Tar bases, coal, lutidine fraction

Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Tar bases, coal, lutidine fraction

EC Number:

293-766-2

EC Name:

Tar bases, coal, lutidine fraction

Cas Number:

91082-52-9

IUPAC Name:

Tar bases, coal, lutidine fraction

Test material form:

liquid

Test animals

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

Administration / exposure

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).

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

236 mg/kg bw

Based on:

test mat.

95% CL:

190 - 293

Effect levels 2

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.

Applicant's summary and conclusion

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.