Propionic anhydride

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Additional information

Due to the very short half-life (4 minutes) in aqueous media, propionic acid is a valid read-across substance for propionic anhydride, as it is the primary hydrolysis product.

There are no reproductive toxicity studies available for n-propionic acid. Data from a 100 days repeated-dose study in dogs did not result in toxicity to reproductive organs.

In a dog study satisfying GLP requirements and OECD 409 TG, propionic acid (> 99% purity) was administered via diet to male and female Beagle dogs (4/sex/dose) for approximately 100 days at diet concentrations of 0, 3000, 10000 and 30000 ppm propionic acid. A recovery period of 6 weeks was allocated for the groups (4/sex/dose) receiving 0 and 3000 ppm propionic acid in the diet. No mortality occurred during the administration period. No substance related clinical signs of toxicity occurred. Calculated from food consumption, the mean daily dose administered were 214.2, 718.9, 2056.3 mg/kg bw for males and 225.1, 749.2, 2071.8 mg/kg bw for females. Dogs from the high-dose group displayed a decrease in appetite, which was attributed as a response due to unpalatability of the diet. This decrease in food consumption however did not seem to significantly affect body weights or body weight gains. No systemic effects were observed even at the highest dose. There were no significant changes in haematology, urinalysis, or clinical chemistry parameters that could be attributed to the test material. Necropsy of dogs after the administration interval revealed no gross lesions. Examination of tissues revealed no lesions except point-of-contact diffuse epithelial hyperplasia of the mucosa of the oesophagus in several high dose dogs. This effect was reversible after a 6 week recovery period. The incidence of focal epithelial hyperplasia in lower dose animals was comparable to controls. There were no effects observed on male or female reproductive organs. The NOAEL for this study for systemic /reproductive organ effects is 3000 ppm propionic acid in the diet or 2056,3 mg/kg bw for male dogs and 2071.8 mg/kg bw for female dogs (BASF, 1988).

Short description of key information:
- No effects on reproductive organs of dogs

Effects on developmental toxicity

Description of key information

Read across to calcium propionate (CAS No.4075-81-4) 
- Rat: NOAEL (maternal toxicity): 300 mg/kg bw; NOAEL (developmental toxicity): 300 mg/kg bw
- Mouse: NOAEL (maternal toxicity): 300 mg/kg bw; NOAEL (developmental toxicity): 300 mg/kg bw
- Rabbit: NOAEL (maternal toxicity): 400 mg/kg bw; NOAEL (developmental toxicity): 400 mg/kg bw
- Hamster: NOAEL (maternal toxicity): 400 mg/kg bw; NOAEL (developmental toxicity): 400 mg/kg bw

Additional information

There are no data available for n-propionic acid. Calcium propionate is an ion pair, which readily dissociates in water. The dissociation constant shows that at the low pH of the stomach, the important moieties from a toxicological standpoint are the unionized free acid and ionized metal. Because of this, mammalian toxicity data for calcium propionate can serve as surrogate data for the acid. Data for calcium propionate in four species (mouse, rat, hamster, and rabbit) are presented.

Calcium propionate was fed to pregnant CD-1 mice and Wistar rats during gestation days 6-15 at dose levels of 3, 14, 65, and 300 mg/kg-bw/day. Pregnant rabbits and hamsters were fed calcium propionate at a doses of 0, 4, 19, 86, and 400 mg/kg-bw/day during gestation days 6-18 (rabbits) or 6-10 (hamsters). Body weights of dams were taken at several intervals during gestation. Dams were observed each day for food and water intake and other measures of appearance and behavior. Dams were sacrificed on gestation day 17 (mice), 20 (rats), 14 (hamsters), or 29 (rabbits). Numbers of implantation sites, resorption sties, and live and dead fetuses were recorded. Body weights of live pups were also recorded. All pups were examined grossly for external congenital abnormalities. One-third of the fetuses of each litter underwent detailed visceral examinations; two-thirds were examined for skeletal defects. In all species, there was no effect on maternal or fetal survival, or on fetal or litter size. No increase in fetal or skeletal abnormalities was observed. The NOAEL for maternal toxicity and developmental in rats is 300 mg/kg bw. The NOAEL for maternal toxicity and developmental in mouse is 300 mg/kg bw. The NOAEL for maternal toxicity and developmental in rabbits is 400 mg/kg bw and the NOAEL for maternal toxicity and developmental in hamster is 400 mg/kg bw (FDA 1972). The study is acceptable for asssessment with restrictions. The authors provided no reason why tests were not performed up to the limit concentration. However, based on the findings from the repeated dose studies, forestomach lesions will be expected to occur at the limit dose.

Justification for classification or non-classification

Classification for reproduction toxicity is not warranted according to the criteria of EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.