3-hydroxy-2-naphthoic acid

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: All information on this study, including the reliability grade, is derived from OECD SIDS 3-hydroxy-2-naphthoic acid CAS: 92-70-6 dated 2004-11-23, as the complete study report is not at hand. The testing laboratory report no. is HRI 10-1636.

Data source

Reference

Reference Type:

secondary source

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD Guideline 415 (One-Generation Reproduction Toxicity Study)

Deviations:

no

GLP compliance:

yes

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 OECD SIDS): 3-Hydroxy-2-naphtoic acid

Test material purity 99.2%,
impurity: 2-naphthol, 0.1%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5% sodium CMC (carboxymethyl cellulose) solution

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

Mating period: max 3 weeks (1:1, until pregnancy or until three weeks had elapsed).

Duration of treatment / exposure:

males: for 10 weeks prior to mating, during the mating period and until the day before necropsy (98 days);
females: for 2 weeks prior to mating, during mating and gestation and until day 20 of lactation.
Explanatory note (not specified in the OECD SIDS): Based on the biology of the laboratory rat the female exposure period was as follows:
treatment prior to mating = 2 weeks
mating period = 0-3 weeks
gestation/pregnancy = 3 weeks
lactation period = 3 weeks
total treatment period females = 8 to 11 weeks

Frequency of treatment:

daily (once per day)

No. of animals per sex per dose:

25 per sex per dose group (parental animals)

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:

NOEL

Effect level:

50 other: mg/kg bw/day (actual dose received by parental animals P)

Basis for effect level:

other: other:

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

There was an increase in the incidence of offspring with external malformations such as kinked tail, brachyury, brachyury with kink or microphthalmus in the high-dose group. Detailed study results including parental toxic effects, reproductive performance and embryotoxic/teratogenic effects are given in Endpoint study record "7.8.1 Toxicity to reproduction: KEY_2004_OECD SIDS_CAS_92-70-6_fert"

Applicant's summary and conclusion

Conclusions:

The no-observed-effect-level (NOEL) for systemic toxicity in parental female animals was 50 mg/kg/day, because of forestomach lesions and adverse effects on bodyweight gain at 200 mg/kg/day. For developmental toxicity and teratogenicity, the NOEL was set at 50 mg/kg/day, because of growthretardation (bodyweight of pups lower than concurrent controls) and malformations (e.g. brachyury, kinked tail, microphthalmus in pups from a limited number of litters) at 200 mg/kg/day. The growth retardation of these pups may have been related to suppressed lactation suggested by the authors of this study. More comprehensive conclusions on the entire study are given in Endpoint study record "7.8.1 Toxicity to reproduction: KEY_2004_OECD SIDS_CAS_92-70-6_fert".

Executive summary:

A comprehensive executive summary is given in Endpoint study record "7.8.1 Toxicity to reproduction: NONKEY_415_2004_OECD SIDS_CAS_92-70-6_fert".