Tar bases, coal, lutidine fraction

Endpoint summary

Description of key information

Oral route

Acute oral toxicity, rat, female: LD50 = 971 mg/kg bw (758 - 1245 mg/kg bw, 95% confidence interval)

Acute oral toxicity, rat, male: LD50 = 1239 mg/kg bw (943 - 1629 mg/kg bw, 95% confidence interval)

Inhalation route

Acute inhalation toxicity, rat, female/male: LC50 >3.61 mg/L (no deaths occurred)

Dermal route

Acute dermal toxicity, rat, female: LD50 = 236 mg/kg bw (190 - 293 mg/kg bw, 95% confidence interval)

Acute dermal toxicity, rat, male: LD50 = 316 mg/kg bw (250 - 400 mg/kg bw, 95% confidence interval)

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

- Principle of test: Groups of five male and five female rats received a single oral dose of the test substance. The animals were then observed daily for a period of 14 days.
- Short description of test conditions: Animals received a single oral dose of the test substance of 200, 600, 1000 or 2000 mg/kg, administered by gavage in corn oil at a standard volume of 10 mL/kg.
- Parameters analysed / observed: Animals were checked regularly for mortality and any sign of toxicity. At the end of the study, surviving animals were humanely killed and were examined by necropsy for any macroscopic abnormalities.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Alderley Park SPF albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: colony maintained in the laboratory at Alderley Park, Cheshire, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: not reported
- Weight at study initiation: bodyweight range 221-390 g for males and 198-253 for females
- Fasting period before study: 26 to 24 hours before dosing
- Housing: not reported
- Diet (e.g. ad libitum): not reported
- Water (e.g. ad libitum): not reported
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20-200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: not reported
- Lot/batch no. (if required): not reported
- Purity: not reported

Doses:

200, 600, 1000 and 2000 mg/kg

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights

Statistics:

The acute oral median lethal dose was calculated from the mortality data using logistic regression. Confidence limits were calculated using a likelihood ratio interval (Williams 1986).

Sex:

female

Dose descriptor:

LD50

Effect level:

971 mg/kg bw

Based on:

test mat.

95% CL:

758 - 1 245

Sex:

male

Dose descriptor:

LD50

Effect level:

1 239 mg/kg bw

Based on:

test mat.

95% CL:

943 - 1 629

Mortality:

Three female and one male animal dosed at 1000 mg/kg died or were killed in extremis on Day 1. All animals dosed 2000 mg/kg died or were killed in extremis on Day 1, and nine out of ten deaths were within the first two hours after dosing.

Clinical signs:

other: Significant signs of toxicity were seen in animals dosed at 200 or 600 mg/kg, but all animals had recovered four or five days after dosing. Extreme signs of toxicity (e.g. exophthalmus, piloerection, upward curviture of spine, urinary incontinence, dehydr

Gross pathology:

No macroscopic observations were detected at necropsy.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The substance was found to be acutely toxic to rats after administration by gavage of a single oral dose.

Executive summary:

The acute oral toxicity of the test substance was investigated under non-GLP in a study similar to an OECD guideline study. The experiment is considered relevant, adequate and conclusive.

Groups of five female and five male Alderley Park SPF albino rats, in the bodyweight range from 198-253 g for females and 221-390 g for males, were fasted for a period of 16 to 24 hours before exposure. Preparations of the test substance, in corn oil, were then dosed at a standard volume of 10 mL/kg. Single doses of 200, 600, 1000 and 2000 mg/kg were administered by gavage to separate groups of animals on Day 1. The animals were observed daily up to Day 15. None of the animals receiving a single dose of 200 or 600 mg/kg died. Three female animals and 1 male animal dosed at 1000 mg/kg died on Day 1. All animals dosed at 2000 mg/kg died on Day 1. Significant signs of toxicity were seen in animals receiving 200 and 600 mg/kg, and extreme signs of toxicity were seen in animals dosed at 1000 or 2000 mg/kg. Surviving animals recovered after four to five days. All animals lost weight initially (due to fasting prior to dosing), but all surviving animals had gained weight at the end of the study. No macroscopic observations were made at necropsy.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

971 mg/kg bw

Quality of whole database:

Although not generated under GLP, the available information on the acute oral toxicity of the substance is considered as relevant, adequate and reliable.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

- Principle of test: 10 rats were exposed nose-only to target concentrations of 1.0 or 3.75 mg/L (200 or 750 ppm) of the test substance for a single 4-hour period and then maintained for a 14-day observation period.
- Short description of test conditions: The atmospheres were generated using a concentric jet glass atomiser and Gage cyclone into a 2-tiered PERSPEX exposure chamber. The test substance was delivered to the atomiser using a peristaltic pump.
Ten male and ten female rats (approximately 7 weeks old) were randomly assigned to two experimental groups, each comprising 5 males and 5 females. The animals were exposed to the target concentrations for a single period of 4 hours and then observed over a period of 14 days.
The total particulate concentration of each test atmosphere was measured gravimetrically, but the particle size distribution of the aerosol was not measured because of the low particulate concentrations. The test atmospheres were analysed for the test substance using an adsorption tube containing CARBOTRAP (40-60 mesh) to initially trap the material. The test substance was then thermally desorbed from the tube into a gas chromatograph equipped with a flame-ionisation detector.
- Parameters analysed / observed: Animals were observed for gross abnormalities during exposure and were then given a regular detailed examination after exposure. Bodyweights were also regularly recorded. On day 15, the animals were humanely killed and subjected to a macroscopic examination. Lungs (with trachea), liver and kidneys were removed and weighed and stored in 10% neutral buffered formol saline.

