Thermal cracking oil from blends of rubber, fuel oils and paraffin waxes, steam-stripped

Endpoint summary

Description of key information

The acute oral median lethal dose (LD50) of the registered substance in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight. The test item did not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures. 
The acute inhalation median lethal dose (LD50) of the read-across substance in the male and female Sprague-Dawley rat strain was estimated to be 4.65mg/l for both sexes. The test substance meets the criteria for classification as Acute Tox 3 according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.
The acute dermal median lethal dose (LD50) of the read-across substance in the male and female New Zealand white rabbit strain was estimated to be greater than 2000 mg/kg body weight. The test item did not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures. 

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was conducted by a GLP accredited laboratory using OECD Testing Guideline 420.

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Female Wistar (RccHan™:WIST) strain rats were supplied by Harlan Laboratories UK Ltd., Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatization 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 body weight variation did not exceed ±20% of the body weight of the initially dosed animal.

The animals were housed in groups of up to four 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 (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed 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. 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.

Rats are the preferred species of choice as historically used for safety evaluation studies and are specified in the appropriate test guidelines.

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

For the purpose of the 2000 mg/kg dose level, the test item was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level. For the purpose of the 300 mg/kg dose level, the test item was freshly prepared, as required, as a solution in arachis oil BP. Arachis oil BP was used because the test item did not dissolve/suspend in distilled water.

The test item was formulated within two hours of being applied to the test system. It is assumed that the formulation was stable for this duration.

No analysis was conducted to determine the homogeneity, concentration or stability of the test item formulation. This is an exception with regard to GLP and has been reflected in the GLP compliance statement.

Doses:

- 300 mg/kg
- 2000 mg/kg

No. of animals per sex per dose:

1 animal received a dose of 300 mg/kg, 5 animals received a dose of 2000 mg/kg

Control animals:

no

Details on study design:

Duration of observation period following administration: 14 days
Frequency of observations and weighing: Day 0 (prior to dosing), Day 7, Day 14, and at death.
Necropsy of survivors performed: yes
Other examinations performed: clinical signs, body weight

Preliminary study:

Dose level 300 mg/kg: No mortality, no signs of systemic toxicity noted during the observation period, the animal showed expected gains in body weight over the observation period and no abnormalities were noted at necropsy. Based on the results at a dose level of 300 mg/kg, a dose level of 2000 mg/kg body weight was investigated.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths were recorded

Clinical signs:

other: At 2000 mg/kg - Hunched posture and red/brown staining around the mouth and snout were noted in the initial treated animal. This animal appeared normal 2 days after dosing. No signs of systemic toxicity were noted in the four additional treated animals du

Gross pathology:

No abnormalities were noted at necropsy

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight. The test item did not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

Executive summary:

The acute toxicity: oral of the test substance was determined in accordance with the OECD Guideline for Testing of chemicals 420. Following a sighting test at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test item at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. At dose level 300 mg/kg there was no mortality, no signs of systemic toxicity noted during the observation period, the animal showed expected gains in body weight over the observation period and no abnormalities were noted at necropsy. Based on the results at a dose level of 300 mg/kg, a dose level of 2000 mg/kg body weight was investigated. At dose level 2000 mg/kg there was no mortality, all animals showed expected gains in body weight and no abnormalities were noted at necropsy. Hunched posture and red/brown staining around the mouth and snout were noted in the initial animal treated at a dose level of 2000 mg/kg. There were no other signs of systemic toxicity noted. The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight. The test item did not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study was conducted by a GLP accredited laboratory using a method similar to OECD Testing Guideline 403 and meets acceptable scientific standards

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

Nose-only exposure would have been more relevant considering the properties of the substance

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute 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 breeding laboratories , Inc
- Age at study initiation: at least 9 weeks
- Weight at study initiation: Males: 250-300g, Females: 200-250g
- Housing: Individual stainless steel and glass chambers of 0.25cubic meter volume
- Diet: ad libitum except during exposure periods, purina certified laboratory chow 5002
- Water: ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24°C
- Humidity (%): 50-68%
- Photoperiod (hrs dark / hrs light): 12 hour light/12 hour dark

