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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:
supporting study
Study period:
2006-04-19 to 2006-06-14
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
GLP, followed OECD guidelines, well conducted with minor deviation: bodyweights at day 1 and 3 were not recorded.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Bodyweights at day 1 and 3 were not recorded.
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Test material form:
liquid
Details on test material:
Batch No.: 049807
Purity: 67.2% (sum of the three main constituents)
Name of test material (as cited in study report): TERPINEOL MULTICONSTITUENT
Physical state: colourless liquid
Storage conditions: +2°C to +8°C, under nitrogen and protected from light
Expiry date: 30 November 2017

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margarate, Kent
- Age at study initiation: between 8 and 12 weeks old
- Weight at study initiation: between 250 g and 350 g
- Housing: housed in groups of 5 by sex in solid-floor polypropylene cages with stainless steel lids
- Diet (e.g. ad libitum): EU rodent Diet 5LF2, BCM IPS Limited, London, UK (ad libitum)
- Water (e.g. ad libitum): normal drinking water (ad libitum)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2006-04-19 To: 2006-06-14

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: concentric jet nebuliser (Radleys, Saffron Walden, Essex, UK)
- Exposure chamber volume: cylindrical chamber with the volume of approximately 30 L: 28 cm diameter x 50 cm high
- Method of holding animals in test chamber: each rat was individually held in a tapered, polycarbonate restraining tube fitted into a single tier of the chamber and sealed by means of rubber "O" ring
- Source and rate of air: compressed air, rate of flow is at 45 L/min providing 90 air changes per hour
- Method of conditioning air: water trap and respiratory quality filters
- System of generating particulates/aerosols: concentric jet nebuliser (Radleys, Saffron Walden, Essex, UK)
- Method of particle size determination: Marple Personal Cascade Impactor (Schaefer Instruments Ltd, Oxon., UK)
- Treatment of exhaust: with high efficiency filter

TEST ATMOSPHERE
- Brief description of analytical method used: the actual concentrations of test material were measured off-line by high performance liquid chromatography. The test atmospheres were sampled after theoritical chamber equilibration and then approximately thirty minute intervals during the exposure period (see table 1).
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: three times during the exposure period using a Marple Personal Cascade Impactor
- Mean MMAD (Mass median aerodynamic diameter): 2.78 µm

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
5 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: at hourly interval during exposure, one hour after termination of exposure, and subsequently once daily for fourteen days. Bodyweights were recorded prior to the treatment on the day of exposure and on days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: The respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy and local toxicity
Statistics:
None

Results and discussion

Preliminary study:
No data
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4.76 mg/L air (analytical)
Exp. duration:
4 h
Mortality:
No mortality
Clinical signs:
Signs of hunched posture and pilo-erection were seen in animals for short periods on removal from the chamber following 4-hour inhalation. Wet fur was recorded both during and for a short period after exposure. Increased respiratory rate, noisy respiration and ataxia were noted in all animals. Frequent instances of increased respiratory rate and occasional instances of decreased respiratory rate were noted.
One day after exposure all animals exhibited hunched posture and pilo-erection. By Day 2 one animal exhibited fur loss. Further animal exhibited
fur loss on Day 12 post-exposure.
Body weight:
Variations in bodyweight gain were seen for female animals during the study.
One male animal showed a reduced bodyweight gain during Week 1 but recovered to show normal development during Week 2.
Gross pathology:
No macroscopic abnormalities were detected among animals at necropsy.
Other findings:
No data

Any other information on results incl. tables

Table 1: Exposure Chamber Atmosphere Concentration

Duration of Exposure (minutes)

Volume of Air Sampled

(L)

Chamber Flow Rate (L/min)

Atmosphere Concentration (mg/L)

2

4

45

3.00

30

4

45

5.96

59

4

45

0.00

90

4

45

5.52

117

4

45

5.78

151

4

45

5.53

180

4

45

5.75

210

4

45

5.64

233

4

45

5.63

Mean achived atmosphere concentration (mg/L) = 4.76

Standard deviation = 2.00

Table 2: Individual body weights

Mean Achieved Atmospere

Concentration

(mg /L)

Animal Number and Sex

Body weight (g) on Day

 

 

 

 

 

0                                    7                     14

Increment (g) During Week

 

 

 

 

1                                  2

 

 

 

 

4.76

1 Male

355

371

395

16

24

2 Male

357

373

406

16

33

3 Male

376

379

410

3

31

4 Male

339

348

369

9

21

5 Male

380

392

436

12

44

6 Female

248

252

248

4

4

7 Female

267

278

291

11

13

8 Female

262

255

258

-7

3

9 Female

237

240

259

3

19

10 Female

239

242

247

3

5

Applicant's summary and conclusion

Interpretation of results:
other: non toxic
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
No deaths occured in a group of ten rats to a mean achieved atmosphere concentrations of 4.76 mg/L for four hours.
It was therefore concluded that acute inhalation median lethal concentration 4 h LC50 of Terpineol multiconstituent was greater than 4.76 mg/L.
Executive summary:

In an acute inhalation toxicity study performed according to the OECD guideline 403, groups of rats (Sprague-Dawley, 5/sex) were exposed by nose-only inhalation to Terpineol multiconstituent for 4 hours at a mean concentration of 4.76 mg/L. The mass median aerodynamic diameter (MMAD) of the Terpineol multiconstituent aerosol was 2.78 µm and approximately 66.3% of the particulates were considered as inhalable (< 4 µm aerodynamic diameter).

Animals were then observed for 14 days.

Clinical signs as exagerated breathing were evident for all test rats from 30 minutes during the exposure and immediately post exposure, persisting for most animals to day 4. Gasping and noisy breathing were noted for a proportion af animals post-exposure, the latter sign persisting in one male to Day 4 of the observation.

One male animal had reduced body weight gain during Week 1 but recovered to show normal development during Week 2.Variations in body weight gain were seen in females but were considered not to be significant.

No mortality occurred: LC50 is higher than 4.76 mg/L.