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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1967
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
No information on housing conditions of animals, body weight of animals not recorded during the study
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1967

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
no information on housing conditions of animals, body weight of animals not recorded during the study
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Turpentine

Test animals

Species:
rat
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 140-200 g


Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Glass cylinder
- Exposure chamber volume: 42 mm * 30 cm
- Pressure in air chamber: 3 mm of water

TEST ATMOSPHERE
- Brief description of analytical method used: 0.4-0.5 mL of sample were withdrawn with a gas-tight syringe and injected into a hydrogen-flame gas chromatograph.
- Samples taken from breathing zone: yes




Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
>= 1 - 6 h
Concentrations:
- 12.6-15.7; 15.8-19.8; 19.9-25.0 and 25.1-31.5 mg/L for 1 hour exposure
- 18-22 mg/L (2 hours exposure); 15-19 mg/L (4 hours exposure) and 7; 8-9; 10-11 and 13-17 mg/L (6 hours exposure)
No. of animals per sex per dose:
10-19 animals per concentration
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 1 week
- Frequency of observations: Turpentine concentration in rat tissue was determined after 15, 30, 60 mins and 2 hours after exposure
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, organ-body weight ratio, distribution and concentration of turpentine in tissues
Statistics:
All LC50 calculations were done by the Litchfield-Wilcoxon (1949) method.

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
male
Dose descriptor:
LC50
Effect level:
13.7 mg/L air (nominal)
Based on:
test mat.
95% CL:
>= 11.1 - <= 14.8
Exp. duration:
4 h
Mortality:
- 8.3% (at 12.6-15.7mg/L); 25.0% (at 15.8-19.8mg/L); 92.3% (at 19.9-25.0mg/L) and 90.0% (at 25.1-31.5 mg/L) at 1 hour exposure of turpentine concentration
Clinical signs:
other: Convulsions and apnea; increase in respiratory rate and decrease in tidal volume
Body weight:
No data
Gross pathology:
Organ body-weight and lesions noticed in lungs were similar in type and extent to those found among controls

Other findings:
- Lung concentrations were higher 30 minutes after 1 and 2 hours after exposure, than after 15 minutes. All tissues, except lung, followed a typical exponential decay curve
- Brain and spleen had the highest concentrations immediately and 60 minutes after exposure

Any other information on results incl. tables

Table 1: Results of a single 1-hour exposure of rats to different concentrations of turpentine vapor

Range of concentrations (mg/L)

Logarithm of difference within range

Mean of range

Logarithm of difference between means

mortality (%)

12.6-15.7

0.1

14.5

8.3

15.8-19.8

0.1

17.1

0.072

25

19.9-25.0

0.1

21.9

0.107

92.3

25.1-31.5

0.1

27.7

0.101

90

 Table 2: Summary of LC50s for rats for various periods of exposure to turpentine vapor

Duration of exposure (hours)

LC50 (mg/L)

Fiducial limits (mg/L)

Slope

Fiducial limits

1

16.9

17.5-22.7

1.24

1.12-1.36

2

16.6

15.9-17.9

1.19

1.12-1.26

4

13.7

11.1-14.8

1.23

1.12-1.35

6

11.7

10.6-12.7

1.21

1.11-1.32

 

Table 3: Concentration of turpentine in tissues of rats at various intervals after a 1-hour or a 2-hour exposure to vapor of turpentine

Tissue

Mean recovery (%)

Concentration after 1 hour exposure (µg/g)

Concentration after 2 hour exposure (µg/g)

Zero time

15 min

30 min

60 min

Zero time

15 min

30 min

60 min

 Brain 

 25 

 160 

 63 

 49 

 20 

 127 

 47 

 21 

 15 

 Spleen 

 50 

 214 

 127 

 39 

 19 

 94 

 32 

 15 

 17 

 Kidney 

 35 

 146 

 58 

 26 

 0 

 97 

 26 

 8 

 12 

 Liver 

 15 

 167 

 43 

 33 

 0 

 157 

 34 

 17 

 8 

 Lung 

50

 101 

 0 

 26 

 0 

 54 

 20 

 25 

 7 

 Blood 

 65 

 24 

 16 

 8 

 1 

 4 

 0.4 

 0.7 

 0.9 

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the test conditions, the inhalation LC50 for turpentine was found to be 13.7 mg/L/4 hours in rats and therefore it is classified as “R20 Harmful by inhalation” according to the annex VI of the Directive 67/548/EEC and category 4 according to the CLP Regulation (EC) N° (1272-2008).
Executive summary:

In an inhalation acute toxicity study performed following a method similar to OECD guideline 403, groups of male rats (10-19/concentration) were exposed to turpentine vapors at concentrations of 12.6-15.7; 15.8-19.8; 19.9-25.0 and 25.1-31.5 mg/L for 1 hour, 18-22 mg/L for 2 hours, 15-19 mg/L for 4 hours and 7; 8-9; 10-11 and 13-17 mg/L for 6 hours. Surviving animals were then observed for mortality and clinical signs of toxicity for one week and were all macroscopically necropsied which included measurement of organ-bodyweight ratios and distribution and concentration of turpentine in tissues.

 

8.3, 25, 92.3 and 90% mortalities were observed when animals were exposed to turpentine vapors for 1 hour at various concentrations of 12.6-15.7, 15.8-19.8, 19.9-25.0 and 25.1-31.5 mg/L, respectively. Deaths were always preceded by convulsions and sudden apnea but these were not always followed by death. Increase in respiratory rate and decrease in tidal volume were noticed in exposed animals. Tissue distribution of turpentine in rats showed that brain and spleen had the highest concentrations immediately and 60 minutes after exposure. Organ body-weights and lesions noticed in lungs were similar in type and extent to those found among controls. The 4 hours LC50 for turpentine vapors was calculated to be 13.7 mg/L.

 

Under the test conditions, the inhalation LC50 for turpentine was found to be 13.7 mg/L/4 hours in rats and therefore it is classified as “R20 Harmful by inhalation” according to the annex VI of the Directive 67/548/EEC and category 4 according to the CLP Regulation (EC) N° (1272-2008).