2,6-Diamino-4,5,6,7-tetrahydrobenzothiazole

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 13 september to 12 october 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted in GLP compliance and in accordance with several internationally established guidelines (OECD, EEC, EPA, see below).

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 401 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,6-Diamino-4,5,6,7-tetrahydrobenzothiazol

IUPAC Name:

2,6-Diamino-4,5,6,7-tetrahydrobenzothiazol

Test material form:

solid - liquid: suspension

Details on test material:

- Name of test material (as cited in study report): SND 919 CL2 Y precursor 2; 2,6-Diamino-4,5,6,7-tetrahydrobenzothiazol
- Physical state: solid
- Purity test date: 12 July 1994
- Lot/batch No.: KRÖ 27

Test animals

Species:

rat

Strain:

other: Chbb:THOM

Sex:

male/female

Administration / exposure

Route of administration:

other: Rekord syring and stomach tube

Vehicle:

sorbitan derivative

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 ml/kg bw (administration volume)

Doses:

200, 280, 400 mg/kg

No. of animals per sex per dose:

5 male/5 female per group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed twice daily and weighed one day before treatment and surviving animals on day 8 and 15 day
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

As only one dose for both sexes and for each of the three time points showed a mortality rate different from 0 and 100%, the LD50 was estimated using the method of Spearman-Kärber. For the same reason, the Spearman-Kärber method was used for the common evaluation of sexes 24 hours after administration. For the remaining two time points 7 and 14 days post administration, the common LD50 of both sexes was estimated by means of a prohibt analysis after taking the dose values to logarithm.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

334.7 mg/kg bw

Based on:

not specified

Mortality:

6 of 15 treated animals died.

Clinical signs:

reduced motility, irregular breathing, exophthalmia, piloerection, discoloured yellow urine and incrusted snout and eye

Body weight:

The body weight of the animals, dosed with 280 mg/kg bw, was slightly reduced 7 days post administration, but was increased comparable to standard values 14 days post administration

Gross pathology:

Incrusted snout, fibric adhesions of intestine and abdominal wall, meteorism of the stomach and intestine, dark brown content of caecum and colon, congestion and hemorrhages of the lung, congestion of the liver, hemorrhages of the adrenals, congestion of the kidneys, hemorrhages in the stomach moucosa, and hemorrhagic content of the intestine.

Any other information on results incl. tables

Study group		(1)		(2)		(3)
Dosage (mg/kg)		200		280		400
Sex (m/f)		m	f	m	f	m	f
Animals per dosage		5	5	5	5	5	5
Deaths	within 6 hours					1
	7 - 24 hours					4	3
	day 2 - 7			1			1
	day 8 - end of observ
	total			1		5	4

LD50: m = 312.2 mg/kg

f = 346.8 mg/kg

m+f = 334.7 mg/kg

For the male animals LD50 values of 334.7 mg/kg (24 h) and 312.2 mg/kg (7 and 14 days), and for the female animals LD50 values of 359.4 mg/kg (24 h) and 346.8 mg/kg (7 and 14 days) were estimated. A common evaluation of the gender resulted in LD50 values of 346.8 mg/kg (24 h) and 334.7 mg/kg (7 and 14 days). Between 24 hours and 7 days one male animal died with 280 mg/kg and one female animal died with 400 mg/kg. As no late death were registered, the LD50 values for 7 and 14 days were identical

LD50: m = 312.2 mg/kg

f = 346.8 mg/kg

m+f = 334.7 mg/kg

(confidence limits: 294.8 - 380.5)

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

With an approximate LD50 of 334.7 mg/kg bw after oral administration in rats the precursor 2 of SND 919 CL2 Y could be classified as minortoxic according to the "Chemikaliengesetz" (German Chemicals Act). Thus the labelling with the R-phrase "minortoxic" regarding the accidental ingestion is necessary.