GLP compliance:

no

Test type:

traditional method

Limit test:

no

Species:

rat

Strain:

other: Alpk:APfsD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: colony maintained in the laboratory at Alderley Park, Cheshire, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approximately 7 weeks
- Weight at study initiation: not reported
- Fasting period before study: not reported
- Housing: not reported
- Diet (e.g. ad libitum): not reported
- Water (e.g. ad libitum): not reported
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 2-tiered PERSPEX exposure chamber
- Exposure chamber volume: not reported
- Method of holding animals in test chamber: not reported
- Source and rate of air: not reported
- Method of conditioning air: not reported
- System of generating particulates/aerosols: atmospheres were generated using a concentric jet glass atomiser and Gage cyclone into the exposure chamber
- Method of particle size determination: particle size distribution was not measured because of the low particulate concentrations
- Treatment of exhaust air: not reported
- Temperature, humidity, pressure in air chamber: not reported

TEST ATMOSPHERE
- Brief description of analytical method used: atmospheres were generated using a concentric jet glass atomiser and Gage cyclone into the exposure chamber
- Samples taken from breathing zone: no

VEHICLE
- Not applicable

TEST ATMOSPHERE
- Particle size distribution: not determined

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

1 and 3.75 mg/L (corresponding to 200 and 750 ppm)

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: During exposure and detailed assessment after exposure on Day 1, 2, 3, 8 and 15, on the other days animals were checked
- Frequency of weighing: On days -1, 2, 3, 8 and 15
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LC0

Effect level:

>= 3.61 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

There were no deaths.

Clinical signs:

other: Abnormalities recorded during exposure were salivation, very reduced response to sound, increased breathing depth and decreased breathing rate. Immediately after exposure, other abnormalities seen were reduced righting reflex, reduced stability, reduced h

Body weight:

There was an initial bodyweight loss seen on day 2 in both groups following exposure on day 1, which was greater in animals exposed to 3.61 mg/L. Males and females exposed to 3.61 mg/L and females exposed to 1.05 mg/L also lost weight on day 3. The weight loss in the top dose animals was statistically significant when compared with control rats of the same age and strain. Thereafter the rate of bodyweight gain was similar to that seen in control rats of the same age and strain.

Gross pathology:

There was a slight decrease in liver weight and liver:bodyweight ratio in males exposed to 3.61 mg/L, when compared with control rats of the same strain and age. There were no significant effects on lung weight, kidney weights, lung:bodyweight or kidney:bodyweight ratios. Changes seen at post mortem were part of the normal spectrum of background change in this strain and were not considered to be treatment-related.

Atmosphere analysis

Target concentration (mg/L)	1.0	3.75
Target concentration (ppm)	200	750
Mean achieved gravimetric concentration (mg/L)	0.75x10^-3	4.5x10^-3
Mean achieved gravimetric concentration (mg/L), standard deviation	0.2x10^-3	1.7x10^-3
Mean analysed concentration (mg/L)	1.05	3.61
Mean analysed concentration (mg/L), standard deviation	0.16	0.42

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LC50 value in this inhalation acute toxicity study was >3.61 mg/L.

Executive summary:

The acute inhalation toxicity of the test substance was investigated in a non-GLP study following to a large extent the OECD regulatory guideline. The experiment is considered relevant, adequate and conclusive.

Ten male and ten female rats (approximately 7 weeks old) were randomly assigned to two experimental groups, each comprising 5 males and 5 females. The animals were exposed nose-only to the target concentrations of 1.0 and 3.75 mg/L for a single period of 4 hours and then observed over a period of 14 days. The total particulate concentration of each test atmosphere was measured gravimetrically, but the particle size distribution of the aerosol was not measured because of the low particulate concentratios. The test atmospheres were analysed for the test substance using an adsorption tube containing CARBOTRAP (40-60 mesh) to initially trap the material. The test substance was then thermally desorbed from the tube into a gas chromatograph equipped with a flame-ionisation detector. The mean analysed concentrations were 1.05 mg/L (± 0.16 mg/L) and 3.61 mg/L (± 0.42 mg/L).

