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Administrative data

Description of key information

An acute oral toxicity study was performed with dipentene multiconstituent. LD50 was found to be greater than 2000 mg/kg bw in rats.

Studies available on d-limonene and l-limonene, two main constituents of Reaction mass of beta-phellandrene and d-limonene and l-limonene, showed dermal LD50 equal to or higher than 5000 mg/kg bw in rabbits.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
The main constituents of dipentene multiconstituent present at concentration above 10% are d-limonène, l-limonène and beta-phellandrene. It has the same main constituents as REACTION MASS OF BETA-PHELLANDRENE AND D-LIMONENE AND L-LIMONENE. Therefore, data on dipentene multiconstituent can be used for extrapolation to REACTION MASS OF BETA-PHELLANDRENE AND D-LIMONENE AND L-LIMONENE. See read-across justification document in section 13.
Reason / purpose:
read-across source
Preliminary study:
Not applicable
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
other: LD50 cut-off
Effect level:
ca. 2 500 mg/kg bw
Based on:
test mat.
Mortality:
1/6 on Day 6
Clinical signs:
- Decrease in spontaneous activity (4/6), muscle tone and righting reflex (3/6); increased salivation and piloerection (3/6) on Day 1; animals recovered to normal at 24 hours post dose.
Body weight:
- 7% decrease in body weight on Day 2 of animal that died on Day 6
- Absence of body weight gain on Day 2, recovered a normal body weight on Day 7
Gross pathology:
- White thinning of the corpus of the animal that died on Day 6
- Thickness (5/5) and white coloration (2/5) of forestomach
Other findings:
None

Table 1: Body weight and weight gain in grams

Animals

Day 0

Day 2

Day 2-Day 0

Day 7

Day 7-Day 0

Day 14

Day 14-Day 0

1

213

198

-15

Dead

Dead

Dead

Dead

2

230

237

7

256

26

285

55

3

207

211

4

245

38

249

42

4

219

225

6

241

22

264

45

5

221

222

1

252

31

268

47

6

225

239

14

263

38

272

47

Mean

219.2

222

2.8

251.4

31

267.2

47.2

Standard deviation

8.3

15.6

9.7

8.7

7.1

13

4.8

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 for dipentene multiconstituent was found to be greater than 2000 mg/kg bw in the Sprague-Dawley rats and therefore it is not classified according to Directive 67/548/EEC and CLP Regulation (EC) N° 1272/2008.
Executive summary:

In an oral acute toxicity study (limit test) performed in accordance with GLP and OECD guideline 423, groups of six Sprague-Dawley female rats received a single oral (gavage) dose of dipentene multiconstituent at 2000 mg/kg bw. Animals were then observed for mortality, body weight and clinical signs of toxicity for 14 days and were all macroscopically necropsied after sacrifice. The observations were compared to historical control data.

One animal died on Day 6 during the study. A decrease in spontaneous activity (4/6), muscle tone and righting reflex (3/6) and increased salivation and piloerection (3/6) was noted on first day of study. All animals recovered to normal behavior at 24 hours post dose. A 7% decrease in body weight on Day 2 was observed in animal that died on Day 6. In surviving animals absence of body weight gain was noted on Day 2 that recovered normal body weight on Day 7. Thickness (5/5) and white coloration (2/5) of forestomach of surviving animals and white thinning of the corpus of the dead animal was noted on necropsy. The oral LD50 was found to be greater than 2000 mg/kg bw in rats.

In accordance with OECD guideline No 423, the LD50 cut-off of the test item may be considered as 2500 mg/kg bw by oral route in the rat.

