Sodium 3-hydroxy-2-naphthoate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Dose descriptor:

NOAEL

200 mg/kg bw/day

Additional information

Reasons for read across

The test item is the sodium salt of a naphthoic acid. In an acidic enviroment (e.g. stomach), the salt complex becomes dissociated into the sodium cation and the organic acid. Therefore, it is acceptable to derive toxicity to reproduction data from the free acid.

Statement of effects on fertility and developmental toxicity (OECD SIDS SIAM 19)

In a one-generation study in Sprague-Dawley rats, performed in accordance with OECD TG 415, males were dosed with 3-hydroxy-2-naphthoic acid (purity 99.2%) by gavage for 10 weeks prior to mating, during the mating period and until the day before necropsy (in total, 98 days) and females for 2 weeks prior to mating, during mating and gestation and until day 20 of lactation (0; 12.5; 50; 200 mg/kg bw/day). The administration of the test substance had no effect on reproductive performance. No adverse effect of the test substance was observed on pairing days until conception and number of vaginal estrous during the mating period. Furthermore, no abnormality was found in delivery and nursing conditions, and no adverse effects of the test substance on gestation index and gestation length were found (No Effect Level (NOEL) for reproductive toxicity: 200 mg/kg bw/day). After dosing, 200 mg/kg bw/day caused transient salivation in both sexes and nasal discharge in males. Body weight gain was significantly reduced in both sexes. 12.5 and 50 mg/kg bw/day had no effects on general condition, body weight gain and food consumption. At necropsy, thickening of the mucosa of the forestomach was observed in some animals of the high-dose group. Histopathological examination revealed hyperplasia of the forestomach squamous epithelium in the male animals of the mid- and high-dose groups and in females of the high-dose group. Three male animals of the high dose group showed enlarged livers without histopathological changes. No histopathological changes were found in bone marrow, spleen, adrenals, pituitary glands, testes, epididymides, coagulating glands, seminal vesicles, prostates, ovaries, uterus, cervix and vagina. 12.5 mg/kg bw/day caused neither macroscopic nor microscopic changes. The NOEL for systemic toxicity was 12.5 mg/kg bw/day in males, and 50 mg/kg bw/day in females.

Administration of the test substance did not affect viability and general condition, including behaviour of the offpring. There was no effect on the number of stillbirth, number of live pups, delivery index, birth index, sex ratio, viability index and weaning index. Decreased body weights were found in the pups of both sexes in the high-dose group from birth (-15% vs control), until day 21 (-9%). The NOEL for toxicity to the offspring was 50mg/kg bw/day. There was an increase in the incidence of offspring with external malformations, such as kinked tail (n=1), brachyury (5), brachyury with kink (1) or microphthalmus (1, dead offspring) in the highdose group (offspring from 2 out of 25 dams; no pup in the control showed morphological changes). In addition, there were two dead offspring of two dams with visceral malformations in this group, such as undescended testes, hypoplasia of the spleen or diaphragmatic hernia. Although all these malformations were found only in offspring of few limited litters, teratogenicity of the compound could not be ruled out from the present results according to the authors of the study. The NOEL for teratogenicity was 50 mg/kg bw/day.

Conclusion

3-Hydroxy-2-naphtoic acid was tested for its reprotoxicity in a one-generation study according to OECD TG 415. The administration of the test substance had no adverse effect on the reproductive abilities of the parental generation. Teratogenicity was observed in the offspring of few litters at maternally toxic doses. No Effect Level (NOEL) for reproductive toxicity: 200 mg/kg bw/day (highest tested dose).

NOEL for toxicity to the offspring: 50mg/kg bw/day. Growth retardation and malformations (reduced body weights, brachyury, kinked tail) were observed at 200 mg/kg bw/day in the offspring. The NOEL for systemic toxicity in males was 12.5 mg/kg bw/day (forestomach lesions at 50 mg/kg bw/day). The NOEL for systemic toxicity in females was 50 mg/kg bw/day (reduced body weight gain, forestomach lesions at 200 mg/kg bw/day).

Short description of key information:
BONA free acid was tested for toxicity to reproduction in an OECD guideline 415 conform study (OECD SISDS SIAM 19). The test item was administered orally by gavage at dose levels of 0; 12.5; 50; 200 mg/kg bw/day to male and female rats.The substance caused hyperplasia of the forestomach epithelium in males and females of the mid and high dose group, enlarged liver in high dose males and some external malformation in the offspring of the high dose group showing parental toxicity.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

50 mg/kg bw/day

Justification for classification or non-classification

The data given above are from secondary sources and not suitable to derive a statement of classificationor non-classification.