2-ethylanthraquinone

Endpoint summary

Description of key information

Three acute oral toxicity studies in rats and one acute dermal toxicity study in rabbits are available. The LD50 was above 2000 mg/kg bw in all studies. 

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:

from 1990-09-18 to 1990-12-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline-conform study performed under GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted on 24 February 1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: SPF-derived Hsd/Cpb:WU Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan/CPB, Zeist, The Netherlands
- Age at study initiation: not reported
- Weight at study initiation: male: 175-200 g, female: 150-175 g
- Fasting period before study: yes (19 hours prior to dosing until 5 hours after dosing)
- Housing: housed continuously in macrolon cages using dust free sawdust as bedding material with two or three animals per cage
- Diet (e.g. ad libitum): ad libitum (standard laboratory diet RHM-TM, Hope Farms, Woerden, The Netherlands) except for a period of about 19 hours prior to dosing until 5 hours after dosing.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23
- Humidity (%): 45-70
- Air changes (per hr): 16
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1990-09-18 To: 1990-10-02

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.29 g/mL
- Amount of vehicle (if gavage): 4.97 mL/kg
- Justification for choice of vehicle: not reported
- Lot/batch no. (if required): not reported
- Purity: not reported

MAXIMUM DOSE VOLUME APPLIED: 7 mL/kg

DOSAGE PREPARATION (if unusual): Test material was suspended in corn oil by grinding the test material with the vehicle at room temperature.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males, 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were weighed one day before dosing, just prior to dosing and at 2, 7 and 14 days after dosing. They were observed from 0-0.5 hour and at 1.5, 3, 5, 24 and 48 hours after dosing and thereafter on each day till the end of the experiment.
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, clinical signs, body weight, gross-autopsy

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One female rat died seven days after treatment.

Clinical signs:

other: The following signs were observed: diminished respiratory rate and respiratory difficulties, diminished locomotor activity, abnormal gait and body posture, pilo-erection, positional passivity, irritability (females), diminished body tone, ptosis (1 male,

Gross pathology:

Gross post-mortem examination of the rat that died during the observation period showed slight staining round nose, dry faeces, absent thymus, dark and enlarged adrenals and blood stained caecal contents. Examination of the animals surviving to the end of the observation period, revealed no effects.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 was established to be greater than 2000 mg/kg in male and female rats. The substance does not to be classified for acute oral toxicity according to Regulation (EC) No 1272/2008 (CLP).

Executive summary:

The aim of this GLP-study was to assess the acute oral toxicity of 2-ethylanthraquinone in male and female rats. The procedure used was in accordance with OECD guideline 401. For this purpose, a single oral dose of 2-ethylanthraquinone suspended in corn oil was given by stomach tube to groups of five male and five female fasted rats. The dose level was 2000 mg/kg in males and females. The animals were weighed one day before dosing, just prior to dosing and at 2, 7 and 14 days after dosing. Any sign of intoxication occurring during the 14-day observation period was recorded. Gross post-mortem examination was done on all rats that died during the study and on the survivors at the end of the 14-day observation period. One female rat died 7 days after dosing. None of the male rats died within the 14-day observation period.

After oral administration of 2-ethylanthraquinone, males and females showed small weight losses or reduced gains during the first few days after dosing. Thereafter the rats grew with normal weight-gains, except for the female rat that died. The clinical signs observed were mainly indicative of effects on motor coordination (decreased locomotor activity, abnormal gait and body posture), on autonomous nervous system (decreased respiratory rate, respiratory difficulties, pilo-erection, diarrhea), on central nervous system (positional passivity), on mood (vocalization, irritability) and on muscle tone (paralysis, diminished body tone). Time of onset of the first signs was within 1.5 hour after dosing. All signs had disappeared in males 5 days after treatment and in females 6 days after treatment, except for the female rat that died during the observation period. Autopsy of the rat that died 7 days after treatment showed slight staining round nose, dry faeces, absent thymus, dark and enlarged adrenals and blood stained caecal contents. At autopsy 14 days after dosing, no abnormalities were observed in the surviving rats.

The acute oral LD50 was established to be greater than 2000 mg/kg in male and female rats. The substance does not to be classified for acute oral toxicity according to Regulation (EC) No 1272/2008 (CLP).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

One Klimisch 1 study, two Klimisch 2 studies

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:

1987-05-23 to 1987-08-21

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline available

Principles of method if other than guideline:

A modification of the techniques described in Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, compiled by the staff of the Division of Pharmacology, Food and Drug Administration, was followed.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

other: albino rabbits

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Summit View Farm, Belvidere, New Jersey
- Age at study initiation: not reported
- Weight at study initiation: not reported
- Housing: not reported
- Diet (e.g. ad libitum): ad libitum (Wayne animal feeds)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: yes (duration not reported)

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: trunk
- Type of wrap if used: occluded patch (sleeve of plasticized material)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, gently cleansed
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 20 g/kg
- For solids, paste formed: no

Duration of exposure:

24 hours

Doses:

20 g/kg

No. of animals per sex per dose:

3 male, 3 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 1, 3, 6, 24 hours after application, 2, 3, 4, 5, 6, 7, 14 days after application
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight, gross pathology

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 20 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: The skins were pliable and non-irritated in all animals. One animal showed a slight depression on day 7 after treatment. No other abnormalities were observed.

Gross pathology:

No gross internal changes observed in any rabbit.

