3-hydroxy-2-naphthoic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: well performed GLP and OECD guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

of 1981

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-hydroxy-2-naphthoic acid

EC Number:

202-180-8

EC Name:

3-hydroxy-2-naphthoic acid

Cas Number:

92-70-6

Molecular formula:

C11H8O3

IUPAC Name:

3-hydroxynaphthalene-2-carboxylic acid

Details on test material:

- Name of test material (as cited in study report): BONS TTR

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG breeding colony
- Weight at study initiation: mean male 197 g, female 191 g
- Fasting period before study: 16h
- Housing: makrolon cages, groups of 5
- Diet (e.g. ad libitum): rat diet Altromin 1324, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 2
- Humidity (%): 55 +/- 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 2% aqueous CMC (carboxymethyl cellulose)

Details on oral exposure:

The test substance was administered as a 25% preparation in the vehicle to each dose group. Hence, the administration volume/kg bw was 1.25 ml/kg bw in the lowest dose group and 5.0 ml/kg bw in the highest dose group.

Doses:

male: 800, 1000, 1250 mg/kg bw
female: 315, 500, 800, 1000, 1250 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (or other?): 14 d
- Frequency of observations and weighing: weighing: 0, 7, 14 days post application, clinical signs: 10, 30, 60 min, 2, 4, 6 h, 1, 2, 3, 4-14 d post application
- Necropsy of survivors and animals found dead performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Probit analysis.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

823 mg/kg bw

95% CL:

>= 581 - <= 1 070

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

869 mg/kg bw

95% CL:

>= 394 - <= 1 350

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

795 mg/kg bw

95% CL:

>= 485 - <= 1 320

Mortality:

315 mg/kg: 0/5 (f)
500 mg/kg: 2/5 (f)
800 mg/kg: 1/5 (m), 2/5 (f)
1000 mg/kg: 3/5 (m), 3/5 (f)
1250 mg/kg: 5/5 (m), 4/5 (f)

Mortality occurred within 35-200 minutes after dosing.

Clinical signs:

other: Clinical signs were similar in both sexes. Principal clinical signs comprised reduced spontaneous activity, ventral and lateral recumbency and crawling in all dose groups, in addition to closure of eyes, hunched posture and accelarated breathing in severa

Gross pathology:

All animals which survived during the 14-day post-dosing observation period were free from macroscopic pathology findings. In decedent animals either light coloured spots or dark discoloration were evident in the liver at 500 and 800 mg/kg , whereas at 1000 and 1250 mg/kg dark discoloration of the liver was evident in all decedents. In addition, invagination, reddening and partial filling with transparent yellow liquid were evident in small intestines and hyperemia and/or yellowish white filling were evident in the gastrointestinal tract in a number of decedents at all doses.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

LD50 male/female: 823 mg/kg bw
LD50 male: 869 mg/kg bw
LD50 female: 795 mg/kg bw

Executive summary:

3-Hydroxy-2-naphthoic acid was tested for its acute toxicity in the rat according to OECD Guideline 401 and in compliance with GLP. An oral LD50 of 823 mg/kg bw was attained for both sexes, 869 mg/kg for males and 795 mg/kg for femles. Mortality occurred within 35-200 minutes after dosing. Principal clinical signs comprised reduced spontaneous activity, ventral and lateral recumbency and crawling in all dose groups, in addition to closure of eyes, hunched posture and accelarated breathing in several dose groups starting at approximately 10 to 30 min post administration. In addition, diarrhea was noted in several dose groups starting mainly at approximately 30 to 60 min post administration. As from the day after the administration all surviving animals were free from clinical signs. Bodyweight was unaffected by treatment with the test substance. No macroscopic pathology findings were evident in animals which survived the 14-day post-dosing observation period, whilst dark or mottled livers and signs of gastrointestinal irritation were evident in decedent animals. There was no indication of relevant sex-related differences in toxicity of the substance after single oral administration.