Distillates (coal tar), heavy oils

Endpoint summary

Description of key information

No acute toxicity was observed after single oral, dermal and inhalational administration of the supporting substance creosote to rats thus characterising AOH by analogy as not being acutely toxic.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, Germany
- Age at study initiation: no data
- Weight at study initiation: males: 160 – 201 grams, females: 160 – 231 grams
- Housing: 5 rats per cage (Macrolon)
- Fasting period before study: 16 h
- Diet: ad libitum until 16 h pre-application and continued from 4 h post-application
- Water: ad libitum
- Acclimation period: =< 7 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +-2
- Humidity (%): 50 - 85
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg

Doses:

3138; 3668; 4184; 5230 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 15 and 45 min, 1, 2 and 3 h, 6 h, 24 and 48 h, 3 and 5 d p.a
Frequency of weighing: day 0 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Probit analysis according to Finney DY (1971)

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 030 mg/kg bw

95% CL:

3 642 - 4 505

Mortality:

see below "Remarks on results..."

Clinical signs:

other: Dose-related increase in apathy, discoordination, anormal posture, cyanosis, piloerection, and slightly reduced respiration

Gross pathology:

No particular organ effects reported in deceased and sacrificed animals. No significant macroscopic abnormalities were found at necropsy.
Residues of test material were found in the gastro-intestinal tract of moribund and deceased animals.

MORTALITY

Dose[mg/kg]	24 h		48 h		3-14 days		Mortality (%)
	Male	female	Male	female	Male	female	Male	female
3138	0/5	0/5	0/5	1/5	0/5	1/5	0	20
3668	0/5	1/5	1/5	2/5	1/5	2/5	20	40
4184	0/5	2/5	2/5	4/5	2/5	4/5	40	80
5230	1/5	4/5	3/5	5/5	4/5	5/5	80	100

The oral LD₅₀ for creosote in rats was 3500 – 4000 mg/kg bw for males and females.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 030 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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Sprague-Dawley derived Crl:CD® BR VAF/Plus®

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
- Age at study initiation: 53 – 75 days
- Weight at study initiation: males: 234 – 283 g, females: 192 – 216 g

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

MMAD +-GSD [µm]:
5000 mg/m³: 3.4 +-1.89 (2.5% of particles ≤ 1 µm diameter)
600 mg/m³: 1.3 +-1.64 (29% of particles ≤ 1 µm diameter)

Analytical verification of test atmosphere concentrations:

yes

Remarks:

GC-FID after sampling (9 key aromatics quantified (approx. 50 % of creosote), then result extrapolated to total creosote by using a factor of 1.64.

Duration of exposure:

4 h

Concentrations:

600, 5000 mg/m^3 (analytical)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

--

Sex:

male/female

Dose descriptor:

discriminating conc.

Effect level:

5 000 mg/m³ air

Based on:

test mat.

Remarks:

analytical (gravimetric)

Exp. duration:

4 h

Mortality:

No deaths occurred at maximum dose.

Clinical signs:

other: 5000 mg/kg: Directly after exposure, 9/10 animals with reduced activity. Three males and one female showed increased salivation. During the 14-day post-exposure period, five males and four females exhibited decreased activity. 60

Body weight:

5000 and 600 mg/kg: bw gain depressed, persisted for 14 days post exposure.

Gross pathology:

No significant macroscopic abnormalities were found at necropsy.

Table A6_1-1.               Table for Acute Toxicity (inhalation)
Dose[mg/m^3air]	Toxicological results*	Duration of clinical signs	Time of death	Mortality (%)	Particles£5mm (%)
males
600	0/2/5	4h – 14d	-	-	99
5000	0/5/5	4h – 14d	-	-	53
LC50value > 5000 mg/m^3air (aerosol)
females
600	0/0/5	4h – 14d	-	-	99
5000	0/4/5	4h – 14d	-	-	53
LC50value > 5000 mg/m^3air (aerosol)

*number of dead animals / number of animals with clinical signs of toxicity / total number of animals

Conclusions:

Based on the results of this study, the four-hour LC50 for Creosote P1/P13 was greater than 5000 mg/m³.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

5 000 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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

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: Iffa Crédo, 69210 L´Arbresle, France
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: males: 258 ±11grams, females: 222 ±5 grams
- Fasting period before study: none
- Housing: polycarbonte cage, 1 animal per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: >= 5 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +-3
- Humidity (%): 50 +-20
- Air changes (per hr): approx. 13
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 30 - 35 cm2
- % coverage: about 10 % of the animals´ total surface.
- Type of wrap if used: gauze and bandage semiocclusive

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.91 ml/kg bw

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: day 0, 5, 8, and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

not applicable

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

none

Clinical signs:

other: No particular findings

Gross pathology:

No local reactions at the site of application / No abnormalities observed following macroscopic examination of organs

Other findings:

none

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

No data on acute toxicity is available for the substance distillates (coal tar), heavy oils (anthracene oil high (> 50 ppm) BaP, AOH) itself. Data obtained originate from the closely related tar oil creosote. Due to the similar production process (fractionated distillation of coal tar using overlapping conditions), composition of both substances correspond to each other. Major components are mid-range PAH for both substances (3- and 4-ring PAH) with some additional 2-ring PAH in creosote but not in AOH.

As acute toxicity of smaller size PAH is comparable, lack of 2-ring PAH in AOH will not result in evident differences in the acute toxicity of both substances. The acute toxicity of both materials can be considered to be similar. Therefore, creosote is used as supporting substance in characterising the acute toxicity of AOH.

Acute toxicity of creosote is demonstrated to be low: LD50(oral, rat) ca. 4000 mg/kg bw, LD50(dermal, rat) > 2000 mg/kg bw, discrimination dose (inhalation, rat) 5000 mg/m³.

Based on data of the supporting substance creosote, AOH is characterised to show no or only week acute toxicity not relevant for classification.

Justification for classification or non-classification

Based on experimental evidence, no classification required (LD/LC 50 values clearly above classification criteria of Regulation (EC) No 1272/2008).