4-hydroxy-3,5-dimethoxybenzonitrile

Endpoint summary

Description of key information

Acute oral and acute dermal toxicity of 4-hydroxy-3,5-dimethoxybenzonitrile were examined in rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

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

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.

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

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.

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008-12-04 to 2008-12/18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

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.

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Received from Ace Animals, Inc, Boyertown, PA, on Nov. 25, 2008
- Age at study initiation: young adult (8-9 weeks)
-Initial weight: male -- 220-244 grams, female -- 178-199 grams
-Number of animals -- 5 male/5 female (non-pregnant)
- 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: 9 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22°C
- Humidity (%): 32-55%
- Photoperiod (hrs dark / hrs light):12 hr light/dark cycle

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: 2x3 inch (approximately 10% of body surface)
- Type of wrap if used: 3 inch durapore tape wrapping the gauze and the entire trunk of each animal

REMOVAL OF TEST SUBSTANCE
- The gauze removed and the site cleaned gently of residual substance.
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg of body weight in a form of dry paste (65% w/w mixture in distilled water)

Duration of exposure:

24 hrs

Doses:

2000 mg/kg of body weight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Frequency of observations and weighing: observed for mortality, gross toxicity, and behaviour changes during the first several hours after application and at least once daily thereafter for 14 days. Weights recorded before the application, day 7 and on day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: At necropsy, tissues and organs of thoracic and abdominal cavities were examined.

Preliminary study:

All animals survived exposure to Mediator SNP. 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.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

All animals survived exposure to the test substance.

Clinical signs:

other: No clinical observations other than the dermal irritations at 3 dose sites between days 1 and 3.

Gross pathology:

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

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the single dose acute dermal LD50 of test substance is greater than 2000 mg/kg of body weight in male and female rats.

Executive summary:

The objective of this study is to determine the potential for Mediator SNP (4-hydroxy-3,5-dimethoxybenzonitrile) to produce toxicity after topical application. The test material was moistened with distilled water and applied to the skin of 10 female rats at 2000 mg/kg body weight. The animals were observed for mortality, signs of systemic toxicity and behavioural changes daily for 14 consecutive days. Body weights were recorded and all animals were killed on day 14 post-dosing.

All animals survived exposure to Mediator SNP. 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 acute dermal LD50 for Mediator SNP was greater than 2000 mg/kg body weight in female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute Toxicity of 4 -hydroxy-3,5-dimethoxybenzonitrile (referred to as Mediator SNP)

Acute oral toxicity in rats – Fixed dose procedure

The objective of this study was to assess the acute toxicity of Mediator SNP 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 and Mediator SNP is classified as “practically non-toxic” by ingestion.

 

Acute dermal toxicity in rats – Limit Test

The objective of this study was to determine the potential for Mediator SNP to produce toxicity after topical application. The test material was moistened with distilled water and applied to the skin of 10 female rats at 2000 mg/kg body weight. The animals were observed for mortality, signs of systemic toxicity and behavioural changes daily for 14 consecutive days. Body weights were recorded and all animals were killed on day 14 post-dosing.

All animals survived exposure to Mediator SNP. 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 acute dermal LD50 for Mediator SNP was greater than 2000 mg/kg body weight in female rats. Mediator SNP can be classified as practically non toxic by dermal application.

Justification for classification or non-classification

Please see above.