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Source and rate of air: 1.7-2.9cfm
- System of generating particulates/aerosols: DeVilbliss No. 40 nebulizer
- Method of particle size determination: Cascade impactor
- Temperature, humidity, pressure in air chamber: temperature: 21-24°C, humidity: 50-68%

TEST ATMOSPHERE
- Samples taken from breathing zone: yes

TEST ATMOSPHERE: tabulated

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 4 h

Concentrations:

2.34, 3.47, 5.06, 6.34 and 7.29mg/l

No. of animals per sex per dose:

five rats per sex per dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed daily and weighed prior to exposure as well as day 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Preliminary study:

A Phase I study was done where 5 young adult rats of each sex were exposed to a target aerosol concentration of 5.0mg/l for 4 hours. No animals died during the exposure to a time weighted average (TWA) concentration of 5.06 ±0.29mg/l; however, three males and one female died during the 14 day observation period, necessitating conduct of phase II in an attempt to define the LC50 of the test material aerosols.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

4.65 mg/L air

Based on:

test mat.

95% CL:

>= 3.89 - <= 5.55

Exp. duration:

4 h

Remarks on result:

other: Calculated using Litchfield and Wilcoxon method

Mortality:

No animals died during the course of the exposure. Three males and one female died during the 14 day observation period following the Phase I trial level exposure, which necessitated conduct of phase II. A number of animals from groups exposed to concentrations of 2.34mg/l and higher died either one or two days post exposure. All of the animals exposed to a concentration of 7.29mg/l of test material aerosols died.

Clinical signs:

other: Most of the exposed animals displayed some hair coat abnormalities and many of them at the higher exposure levels showed a crust around the nose 2 to 4 days post exposure. A number of rats of both sexes developed skin abnormalities late in the observation

Body weight:

There was a dose-related suppression in body weight gain in the day 7 weighing that was still apparent in the animals that survived to the terminal necropsy, especially the males.

Gross pathology:

The three males and one female that died the day after phase I exposure exhibited dark red lungs, blood-tinged stains around the nose and stained coats, but animals surviving to term appeared normal. Similar gross necroscopy observations were made on most of the higher exposure level phase II rats, group 3 (7.29mg/l) and group 5 (6.34mg/l) and in the two rats that died after exposure to lower levels.

While the changes seen in the lungs of the phase I animals that were killed terminally were mild, morphologic changes in the four animals that died were severe. There was congestion and edema with extravastion of red blood cells accompanied by necrosis of alveolar lining cells. They also exhibited spotty necrosis of bronchiolar epithelium, particularly of small bronchioles. These morphologic changes were severe enough to have caused death, while those seen in the surviving animals were indicative of recovery.

The histologic changes seen in the phase II animals that died one to two days post exposure duplicated those of the early death phase I animals, while animals surviving to term exhibited changes that were generally mild and chronic in nature. Interstitial inflammation, focal alveolar histocytosis, and localized emphysema seemed to be related to exposure level. a few skin lesions were seen in both phase I and phase II animals.

These histologic changes in animals that died are indicative of deep irritation and were considered to be compatible with acute hydrocarbon toxicity. They were severe enough to be the cause of death.

Mortality data

Phase and GroupNumber	Measured concentration TWA (mg/l)	Mortality
		Male		Female		Total
		Number	Percent	Number	Percent	Number	Percent
PII-G1	0.00	0	0	0	0	0	0
PII-G2	2.34	1	20	0	0	1	10
PII-G4	3.47	0	0	1	20	1	10
PI-G1	5.06	3	60	1	20	4	40
PII-G5	6.34	3	60	5	100	8	80
PII-G3	7.29	5	100	5	100	10	100

Mean body weight data expressed as a percentage of pre-exposure data

Phase and group number	Measured concentrationTWA (mg/l)	Pre-exposure body weight day 0 (%)	Body weight expressed as percentage of day 0 weight
			Male		Female
			Day 7	Day 14	Day 7	Day 14
PII-G1	0.00	100	111.2	120.4	107.0	113.2
PII-G2	2.34	100	99.6	113.4	105.2	108.4
PII-G4	3.47	100	100.4	111.4	100.1	105.8
PI-G1	5.06	100	99.7	116.4	99.3	111.5
PII-G5	6.34	100	92.1	103.2	-	-
PII-G3	7.29	100	-	-	-	-

