Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
In a GLP study conducted according to OECD TG 422 and OPPTS 870.3650, n-propyl propionate was evaluated for reproductive and developmental toxicity endpoints. 
Effect on fertility: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
2 411 mg/m³
Study duration:
subchronic
Species:
rat
Quality of whole database:
good
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Reproduction toxicity data on n-propyl propionate:

In a reproduction/developmental toxicity screening study (OECD TG 422) available, exposure to n-propyl propionate resulted in slight reductions in food consumption and body weight throughout the study in females exposed to 250 and 500 ppm. Treatment related histopathologic effects were also evident in the nasal tissues of males and females exposed to all test concentrations. The nasal tissue effects consisted of very slight degeneration of the olfactory epithelium. In addition males exposed to 500 ppm and females exposed to ≥ 50 ppm had a higher incidence of adipose tissue atrophy than the controls. This was interpreted to have questionable significance. No treatment-related effects were seen in reproductive performance, pup survival and growth, neurologic function, clinical chemistry, or hematology. Therefore, the low-observed-effect concentration (LOEC) for general toxicity for male and female rats was considered to be 500 ppm and the NOEC for reproductive effects and neurological function was 500 ppm (2411 mg/m3), the highest concentration tested.

Conclusion:

 

In all the available studies on category members there is an absence of any (or any significant) reproduction toxicity . Therefore, it is concluded that propyl propionate is unlikely to cause any reproduction toxicity.

Effects on developmental toxicity

Description of key information
There is an inhalation developmental toxicity study available for butyl propionate.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
10 808 mg/m³
Study duration:
subacute
Species:
rat
Quality of whole database:
good
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

There is an inhalation developmental toxicity studies available for the category member butyl propionate.

In a GLP study conducted according to EPA OTS 798.4900 (Prenatal Developmental Toxicity Study), groups of Sprague Dawley rats were exposed (whole body) via inhalation to vapours of butyl propionate at levels of 500, 1000 and 2000 ppm for 6 hours/day, 10 consecutive days (gestation days 6-15). Based on effects on body weight and food consumption observed at exposure concentrations, a NOAEL (no observed adverse effect level) for maternal toxicity was not determined. The exposure concentration of 500 ppm was considered to be the LOAEL (lowest observed adverse effect level) for maternal toxicity. Alternatively, no treatment-related developmental toxic effects were noted for the three tested exposure concentrations. Therefore, the highest exposure 2000 ppm, was considered to be the NOAEL for developmental toxicity.

In a GLP study conducted according to OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test), groups of male and female Crl:CD(SD) rats were exposed via inhalation (whole body) to vapours of propyl propionate at levels of 0, 250, 500 and 1000 ppm for 6 hours/day, 7 days/week for a period of approximately 6-8 weeks.Treatment related histopathologic effects were also evident in the nasal tissues of males and females exposed to all test concentrations. The nasal tissue effects consisted of very slight degeneration of the olfactory epithelium. No treatment-related effects were seen in reproductive performance, pup survival and growth, neurologic function, clinical chemistry, or hematology. Therefore, the low-observed-effect concentration (LOEC) for general toxicity for male and female rats was considered to be 500 ppm and the NOEC for reproductive effects and neurological function was 500 ppm, the highest concentration tested.

 

On the basis of the studies conducted it can be concluded that pentyl propionate is unlikely to cause any developmental toxicity.

Compound tested

Species tested

Duration of exposure

GLP status

Doses tested

Guideline

Result - Maternal toxicity

Result - Developmental toxicity

Butyl propionate

SD rats

GD 6-15, 6 hours/day

Yes

0, 500, 1000, 2000 ppm

EPA OTS 798.4900

LOAEL – 500 ppm

NOAEL – 2000 ppm

Propyl propionate

SD rats

Approximately 6-8 weeks

Yes

0, 250, 500, 1000 ppm

OECD 422

LOEC – 500 ppm

NOEC – 500 ppm

Developmental toxicity data on n-butyl propionate:

In this GLP study conducted according to EPA OTS 798.4900 (Prenatal Developmental Toxicity Study), groups of Sprague Dawley rats were exposed (whole body) via inhalation to vapours of butyl propionate at levels of 500, 1000 and 2000 ppm for 6 hours/day, 10 consecutive days (gestation days 6-15). Based on effects on body weight and food consumption observed at exposure concentrations, a NOAEL (no observed adverse effect level) for maternal toxicity was not determined. The exposure concentration of 500 ppm was considered to be the LOAEL (lowest observed adverse effect level) for maternal toxicity. Alternatively, no treatment-related developmental toxic effects were noted for the three tested exposure concentrations. Therefore, the highest exposure 2000 ppm, was considered to be the NOAEL for developmental toxicity.

Developmental toxicity data on n-propyl propionate:

In a reproduction/developmental toxicity screening study (OECD TG 422) available, exposure to n-propyl propionate resulted in slight reductions in food consumption and body weight throughout the study in females exposed to 250 and 500 ppm. Treatment related histopathologic effects were also evident in the nasal tissues of males and females exposed to all test concentrations. The nasal tissue effects consisted of very slight degeneration of the olfactory epithelium. In addition males exposed to 500 ppm and females exposed to ≥ 50 ppm had a higher incidence of adipose tissue atrophy than the controls. This was interpreted to have questionable significance. No treatment-related effects were seen in reproductive performance, pup survival and growth, neurologic function, clinical chemistry, or hematology. Therefore, the low-observed-effect concentration (LOEC) for general toxicity for male and female rats was considered to be 500 ppm and the NOEC for reproductive effects and neurological function was 500 ppm, the highest concentration tested.

 

Conclusion:

There is an absenceof any developmental toxicity based on the available study with propyl propionate, as well as a lack of developmental toxicity on a second catgegory substances. Therefore, it is concluded that propyl propionate is unlikely to cause any developmental toxicity.

Justification for selection of Effect on developmental toxicity: via inhalation route:
Key study on a category member

Toxicity to reproduction: other studies

Additional information

There are no other reproduction toxicity studies available for pentyl propionate.

Justification for classification or non-classification

In the absence of any effects observed in the reproduction screening test for propyl propionate and the developmental toxicity test for butyl propionate and based on the Guidance to Regulation (EC) No. 1272/2008 on Classification, Labelling and Packaging of substances and mixtures, butyl propionate will not be classified for reproduction and developmental toxicity.