3-[[2-(2-cyanoethoxy)ethyl][4-[(4-nitrophenyl)azo]phenyl]amino]propiononitrile

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from February 8 to March 21, 1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

92/69/EEC

Principles of method if other than guideline:

In accordance with Safepharm Standard Operating Procedures.

GLP compliance:

yes

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

Disperse Orange 080

IUPAC Name:

Disperse Orange 080

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: harlan U.K. Ltd..
-Age at study initiaqtion: 5 - 8 weeks old.
- Weight at study initiation: males 140 - 160 g; females 128 - 154 g.
- Fasting period before study: overnight immediately before dosing and for approximately 2 hours after dosing.
- Housing: in groups up to 5/sex in solid floor polyprpylene cages.
- Diet: ad libitum.
- Water: ad libitum.
- Acclimation period: minimum 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 23 °C.
- Humidity: 38 - 59 %.
- Air changes: 15 per hours.
- Photoperiod: 12 hours dark and 12 hours light.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Doses:

Range-finding study: 2000 mg/kg.

Main test: 500, 1000, 2000 mg/kg (females) and 1000 mg/kg (males).

No. of animals per sex per dose:

Range-finding study: 1 male and 1 female.

Main test: 5/sex/dose.

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: once daily for death or overt signs of toxicity; on day 0, 7, 14 or at death for weight.
- Necropsy of survivors performed: yes.
- Other examinations performed: mortality data, clinical signs and body weight.

Results and discussion

Preliminary study:

One female animal was found dead one day after dosing. Common signs of systemic toxicity were ataxia, hunched posture, lethargy, pilo-erection, decreased respiratory rate, laboured respiration, red/brown stains around the mouth and snout and splayed gait with isolated incidents of increased lacrimation and ptosis.

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 1 414 mg/kg bw

Based on:

test mat.

Remarks on result:

other: purity ca. 45 %

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 636.3 mg/kg bw

Based on:

act. ingr.

Mortality:

All females treated with 2000 mg/kg were found dead one day after dosing.

Clinical signs:

No clinical signs of systemic toxicity were noted.

Body weight:

Surviving animals showed gain in bodyweight.

Other findings:

Abnormalities noted at necropsy of females treated with 2000 mg/kg and dead during the study were haemorrhagic lungs, dark liver, dark kidneys, haemorrhage of the non-glandular epithelium of the stomach and haemorrhage of the small and large intestines. No abnormalities were noted at necropsy of animals treated with 500 or 1000 mg/kg, killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:

other: category 4 according to the CLP Regulation (EC 1272/2008).

Conclusions:

The LD50 of the the test material in rats was calculated to be 1414 (1000 - 2000) mg/kg bw by for females only. No difference in toxicity was noted between male and female animals. Male animals were considered not to be markedly more sensitive to the test material than female animals.

Executive summary:

Method

Single dose study in rats by oral gavage at doses of 1000 mg/kg (males) and 500, 1000, 2000 mg/kg (females) . Animals were observed for 14 days after dosing.

Results

Mortality occurred at dose of 2000 mg/kg, where 5/5 female rats were found dead. No mortality occurred at lower doses (1000 and 500 mg/kg) in both sexes. At post mortem necropsy no abnormalities were seen at doses of 500 and 1000 mg/kg. In females exposed to a dose of 2000 mg/kg, macroscopic observations at necropsy were: haemorrhagic lungs, dark liver and kidneys, haemorrhagic gastric mucosa, slight haemorrhagic non-glandular epithelium of stomach, haemorrhagic small and large intestines.

Based on females only, the LD50 value is 1414 mg/kg, equivalent to 636.3 mg active ingredient/kg bw, with test material purity of 45 %. No difference in toxicity was noted between male and female animals.