdued behaviour with piloerection, but recovered for the signs.
The other animals in the 500 mg/kgbw group, although showing subdued behaviour, laboured respiration and piloerection, recovered to survive to the end fo the study.
Body weight:
No data
Gross pathology:
No data
Other findings:
- Histopathology:
Renal changes (1) eosinophilic deposits in the lumen of the distal tubules and collecting ducts associated with degeneration of the distal tubular epithelia were seen in the 3 male mice killed at 2000 mg/kgbw and 1 to 500 mg/kgbw. and 1 female mice dosed at 1000 mg/kgbw (both of which survived) (2) papillary necrosis with an associated intravascular thrombosis in one male and both female mice receiving 1000 mg/kgbw and (3) marked dilatation of both corical and medullary tubules in both female mice dosed at 1000 mg/kgbw.
Gastric changes consisted of lesions in the forestomach and glandular region. These changes are seen in all but one of the mice dosed at 1000 and 500 mg/kgbw, included focal splitting of the squamous epithelium which was generally associated with vascular congestion and an acute inflammatory cell infiltration. Sloughing of the superficial epithelium of the glandular mucosa was observed in all mice dosed at 2000 mg/kgbw, in one male and one female mouse receiving 500 mg/kgbw. Generally, this change was associated with vascular congestion and an acute inflammatory cell inflitration.
- Potential target Organs : No data
- Other observations: no differences in the haematology or clinical chemistry data obtained from the control goup and those dosed with naphthol.

Applicant's summary and conclusion

Interpretation of results:
other: study not considered for classification, but effect level is in line with harmonized Cat 4 classification
Remarks:
Note: substance has a harmonized classification as Cat 4
Conclusions:
The LD50 was estimated to be between 1000 to 2000 mg/kg bw.
Executive summary:

Four mice (2/sex) were exposed to 1-naphthol at doses of 500, 1000 and 2000 mg/kg bw in propane-1,2-diol by gavage. One male in the 500 mg/kg bw group was killed in extremis two hours post dosage. Other animals in this group showed piloerection and laboured respiration. Animals in the 1000 mg/kg bw group showed piloerection, but survived to the end of the study. Shortly after dosing animals exposed to 2000 mg/kg bw showed abnormal respiration and soon after dosing collapsed. All animals in this dosage group were killed in extremis from 15 to 90 minutes.