Naphthalene-2-sulphonic acid

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

no satellite group for recovery; no neurofunctional tests

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

naphthalensulfonic acids, sodium salts

IUPAC Name:

naphthalensulfonic acids, sodium salts

Details on test material:

- Name of test material (as cited in study report): Naphthalinsulfonsäure Natriumsalz
- Physical state: solid
- Analytical purity: ca. 82 %
- Stability under test conditions: Before the beginning of the study, the stability of the test substance in the vehicle over a period of 4 and 8 days at
room temperature was checked.
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. Karl THOMEAE, Biberach/Riss
- Age at study initiation: 42 days
- Weight at study initiation: males mean: 191 g (178-204 g), females mean: 152 g (142-164 g)
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
The test substance was administered as a solution in drinking water. To prepare the solutions, the test substance was weighed out for the respective test groups, and the appropriate amount of drinking water was added (also weighed). These mixtures were subsequently stirred with a magnetic stirrer for at least 30 minutes to reach complete solubility of the test substance in the drinking water. The drinking water solutions were prepared twice a week (Tuesday and Friday).

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

At the start of the study samples of each concentration were sent to the analytical laboratory for concentration control analysis.

Duration of treatment / exposure:

28 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
600, 3000, 15000 ppm (ca. 62, 331, 1835 mg/kg bw)
Basis:
actual ingested

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: The selection of the concentrations for this study was based on the results of a prior palatability study. In that study the test substance was administered to 3 male and female Wistar rats at a concentration of 15000 ppm in the drinking water for 1 week. 2 male and female Wistar rats were used as controls. No substance-induced changes were observed.
Therefore, the following concentrations were chosen for the present study:
600 ppm: as lowest concentration
3000 ppm: as intermediate concentration
15000 ppm: as highest concentration, resulting in an expected test substance intake of at least 1000 mg/kg body weight

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS/DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily from Mondays-Fridays and once daily on Saturdays, Sundays and public holidays.


BODY WEIGHT: Yes
- Time schedule for examinations: The body weight was determined before the start of the administration period in order to randomize the
animals. During the conduct of the study, the body weight was determined on day 0 (start of administration period) and thereafter once a week.
The difference between the body weight on the respective day of weighing and the body weight on day 0 was calculated as body weight change.

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes


FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: The water consumption was determined once a week over a period of 4 days (Fridays - Tuesday). The values
were calculated as mean water consumption in grams per animal and day.
The mean daily intake of the test substance (group means) was calculated based upon individual values for body weight and water consumption using
the following equation:
Substance intake for day x = ((mean daily water consumption on day X [g] x ppm in the diet [mg/kg]) / bodyweight on day X [g)


OPHTHALMOSCOPIC EXAMINATION: No data


HAEMATOLOGY: Yes
- Time schedule for collection of blood: in the morning
- Anaesthetic used for blood collection: No
- Animals fasted: No
- How many animals: 5 animals per test group and sex
- Parameters examined: leukocytes, erythrocytes, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean
corpuscular hemoglobin concentration, platelets, differential blood cell count, clotting analyses (prothrombin time)


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: in the morning
- Animals fasted: No
- How many animals: 5 animals per test group and sex
- Parameters examined: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, serum-gamma-glutamyltransferase,
sodium, potassium, chloride, inorganic phosphate, calcium, urea, creatinine, glucose, total bilirubin, total protein, albumin, globulins, triglycerides,
cholesterol, magnesium


URINALYSIS: Yes
- Time schedule for collection of urine: overnight
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters examined: volume, color, turbidity, nitrite, pH, protein, glucose, ketones, urobilinogen, bilirubin, blood, specific gravity, sediment


NEUROBEHAVIOURAL EXAMINATION: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, not specified
HISTOPATHOLOGY: Yes, not specified

Statistics:

