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Key value for chemical safety assessment

Effects on fertility

Description of key information

An OECD guideline 421 study in rats is currently on-going with alpha-pinene multiconstituent.

Effect on fertility: via oral route
Endpoint conclusion:
no study available (further information necessary)
Effect on fertility: via inhalation route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LOAEC
566.5 mg/m³
Study duration:
subchronic
Species:
mouse
Quality of whole database:
The relevance of the effects observed in male rats and mice can be questioned: first, the heat fixation at 65°C of caudae samples for sperm counts may have altered the integrity of the samples; secondly, these changes in sperm levels were not corroborated by other findings such as histopathological changes in other reproductive organs/tissues or other sperm parameters (motility, spermatid counts, etc.). In addition animals were exposed whole body by inhalation, which likely resulted in systemic exposure much higher than intended exposure from target doses (animals likely exposed by oral route through grooming).
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

In a 90-day inhalation study conducted by NTP similarly to OECD guideline 413, male rats exposed to alpha-pinene showed effects on renal and reproductive systems. The effects on kidneys are not relevant to humans as they are based on sex- and species-specific renal effects linked to alpha 2µ-globulin accumulation. A decrease in sperm count in cauda epididymis at 200 and 400 ppm was observed. Therefore the NOAEC identified for male rats is 100 ppm. A lower body weight gain and death of 6 out of 10 females in the high dose group (400 ppm) were observed. A NOAEC could be defined in female rats at 200 ppm on the basis of mortality and a lower body weight gain.

 

In a 90-day inhalation study conducted by NTP similarly to OECD guideline 413, mice were exposed to alpha-pinene. Minimal to moderate hyperplasia have been observed in the transitional epithelium of the urinary bladder from 100 ppm in both sexes.

Decreased numbers of sperm per mg cauda in 200 and 400 ppm males and cauda sperm in 100, 200, and 400 ppm males were observed.

A NOAEC for female mice has been set at 50 ppm based on minimal to moderate hyperplasia observed in the transitional epithelium of the urinary bladder and a LOAEC for males at 100 ppm has been determined based on significantly decreased sperm count per mg cauda .

However, the relevance of the effects observed in male rats and mice can be questioned: first, the heat fixation at 65°C of caudae samples for sperm counts may have altered the integrity of the samples; secondly, these changes in sperm levels were not corroborated by other findings such as histopathological changes in other reproductive organs/tissues or other sperm parameters (motility, spermatid counts, etc.). In addition animals were exposed whole body by inhalation, which likely resulted in systemic exposure much higher than intended exposure from target doses (animals likely exposed by oral route through grooming).

Effects on developmental toxicity

Description of key information

A testing proposal for an OECD guideline 414 on alpha-pinene multiconstituent in rats is submitted.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available (further information necessary)
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Justification for classification or non-classification

In 90-day repeated dose toxicity studies by inhalation performed in rats and mice, a decrease in sperm count in cauda epididymis at 200 and 400 ppm was observed in rats and decreased sperm count per mg cauda epididymis at 200 and 400 ppm and decreased sperm count in cauda epididymis at 100, 200, and 400 ppm were observed in mice.

However, the relevance of these effects can be questioned: first, the heat fixation at 65°C of caudae samples for sperm counts may have altered the integrity of the samples; secondly, these changes in sperm levels were not corroborated by other findings such as histopathological changes in other reproductive organs/tissues or other sperm parameters (motility, spermatid counts, etc.). Also, these decreases might be secondary to stress induced by hyperplasia of bladder epithelium at the 3 highest doses in mice. In addition animals were exposed whole body by inhalation, which likely resulted in systemic exposure much higher than intended exposure from target doses (animals likely exposed by oral route through grooming).

Further studies on alpha-pinene multiconstituent are on-going or proposed. As a consequence, no classification can be currently determined.