4-hydroxy-3,5-dimethoxybenzonitrile

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008-12-12 to 2009-01-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Dose level selection changed to limit test at 5000 mg/kg

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-hydroxy-3,5-dimethoxybenzonitrile

Cas Number:

72684-95-8

IUPAC Name:

4-hydroxy-3,5-dimethoxybenzonitrile

Test material form:

solid

Specific details on test material used for the study:

- Composition of test material, percentage of components: syringonitrile 99.8%
- Expiration date of the lot/batch: May 2010
-Physical description: pale yellow powder
-solubility: soluble in water
-stability: test substance was expected to be stable for the duration of the testing.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Received from Ace Animals Inc, Boyertown, PA, on Nov. 25 and Dec. 30, 2008
- Age at study initiation: young adult (9-11 weeks)
-Weight at study initiation: 178-220 grams
- Housing: singly housed in suspended stainless steel cage
- Diet (e.g. ad libitum): pelleted Purina Rodent Chow
- Water (e.g. ad libitum): filtered tap water was supplied ad libitum by an automatic water dispensing system.
- Acclimation period:10-20 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21°C
- Humidity (%): 15-60%
- Photoperiod (hrs dark / hrs light):12 hr light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

- Concentration in vehicle: Test substance was administered as a 35% w/w mixture in a 0.5% solution of carboxymethyl cellulose in distilled water using a stainless steel ball-tipped gavage needle attached to an appropriate syringe.

Doses:

Limit test at 5000 mg/kg

No. of animals per sex per dose:

3 female rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed for gross toxicity, mortality and behavioural changes during the first several hours after dosing and at least once daily thereafter for 14 days. Weights recorded pre-dosing, day 7 and day 14.
- Necropsy of survivors performed: yes -- tissues and organs of thoracic and abdominal cavities were examined.

Results and discussion

Preliminary study:

No mortality was recorded in this study. There were no overt signs of systemic toxicity throughout the 14-day observation period and at necropsy. There were no adverse effects on body weights and body weight gains. No gross abnormalities were noted at necropsy.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

All animals survived.

Clinical signs:

other: Following administration, two out of three rats were hypoactive/exhibited piloerection, hunched posture and reduced faecal volume. However, the animals recovered by day 2, appeared active and healthy for the remainder of 14-day observation period.

Gross pathology:

No gross abnormalities observed when necropsied at the end of 14-day study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of the test substance is greater than 5000 mg/kg of body weight in female rats.

Executive summary:

The objective of this study was to assess the acute toxicity of Mediator SNP (4-hydroxy-3,5-dimethoxybenzonitrile) when administered as a single oral dose followed by a 14-day period of observation. The information is used for both hazard assessment and ranking purposes. The study was initiated with an initial limit dose of 5000 mg/kg body weight in three female rats. The test substance was administered as a 35% w/w mixture in a 0.5% solution of carboxymethylcellulose (CMC) in distilled water.

No mortality was recorded in this study. There were no overt signs of systemic toxicity throughout the 14-day observation period and at necropsy. There were no adverse effects on body weights and body weight gains. No gross abnormalities were noted at necropsy. Under the conditions of this study, the oral LD50 was >5000 mg/kg body weight.