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Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Additional information

Fertility

In a reproductive study according to GLP requirements, naphthalene sulfonic acids, potassium salts (purity 99.9%) were administered to groups of 25 male and 25 female healthy young Wistar rats (FO parental generation) as a homogeneous addition to the food in different dietary concentrations, which were adjusted regularly to obtain a constant test substance intake of 0, 100, 300 and 1000 mg/kg bw/day (BASF AG 2003). The study followed OECD test guideline 415 with observation of additional reproductive parameters (extended one-generation study). At least 75 days after the beginning of treatment, F0 animals were mated to produce a litter (F1 descendant generation).

After litter standardization on day 4 p.p. (post partum) F1 pups were reared until weaning.

At this time 25 male and 25 female pups per group were selected and allowed to grow up until sexual maturity. The latter rats ("selected F1 animals") were treated with the compound after weaning (day 21 p.p.) until sacrifice at the same dose levels and in the same manner as the F0 parental animals. The study was terminated with the sacrifice and gross necropsy of all F0 and F1 animals. The state of health of the F0 and F1 rats was checked each day, and the F0 parental animals were examined for their mating and reproductive performance. Water consumption of the F0 parents was determined regularly during the first 10 weeks after the start of the respective study period (once weekly generally over a period of 3 days each), and additionally during gestation for days 0-1, 6-7, 13-14, and 19-20 p.c. (post coitum) and during lactation periods for days 1-2, 4-5, 7-8, and 14-15 p.p. (p.p. = post partum) of the F0 females. No water consumption was determined for the selected F1 animals. Food consumption of the F0 parents was determined regularly during premating (once weekly over a period of 6 days each), and during gestation (days 0-7, 7-14, 14-20) and lactation periods (days 1-4, 4-7, 7-14). Food consumption of the selected F1 animals was determined once weekly after weaning (over a period of 6 days). In general, body weights of F0 parents and selected F1 animals were determined once weekly (each time for a period of 7 days). However, F0 females were weighed on days 0, 7, 14 and 20 of gestation and on days 1, 4, 7, 14 and 21 of lactation. The body weights of the selected F1 animals were additionally determined on the day of preputial

separation/ vaginal opening. Estrous cycle data were evaluated in F0 generation females over a three week-period prior to mating and throughout the following mating period until individual evidence of mating occurred. Moreover, the estrous stage of each F0 female was determined on the day of scheduled sacrifice.

Various sperm parameters (sperm head counts and morphology) were assessed in all control and high dose F0 generation males, while sperm motility was examined in the F0 males of all groups at scheduled sacrifice or after appropriate staining. All F1 pups were sexed on the day of birth and were weighed on the subsequent day as well as on day 4 after birth. Their viability was recorded. Standardized litters were weighed on days 4, 7, 14 and 21 p.p.. After weaning the non-selected pups were subjected to gross necropsy (including weight determinations of brain, spleen and thymus in one pup/sex/litter).

The selected F1 weanlings were further reared and the time of sexual maturation (day of

preputial separation/vaginal opening) was determined. Thereafter, these pups were killed and examined macroscopically at necropsy. In the F0 animals of both genders organ weights were determined and histopathological examinations were performed in selected organs. Particular attention was focused to the reproductive organs. The measured intakes of NSA potassium salts by the different test groups correlated well with the desired target concentrations.

The following test substance-related findings were observed in the F0 animals:

Decreased total bilirubin was observed in both sexes in the high dose group (-24% males; - 33% females) and in the mid dose group (-13% males; - 22% females), but not in the low dose group. The clinical, gross and histopathological examinations as well as organ weight determinations of the F0 parental rats for general signs of toxicity failed to reveal substance-induced effects up to and including the dose of 1,000 mg/kg body weight/day. No test substance-related findings were observed in the F1 animals up to and including the dose of 1,000 mg/kg body weight/day.

Under the conditions of this study NSA potassium salts had no adverse effects on fertility and reproductive performance of the F0 parental animals of both genders at 100; 300 and

1,000 mg/kg body weight/day. Estrous cycle data, mating behavior, conception, gestation, parturition, lactation and weaning as well as sperm parameters, sexual organ weights and gross and histopathological findings of these organs (including differential ovarian follicle counts) were similar between the rats of the substance-treated groups and the corresponding controls. Nearly all of the F0 parental animals proved to be fertile. The scattered occurrence of a few non-breeders throughout the different dose groups (1 / 2/ 4/ 0 at 0, 100, 300, and 1,000 mg/kg body weight/day) without any relation to dosing does not suggest any relation to treatment.

