Creosote oil, acenaphthene fraction

Endpoint summary

Description of key information

No acute toxicity after single oral, dermal and inhalational administration to rats, based on experimental data on wash oil itself, single components, and structure-analogous compounds.

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

Study period:

19 Aug. - 03 Sep. 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted 24.2.1987

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: TOP VELAZ s.r.o., Koleč subsidiary
- Age at study initiation: 6 - 7 weeks
- Weight at study initiation: males: 193 g (range: 170 - 208 g) / females: 157 g (range: 150 - 165 g)
- Fasting period before study: ~20 h before treatment
- Housing: conventional, 5 per sex
- Diet: from 30 min post-application
- Water: ad libitum
- Acclimation period: >= 5 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: From: To:

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

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: 2x/d (day 1 and 2), then 1x/d
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Mortality:

none

Clinical signs:

other: Hunched, lateral or prone posture, apathy, inappetence, cyanotic or pale skin and ischemic mucous membranes recovery within 2 d

Gross pathology:

Changes in the lung, more pronounced in female rats: focal emphysema, point-shaped dark-red foci
(indicating to vascular disorder expressed by ischemia peripheric tissues and organs (see lung) probably following a shock-like response).

Table 1: Male body weights (g) – 2000 mg/kg

Animal No.	Before administration	Day 8	Day 15	Increment
1	203.7	240.9	259.8	56.1
2	186.8	214.9	237.3	50.5
3	195.5	222.8	245.7	50.2
4	170.1	199.8	228.8	58.7
5	207.8	238.6	267.9	60.1
Average	192.8	223.4	247.9	55.1

Table 2: Female body weights (g) – 2000 mg/kg

Animal No.	Before administration	Day 8	Day 15	Increment
1	156.3	173	188.3	27
2	150.4	171	175.3	24.9
3	158.3	172	183.1	24.8
4	164.9	189	205.6	40.7
5	153.2	168	182.9	29.7
Average	156.6	174	187	29.4

Table 3: Pathological examination of the male and female rats – 2000 mg/kg

Animal No.	Autopsy finding
	males	females
1	No macroscopic changes	Lungs – dark-red dot-like foci
2	Lungs – emphysematous foci	Lungs – emphysematous foci
3	Lungs – dark-red dot-like foci	Lungs – dark-red dot-like foci
4	No macroscopic changes	Lungs – dark-red dot-like foci
5	No macroscopic changes	Lungs – dark-red dot-like foci

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study, limited documentation, acceptable for assessment of sub-lethal effects

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

: male animals only, no post-exposure observation, lethal doses not technically attainable, additional testing (neurotoxic effects)

Principles of method if other than guideline:

The focus of the study was laid on test substance induced depression of CNS functions, thus allowing for the evaluation of sub-lethal effects.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: IMP: DAK outbred stock
- Weight at study initiation: 250 - 300 g
- Housing: wire-mesh stainles steel cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week, used within 4 weeks after arrival

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 25
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: dynamic inhalation chamber
- Exposure chamber volume: 0.25 m3
- Air change 12 - 15x
- Method of holding animals in test chamber:
- Source and rate of air:
- Method of conditioning air:
- System of generating particulates/aerosols: Vapours were generated by heating the solvent in a washer to 85 °C.
- Method of particle size determination: none
- Treatment of exhaust air:
- Temperature, humidity, pressure in air chamber:

TEST ATMOSPHERE
- Brief description of analytical method used:
- Samples taken from breathing zone: yes/no

VEHICLE
- Composition of vehicle (if applicable):
- Concentration of test material in vehicle (if applicable):
- Justification of choice of vehicle:
- Lot/batch no. (if required):
- Purity:

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:

Analytical verification of test atmosphere concentrations:

yes

Remarks:

GC FID, every 30 min

Duration of exposure:

4 h

Concentrations:

nominal: 150 - 500 mg/m3
1-MN - mean analytical concentrations: 152, 253, and 407 mg/m3 (the latter maximally attainable)
2-MN - mean analytical concentrations: 229, 325, and 522 mg/m3 (the latter maximally attainable)

No. of animals per sex per dose:

10 - 20

Control animals:

yes

Details on study design:

- Duration of observation period following administration: < 2 d
- Frequency of observations and weighing:
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, behaviour, pain tolerance

Statistics:

Kruskal-Wallis test for evaluating the decrease in the sensitivity to pain.

Sex:

male

Dose descriptor:

LC0

Effect level:

> 404 mg/m³ air (analytical)

Based on:

test mat.

Remarks:

1-MN

Exp. duration:

4 h

Remarks on result:

other: concentration maximally attainable

Sex:

male

Dose descriptor:

LC0

Effect level:

> 522 mg/m³ air (analytical)

Based on:

test mat.

Remarks:

2-MN

Exp. duration:

4 h

Remarks on result:

other: concentration maximally attainable

Sex:

male

Dose descriptor:

other: NOAEC (pain sensitivity)

Effect level:

152 mg/m³ air (analytical)

Based on:

test mat.