Frequency of occurance of pharmatoxic signs

Pharmacotoxic sign	0mg/l		2.34mg/l		3.47mg/l		5.06mg/l		6.34mg/		7.29mg/l
	M	F	M	F	M	F	M	F	M	F	M	F
Oily coat	0	0	5	5	5	4	5	5	3	1	0	2
Wetness on coat	0	0	5	5	5	5	5	5	5	5	5	5
Crust around nose (red or otherwise)	0	0	2	0	1	4	4	5	1	2	0	3
Hair loss	1	1	4	1	1	0	2	4	2	0	0	0
Skin abnormal (scabs, flaky)	2	1	4	0	3	0	2	4	2	1	0	0
Trembling	0	0	1	0	0	1	0	0	0	0	0	0
Nasal discharge/wet	0	0	0	0	4	3	0	0	0	0	4	2
Urine stain on coat	0	0	2	0	1	1	0	1	3	1	0	0
Rapid breathing	0	0	0	0	0	0	1	0	0	0	0	1
Decreased activity/mobility	0	0	0	0	5	5	0	0	2	3	0	3
Eye abnormalities (partially or fully closed, crust around)	0	0	1	0	0	5	0	2	2	0	0	1
Discharge (forelimb)	0	0	0	0	1	0	0	0	0	0	0	0

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute inhalation median lethal dose (LD50) of the test item in the male and female Sprague-Dawley rat strain was estimated to be 4.65mg/l for both sexes. The test substance meets the criteria for classification as Acute Tox 4 Acute Tox 4 according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

Executive summary:

The acute toxicity: inhalation of the registered substance was determined using a method similar to the OECD Guideline for Testing of chemicals 403. Inhalation of the aerosolized read-across substance by male and female rats at a TWA concentration of about 5.1mg/l for 4 hours was acutely toxic, resulting in the death of three of 5 males and one of 5 females within a couple days of exposure. All the animals showed some pharmacotoxic signs during the first few post exposure days and these were more severe in females. Histopathalogic lesions of the lung were interpreted to have resulted from exposure to a deep irritant, but surviving animals showed recovery. Since 4 deaths occurred at this trial level exposure, phase II was carried out at a target dose level of 0,2.5, 3.5, 6.25 and 7.5mg/l. Measured TWA concentrations ranged from 2.34 to 7.29mg/l. One animal died at each of the two lower test compound level, while all 10 rats exposed to the highest level died 1 to 2 days post exposure, with intermediate numbers succumbing at the other dose levels. Gross and histologic lesions seen in the animals that died mirrored those seen in phase I. The combined male and female data gave a value of 4.65mg/l for the LC50, with a 95% confidence limits of 3.89 to 5.55mg/l. The test substance meets the criteria for classification as Acute Tox 3 according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

4 650 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

From 26 April 1984 to 10 May 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study was conducted by a GLP accredited laboratory using a method similar to OECD Testing Guideline 402 and meets acceptable scientific standards

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

2 males and 2 females had the shaved area abraded, instead of using 5 animals/sex with intact skin.

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Dutchland, Inc
- Age at study initiation: approx. 14 weeks
- Weight at study initiation: 2,213-2,565g
- Diet: ad libitum Purina certified Rabbit chow f5322
- Water: ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23°C
- Humidity (%): 42-74%
- Photoperiod (hrs dark / hrs light): 12 hour light/12 dark cycle

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: The back of the abdomen
- % coverage: approx. 10%
- Type of wrap if used: Saran wrap and Elastoplast tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes with wet disposable towels (not washed) as thoroughly as possible without irritating the skin
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000mg/kg
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

4 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: hourly for first 6 hours after dosing, then daily for dermal irritation, and twice daily for clinical signs and mortality
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None observed

Clinical signs:

other: All animals appeared normal throughout the study duration

Gross pathology:

The skin of the test area was thickened in one of the males and two of the females

Average body weights (g)

Dose level (mg/kg)	Initial	Day 7	Terminal	Mortality (number dead/number dosed)
Male
2000	2391	2500	2696	0/2
2000	2326	2385	2573	0/2
Female
2000	2495	2456	2698	0/2
2000	2389	2450	2669	0/2

