Registration Dossier

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Administrative data

Description of key information

All available studies show oral LD50 equal to or higher than 3700 mg/kg bw in rats.
All available studies show dermal LD50 equal to or higher than 2000 mg/kg bw in rabbits.


All available studies show inhalation LC50 between 1.05 and 5.07 mg/L in rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
4 800 mg/kg bw
Quality of whole database:
One acute oral toxicity study was available for each of the substances used in the registration dossier of delta-3-carene, i.e. delta-3-carene, alpha pinene and camphene. They showed LD50 of 4800, 3700 and >5000 mg/kg bw, respectively. Although these studies were old and briefly described, they all show consistent results about all these structure-related substances.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Quality of whole database:
The study is GLP compliant and of high quality (Klimisch score = 1).

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
One acute dermal toxicity study was available for each of the substances used in the registration dossier of delta-3-carene, i.e. delta-3-carene, alpha pinene and camphene. They showed LD50 >5000, >5000 and >2500 mg/kg bw, respectively. Although these studies were old and briefly described, they all show consistent results about all these structure-related substances. Morevover, the low dermal toxicity is consistent with and confirmed by the low oral toxicity found with all these substances.

Additional information

One acute oral toxicity study was available for each of the substances used in the registration dossier of delta-3-carene, i.e. delta-3-carene, alpha pinene and camphene. They showed LD50 of 4800, 3700 and >5000 mg/kg bw, respectively. Although these studies were old and briefly described, they all show consistent results about all these structure-related substances.


One acute dermal toxicity study was available for each of the substances used in the registration dossier of delta-3-carene, i.e. delta-3-carene, alpha pinene and camphene. They showed LD50 >5000, >5000 and >2500 mg/kg bw, respectively. Although these studies were old and briefly described, they all show consistent results about all these structure-related substances. Morevover, the low dermal toxicity is consistent with and confirmed by the low oral toxicity found with all these substances.


 


Justification for selection of acute toxicity – oral endpoint
No robust study summary was chosen for this endpoint because a weight of evidence approach was adopted; therefore, it was not possible to select only one of the studies used for this endpoint.

Justification for selection of acute toxicity – inhalation endpoint


A key study was identified (PSL, 2018, rel. 1).


In an acute inhalation toxicity study (Acute Toxic Class Method) performed in accordance with GLP and OECD guideline 436, groups (3/sex) of Sprague Dawley rats were exposed by inhalation route for 4 hours to nose-only at a single exposure. After establishing the desired generation procedures during the pre-test trials,twelve healthy rats were selected for test and equally distributed into two exposure groups (3 males and 3 females per exposure): one exposure group with vapour concentation of 5.07 mg/L and second exposure group at 1.05 mg/L. Chamber concentration and particle size distributions of the test atmosphere were determined periodically during the exposure period.


Animals were then observed for mortality and clinical signs, gross toxicity and behavioral changes at least once daily for 14 days following exposure or until death occured. Bodyweights were recoeded prior to exposure (initial) and again on Days 1, 3, 7 and 14 (terminal) or after death. Necropsies were performed in all animals for macroscopical examination. At the high dose level, the gravimetric chamber and nominal chamber concentrations were 5.07 mg/L and 82.90 mg/L, respectively. The average mass median aerodynamic diameter was estimated to be 2.28 µm based on graphic analysis of the particle size distribution as measured with a 1 ACFM Andersen Ambient Particle Sizing Sampler with an avergae geometric standard deviation of 2.49.
One female rat was found dead at chamber removal and the remaining five animals were euthanized for humane reasons following exposure to the test atmosphere. Prior to death, the euthanized animals were hypoactive and exhibited abnormal respiration, prone posture, and clonic convulsions. Gross necropsy of the decedents revealed discoloration of the lungs and/or distention of the intestines.


At the low dose level, the gravimetric chamber and nominal chamber concentrations were 1.05 mg/L and 15.62 mg/L, respectively. The average mass median aerodynamic diameter was estimated to be 2.32 µm based on graphic analysis of the particle size distribution as measured with a 1 ACFM Andersen Ambient Particle Sizing Sampler with an avergae geometric standard deviation of 1.98. All animals survived at the test item exposure and gained body weight during the study. Four rats were hypoactive and all animals exhibited abnormal respiration and/or ano-genital staining. However, all animals recovered by Day 3 and appeared active and healthy for the remainder of the 14-day observation period. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.


Under the test conditions of this study, the inhalation LC50 (male/female) is between 1.05 mg/L and 5.07 mg/L (LC50 cut-off of 5 mg/L). The test material is classified Category 4 (H332: Harmful if inhaled) according to the Regulation (EC) No. 1272/2008 and of the GHS as the LC50 value is comprised between 1 and 5 mg/L/4h.


 


Justification for selection of acute toxicity – dermal endpoint
No robust study summary was chosen for this endpoint because a weight of evidence approach was adopted; therefore, it was not possible to select only one of the studies used for this endpoint.

Justification for classification or non-classification

Harmonised classification:


The substance has no harmonised classification for acute toxicity according to the Regulation (EC) No. 1272/2008 (CLP).


Self classification:


Acute toxicity via Oral and Dermal route:


For all substances, oral and dermal LD50 are higher than 2000 mg/kg bw in rats and rabbits, respectively, therefore the registered substance does not need to be classified for acute dermal and oral toxicity according to Directive 67/548/CEE and CLP Regulation (EC) N° 1272/2008.


Acute toxicity via Inhalation:


Based on the available data, the substance is classified Acute Tox. (Inhalation) Category 4 (H332: Harmful if inhaled) according to the Regulation (EC) No. 1272/2008 and of the GHS as the LC50 value is comprised between 1 and 5 mg/L/4h.


Specific target organ toxicity: single exposure (Oral):


No data available.


Specific target organ toxicity: single exposure (Dermal):


No data available.


Specific target organ toxicity: single exposure (Inhalation):


The classification criteria according to the CLP and to the GHS as specific target organ toxicant (STOT) – single exposure, inhalation are not met since no significant adverse health effects were observed on specific organs immediately or delayed after exposure. No classification is required.


Aspiration hazard:


No data available.

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