3-(2-hydroxyethyl)-p-phenylenediammonium sulphate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-(2-hydroxyethyl)-p-phenylenediammonium sulphate

EC Number:

298-995-1

EC Name:

3-(2-hydroxyethyl)-p-phenylenediammonium sulphate

Cas Number:

93841-25-9

Molecular formula:

C8H12N2O.H2O4S

IUPAC Name:

2-(2,5-Diaminophenyl)ethanol sulfate (1:1)

Specific details on test material used for the study:

Trade name : Betoxol
Purity : >98%

Test animals

Species:

mouse

Strain:

other: Him : OFl

Sex:

male/female

Details on test animals or test system and environmental conditions:

Number in the preliminary study : Four females
Number in the main study : Twenty five males and twenty five females
Age : Approx 8 weeks at the time of administration

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Distilled water

Doses:

20, 36, 63, 112, 200 mg/kg bw

No. of animals per sex per dose:

Ten (5 males and 5 females) per dose group

Control animals:

yes

Details on study design:

Justification for the selection of the doses : In a preliminary test 4/4 animals (2 per dose) died at doses of 200 and 2000 mg/kg bw. Based on this information, 200 mg/kg bw was chosen as the highest dose. The lowest dose was 10% of the highest dose. The other doses were interpolated. Behaviour, reactions and physical signs of the animals were observed 1, 10, 30 min, 1, 2, 4 and 6 hours after administration and then at least once a day for 2 weeks. Findings were recorded. Body weight was determined before administration, 7 days and 14 days post administration. All animals that died were dissected and examined macroscopically in an attempt to identify the target organs. All surviving animals were sacrificed by CO2 14 days post administration and examined macroscopically.

Statistics:

LD50 and 95 CL were calculated according to Thompson (Bact. Rev. 11 (1947)).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

80 mg/kg bw

Based on:

test mat.

95% CL:

>= 71 - <= 89

Mortality:

1/10 animals in group 3 (63 mg/kg bw), 10/10 in group 4 (112 mg/kg bw) and 10/10 in group 5 (200 mg/kg bw) died early. Death occurred within 2 hours (males) and 1 hour (females) after test substance administration in the highest dose group 5 (200 mg/kg bw), within 6 hours (males) and 4 days (females) in group 4 (112 mg/kg bw), within 4 hours (one male) in group 3 (63 mg/kg bw).

Clinical signs:

other: Some unspecific signs of general malaise, decreased motor activities, ruffled fur, closed eyes, hunched posture, decreased muscular tension, unconsciousness were noted during the observation time in all animals. In some animals ataxia, dyspnoea or minor c

Gross pathology:

At post mortem examination of the early deaths alterations of the small intestine, discoloured liver, small spleen and lung oedema were observed. Post mortem findings indicated an irritative effect to small intestine which was deemed to be the cause of death and additionally a hepatotoxic effect. All surviving animals and seven of the early died animals were normal at post mortem examination. In most of the other early died animals an abundant yellow aqueous content in the small intestine was observed. In some of these anmals pale yellow liver, white foci on the liver or small spleen were observed. In one of the early died animals an aqueous bloody content in the small intestine, in another oedema of the lungs were observed. Shock due to severe gastrointestinal irritation is assumed to be the cause of death. Liver changes indicate a hepatotoxic effect. Lung oedema is attributed to agonal circulatory breakdown. Small spleen may be caused by haemodynamic disorder or blood loss after intestinal irritation. Chromodacryorrhoeais regarded as a unspecific sign of reduced well being.

Other findings:

At terminal necropsy of the surviving animals no changes were noted. All animals were normal.

Any other information on results incl. tables

The LD50 (oral) calculated for both sexes combined was determined to be 80mg/kg bw in mice. The confidence limits (95%) are 71 and 89 mg/kg bw. No pronounced differences in the LD50 values between males (75 mg/kg bw) and females (84 mg/kg bw) were observed.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the experimental conditions of the study, the LD50 was determined to be 80 mg/kg bw (71-89 mg/kg bw 95% CI) for both sexes combined