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Administrative data

Description of key information

90-day inhalation toxicity study conducted in rats showed a LOAEL of 50 ppm for males based on male specific renal effects linked to alpha2µ-globulin accumulation and a NOAEL of 200 ppm for females based on mortality and a lower body weight gain. Mortality was observed in female rats in the high dose group. As no specific target organ was sufficiently impaired by the treatment to cause mortality, it may be concluded that these deaths have a general systemic toxicity origin.
90-day inhalation toxicity study conducted in mice showed a NOAEL in male and female mice of 50 ppm based on minimal to moderate hyperplasia observed in the transitional epithelium of the urinary bladder in animals treated at 100 ppm and higher doses.

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
283.24 mg/m³
Study duration:
subchronic
Species:
mouse

Additional information

90-day inhalation toxicity study conducted in rats showed a LOAEL of 50 ppm for males based on male specific renal effects linked to alpha2µ-globulin accumulation and a NOAEL of 200 ppm for females based on mortality and a lower body weight gain. Mortality was observed in female rats in the high dose group. As no specific target organ was sufficiently impaired by the treatment to cause mortality, it may be concluded that these deaths have a general systemic toxicity origin.

90-day inhalation toxicity study conducted in mice showed a NOAEL in male and female rats of 50 ppm based on minimal to moderate hyperplasia observed in the transitional epithelium of the urinary bladder in animals treated at 100 ppm and higher doses.

As the accumulation of alpha2μ-globulin in renal proximal tubule cells observed in male rats is sex and species-specific, the LOAEL defined for male rats is not relevant for humans (Meek, 2003). Thus, the NOAEL selected is based on minimal to moderate hyperplasia observed in the transitional epithelium of the urinary bladder found in mice at 100 ppm and higher doses.

NOAEC mouse inhalation (mg/m3) = (NOAEL (mg/kg bw/day) * molecular weight) / Vmol = (50 * 136.24) / 24.05 = 283.24 mg/m3

Reference: Meek M.E. et al. (2003) A Framework for Human Relevance Analysis of Information on Carcinogenic Modes of Action, Critical Reviews in Toxicology, 33(6): 591 -653.


Repeated dose toxicity: inhalation - systemic effects (target organ) urogenital: urinary bladder

Justification for classification or non-classification

The CLP classification for Specific Target Organ Toxicity in repeated exposure is based on results found in rats therefore the results found in mice are not taken into account. The LOAEL in male rats is the lowest dose level tested, but it is not relevant to humans as it is based on renal effects linked to alpha2µ-globulin accumulation. When considering effects other than those on kidneys in males, a lower body weight gain was observed at 400 ppm when compared to controls. A NOAEL could be defined in female rats at 200 ppm on the basis of mortality and a lower body weight gain at the next dose level when compared to controls. The overall NOAEL relevant for humans is 200 ppm.

Although the NOAEL relevant for humans is 200 ppm and the limit dose for Specific Target Organ Toxicity in repeated exposure classification according to CLP regulation is 250 ppm, there is no critical adverse effects identified in a specific target organ that could lead to classification for Specific Target Organ Toxicity in repeated exposure.

Therefore, considering read across approach, (-)-beta-pinene does not need to be classified Category 2 for Specific Target Organ Toxicity in repeated exposure according to CLP Regulation (EC) No 1272/2008.