Tar acids (shale oil), C6-9-fraction, alkylphenols

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07 April 2004 - 21 April 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

5-methylresorcinol

EC Number:

207-984-2

EC Name:

5-methylresorcinol

Cas Number:

504-15-4

Molecular formula:

C7H8O2

IUPAC Name:

5-methylbenzene-1,3-diol

Constituent 2

Reference substance name:

Resorcinol

EC Number:

203-585-2

EC Name:

Resorcinol

Cas Number:

108-46-3

Molecular formula:

C6H6O2

IUPAC Name:

benzene-1,3-diol

Constituent 3

Reference substance name:

2,5-dimethylresorcinol

EC Number:

207-688-3

EC Name:

2,5-dimethylresorcinol

Cas Number:

488-87-9

Molecular formula:

C8H10O2

IUPAC Name:

2,5-dimethylbenzene-1,3-diol

Constituent 4

Reference substance name:

2-methylresorcinol

EC Number:

210-155-8

EC Name:

2-methylresorcinol

Cas Number:

608-25-3

Molecular formula:

C7H8O2

IUPAC Name:

2-methylbenzene-1,3-diol

Constituent 5

Reference substance name:

4-methylresorcinol

EC Number:

207-827-8

EC Name:

4-methylresorcinol

Cas Number:

496-73-1

Molecular formula:

C7H8O2

IUPAC Name:

4-methylbenzene-1,3-diol

Constituent 6

Reference substance name:

4,5-dimethylbenzene-1,3-diol

EC Number:

610-895-5

Cas Number:

527-55-9

Molecular formula:

C8H10O2

IUPAC Name:

4,5-dimethylbenzene-1,3-diol

Constituent 7

Reference substance name:

5-ethylbenzene-1,3-diol

Cas Number:

4299-72-3

Molecular formula:

C8H10O2

IUPAC Name:

5-ethylbenzene-1,3-diol

Constituent 8

Reference substance name:

2-ethyl-5-methylbenzene-1,3-diol

Cas Number:

27465-63-0

Molecular formula:

C9H12O2

IUPAC Name:

2-ethyl-5-methylbenzene-1,3-diol

Constituent 9

Reference substance name:

5-ethyl-2-methylbenzene-1,3-diol

Cas Number:

34745-52-3

Molecular formula:

C9H12O2

IUPAC Name:

5-ethyl-2-methylbenzene-1,3-diol

Constituent 10

Reference substance name:

2,4,5-trimethylbenzene-1,3-diol

Cas Number:

20427-81-0

Molecular formula:

C9H12O2

IUPAC Name:

2,4,5-trimethylbenzene-1,3-diol

Constituent 11

Reference substance name:

2,4-dimethylresorcinol

EC Number:

211-213-5

EC Name:

2,4-dimethylresorcinol

Cas Number:

634-65-1

Molecular formula:

C8H10O2

IUPAC Name:

2,4-dimethylbenzene-1,3-diol

Constituent 12

Reference substance name:

Phenol

EC Number:

203-632-7

EC Name:

Phenol

Cas Number:

108-95-2

Molecular formula:

C6H6O

IUPAC Name:

phenol

Constituent 13

Reference substance name:

Cresol

EC Number:

215-293-2

EC Name:

Cresol

Cas Number:

1319-77-3

Molecular formula:

C7H8O

IUPAC Name:

cresol

Constituent 14

Reference substance name:

not applicable

Molecular formula:

not applicable

IUPAC Name:

not applicable

Test material form:

liquid

Details on test material:

Sponsor's identification: Total shale oil phenols
Description: dark brown extremely viscous liquiy
Batch number: Part No. 3
Date received: 30 January 2004
Storage conditions: room temperature, in the dark

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Female Sprague-Dawley CD (Crl: CD® (SD) IGS BR) strain rats were supplied by Charles River (UK) Ltd, Margate, Kent, UK. On receipt the animals were randomly allocated to cages. The animals were nulliparous and non-pregnant. After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals
were eight to twelve weeks of age. The bodyweights fell within an interval of + 20% of the mean
initial bodyweight of the first treated group.
The animals were housed in groups of three in suspended solid-floor polypropylene cages
furnished with woodflakes. With the exception of an overnight fast immediately before dosing
and for approximately three to four hours after dosing, free access to mains drinking water and
food (Certified Rat and Mouse Diet (Code SLF2) supplied by BCM IPS Limited, London, UK)
was allowed throughout the study. The diet, drinking water and bedding were routinely analysed
and were considered not to contain any contaminants that would reasonably be expected to affect
the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70%
respectively. Any occasional deviations from these targets were considered not to have affected
the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per
hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00
to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to
contain any contaminant of a level that might have affected the purpose or integrity of the study.

Administration / exposure

Route of administration:

oral: feed

Vehicle:

arachis oil

Details on oral exposure:

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each group and each dose level to confirm the survival of the previously dosed animals.

The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing
and subsequently once daily for up to fourteen days.

Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment
or at death.

At the end of the observation period the surviving animals were killed by cervical dislocation. All
animals were subjected to gross pathological examination. This consisted of an external
examination and opening of the abdominal and thoracic cavities for examination of major organs.
The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Doses:

300 mg/kg
2000 mg/kg
300 mg/kg

No. of animals per sex per dose:

3

Control animals:

no

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 300 - <= 500 mg/kg bw

Based on:

test mat.

Mortality:

300 mg/kg bw: 0/6
2000 mg/kg bw: 3/3

Any other information on results incl. tables

 Mortality data:

Dose Level mg/kg bw	Sex	Number of animals treated	Deaths during Day of Dosing (Hours)				Deaths during Period after Dosing (Days)								Deaths
			0.5	1	2	4	1	2	3	4	5	6	7	8-14
300	Female	3	0	0	0	0	0	0	0	0	0	0	0	0	0/3
300	Female	3	0	0	0	0	0	0	0	0	0	0	0	0	0/3
2000	Female	3	0	0	3	-	-	-	-	-	-	-	-	-	3/3

 

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be in the range of 300 - 500 mg/kg bodyweight.

Executive summary:

Introduction:

The study was performed to assess the acute oral toxicity of the test material following a single oral administration in the Sprague-Dawley CD strain rat. The method was designed to meet the requirements of the following:

OECD Guidelines for the Testing of Chemicals No. 423 “Acute Oral Toxicity — Acute Toxic Class Method” (adopted 17 December 2001)

Method:

A group of three fasted females was treated with the test material at a dose level of 300 mg/kg bodyweight. Based on the results from this dose level further groups of fasted females were treated at dose levels of 2000 or 300 mg/kg bodyweight. Dosing was performed sequentially. The test material was administered orally as a suspension in arachis oil BP. Clinical signs and

bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality:

All animals treated at a dose level of 2000 mg/kg were found dead two hours after dosing. There were no deaths noted at a dose level of 300 mg/kg.

Clinical Observations:

Signs of systemic toxicity noted in animals treated at a dose level of 2000 mg/kg were hunched posture, lethargy, decreased respiratory rate, laboured respiration, ptosis, body tremors or occasional body tremors, increased salivation, ataxia, loss of righting reflex and splayed gait. Signs of systemic toxicity noted in animals treated at a dose level of 300 mg/kg were hunched posture and lethargy. Animals treated at a dose level of 300 mg/kg recovered one or two days after dosing.

Bodyweight:

The surviving animals showed expected gains in bodyweight over the study period.

Necropsy:

Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver, dark kidneys and epithelial sloughing of the gastric mucosa. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Conclusion:The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be in the range of 300 - 500 mg/kg bodyweight.