The statistical evaluation and calculation of the data were carried out on the computer systems of the Department of Toxicology of BASF
Aktiengesellschaft.
Statistical evaluation of clinical examination data was done by the calculation of means and standard deviations, the non-parametric one-way analysis using the Kruskal-Wallis test, in case of a resulting p-value equal or less than 0.05 a pairwise comparison of each dose group with the control via the Mann-Whitney U-test for hypothesis of equal medians was performed. (P-levels of significance were p <= 0.05, p <= 0.02 and p <= 0.002). Both tests were performed two-sided. For clinical chemistry and hematology means and standard deviations were calculated. A non-parametric one-way analysis using the Kruskal-Wallis test was performed as well as a pairwise comparison of each dose group with the control via the Mann-Whitney U-test for the hypothesis of equal medians in case of p-values <= 0.05. (P-levels of significance were p <= 0.05, p <= 0.02 and p <= 0.002). Again both tests were performed two-sided. For urinalyses data a pairwise comparison of each dose group with the control was carried out using Fisher's exact test for the hypothesis of equal proportions. (P-levels of significance were p <= 0.05 and p <= 0.01). For pathology mean and standard deviations were calculated for the variable of terminal body weight and of absolute and relative organ weights (related to terminal body weight). A non-parametric one-way analysis of variance was done via the Kruskal-Wallis-H-test. In case of a resulting p-value less than 0.05 a pairwise comparison of each dose group with the control group was carried out using the Wilcoxon-Test for the hypothesis of equal medians. (P-levels of significance were p <= 0.05 and p <= 0.01)

Results and discussion

Results of examinations

Details on results:

CLINICAL SIGNS AND MORTALITY
No substance-related effects were obtained ; the only abnormal findings was (partial) alopecia in one mid dose male animal. However, this was assessed as being incidental, as it was observed only in a single animal. No animal died during the course of the study.

BODY WEIGHT AND WEIGHT GAIN
Body weight and body weight change values of the treated animals did not differ statistically or biologically significant from control values.

FOOD CONSUMPTION
The values of the treated animals did not differ statistically or biologically significant from control values.

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study)
The values of the treated animals did not differ statistically or biologically significant from control values.
Test group Concentration Mean daily substance intake in mg/kg body weight
in drinking water male animals female animals all animals
(ppm)
1 600 about 57 about 67 about 62
2 3000 about 323 about 338 about 331
3 15000 about 1636 about 2034 about 1835

HAEMATOLOGY
No substance-related changes were observed in the results of the hematology examinations of either sex.
There are statistically significant intergroup differences in the results of the white blood cell count in the males of test groups 1 and 2. These deviations are marginal, inconsistent, when compared with the other sex, and lack dosage-relationship. Accordingly, the increase in white blood cells is considered to be of no toxicological significance.
No substance-related changes were observed in the results of the clotting analyses of either sex.
No substance-related changes were observed in the results of the serum enzyme examinations of either sex.

CLINICAL CHEMISTRY
No substance-related changes were observed in the results of the blood chemistry examinations of either sex.
In clinical chemistry examinations statistically significantly decreased total bilirubin concentrations were detected in all test groups males and in test groups 2 and 3 females. Although total bilirubin was reduced in the serum of both sexes after treatment, these findings are not considered to be substance-related. First of all, the decreased total bilirubin concentrations seen in the serum of the male and female animals are within historical limits and no dose-response relationship was observed in the males. Furthermore, decreased total bilirubin concentrations are not thought to be toxicologically meaningful. Therefore, it is concluded that the fall in bilirubin is not a test substance-related effect.

URINALYSIS
No substance-related changes were observed in the results of the urinalyses of either sex.


ORGAN WEIGHTS
No substance-related findings were obtained.

GROSS PATHOLOGY
No substance-related findings were obtained.

HISTOPATHOLOGY: NON-NEOPLASTIC
No substance-related findings were obtained.

Effect levels

Dose descriptor:

NOAEL

Remarks:

toxicity

Effect level:

>= 1 835 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: corresponding to 15000 ppm; no effects observed

Target system / organ toxicity

Critical effects observed:

not specified