No deaths occured during the exposure period or the 14-day exposure period. A number of clinical signs were observed during exposure and on the first days after exposure. The animals had generally recovered by day 2 although abnormal respiratory noise persisted in males of both test groups up to day 5. There was an initial decrease in the bodyweight, buth the rate of bodyweight gain was similar to that seen in control rats of the same age and strain after day 3 post exposure. The only pathological finding was a slight decrease in liver weight and liver:bodyweight ratio in males exposed to 3.61 mg/L, when compared to control rats. Changes seen post mortem were part of the normal spectrum of background change in this strain and were not considered to be treatment-related.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

Although not generated under GLP, the available information on the acute inhalation toxicity of the substance is considered as relevant, adequate and reliable.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

- Principle of test: Groups of five male and five female rats received a single dermal dose of the test substance. The animals were then observed daily for a period of 14 days.
- Short description of test conditions: Animals received a single dermal dose of the test substance of 0.05, 0.15, 0.25 and 0.4 mL/kg. The undiluted test substance was applied to the shorn back of each animal and was kept in contact with the skin for 24 hours under occlusive dressing. At the end of the exposure period, the dressings were removed.
- Parameters analysed / observed: Animals were checked regularly for mortality and any sign of toxicity. At the end of the study, surviving animals were humanely killed and were examined by necropsy for any macroscopic abnormalities.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Alderley Park SPF albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: colony maintained in the laboratory at Alderley Park, Cheshire, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: not reported
- Weight at study initiation: bodyweight range 164-278 g for females and 230-288 g for males
- Fasting period before study: not reported
- Housing: not reported
- Diet (e.g. ad libitum): not reported
- Water (e.g. ad libitum): not reported
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: not reported
- Type of wrap if used: not reported

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): appropriate volumes of the test substance were applied to achieve the envisaged dermal doses

Duration of exposure:

24 hours

Doses:

0.05, 0.15, 0.25 and 0.4 mL/kg (dose levels were converted to mg/kg by applying a factor of 1000).

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights

Statistics:

The acute dermal median lethal dose was calculated from the mortality data using logistic regression. Confidence limits were calculated using a likelihood ratio interval (Williams 1986).

Sex:

female

Dose descriptor:

LD50

Effect level:

236 mg/kg bw

Based on:

test mat.

95% CL:

190 - 293

Sex:

male

Dose descriptor:

LD50

Effect level:

316 mg/kg bw

Based on:

test mat.

95% CL:

250 - 400

Mortality:

None of the animals died following a single dermal dose of 0.05 or 0.15 mL/kg. Three out of five females dosed at 0.25 mL/kg and all ten animals dosed at 0.4 mL/kg died or were killed in extremis.

Clinical signs:

other: No significant signs of toxicity were seen in the animals dosed at 0.05 or 0.15 mL/kg. Moderate irritation effects were seen in some of these animals and persisted for most of the study. Slight signs of toxicity were seen for the first few days in the mal

Gross pathology:

No macroscopic abnormalities were detected during necropsy.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The test substance was found to be acutely toxic to rats when applied as a single dose of undiluted material to the shorn skin and kept under occlusion for 24 hours.

Executive summary:

The acute dermal toxicity of the test substance was investigated under non-GLP in a study similar to an OECD guideline study. The experiment is considered relevant, adequate and conclusive.

Groups of five female and five male Alderley Park SPF albino rats, in the bodyweight range from 164-278 g for females and 230-288 g for males, were used for each dose. Single doses of 0.05, 0.15, 0.25 and 0.4 mL/kg (corresponding to 50, 150, 250 and 400 mg/kg) of undiluted substance were applied to the shorn skin on the back of test animals on Day 1. The animals were observed daily up to Day 15. None of the animals receiving a single dose of 0.05 and 0.15 mL/kg died. Three female animals dosed at 0.25 mL/kg died on Day 1. All animals dosed at 0.4 mL/kg died on Day 1. No significant signs of toxicity were seen at the two lowest doses, but moderate skin irritation was observed that persisted for most of the study. Slight signs of toxicity were seen in males dosed at 0.25 mL/kg for the first four days after exposure, and severe skin irritation occurred that persisted for most of the study. Marked signs of toxicity were seen in the surviving females dosed at 0.25 mL/kg, and slight irritation was also seen in these animals. Signs of toxicity including mydriasis, prostration and breathing abnormalities were seen in animals of the top dose group. All surviving animals gained weight throughout the study. No macroscopic abnormalities were detected at necropsy.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

236 mg/kg bw

Quality of whole database:

Although not generated under GLP, the available information on the acute dermal toxicity of the substance is considered as relevant, adequate and reliable.

Justification for classification or non-classification

The results obtained in the available acute toxicity studies are reliable, relevant and appropriate for the purpose of classification of the substance under the CLP Regulation (EC) No. 1272/2008. Based on the effect concentrations established in the acute toxicity studies, the following classification is applicable:

Oral route: Acute Cat. 4

Inhalation route: Acute Cat. 4

Dermal route: Acute Cat. 3