Reaction mass of 2-(1,1-dimethylpropyl)anthraquinone and 2-(1,2-dimethylpropyl)anthraquinone

Endpoint summary

Description of key information

In an acute oral toxicity study with rats performed according to OECD guidelines, the LD50 was determined to be between 1000 and 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan/CPB, Zeist, The Netherlands.
- Weight at study initiation: 209-214 g males / 159-168 g females.
- Fasting period before study: 18-19 hours prior to dosing until 5.5-6 hours after dosing.
- Housing: stainless steel wire cages with two or three animals per cage.
- Diet: ad libitum.
- Water: ad libitum.
- Acclimation period: five days.

ENVIRONMENTAL CONDITIONS
- Temperature: 21-23°C.
- Humidity: 40-70%.
- Air changes: approximately 16 air changes per hour.
- Photoperiod: 12 hours light / 12 hours dark.

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.05, 0.1 and 0.2 g/ml corn oil.
- Amount of vehicle (if gavage): 5 ml/kg.

Doses:

250, 500, 1000 and 2000 mg/kg

No. of animals per sex per dose:

five males and five females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: the rats were observed 0-0.5, 1.5, 3, 5-5.5, 24 and 48 hours after application and thereafter once daily till the end of the study. Rats were weighed one day before and at 2, 7 and 14 days after dosing.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 1 000 - <= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Oral administration of a single dose of 2000 mg/kg killed all male and female rats within 5-48 hours after dosing. All animals dosed at lower levels survived the 14-day observation period.

Clinical signs:

other: Clinical signs at dose level 2000 mg/kg b.w.: clinical signs were slight to severe in intensity (e.g. apathy, abnormal gait and posture, decreased body tone, decreased respiratory rate, respiratory difficulties, decreased locomotor activity, positional pa

Gross pathology:

Post-mortem examination of male and female rates that died during the observation period revealed rigor, dark urine, small and maculate thymus
glands, enlarged and dark adrenals and food-filled stomachs. In the animals that survived the 14-day observation period, slightly darkened adrenals were observed in one male dosed at 1000 mg/kg. Adrenals were found to be enlarged in 2 females given 1000 mg/kg and in 1 female dosed at 250 mg/kg.

Interpretation of results:

other: Based on Regulation 1272/2008/EC, the substance is classified as Acute Tox. 4, H302.

Conclusions:

In a GLP-compliant guideline study, acute oral LD50 of 2-amylanthraquinone in rats was calculated to be between 1000-2000 mg/kg bw. Based on this classification of the substance as Acute Tox. 4, H302 is warranted under Regulation 1272/2008/EC.

Executive summary:

In a GLP-compliant OECD Guideline 401 study 2 -amylanthraquinone was administered by gavage in doses of 250, 500, 1000 and 2000 mg/kg bw to the groups of five males and five females. Administration of a single dose of 2000 mg/kg killed all male and female rats within 5-48 hours after dosing. All animals dosed at lower levels survived the 14-day observation period. Male rats dosed at 1000 mg/kg and females dosed at 500 or 1000 mg/kg lost some weight in the first few days after treatment.

The LD50 was calculated as 1000-2000 mg/kg bw. Based on this the substance should be classified as Acute Tox. 4, H302 (Harmful if swallowed) under Regulation 1272/2008/EC.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Limited, UK.
- Weight at study initiation: 115-126 g males / 101-118 g females.
- Age at study initiation: approximately 5 weeks.
- Fasting period before study: 18-19 hours prior to dosing until 3 hours after dosing.
- Housing: Stainless steel wire cages with five animals per cage.
- Diet: ad libitum.
- Water: ad libitum.
- Acclimation period: at least six days.

ENVIRONMENTAL CONDITIONS
- Temperature: 21°C (range 18-25°C).
- Humidity: 55% (range 40-70%)
- Air changes: approximately 17 air changes per hour.
- Photoperiod: 12 hours light / 12 hours dark.

Route of administration:

oral: gavage

Vehicle:

other: 0.5% w/v methylcellulose and 0.1% w/v Tween in distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25% w/v suspension.
- Amount of vehicle (if gavage): 20 ml/kg.

Doses:

5000 mg/kg

No. of animals per sex per dose:

A single group of five male and five females.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days.
- Frequency of observations and weighing: the rats were observed three separate inspections during the first Day after administration an application and thereafter twice daily till the end of the study. Bodyweight of each animal was recorded on the day before dosing and Days 1, 8 and 15.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

One male rat died during Day 2. The only sign preceding death was decreased motor activity, one to four hours after dosing. Necropsy findings revealed fur staining and abnormal intestinal contents.

Clinical signs:

other: Signs displayed by the surviving animals comprised decreased motor activity in all animals during Day 1 and in the four males on Day 4, and lethargy, breathing irregularities and pigmented orbital secretion in one animal during the morning of Day 2. Recov

Gross pathology:

Necropsy findings for surviving animals on Day 15 were unremarkable.

Interpretation of results:

other: not used for classification and labelling purposes

Conclusions:

In a GLP-compliant guideline study acute oral LD50 of 2-amylanthraquinone in rats was determined to exceed 5000 mg/kg bw. As a more recent acute oral toxicity study with rats is available, demonstrating toxicity at lower dose levels, this study was not used for classification and labelling purposes.

Executive summary:

In a GLP-compliant OECD Guideline 401 study a single oral administration of 2-amylanthraquinone at a dose level 5000 mg/l to a group of 5 male and 5 female rats led to death of one animal on day 2. The only sign preceding death was decreased motor activity, one to four hours after dosing. Necropsy findings revealed fur staining and abnormal intestinal contents. Signs displayed by the surviving animals comprised decreased motor activity in all animals during Day 1 and in the four males on Day 4, and lethargy, breathing irregularities and pigmented orbital secretion in one animal during the morning of Day 2. Recovery was complete in the females by Day 2 and in the males by Day 5. All surviving animals made anticipated body weight gains during the 14-day observation period.

The oral LD50 of the test substance is estimated to be greater than 5000 mg/kg bw under the conditions of this study. As a more recent acute oral toxicity study is available, demonstrating toxicity at lower dose levels, this study was not used for classification and labelling purposes.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 000 mg/kg bw

Quality of whole database:

Based on a reliable GLP-compliant guideline study.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

2-Amylanthraquinone was administered by gavage in doses of 250, 500, 1000 and 2000 mg/kg to groups of five males and five females. Administration of a single dose of 2000 mg/kg killed all male and female rats within 5-48 hours after dosing. All animals dosed at lower levels survived the 14-day observation period. Male rats dosed at 1000 mg/kg and females dosed at 500 or 1000 mg/kg lost some weight in the first few days after treatment. The LD50 was calculated as 1000-2000 mg/kg bw.

Justification for classification or non-classification

The LD50 value in oral acute toxicity test was between 1000 and 2000 mg/kg b.w. Therefore, the substance does need to be classified for acute toxicity according to CLP Regulation (EC) No 1272/2008 as Acute tox Cat.4, H302.