Remarks:

1-MN

Exp. duration:

4 h

Remarks on result:

other: Test for central-nervous effects

Sex:

male

Dose descriptor:

other: NOEC (pain sensitivity)

Effect level:

229 mg/m³ air (analytical)

Based on:

test mat.

Remarks:

2-MN

Exp. duration:

4 h

Remarks on result:

other: Test for central-nervous effects

Sex:

male

Dose descriptor:

other: NOAEC (balance reflexes)

Effect level:

404 mg/m³ air (analytical)

Based on:

test mat.

Remarks:

1-MN

Exp. duration:

4 h

Remarks on result:

other: Test for central-nervous effects

Sex:

male

Dose descriptor:

other: NOAEC (balance reflexes)

Effect level:

522 mg/m³ air (analytical)

Based on:

test mat.

Remarks:

2-MN

Exp. duration:

4 h

Remarks on result:

other: Test for central-nervous effects

Mortality:

none

Clinical signs:

other: no details

Body weight:

not applicable

Gross pathology:

not performed

Other findings:

Other observations:
1. Rotarod test (according to Kaplan and Murphy 1972):
No statistically significant influence on performance,
but 1/10 animals of the high-dose 2-MN group failed. (n = 10 per group)

2. Pain tolerance test (hot plate):
A statistically significant concentration-related influence on the paw-lick response was observed (see below).

Latency of the paw-lick response (hot-plate behaviour) in rats exposed to 1- or 2 -Methylnaphthalene, respectively

(Report, Table 3 and 4):

Group [mg/m^3]	Animal number	Latency of response [sec]	Mean decrease in pain sensitivity [%] #
1-Methylnaphthalene
Control	50	10.2 ±2.3	0
152	10	12.8 ±2.9	4.8
253	20	24.8 ±15.9 *	29
407	20	36.1 ±18.6 *	51.8
2- Methylnaphthalene
Control	20	10.5 ±2.6	0
229	10	13.9 ±3.3	6.8
352	10	25.7 ±6.3 *	30.7
525	20	33.3 ±19.9*	46.0

* Statistically significant difference from control: p =< 0.001

# Latency elongation to 60 sec over the control was taken as 100 % decrease in pain sensitivity

Interpretation of results:

other: not classifiable

Executive summary:

1 -Methyl- and 2 -methylnaphthalene vapours were not lethal to rats exposed for 4 h to concentrations that were maximally attainable (407 and 522 mg/m3, respectively). They produced significant CNS depression shown by concentration-related decrease in the pain tolerance. The NOAECs for this sublethal effect were approx. 150 and 200 mg/m3 for 1 -MN and 2 -MN, respectively.

No significant but only slight impairment of the trained rotarod performance was observed with 1 of 10 failures in the high-dose 2 -MN group.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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

For creosote oil, acenaphthene fraction (wash oil) itself, only data on oral acute toxicity are available. In addition, oral acute toxicity was also tested with naphthalene and 2-methylnaphthalene. For inhalation exposure, data on 1- and 2-methylnaphthalene were identified. Dermal acute toxicity is covered by data originating from a study with the closely related tar oil creosote.

Naphthalene and methylnaphthalenes are major constituents amounting to about 40% of total wash oil (typical concentration). Due to their relatively high vapour pressure, they are well suited to represent the inhalation acute toxicity of wash oil. Creosote is closely related to wash oil with major constituent the same as in wash oil. Small differences exist for the concentration of methylnaphthalenes (somewhat lower) and of phenanthrene to fluoranthene (somewhat higher) due to a slightly different distillation range (200 to 355°C for creosote compared to 210 to 300°C for wash oil).

The acute toxicity tests did not show any relevant toxicity. Wash oil itself showed no acute toxicity after single oral administration to rats: LD50 > 2000 mg/kg bw. LD50 values for naphthalene (> 2000 mg/kg bw) and 2-methylnaphthalene (3710 mg/kg bw) confirm the low acute oral toxicity demonstrated for wash oil itself.

No lethal exposure concentration could be attained on inhalation exposure of rats to 1- and 2 -methylnaphthalene, major components in wash oil. Maximum achievable concentrations in the study (404 and 522 mg/m³ for 1- and 2-methylnaphthalene) correlate well with the saturated vapour concentration (404 and 522 mg/m³) calculated based on vapour pressure of 1- and 2-methylnaphthalene (7.2 and 9.1 Pa, respectively).

Creosote failed to produce sub-lethal and lethal effects in rats receiving the maximum dermal dose of 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
Study with wash oil (creosote oil, acenaphthene fraction - CAS no. 90640-84-9)

Justification for selection of acute toxicity – inhalation endpoint
Study with focus on sub-lethal effects (related to 1- and 2-methylnaphthalene, two major wash oil constituents), no lethal effects observed up to the maximal achievable air concentration (similar to saturated vapour concentration)

Justification for selection of acute toxicity – dermal endpoint
Study with structure-related tar oil creosote (CAS no. 8001-58-9)

Justification for classification or non-classification

Based on experimental evidence, no classification required (LD50 values clearly above classification criteria). For inhalation exposure, no lethality was observed at the maximum obtainable vapour concentration of two of the most volatile constituents of wash oil with an acute toxicity estimated to be representative of total wash oil.