There occurred no substance-induced signs of developmental toxicity in the progeny of the F0 parents, i.e. in the F1 pups and those F1 pups, which were raised after weaning until sexual maturity (i.e. selected F1 rats). Pup mortality and survival rate, sex ratio, body weight data, clinical and necropsy findings, organ weights and sexual maturation data were unaffected by treatment.

Thus, under the conditions of the present extended one-generation study the NOAEL (no observed adverse effect level) of >= 1,000 mg/kg body weight/day could be fixed for fertility and reproductive performance of the F0 parental rats (both genders), overall general toxicity of the test substance and developmental toxicity (growth and development of the F1 offspring until sexual maturity).

Read across justification:

The registration item contains ca. 78.89% of naphthalene-2-sulphonic acid (CAS # 120-18-3) and ca. 6.5 % of naphthalene-1-sulphonic acid (CAS # 85-47-2). These two substances have the same molecular weight and are structurally almost identical. Therefore naphthalene-2-sulphonic acid and naphthalene-1-sulphonic acid and their respective salts are suitable for read across in order to fulfill the data requirements.


Short description of key information:
Fertility
oral, rat, ext. 1-gen, TS: naphthalenesulfonic acids, potassium salts: NOAEL F0 fertility >= 1000 mg/kg (GLP; OECD 415/416; BASF AG 2003)

Effects on developmental toxicity

Description of key information
Developmental toxicity
oral, rat, gestation day 6-19, TS: naphthalene-2-sulfonic acid, sodium salt: NOAEL maternal/ developmental toxicity >=1000 mg/L (OECD 414; Kao Corp. 2000).
oral, rat, ext. 1-gen, TS: naphthalenesulfonic acids, potassium salts: NOAEL F1 developmental toxicity >= 1000 mg/kg (GLP; OECD 415/416; BASF AG 2003)
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Additional information

Developmental toxicity

The potential maternal toxicity and prenatal developmental toxicity of naphthalene-2-sulfonic acid, sodium salt were evaluated in a developmental toxicity study according to OECD 414 and GLP requirements (Kao Corp. 2000). The test article, BNS-Na (purity 97.7%), in the vehicle, distilled water, was administered to three groups of 25 bred Crl:CD (SD)IGS BR rats once daily from gestation days 6 through 19. Dosage levels were 100, 300 and 1000 mg/kg bw/day administered at a dose volume of 5 ml/kg. A concurrent control group composed of 25 bred females received the vehicle, distilled water, on a comparable regimen at 5 mL/kg. The route of administration was oral by gavage. Clinical observations, body weights and food consumption were recorded. On gestation day 20, a laparohysterectomy was performed on all surviving animals. The uteri and ovaries were examined and the numbers of fetuses, early and late resorptions, total implantations and corpora lutea were recorded. Gravid uterine weights were recorded and net bodyweight changes were calculated for each group. The fetuses were weighed, sexed and examined for external, soft tissue and skeletal malformations and variations.

All animals survived to the scheduled necropsy on gestation day 20. No treatment-related clinical observations or internal findings were noted at any dose level. Mean body weights, body weight gains, gravid uterine weights, net body weights, net body weight gains and food consumption were unaffected by treatment.

Intrauterine growth and survival were unaffected by treatment in the 100, 300 and 1000 mg/kg/day groups. No test article-related malformations or developmental variations were observed in fetuses in this study. Based on the results of this study, the NOAEL (no-observed-adverse-effect level) for maternal and prenatal developmental toxicity was considered to be >= 1000 mg/kg bw/day.

Read across justification:

 

The regsitered substance contains ca. 78.89% of naphthalene-2-sulphonic acid (CAS # 120-18-3) and ca. 6.5 % of naphthalene-1-sulphonic acid (CAS # 85-47-2). These two substances are both corrosive, have the same molecular weight and are structurally almost identical. Therefore naphthalene-2-sulphonic acid and naphthalene-1-sulphonic acid and there respective salts are suitable for read across in order to fulfill the data requirements.

Justification for classification or non-classification

Due to the lack of toxicity on fertility and development in definite studies with sodium salts naphthalenesulfonic acids in rats, there is no need for classification naphthalenesulfonic acids according to reproductive toxicity.

Additional information

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