Acute Dermal Toxicity in Rabbits

Dose [g/kg]

Animal number and Sex

Bodyweight [kg]

Hours:

Days:

Bodyweight [kg]

1

3

6

24

2

3

4

5

6

7

14

20.0

1 Ma

1.66

N

N

N

N

N

N

N

N

N

N

N

1.85

2 M

1.50

N

N

N

N

N

N

N

N

N

N

N

1.64

3 Ma

3.18

N

N

N

N

N

N

N

N

N

N

N

3.51

4 F

2.77

N

N

N

N

N

N

N

N

N

N

N

2.84

5 Fa

2.66

N

N

N

N

N

N

N

N

N

N

N

2.79

6 F

1.65

N

N

N

N

N

N

N

N

N

SD

N

1.89

a = abraded skin

N = Normal

D = Depression

SD =Slight Depression

XD = Severe Depression

+ = Animal Death

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of the test substance is greater than 20 g/kg. The substance is therefore not classified for acute dermal toxicity according to Regulation (EC) No 1272/2008 (CLP).

Executive summary:

The acute dermal toxicity of the test item 2 -ethylanthraquinone was assessed.

A single application of 20 g/kg (test substance used as received) was given to 3 male and 3 female under an occluded patch. After 24 hours, the treated skin sites were gently cleansed. All animals were then observed for mortality, skin response and general behaviour for 14 days subsequent to exposure to the test material. One animal showed a slight depression on day 7 after treatment. No other abnormalities were observed.

The LD50 of the substance is greater than 20 g/kg. The substance is therefore not classified for acute dermal toxicity according to Regulation (EC) No 1272/2008 (CLP).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

One Klimisch 2 study

Additional information

Acute oral toxicity

Three acute oral toxicity studies in the rat are available. The study conducted by Snoeij et al (1990) and the one reported in the OECD SIDS followed OECD TG 401 and were performed under GLP. The study performed by Lewis was conducted according to a procedure suggested by Hagan (1959). The study performed by Snoeij (1990) was chosen as the key study for acute oral toxicity as it was performed under GLP and followed the OECD TG 401.

In the study performed by Snoeij et al (1990), 2000 mg/kg bw of the test substance was applied to 5 male and 5 female rats. One female rat died 7 days after dosing. None of the male rats died within the 14-day observation period. The observed clinical signs were mainly indicative of effects on motoric coordination, autonomous nervous system, central nervous system, mood and muscle tone. All signs of toxicity had disappeared in males 5 days after treatment and in females 6 days after treatment, except for the female rat that died during the observation period. Autopsy of the rat dying 7 days after treatment showed slight staining round the nose, dry faeces, absent thymus, dark and enlarged adrenals and blood stained caecal contents. At autopsy 14 days after dosing, no abnormalities were observed in the surviving rats. The acute oral LD50 was established to be greater than 2000 mg/kg in male and female rats.

In the study reported in the OECD SIDS (2010), 2000 mg/kg bw of the test substance was applied to 5 male and 5 female rats. No deaths occurred in either sex. Brown urine and slight depression of body weight were observed in this study. The acute oral LD50 value was found to be greater than 2000 mg/kg in both sexes.

In the study conducted by Lewis (1987), groups of 10 rats (5 male, 5 female) were dosed orally by gavage with 1000, 2000, 2520, 5000 and 6300 mg/kg bw. One rat dosed with 1000 mg/kg bw died on day 2 after treatment, 2 animals treated with 2000 mg/kg bw died on day 2 and 5, respectively. 5 animals treated with 2520 mg/kg bw, 8 animals treated with 5000 mg/kg bw and 9 animals treated with 6300 mg/kg bw died within the 14 day observation period. Further, slight to severe depression was observed in some animals. The acute oral LD50 was determined to be 2795 mg/kg bw with a confidence interval of 2070 - 3773 mg/kg bw.

Acute dermal toxicity

The acute dermal toxicity of the test item to healthy albino rabbits was assessed in a study by Lewis (1987). A modification of the techniques described in Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics by the US Food and Drug Administration was used in this study, which was not performed under GLP. The used techniques deviate from the current OECD testing guidelines. A single application of 20 g/kg (test substance used as received) to the clipped skin was given to 3 male and 3 female rabbits under an occluded patch. After 24 hours, the patch was removed and treated skin sites were gently cleansed. All animals were then observed for mortality, skin response and general behaviour for 14 days subsequent to exposure to the test material. One animal showed a slight depression on day 7 after treatment. No other abnormalities were observed. The acute dermal LD50 of the substance was determined to be greater than 20 g/kg.

Justification for selection of acute toxicity – oral endpoint
The selected key study was performed under GLP and in accordance with OECD TG 401. Two supporting studies are available. One of them is part of the SIDS Initial Assessment Report for SIAM 30 which was peer-reviewed by the Japanese government. The full study report is not available to the registrant and the study is therefore not selected as the key study although it followed the method described in OECD TG 401 and was performed under GLP. The third study followed no guideline and was not performed under GLP.

Justification for selection of acute toxicity – dermal endpoint
The selected key study is well documented and meets generally accepted scientific principles. No other studies are available.

Justification for classification or non-classification

The substance does not need to be classified for acute oral toxicity or acute dermal toxicity according to Regulation (EC) No 1272/2008 (CLP) because the oral and dermal acute LD50 values were greater than 2000 mg/kg bw.