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal median lethal dose (LD50) of the test item in the male and female New Zealand white rabbit strain was estimated to be greater than 2000 mg/kg body weight for both sexes. It did not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

Executive summary:

The acute dermal toxicity of light catalytic cracked distillate was tested in male and female New Zealand white rabbit using a method similar to the OECD Guideline for Testing of chemicals 402. Dosage levels were 2000 mg/kg for both male and females. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. At dose level 2000 mg/kg there was no mortality, no signs of systemic toxicity noted during the observation period and the animal showed expected gains in body weight over the observation period. No mortality was observed and at necropsy one of the males and 2 females showed thickened skin.The acute oral median lethal dose (LD50) of the test item in the male and female male and female New Zealand white rabbit was estimated to be greater than 2000 mg/kg body weight. It did not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

The acute toxicity: oral of the registered substance was determined in accordance with the OECD Guideline for Testing of chemicals 420. Following a sighting test at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test item at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. At dose level 300 mg/kg there was no mortality, no signs of systemic toxicity noted during the observation period, the animal showed expected gains in body weight over the observation period and no abnormalities were noted at necropsy. Based on the results at a dose level of 300 mg/kg, a dose level of 2000 mg/kg body weight was investigated. At dose level 2000 mg/kg there was no mortality, all animals showed expected gains in body weight and no abnormalities were noted at necropsy. Hunched posture and red/brown staining around the mouth and snout were noted in the initial animal treated at a dose level of 2000 mg/kg. There were no other signs of systemic toxicity noted. The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight.

The acute toxicity: inhalation of the registered substance was determined using a method similar to age OECD Guideline for Testing of chemicals 403. Inhalation of the aerosolized read-across substance by male and female rats at a TWA concentration of about 5.1mg/l for 4 hours was acutely toxic, resulting in the death of three of 5 males and one of 5 females within a couple days of exposure. All the animals showed some pharmacotoxic signs during the first few post exposure days and these were more severe in females. Histopathalogic lesions of the lung were interpreted to have resulted from exposure to a deep irritant, but surviving animals showed recovery. Since 4 deaths occurred at this trial level exposure, phase II was carried out at a target dose level of 0,2.5, 3.5, 6.25 and 7.5mg/l. Measured TWA concentrations ranged from 2.34 to 7.29mg/l. One animal died at each of the two lower test compound level, while all 10 rats exposed to the highest level died 1 to 2 days post exposure, with intermediate numbers succumbing at the other dose levels. Gross and histologic lesions seen in the animals that died mirrored those seen in phase I. The combined male and female data gave a value of 4.65mg/l for the LC50, with a 95% confidence limits of 3.89 to 5.55mg/l.

The acute dermal toxicity of light catalytic cracked distillate was tested in male and female New Zealand white rabbit using a method similar to the OECD Guideline for Testing of chemicals 402. Dosage levels were 2000 mg/kg for both male and females. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. At dose level 2000 mg/kg there was no mortality, no signs of systemic toxicity noted during the observation period and the animal showed expected gains in body weight over the observation period. No mortality was observed and at necropsy one of the males and 2 females showed thickened skin. The acute oral median lethal dose (LD50) of the test item in the male and female male and female New Zealand white rabbit was estimated to be greater than 2000 mg/kg body weight.

Justification for selection of acute toxicity – oral endpoint
Study was conducted by a GLP accredited laboratory using OECD Testing Guideline 420.

Justification for selection of acute toxicity – inhalation endpoint
Study was conducted by a GLP accredited laboratory using a method similar to OECD Testing Guideline 403 and meets acceptable scientific standards

Justification for selection of acute toxicity – dermal endpoint
Study was conducted by a GLP accredited laboratory using a method similar to OECD Testing Guideline 402 and meets acceptable scientific standards

Justification for classification or non-classification

The acute oral median lethal dose (LD50) of the registered substance in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight. The test item did not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

The acute inhalation median lethal dose (LD50) of the read-across substance in the male and female Sprague-Dawley rat strain was estimated to be 4.65mg/l for both sexes. The test substance meets the criteria for classification as Acute Tox 3 according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

The acute dermal median lethal dose (LD50) of the read-across substance in the male and female New Zealand white rabbit strain was estimated to be greater than 2000 mg/kg body weight. The test item did not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.