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Description of key information

The acute oral toxicity of Tarwood was investigated in a study in rats that was performed in accordance with the requirements of the following guidelines and test methods:
- OECD GUIDELINES FOR TESTING OF CHEMICALS 423 (17th December 2001)
- Council Regulation (EC) No 440/2008 (30 May 2008),
- Regulation (EC) No. 1272/2008

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:
21.01.2014 - 06.02.2014
Reliability:
1 (reliable without restriction)
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: Crl:(WI)BR rats
Sex:
female
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Doses:
2000 mg/kg bw
Control animals:
not specified
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw

see study report for further information

Interpretation of results:
not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
The method used, was not intended for the precise calculation of a precise LD50 value. The test item was ranked into classes of Globally Harmonized Classification System (GHS) described in the OECD Guideline No. 423.
Executive summary:

An acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level, therefore treatment with 2000 mg/kg bw was repeated on further three female rats. No animal died in the second step, too, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423 (presented in Appendix VII) was met. Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out on the 15th day after the treatment.

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:
experimental study
Adequacy of study:
key study
Study period:
23 August 2019 - 20 September 2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 433 draft (Acute Inhalation Toxicity: Fixed Concentration Procedure) (not officially approved)
Version / remarks:
2018
Deviations:
not specified
GLP compliance:
yes (incl. QA statement)
Test type:
fixed concentration procedure
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Raleigh, North Carolina 27610
- Age at study initiation: Approximately 9 weeks
- Weight at study initiation: 249.7 g to 265.2 g
- Fasting period before study: not specified
- Housing: Teklad 7070C Certified Diamond Dry Cellulose Bedding, Envigo, Madison, Wisconsin; 2-3 animals per cage; entichment provided
- Diet ad libitum: Teklad Global 16% Protein Rodent Diet (Certified), 2016C, Envigo, Madison, Wisconsin
- Water ad libitum: pot water
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 26 °C
- Humidity (%): 30 to 70%.
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:
AM Morning observation
PM Afternoon observation
RTC Observations upon return to their home cage after exposure
1HrPD Observations 1 hour after exposure
2HrPD Observations 2 hours after exposure
NDD Observations on non-exposure days
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Remarks:
liquid aerosol
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
ca. 2.2 µm
Geometric standard deviation (GSD):
>= 1.78 - <= 1.81
Remark on MMAD/GSD:
MMAAD Gravimetr.: 2.3 (std: 1.77 - 1.82)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:
- Exposure chamber volume:
- Method of holding animals in test chamber:
- Source and rate of air:
- Method of conditioning air:
- System of generating particulates/aerosols:
- Method of particle size determination:
- Treatment of exhaust air:
- Temperature, humidity, pressure in air chamber: 20°C, 56% rel hum.

TEST ATMOSPHERE
- Brief description of analytical method used: HPLC/UV
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle (if applicable): not applicble
- Concentration of test material in vehicle (if applicable): not applicble
- Justification of choice of vehicle: not applicble
- Lot/batch no. (if required): not applicble
- Purity: not applicble

TEST ATMOSPHERE (if not tabulated)


CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: Wood Tar has been evaluated for acute oral toxicity in rats and was found to be non-lethal at 2000 mg/kg. Also, an in vitro evaluation of dermal toxicity was done using human skin and the test item was found to be irritating but not corrosive. On the basis of these results which indicate that the test might have low toxicity, the initial exposure level for this study was selected to be 1.0 mg/L as per the OECD Guidelines (OECD 433, 2018).
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
target: 1,0 mg/L
analytical: 1,6 mg/L
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: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Key result
Sex:
male
Dose descriptor:
LC0
Effect level:
1.6 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
> 1.6 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
not determinable because of methodological limitations
Mortality:
Not occured
Clinical signs:
other: not occured
Body weight:
unchanged
Gross pathology:
No macropathology findings, in one animal testes small bilateral, soft bilateral. Not considered to be an effect of treatment.
Interpretation of results:
study cannot be used for classification
Conclusions:
The presented GLP-inhalation study followed international guidance and no deviations from guideline were reported.
The single reported effect concentration is the starting concentration of a planned series of concentrations, and represents the only achievable concentration of the test item. Therefore it is concluded the reported value represents the NOEC and the LOEC and LOEC and the LC50 must be >1.6 mg/L.
Executive summary:

Sprague-Dawley CD® rats (5 males) were exposed once to Wood Tar by nose-only inhalation of liquid aerosol at 1.0 mg/L of air for 4 hours. After a 14-day observation period the animals were euthanized and necropsied. Parameters evaluated during the study were: viability, clinical observations, body weights and macroscopic observations.

Wood Tar was exposed to rats for 4 hours at 1.6 mg/L based on analytical results. This exposure level was well tolerated and a higher exposure level of 5.0 mg/L was thus planned. However, additional aerosol trials demonstrated that the exposure at the target of 1.0 mg/L was essentially a maximum attainable exposure level. Therefore, the 5.0 mg/L exposure was not conducted and the study was considered completed.

Thus, the LC50 would be estimated to be >1.6 mg/L.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
1 600 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

An oral acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level, therefore treatment with 2000 mg/kg bw was repeated on further three female rats. No animal died in the second step, too, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423 (presented in Appendix VII) was met. Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out on the 15th day after the treatment.

A second study following the inhalation expsoure route was conducted with the only achived test concentration of 1.5 mg/L and did not revealed any effects.

Lethality, Clinical symptoms and Body weight:

No lethality was noted at single oral dose of 2000 mg/kg bw. No clinical symptoms were observed on the day of the treatment and during the 14-day observation period, the general state and behaviour of experimental animals were normal. The body weight development was undisturbed in all animals.

Gross pathology:

All animals survived until the scheduled autopsy on Day 15. All organs of all experimental animals proved to be free of treatment related gross pathological changes.

Evaluation:

The method used is not intended to allow the calculation of a precise LD50 value. The test item was ranked into classes of Globally Harmonized Classification System (GHS) described in the OECD Guideline No. 423 as below:

Dose (mg/kg bw)

Mortality (dead/treated)

LD50(mg/kg bw)

GHS

category

2000

0/6

above 2000

5



Justification for selection of acute toxicity – inhalation endpoint
The inhalation toxicity of Tarwood has been tested on Sprague-Dewley rats following OECD TG 433 in a valid GLP study. At the highest technical achievable concentration of 1.6 mg/L over 4 hours no toxic effects or signs of clinical symptoms have been observed. Therefore is it concluded 1.6 mg/L < LC50 inhalation in rats.

Justification for classification or non-classification

Following OECD GUIDELINE FOR TESTING OF CHEMICALS No 423 Annex 2d no mortality was observed.

No death occurred at 2000 mg/kg bw single oral dose of Tar wood. All female rats in step 1 and step 2 survived.

The acute inhalation test following OECD TRG 433 with 1.6 mg/L over a period of 4 hours in rats did not led to any symptoms, all animals survived.