2-naphthol

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: A well documented study according to OECD and GLP guidelines. In the OECD SIDS on 2-Naphthol (2002) a similar reliability was assigned.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-naphthol

EC Number:

205-182-7

EC Name:

2-naphthol

Cas Number:

135-19-3

Molecular formula:

C10H8O

IUPAC Name:

2-naphthol

Details on test material:

purity 99.6 wt %

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

- Age at study initiation: 5 weeks (males), 10 weeks (females)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5% sodium carboxymethylcellulose solution

Details on mating procedure:

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

Duration of treatment / exposure:

Exposure period: 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.
Premating exposure period: Male : 10 weeks / Female : 2 weeks

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0; 10; 40; 160 mg/kg bw
Basis:

No. of animals per sex per dose:

25 per sex per dose group.

Control animals:

yes, concurrent vehicle

Details on study design:

Pregnant females were allowed to deliver spontaneously and were sacrificed on day 21 of lactation together with their offspring. Test substance was applied until the day before sacrifice.

Examinations

Maternal examinations:

Principal organs, pituitary gland, stomach, adrenal glands, testes, epididymides, coagulating glands, seminal vesicles and prostate were isolated and examined. The organs from the control and the high-dose group and all organs with macroscopic abnormalities were processed for histopathological examinations.
Pregnant females were allowed to deliver spontaneously and were sacrificed on day 21 of lactation together with their offspring. Test substance was applied until the day before sacrifice. At necropsy, all females were examined for abnormalities of the principal organs, the uteri were isolated and the number of implantations counted. In addition, pituitary gland, stomach, adrenal glands, ovaries, cervix and vagina were examined. All organs with macroscopic abnormalities were processed for histopathological examinations.

Statistics:

Frequency/length of estrous cycle, copulation and fertility indices and frequency of offspring with morphological abnormalities were analyzed by Fisher's exact probability test. Differences in histopathological findings, the graded data and total numbers of postitives were analyzed by Mann-Whitney`s U-test and one-tailed Fisher's exact probability test, respectively. Individual data or mean values of each litter were treated as a single sample, and homogeneity of variance of these samples among groups was analyzed using Bartlett's test. When homogeneity of variance was confirmed, one-way analysis of variance was applied to detect significance between groups. If a significant difference was detected, the Dunnett's test was applied for multiple comparisons. When variance was not
homogenous or zero, the Kruskal-Wallis analysis of ranks was applied, and, if significance was detected, the Dunnett's test applied for multiple comparisons.
Significance levels: p=0.01 and 0.05

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Details on maternal toxic effects:
All females showed normal estrous cycle, and all animals performed fertile copulation. No adverse effect of the test substance was observed on pairing days until conception and number of vaginal estrous during the mating period. Though some females in each group did not become pregnant after copulation, 2-naphthol treatment did not affect fertility index. Furthermore, no abnormality was found in delivery, on gestation index and gestation length. According to the authors of the study, 160 mg/kg bw could however suppress nursing behaviour, since 2-naphthol was shown to depress activity in dams.

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

10 other: mg/kg bw

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

> 160 other: mg/kg bw

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

A one-generation reproduction toxicity test on 2-naphthol was performed on Sprague-Dawley male rats. It permitted to identify 2 NOAEL: 10 mg/kg bw for maternal toxicity and > 160 mg/kg bw for teratogenicity.

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