2,2'-dithiodi(benzoic acid)

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,2'-dithiodi(benzoic acid)

EC Number:

204-352-8

EC Name:

2,2'-dithiodi(benzoic acid)

Cas Number:

119-80-2

Molecular formula:

C14H10O4S2

IUPAC Name:

2-[(2-carboxyphenyl)disulfanyl]benzoic acid

Test material form:

other: Solid

Details on test material:

The test material had a purity of 75.7%

Test animals

Species:

rat

Strain:

other: Alpk:APfSD

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Samples of dose formulation were analysed by HPLC

Duration of treatment / exposure:

28 days

Frequency of treatment:

Daily

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
350 mg/kg
Basis:
other: Nominal in corn oil

Doses / concentrations 2

Remarks:

Doses / Concentrations:
150 mg/kg
Basis:
other: Nominal in corn oil

Doses / concentrations 3

Remarks:

Doses / Concentrations:
30 mg/kg
Basis:
other: Nominal in corn oil

No. of animals per sex per dose:

5 males and 5 females

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily, after dosing

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily, immediately prior to dosing

BODY WEIGHT: Yes
- Time schedule for examinations: Daily, immediately prior to dosing

FOOD CONSUMPTION: Yes
- Time schedule: Recorded continuously and calculated on a weekly basis

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: At termination
- Anaesthetic used for blood collection: Yes (halothane)
- How many animals: All animals
- Parameters checked: Haemoglobin, total white cell count, red cell count, mean cell volume, mean cell haemoglobin, mean cell haemoglobin concentration, haematocrit and platelet count

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At termination
- How many animals: All animals
- Parameters examined: Urea, creatinine, glucose, albumin, total protein, cholesterol, triglycerides, total bilirubin, sodium, potassium, calcium, chloride, phosphorus (as phosphate), alkaline phosphatase activity, alanine transaminase activity, creatine kinase activity, aspartate transaminase activity and gamma-glutamyl transferase activity.

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

ORGAN WEIGHTS: Yes - testes, adrenal glands, kidneys and liver
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Adrenal glands, heart, kidney, liver and spleen

Statistics:

All analyses were carried out using SAS (1989).

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Details on results:

CLINICAL SIGNS AND MORTALITY: One female dosed at 700 mg/kg was found dead.

CLINICAL CHEMISTRY: Alanine and aspartate transaminase activities were increased in the top dose males.

ORGAN WEIGHTS:
Kidney weights showed a dose related increase at all dose levels in males and in top/middle dose females.
Liver weights were increased in top dose males and in top/middle dose females.
Testis weights were increased at all dose levels.

GROSS PATHOLOGY: Discolouration of the stomach and intestines was seen in the animal which died.

HISTOPATHOLOGY: NON-NEOPLASTIC: There were no treatment related effects in male rats. There was no adverse histopathology of the liver in female rates. Histopathological changes involving lithiasis was seen in all female dose groups.

Effect levels

Dose descriptor:

NOAEL

Effect level:

150 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The NOAEL for male rats was 150 mg/kg. A NOAEL for females or a NOEL for either sex was not established in this study. However the lowest dose of 30 mg/kg produced minimal toxicity in females.