The oral LD50 for dipentene multiconstituent was found to be greater than 2000 mg/kg bw in the Sprague-Dawley rats and therefore it is not classified according to Directive 67/548/EEC and CLP Regulation (EC) N° 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
D-Limonene is one of the main constituents of multiconstituent substance REACTION MASS OF BETA-PHELLANDRENE AND D-LIMONENE AND L-LIMONENE. Therefore, data on d-limonene can be used for extrapolation to REACTION MASS OF BETA-PHELLANDRENE AND D-LIMONENE AND L-LIMONENE. See read-across justification document in section 13.
Reason / purpose:
read-across source
Preliminary study:
Not applicable
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality
Clinical signs:
No evidence of toxicity; all animals appeared normal at the end of the study
Body weight:
Normal gain in bodyweight
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Dermal reactions:
- Slight erythema in 6, 6, 3 and 1 animals on Days 1, 2, 3 and 4, respectively; moderate erythema in 3 animals on Day 1
- Slight edema in 5, 5, 4 and 1 animals on Days 1, 2, 3, and 4, respectively; moderate edema in 4 and 1 animals on Days 1 and 2
- Complete recovery within 5 days
- No signs of atonia were observed during the study

None

Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal LD50 of d-limonene is greater than 2000 mg/kg bw in rabbits therefore it is not classified according to Directive 67/548/EEC and CLP Regulation (EC) N° 1272/2008.
Executive summary:

In an acute dermal toxicity study (limit test), a group of 10 New Zealand White rabbits were administered a single dermal dose of d-limonene at 5000 mg/kg bw on clipped abraded abdominal skin using an occlusive patch for 24 hours. Animals were then observed for mortality, clinical signs, bodyweights and dermal reactions for 7 days and were all macroscopically necropsied after sacrifice.

 

No deaths occurred throughout the study. Normal body weight gain was observed in all animals. At necropsy, macroscopic examination of main organs showed no abnormalities. Adverse dermal reactions noted were slight to moderate erythema and edema, which completely recovered to normal within five days. The acute dermal LD50 was found to be greater than 5000 mg/kg bw.

 

The acute dermal LD50 of d-limonene is greater than 2000 mg/kg bw in rabbits therefore it is not classified according to Directive 67/548/EEC and CLP Regulation (EC) N° 1272/2008.

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
L-Limonene is one of the main constituents of multiconstituent substance REACTION MASS OF BETA-PHELLANDRENE AND D-LIMONENE AND L-LIMONENE. Therefore, data on l-limonene can be used for extrapolation to REACTION MASS OF BETA-PHELLANDRENE AND D-LIMONENE AND L-LIMONENE. See read-across justification document in section 13.
Reason / purpose:
read-across source
Preliminary study:
Not applicable
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
No
Body weight:
No data
Gross pathology:
No data
Other findings:
- Dermal reactions: moderate redness (3/10 rabbits) and moderate edema (6/10 rabbits)

None

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 for l-limonene is higher than 5000 mg/kg bw in rabbits therefore it is not classified according to Directive 67/548/EEC and CLP Regulation (EC) N° 1272/2008.
Executive summary:

In an acute dermal toxicity study, 10 rabbits were administered a single dermal dose of l-limonene at 5000 mg/kg bw. Animals were then observed for mortality and clinical signs of toxicity for 14 days. No deaths and clinical signs of toxicity occurred during the observation period. Dermal reactions noted were moderate redness (3/10 rabbits) and moderate edema (6/10 rabbits) at the site of application.

 

The dermal LD50 for l-limonene is higher than 5000 mg/kg bw in rabbits therefore it is not classified according to Directive 67/548/EEC and CLP Regulation (EC) N° 1272 /2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw

Additional information

The key study selected for acute oral toxicity endpoint is a study performed with dipentene multiconstituent, according to Guideline

OECD 423. The oral LD50 was found to be greater than 2000 mg/kg in rats.

Two acute dermal toxicity studies were available on d-limonene and l-limonene. All these studies demonstrated oral LD50 greater than 5000 mg/kg bw on rat. Although these studies were old and briefly described, they all show consistent results about these two main constituents of substance Reaction mass of beta-phellandrene and d-limonene and l-limonene.

Justification for classification or non-classification

The acute oral LD50 is higher than 2000 mg/kg bw in rats in a study performed on dipentene multi-constituent, a structurally related substance. All dermal LD50 of dl-limonene, two main constituents of the registered substance, are higher than 2000 mg/kg bw in rabbits. Therefore, Reaction mass of beta-phellandrene and d-limonene and l-limonene does not need to be classified according to Directive 67/548/CEE and the CLP Regulation (EC) No 1272/2008.

For further information on read-across justification, see section 13 "justification of read-across".